Wednesday 08 September
08:00

"Wednesday 08 September"

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C10
08:00 - 13:00

Satellite course in advanced imaging
Brain Imaging - Postprocessing in Functional Neurosurgery

Moderators: Nadine GIRARD (Marseille, France), Viktor JIRSA (Aix-Marseille University, Local Host, EBRAINS AISBL) (Marseille, France), Ludvic ZRINZO (Professor of Neurosurgery) (London, UK, United Kingdom)
08:00 - 08:30 Basics MR. Jean-Philippe RANJEVA (CNS team leader) (Keynote Speaker, Marseille, France)
08:30 - 09:00 Stereotactic MRI. Ludvic ZRINZO (Professor of Neurosurgery) (Keynote Speaker, London, UK, United Kingdom)
09:00 - 09:30 Statistical approach of the functioning brain. Demian BATTAGLIA (CNRS research scientist) (Keynote Speaker, Marseille, France)
09:30 - 10:00 Morphometry in the brain, VBM …. François MANGIN (Keynote Speaker, France)
10:00 - 10:30 Coffee Break.
10:30 - 11:00 Tractography. Harith AKRAM (Associate Professor) (Keynote Speaker, London, United Kingdom)
11:00 - 11:30 Functionbal connectivity Resting state MRI. Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Keynote Speaker, Lausanne, Switzerland)
11:30 - 12:00 PET. Eric GUEDJ (Directeur DHU Imaging) (Keynote Speaker, Marseille, France)
12:00 - 12:30 Multimodality approaches and ultra-high field MRI. Maxime GUYE (Neurologist) (Keynote Speaker, Marseille, France)
12:30 - 13:00 Discussion.
Espace Vieux-Port

"Wednesday 08 September"

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D10
08:00 - 14:30

EANS ESSFN European Diploma of Radiosurgery
Vascular

Moderators: Bodo LIPPITZ (Co-Director) (Hamburg, Germany), Selcuk PEKER (Neurosurgeon) (Istanbul, Turkey)
08:00 - 10:00 I - Arterio Venous Malformations.
08:00 - 08:30 a) Basics, radiobiology predictive factors, angioarchitecture & technical issues. Jean REGIS (PROFESSEUR) (Keynote Speaker, MARSEILLE, France)
08:30 - 09:00 b) Patient selection, natural history, bleeding risk predictors role of imaging modalities, scoring. Piero PICOZZI (Consultant) (Keynote Speaker, Milano, Italy)
09:00 - 09:30 c) Follow up, Outcome, definition of cure, management of failures. Brigitte GATTERBAUER (Gamma Knife) (Keynote Speaker, Vienna, Austria)
09:30 - 10:00 d) Toxicity & complication management and prediction. Bodo LIPPITZ (Co-Director) (Keynote Speaker, Hamburg, Germany)
10:00 - 10:30 Coffee Break.
10:30 - 11:30 II - Fistulas.
10:30 - 10:50 a) Definition indications of the different approaches’ outcome definition of cure. Giorgio SPATOLA (Neurosurgeon) (Keynote Speaker, Brescia, Italy)
10:50 - 11:10 b) Targeting, technic of radiosurgery and outcome (safety efficacy). Selcuk PEKER (Neurosurgeon) (Keynote Speaker, Istanbul, Turkey)
11:10 - 11:30 c) Spinal AVM and FAV indications and results of radiosurgery. Roberto MARTINEZ-ALVAREZ (Neurosurgeon) (Keynote Speaker, Madrid, Spain)
11:30 - 12:30 III - Cavernomas.
11:30 - 11:55 a) Epidemiology, pathology, clinical presentation, natural history and bleeding risk. Mohamed Yassine BELTAIFA (Praticien attaché associé) (Keynote Speaker, Marseille, France)
11:55 - 12:20 b) Role of Radiosurgery and alternatives, efficacy and complication of SRS. Roberto MARTINEZ-ALVAREZ (Neurosurgeon) (Keynote Speaker, Madrid, Spain)
12:20 - 12:30 Discussion & Closure.
12:30 - 13:00 Free Lunch time.
13:00 - 14:00 Manufacturer/demo sessions: How I do with the Gamma Plan.
14:00 - 14:30 Manufacturer/demo sessions: How I do with Element. Selcuk PEKER (Neurosurgeon) (Keynote Speaker, Istanbul, Turkey)
Salle 120
14:00

"Wednesday 08 September"

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C12
14:00 - 18:00

Workshop
Recent advances in Peripheral Nerve Stimulation (PNS) for intractable pain

Moderators: Denys FONTAINE (Neurosurgeon) (NICE, France), Konstantin V. SLAVIN (professor) (Chicago, USA)
14:00 - 14:30 Mechanisms of action of PNS. Anne BALOSSIER (Dr) (Keynote Speaker, Marseille, France)
14:30 - 15:00 Facial PNS for facial pain. Konstantin V. SLAVIN (professor) (Keynote Speaker, Chicago, USA)
15:00 - 15:30 Occipital Nerve Stimulation for non-primary headache and cervical pain. Sylvie RAOUL (MEDECIN) (Keynote Speaker, NANTES, France)
16:00 - 16:30 Brachial plexus roots PNS for upper limb pain. Denys FONTAINE (Neurosurgeon) (Keynote Speaker, NICE, France)
16:30 - 17:00 Peripheral Nerve Field Stimulation for chronic low back pain. Philippe RIGOARD (Head of Departement Spine-Neurostimulation) (Keynote Speaker, Poitiers, France)
17:00 - 17:30 Dorsal Root Ganglion stimulation. Andrei BRINZEU (MD) (Keynote Speaker, Lyon, France)
17:30 - 18:00 Discussion.
Espace Vieux-Port
15:30 COFFEE BREAK
18:00

"Wednesday 08 September"

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A14
18:00 - 19:00

WELCOME LECTURES

Moderators: Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (LISBON, Portugal), Joachim K. KRAUSS (Chairman and Director) (Hannover, Germany), Paul KRACK (Head Center Parkinson and Movement Disorders) (Bern, Switzerland), Jean REGIS (PROFESSEUR) (MARSEILLE, France)
18:00 - 18:15 The DNA of the ESSFN. Marwan HARIZ (neurosurgeon) (Keynote Speaker, Umeå, Sweden)
18:15 - 18:25 Honorary session.
Alim Louis Benabid, Bergman Hagai, Pierre Pollak
18:25 - 19:00 The stunning undersea world of Marseille: portrait of two iconic dwellers in a challenging environment. Jean-Georges HARMELIN (Keynote Speaker, Marseille, France)
Auditorium
18:30 WELCOME RECEPTION - EXHIBITION AREA
Thursday 09 September
08:30

"Thursday 09 September"

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A21
08:30 - 10:00

Plenary Session 1 - OPENING CEREMONY & SPECIAL LECTURES

Moderators: Patric BLOMSTEDT (Neurosurgeon) (Umeå, Sweden), Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (LISBON, Portugal), Jean REGIS (PROFESSEUR) (MARSEILLE, France)
08:30 - 08:45 Opening Lecture. Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (Keynote Speaker, LISBON, Portugal)
08:45 - 09:15 Stereotactic Navigation: 4 centuries BC. Jean REGIS (PROFESSEUR) (Keynote Speaker, MARSEILLE, France)
09:15 - 10:00 Lesion versus stimulation for OCD & depression. Ludvic ZRINZO (Professor of Neurosurgery) (Keynote Speaker, London, UK, United Kingdom), Veerle VISSER-VANDEWALLE (Head of Dep. of Ster. and Funct. NS) (Keynote Speaker, Cologne, Germany)
Auditorium
10:00 COFFEE BREAK & VISIT OF POSTERS AND EXHIBITION
10:30

"Thursday 09 September"

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A22
10:30 - 12:00

Plenary Session 2 - Movement Disorders

Moderators: Jorge GURIDI (Neurosurgery) (Pamplona, Spain), Andres LOZANO (Alan & Susan Hudson Cornerstone Chair in Neurosurgery, University Health Network) (Toronto, Canada), Tatiana WITJAS (neurologist) (Marseille, France)
10:30 - 10:50 PPN stimulation for gait disorders in PD. Stephan CHABARDÈS (head of the department) (Keynote Speaker, GRENOBLE, France)
10:50 - 11:10 Spinal cord stimulation for gait disorders in PD. Grégoire COURTINE (Prof. Dr. Courtine) (Keynote Speaker, Geneve, Switzerland)
11:10 - 11:30 STN DBS a new treatment of impulse control disorders in PD? Paul KRACK (Head Center Parkinson and Movement Disorders) (Keynote Speaker, Bern, Switzerland)
11:30 - 11:50 Rational past & future of PTT in Parkinson disease. Jorge GURIDI (Neurosurgery) (Keynote Speaker, Pamplona, Spain)
11:50 - 12:00 Discussion.
Auditorium
12:00 INDUSTRIAL LUNCH WORKSHOPS
13:30

"Thursday 09 September"

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A24
13:30 - 15:00

Plenary Session 3 - LESIONING

Moderators: Kostiantyn KOSTIUK (Neurosurgeon) (KYIV, Ukraine), Ido STRAUSS (Neurosurgeon) (Tel Aviv, Israel), Ludvic ZRINZO (Professor of Neurosurgery) (London, UK, United Kingdom)
13:30 - 13:50 HIFU for Tremor. Jordi RUMIA (Coordinator. Adult and Paediatric Functional Neurosurgery Program) (Keynote Speaker, Barcelona, Spain)
13:50 - 14:10 Is there a future role of LITE in Movement Disorders. Michael SCHULDER (Vice Chair, Neurosurgery) (Keynote Speaker, Lake Success, NY, USA)
14:10 - 14:30 HIFU for OCD. Jin Woo CHANG (Keynote Speaker, Seoul, Korea)
14:30 - 15:00 P&C FUS versus DBS in essential tremor (Vim) & PD (STN) - Pros and cons. Ron ALTERMAN (Chairman) (Keynote Speaker, Boston, USA), Rees COSGROVE (Director, Epilepsy and Functional Neurosurgery) (Keynote Speaker, Boston, USA)
Auditorium
15:00 COFFEE BREAK & VISIT OF POSTERS AND EXHIBITION
15:30

"Thursday 09 September"

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A25
15:30 - 16:30

Parallel Session 1
Restorative Surgery

Moderators: Jocelyne BLOCH (Médecin Cadre) (Lausanne, Switzerland), Stéphane PALFI (HEAD) (PARIS, France)
15:30 - 15:45 Restorative transplantation and viral vectors. Nicole DEGLON (Prof.) (Keynote Speaker, Lausanne, Switzerland)
15:45 - 16:00 Restorative transplantation and viral vectors. Stéphane PALFI (HEAD) (Keynote Speaker, PARIS, France)
16:00 - 16:15 #26251 - Efficient representation of hand biomechanics for upper limb neuroprostheses.
Efficient representation of hand biomechanics for upper limb neuroprostheses.

Background

Loss of upper limb function has a major impact on functional independence and quality of life. Neuroprosthetic technologies have been developed to restore function by extracting information from the intact motor cortex to control assistive technologies. However, most current approaches do not take advantage of the latent structure of natural movements.

 

Hand movements have a large number of possible degrees of freedom, however natural movements tend to be stereotyped combinations of simple movements. The ability to represent complex movements efficiently is valuable. A representation that allows reconstruction of high-dimensional, continuous control signals and classification of movements would allow for more efficient prosthetic systems with increased performance. The ability to interpolate movements beyond the movements used in training, would open the possibility of truly generalizable, naturalistic prosthetic control.

 

Methods

Detailed kinematic data was collected during a series of complex, everyday hand movements.

Linear dimensionality reduction was performed using principal component analysis. The latent structure of hand movements was investigated using the proportion of variance explained by a low-dimensional representation. The quality of movement reconstruction was quantified using the mean squared error between actual and predicted control signals. Classifiers were used to investigate the ability of low-dimensional representations to separate movement classes. Interpolation performance was assessed by measuring the ability to reconstruct movements not contained in the training data.

 

A deep learning approach was then employed to overcome limitations of these linear approaches. A two-stage autoencoder architecture was developed with recurrent neural networks in both the encoder and decoder. This model was trained using a variety of loss functions in order to tailor the resulting low-dimensional representation to achieve the desired characteristics. The ability of these models to reconstruct, classify and interpolate movements was compared to linear methods.

 

Results

Naturalistic hand movements can be represented in a low-dimensional space, with >95% of the variance accounted for by 9 dimensions. A linear transformation from this low-dimensional space can accurately reconstruct continuous control signals. Linear classifiers can accurately classify movements within this space, with a softmax regression algorithm achieving accuracy of >80%. New movements can be accurately reconstructed and classified by interpolating their position in latent space, and only a subset of training tasks are required to characterize this space.

 

A deep learning approach based on a recurrent autoencoder network overcomes many of the limitations of the linear methods developed. Reconstruction error is reduced by >80% using this approach, while customizing the training loss function allows the movement representation to be optimized for movement classification and interpolation, further increasing performance.

 

Discussion

Our results indicate that hand biomechanics have a latent structure. This structure can be exploited in order to efficiently represent detailed hand kinematics. This allows for efficient transmission of movement information. Further, this representation allows for the reconstruction and interpolation of movement data, including of previously unseen movements.

 

This has important implications for neuroprosthetics and brain-computer interfaces. The ability to produce complex movements using low-dimensional data and to generalize accurately to new, unseen movements opens the possibility for complex, naturalistic control of assistive technologies. Further, our results identify a subset of movements required to characterize the space of movement representations, allowing for highly efficient training: by training only the movements required to interpolate generalizable control, the major barrier to translation of excessive training requirements can be overcome.

 

Overall, our results identify a latent structure in hand biomechanics and a set of hand movement primitives that define this structure. We demonstrate that this structure can be exploited to represent complex hand movements using a low-dimensional representation, and that new hand movements can be interpolated using this latent space model. We show that this approach has potential utility to restoration of naturalistic hand movements in neuroprosthetic systems.


Keogh CONOR (Oxford, United Kingdom), Fitzgerald JAMES
Auditorium

"Thursday 09 September"

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B25
15:30 - 19:00

Parallel Session 2
Movement Disorders

Moderators: Juan Antonio BARCIA (Neurosurgeon) (Barcelona, Spain), Alexandre EUSEBIO (Professor) (Marseille, France), Niels Anthony VAN DER GAAG (neurosurgeon) (The Hague, The Netherlands)
15:30 - 15:40 #23357 - Long-term evaluation of deep brain stimulation for treatment of Parkinson's disease using a multiple-source, constant- current rechargeable system: 4-year follow-up of a prospective, double-blind RCT.
Long-term evaluation of deep brain stimulation for treatment of Parkinson's disease using a multiple-source, constant- current rechargeable system: 4-year follow-up of a prospective, double-blind RCT.

Objective: The long-term effectiveness of a Deep Brain Stimulation (DBS) device capable of Multiple Independent Current Control (MICC) is assessed in a prospective, sham-controlled, double-blind randomized controlled trial (RCT) where participants are followed for up to 5-years for the treatment of motor symptoms of Parkinson’s disease (PD).

Background: Subthalamic Nucleus (STN) DBS is an established therapeutic option for managing the motor symptoms of PD, and here we report long-term open-label outcomes (up to 4-years) of a double-blind RCT with sham control using an MICC-based DBS device.

Methods: INTREPID (Clinicaltrials.gov identifier: NCT01839396) is a multi-center, prospective, double-blinded randomized controlled trial (RCT) sponsored by Boston Scientific. Subjects with advanced PD were implanted bilaterally in the STN with a multiple-source, constant-current DBS system (Vercise, Boston Scientific). Subjects were randomized to either receive active versus control settings for 12 weeks. Upon completion of the 12-week blinded period, subjects received their best therapeutic settings in the open-label phase up to 5 years. During long-term follow-up, motor improvement and quality of life was evaluated using UPRDS, PDQ39, and Schwann and England. Adverse events were also collected.

Results: Analysis of the pre-specified primary endpoint demonstrated a mean difference of 3.03 ± 4.52 hours (p<0.001) between active and control groups in ON time without troublesome dyskinesia, with no increase in antiparkinsonian medication, from post-implant baseline to 12-weeks post-randomization. A 49% (p<0.001) improvement in UPDRS III scores (meds off) at 1-year was previously reported and sustained up to 3-year follow-up (46%, p<0.001). Eighty-nine percent of patients at 3-year follow-up reported high satisfaction with their treatment. At 4-year follow-up, improvement in motor function (41%, UPDRSIII scores) and quality of life was sustained.

Conclusions: Long-term follow-up from the INTREPID RCT demonstrates that the use of a multiple-source, constant-current DBS system is safe and effective with sustained improvement in motor function and quality of life up to 4-years post-implant.


Philip STARR (san francisco, USA), Roshini JAIN, Lilly CHEN, Alexander TRÖSTER, Lauren SCHROCK, Paul HOUSE, Monique GIROUX, Adam HEBB, Sierra FARRIS, Donald WHITING, Timothy LEICHLITER, Jill OSTREM, Marta SAN LUCIANO, Nicholas GALIFIANAKIS, Leo VERHAGEN METMAN, Sepehr SANI, Jessica KARL, Mustafa SIDDIQUI, Stephen TATTER, Ihtsham UL HAQ, Andre MACHADO, Michal GOSTKOWSKI, Michele TAGLIATI, Adam MAMELAK, Michael OKUN, Kelly FOOTE, Guillermo MOGUEL-COBOS, Francisco PONCE, Rajesh PAHWA, Jules NAZZARRO, Cathrin BUETEFISCH, Robert GROSS, Corneliu LUCA, Jonathan JAGID, Gonzalo REVUELTA, Istvan TAKACS, Michael POURFAR, Alon MOGILNER, Andrew DUKER, George MANDYBUR, Joshua ROSENOW, Scott COOPER, Michael PARK, Suketu KHANDHAR, Mark SEDRAK, Fenna PHIBBS, Julie PILITSIS, Ryan UITTI, Jerrold VITEK
15:40 - 15:50 #23378 - Stereotactic venture-intermediate nucleus for essential tremor tremor normalizes aberrant dynamic functional connectivity of extrastriate visual system: a resting-state functional MRI study.
Stereotactic venture-intermediate nucleus for essential tremor tremor normalizes aberrant dynamic functional connectivity of extrastriate visual system: a resting-state functional MRI study.

Introduction: 

Tremor circuitry has been commonly hypothesized as driven by one or multiple pacemakers within the cerebello-thalamo-cortical pathway, including the cerebellum, contralateral motor thalamus and M1. However, previous studies, using multiple methodologies, have advocated that tremor could be influenced by visual feedback. Furthermore, visual feedback itself would increase tremor and would be accompanied by abnormal changes, spreading outside the cerebello-thalamo-cortical pathway, in the visual system. 

Methods:

The study included 42 participants: 12 HC (group 1), 15 patients with essential tremor (ET) (group 2; right-sided, drug-resistant) before ventro-intermediate ncuelus (Vim) radiosurgery (RS) and the same 15 (group 3) one year after left unilateral Vim RS. Imaging was done on a head-only 3T magnetic resonance imaging (MRI) scanner, SIEMENS SKYRA (Munich, Germany, 32-channel receive-only phased-array head coil). We used blood-oxygenation-level-dependent (BOLD) fMRI during resting state to characterize dynamical interactions of the extrastriate cortex, and compare healthy controls (HC) against ET patients before and 1 year after Vim RS. In particular, we applied the co-activation patterns (CAPs) methodology to extract whole-brain spatial patterns of brain activity that occur dynamically over time. 

Results:

We found that three different patterns are equally occurring in HC and ET and were reminiscent for the “cerebello-visuo-motor” (1), “thalamo-visuo-motor”(including the targeted thalamus, 2), and “basal ganglia and extrastriate” (3) networks. The occurrence of the first one was decreased in pretherapeutic ET as compared to HC, while the other two showed increased occurrences. This suggests a misbalance between the more prominent cerebellar circuitry and the thalamo-visuo-motor and basal ganglia networks. Multiple regression analysis showed that pretherapeutic standard tremor scores negatively correlated with the increased occurrence of the thalamo-visuo-motor network, suggesting a compensatory pathophysiological trait. The clinical improvement after thalamotomy was related to changes of occurrences of the basal ganglia and extrastriate cortex circuitry, which came back to HC values after the intervention, thus suggesting a role of dynamics of the extrastriate cortex in tremor generation and further arrest after the intervention. 

Conclusion:

In sum, we found that resting-state dynamic functional connectivity of the extrastriate cortex can be characterized by three CAPs. These patterns corresponded to (1) a “cerebello-visuo-motor”, (2) a “thalamo-visuo-motor” and (3) a “basal ganglia and extrastriate” network. The first one is decreased in occurrence in pretherapeutic ET as compared to HCs, while the following two rather display increased occurrences. This would suggest a balance between the cerebellar circuitry, and the thalamo-visuo-motor and further basal ganglia ones. The pretherapeutic tremor scores correlated with the abnormal increase in occurrence of the thalamo-visuo-motor network, suggesting a compensatory pathophysiological trait. The improvement in tremor scores after Vim RS is more related to changes within the basal ganglia and extrastriate cortex. All these circuitries aligned to healthy controls after thalamotomy, suggesting a prominent role of the extrastriate cortex and its dynamic connectivity in tremor generation and further arrest after interventional procedures. This opens the discussion for a potential new target for tremor, as we previously advocated in earlier studies, aiming at the extrastriate cortex. These findings support the idea that the visual system plays a prominent role in tremor generation and further arrest after interventional procedures, such as Vim RS.


Constantin TULEASCA (Lausanne, Switzerland), Thomas BOLTON, Jean RÉGIS, Elena NAJDENOVSKA, Tatiana WITJAS, Nadine GIRARD, Mohamed FAOUZI, Jean-Philippe THIRAN, Meritxell BACH CUADRA, Marc LEVIVIER, Dimitri VAN DE VILLE
15:50 - 16:00 #23786 - Asleep deep brain stimulation for essential tremor using a machine-learning approach for targeting: preliminary results of a phase-2 clinical trial (OPTI-VIM).
Asleep deep brain stimulation for essential tremor using a machine-learning approach for targeting: preliminary results of a phase-2 clinical trial (OPTI-VIM).

Background:

DBS of the VIM nucleus is an efficacious treatment for refractory essential tremor, although targeting the intra-thalamic nuclei remains challenging. In a previous work, using machine-learning algorithms, we were able to predict a clinical target for DBS in essential tremor. The learning database consisted in clinical and radiological features of patients previously operated on with optimal outcomes. The OPTI-VIM trial (NCT03760406) is now ongoing to validate this approach.

Patients and Methods:

In this prospective bi-centric (Lyon and Bordeaux), non-comparative, phase-2 clinical trial, we planned to include 22 patients with severe essential tremor despite optimal medical management, aged between 18 and 75 years, with normal MRI, without cognitive impairment (MDRS score ≥ 130) or depression (BDI scale < 20).

The primary endpoint is the efficacy of the procedure on tremor as assessed by the improvement on the Fahn-Tolosa-Marin (FTM) scale between the pre- and post-operative assessments 3 months after surgery. Secondary endpoints are (1) the efficacy of the procedure on tremor as assessed by accelerometry recordings; (2) complications related to surgery and neurostimulation-related side effects, mainly dysarthria and ataxia assessed by the SARA scale (scale for assessment and rating of ataxia); (3) improvement in quality of life’s mPDQ-39 scale between the pre-operative and post-operative assessments; and (4) the stereotactic accuracy was evaluated by calculation of the Euclidian distance between the target and the electrode by co-registration between the marked MRI with the target and the postoperative CT scan.

The target was planned with the “Optim-DBS” software we developed, on a 3D T1 MRI at 1.5 or 3 Tesla. DBS surgery was performed under general anaesthesia, without intra-operative clinical and electrophysiological testing.

Preliminary results:

Seven patients underwent surgery under general anaesthesia between June 2019 and January 2020 (4M/3F, mean age 63 years old).

The (pre-operative / post-operative) FTM scale means were 55/23.3. The mean improvement of the tremor was 55% on the FTM scale and 76% for the subscore of upper limb tremor. These scores were confirmed by accelerometry.

The (pre-operative / post-operative) SARA means were 5.9/4.2. Two patients worsened their SARA, the first one significantly worsened his ataxia with a score which increased from 4.5 to 10.5. The second one increased his score non-significantly from 3 to 4.

The (pre-operative / post-operative) PDQ39 means were 42.8/18.5, respectively. The mean improvement of quality of life were 58% on the PDQ39.

There were no surgical or device-related complications during the 3 months of follow-up.

The mean distance between the target and the electrode surface was 0.98mm (min 0, max 2.3).

Conclusions:

Asleep DBS for essential tremor using our machine-learning model for targeting may be a safe, efficient procedure leading to outcomes comparable to those published in the literature for standard awake DBS surgery. The final conclusions will be drawn once the study has been completed.


Julien ENGELHARDT, Emile SIMON, Dominique GUEHL, Stephane THOBOIS, Nathalie DAMON-PERRIERE, Teodor DANAILA, Louis NADAL, Pierre BRIAU, Olivier BRANCHARD, Nicolas AUZOU, Marie BONNET, Wassilios MEISSNER, Antoine BENARD, Pierre BURBAUD, Polo GUSTAVO, Patrick MERTENS, Emmanuel CUNY (bordeaux)
16:00 - 16:10 #23788 - Study of MRgFUS thalamotomy lesions in essential tremor and Parkinson disease in a large cohort of patients.
Study of MRgFUS thalamotomy lesions in essential tremor and Parkinson disease in a large cohort of patients.

Objective

To assess the clinical and radiological outcome of 134 patients with esential tremor (ET) and tremor dominant Parkinson’s disease (PD) at 6 month follow up treated by magnetic resonance guided focused ultrasound (MRgFUS).

Background

The efficacy of unilateral Vim (Ventralis Intermedius) thalamotomies by MRgFUS in tremor has been reported. Some authors consider this nucleus as part of the VLp (Ventral Lateralis posterior). It receives projections from the dentato-rubro-thalamic tract (DRT).

MRgFUS is an image-guided, incision-less procedure based on the focalization of high intensity ultrasound beams in a precise area of the brain where it produces a thermal ablation.

The resultant lesion usually presents 3 different areas visible in magnetic resonance (MR): a central necrosis (i) surrounded by cytotoxic (ii) and vasogenic (iii) edema.

Methods

Treatment was performed using MRgFUS equipment (Ex Ablate 4000, InSightec) coupled with a high field MR (3T Skyra, Siemens). Skull density ratio (SDR) was calculated in all patients before treatment. Parameters like intensity and duration of sonications were modulated during the procedure to achieve the target temperature.

Pre-treatment and immediately after treatment 3T MR studies were acquired in all patients. Classic coordinates were used for targeting of the Vim. Probabilistic tractography of the DRT was performed placing the regions of interest (ROIs) in the thalamus, premotor cortex and dentate nucleus (SyngoVia, Siemens).

Volumetry (areas i, ii and iii) and diameter of the lesions were analyzed by manual delineation on 3D T2 SPACE MR sequences with the Iplannet planification software (Brainlab). The volumes were exported as 3D objects and were superimposed onto individualized probabilistic atlas of the thalamic nuclei. Overlapping regions were studied.

Tremor severity was assessed at baseline, 1 (1m), 3 (3m), and 6(6m) month (follow-up using the Clinical Rating Scale for Tremor (CRST) in ET patients and the tremor items of the Unified PD Rating Scale (UPDRS) in PD patients.

Side effects were classified as mild (slight disturbances), moderate (partial impairment of daily activities), or severe (established neurological deficit with any level of disability).

For the statistical analysis, Mann Whitney U and Pearson correlation tests were applied with the STATA statistical tool.

Results

134 patients (87 ET, 47 PD; mean age 72.9 y.o; male 77%) underwent Vim thalamotomy contralateral to the patient´s hand tremor from october 2018 to december 2019. In patients with ET, the contralateral CRST score improved 80,98% (1m, 83 patients), 74% (3m,58 pt), 78% (6m, 34 pt). In PD patients, tremor improvement was 84,78% (1m, 37 pt), 78,84% (3m, 24 pt) and 65,35% (6m,16 pt). 

The most common side effects were gait instability and dysmetria, followed by dysarthria and finger or lip/tongue paresthesias. At 1m, 64% of the patients presented adverse events; 27,5% at 3m and 12,5% at 6m. More than 80-90% were mild, 10-15% were moderate and 0-4% were severe along the 6m period.  

Average volume of the lesions was 11,5 (i); 157,6(ii) and 376,3 (iii) cm3. The average outer volume of the lesions was 404,4 cm3. Mean diameter: 8,9 mm. Larger volumes were directly correlated with a greater number and severity of side effects at 1m, 3 m and 6m (moderate correlation; p<0,05).

Overlapping of individual atlas segmentation and lesions was performed in 47 patients. The mean overlapping percentage of the atlas VLp and the lesion was 70.44% (i), 58,37(ii) and 47,08 (ii). The overlapping region of the necrosis was inferior in those patients whose tremor responded worse to treatment (p<0,01)

Pre-treatment DRT tracts were used as an adjuvant tool during treatment to adjust the targeting coordinates when initial clinical response was poor.

Mean temperature (t) was 58,22º. SDR values were directly correlated with t (r=0,43; p<0,001); i and ii volumes (r=0,28 and 0,37; p<0,001); and inversely correlated with intensity (r=-0,64; p<0,01) and sonication duration( r=- 0,53; p<0,01).

Conclusions

MRgFUS thalamotomy for ET and PD is associated with a great improvement of tremor at 6m follow-up. Although side effects are frequent, the majority are mild. Larger lesions have an impact on its occurrence. SDR values play a role on the treatment outcome.


Olga Maria PARRAS (Basque country, Spain), Jorge GURIDI LEGARRA, Mari Cruz RODRÍGUEZ OROZ, Miguel FERNÁNDEZ MARTÍNEZ, Arantza GOROSPE OSINALDE, Iciar AVILÉS OLMOS, Laín Hermes GONZÁLEZ QUARANTE
16:10 - 16:20 #23801 - Structure-Function Relationship of the Posterior Subthalamic Area with Directional Deep Brain Stimulation for Essential Tremor.
Structure-Function Relationship of the Posterior Subthalamic Area with Directional Deep Brain Stimulation for Essential Tremor.

Objective Deep Brain Stimulation (DBS) of the Posterior Subthalamic Area (PSA) is an emergent target for the treatment of Essential Tremor (ET). Due to the hetereogenous and complex anatomy of the PSA  it remains unclear which specific structures mediate tremor suppression and different sorts of side effects. The objective of the current work was to yield a better understanding of what anatomical structures mediate different clinical effects observed during directional DBS of the PSA.

Methods We analysed a consecutive series of 12 ET patients. Imaging analysis and systematic clinical testing performed 4-6 months postoperatively yielded location, clinical efficacy and corresponding therapeutic windows for 160 directional contacts. Overlap ratios between individual stimulation activation volumes (VTA) and neighbouring thalamic and subthalamic nuclei as well as individual fiber tracts were calculated. Further, we generated stimulation heatmaps to assess the area of activity and structures stimulated during tremor suppression and occurrence of side effects.

Results Stimulation of the Dentato-Rubrothalamic Tract (DRTT) and the Zona incerta (Zi) was most consistently correlated with tremor suppression. Both individual and group analysis demonstrated a similar pattern of activation for tremor suppression and different sorts of side-effects. Unlike current clinical concepts, induction of spasms and paresthesia were not correlated with stimulation of the corticospinal tract and the medial lemniscus.  Furthermore, we noticed a significant difference in the therapeutic window between the best and worst directional contacts while the best directional contacts did not provide significantly larger windows than omnidirectional stimulation at the same level.

Conclusion PSA DBS is effective in suppressing all aspects of ET but can be associated with concomitant side effects limiting the therapeutic window. Activation patterns for tremor suppression and side effects were similar and predominantly involved the DRTT and the Zi. We found no different activation patterns between different types of side effects and no clear correlation between structure and function. Future studies with use of more sophisticated VTA modelling taking into account fiber heterogeneity and orientation may eventually better delineate these different clusters, which may allow for a refined targeting and programming within this area.


Andreas NOWACKI (Bern, Switzerland), Jean-Philippe LÉVY, Anh Khoa NGUYEN, Lennard LACHENMAYER, Ines DEBOVE, Gerd TINKHAUSER, Katrin PETERMANN, Joan MICHELIS, Michael SCHÜPBACH, Claudio POLLO
16:20 - 16:30 #23885 - Long-term local field potential-guided directional deep brain stimulation in Parkinson’s disease.
Long-term local field potential-guided directional deep brain stimulation in Parkinson’s disease.

INTRODUCTION

High-frequency deep brain stimulation of the subthalamic nucleus is the preferred surgical treatment for advanced Parkinson's disease. A recent innovation in this technique is the advent of directional leads allowing for current steering, which can increase the stimulation threshold for adverse effects and widen the therapeutic window. However, selecting programming settings is time consuming as it entails a thorough monopolar clinical review. To overcome this, directional stimulation programming may be guided by intraoperatively recording local field potential beta oscillations (13-35Hz) from the implanted leads.

OBJECTIVE

Objective of this study is first, to evaluate whether the power of beta oscillations intraoperatively recorded from directional local field potentials can predict the clinically most effective contacts; and second, to assess the clinical impact of beta-based programming of directional deep brain stimulation at long term follow-up.

MATERIAL AND METHODS

We conducted a non-randomized, open-label, prospective study with 24 Parkinson`s Disease patients (mean age 55.8 years, 66.7% male), divided in two groups. In the group A (14 patients, 2016-2018), we investigated whether beta activity in the directional contacts correlated with clinical efficacy (defined by clinical monopolar review, blinded to beta activity). Stimulating parameters were selected according to the clinical monopolar review, assessed with a mean follow-up of 27 months (15-38 months). In the group B (10 patients, 2018-2019), stimulating parameters were selected according to beta activity and assessed with a mean follow-up of 14 months (6-21 months).

RESULTS

Neurophysiological results showed that the strongest correlation between beta activity and clinical efficacy was obtained with the low-beta sub-band (13-20Hz) rather than with total beta activity (13-35 Hz). Contacts with highest beta peaks increased the threshold window by 25%. Selecting the two contacts with highest beta peaks provided 82% probability of selecting the best clinical contact. Clinical results showed similar improvement of motor features with reduced need of dopaminergic medication in both groups.  In group A (stimulation parameters based on clinical monopolar review), showed a 78% UDPRS-III reduction and 60% LEDD reduction. In group B (stimulation parameters based on beta peak power), showed a 75% UDPRS-III reduction and 62% LEDD reduction. Importantly, this clinical improvement was maintained at long-term follow up.

CONCLUSION

Our results demonstrate the clinical efficacy of directional stimulation over 3 years of follow up and validate the use of intraoperative local field potentials beta oscillations to guide the initial programming of long-term directional deep brain stimulation in Parkinson`s disease. Local field potential-guided programming provides a unique opportunity to adjust the stimulation for each individual patient, and the combination of physiological guidance with directionality will allow us to shape activation volumes tailored to patient needs  


Carla FERNANDEZ GARCIA (Madrid, Spain), Victor GOMEZ MAYORDOMO, Mariana H.G. MONJE, Maria Jose CATALAN, Maria Mercedes GONZALEZ HIDALGO, Jordi MATIAS-GUIU GUIA, Fernando ALONSO FRECH
16:30 - 16:40 #23910 - Effects of deep brain stimulation on depressive symptoms and cerebral glucose metabolism in parkinson’s disease.
Effects of deep brain stimulation on depressive symptoms and cerebral glucose metabolism in parkinson’s disease.

Background:Subthalamic nucleus (STN) deep brain stimulation (DBS) can ameliorate motor symptoms in Parkinson’s disease (PD), however, its utility as well as mechanism in reducing comorbid major depression remained uncertain. Here, we shed light on the neural mechanism of STN-DBS in managing comorbid treatment-resistant depression (TRD) in PD.

Objective:To assess motor symptoms, depressive symptoms, quality of life, and regional cerebral glucose metabolism before and after STN-DBS in PD patients with TRD.

Method:We prospectively studied 18 PD patients with TRD (d-PD) who underwent bilateral STN-DBS and an age- and sex-matched group containing 16 health controls. Clinical assessments were performed before and after STN-DBSat approximately 1-year follow-up. Cerebral regional glucose metabolism was assessed by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) before and after STN-DBS.

Results:After STN-DBS, the d-PD patients presented a substantial reductionon both motor and depressive symptoms. Improvement was also observed in their daily functioning and quality of life, whereas cognitive functioning was not significantly modified. Compared to controls, d-PD patients had widespread abnormalities in cerebral regional glucose metabolism before surgery  which were partially restored after STN-DBS. Moreover, improvement in depressive symptoms were associated with metabolic patternrestoration in brain regions implicated in emotional regulation (i.e., right inferior frontal gyrus, right orbitofrontal cortex and right lingual gyrus.).

Conclusion:STN-DBS may offer additional benefits in d-PD patients. The antidepressant effects appears to be associated with the restoration of abnormal glucose metabolism in widely distributed networks involved in emotion, motivation, and attention.


Xiaoxiao ZHANG (Shanghai, China), Bomin SUN, Chencheng ZHANG
16:40 - 16:50 #23914 - MRgFUS thalamotomy sensory side effects follow the thalamic structural and functional homonculus.
MRgFUS thalamotomy sensory side effects follow the thalamic structural and functional homonculus.

Introduction: Magnetic Resonance-guided focused ultrasound thalamotomy (MRgFUS) is an effective treatment for tremor, however, side effects may occur. The purpose of the present study was to investigate the spatial relationship between thalamotomies and specific sensory side effects as well as their functional connectivity with somatosensory cortex and relationship to the medial lemniscus (ML).

Methods: Of 103 patients treated with MRgFUS for tremor, 17 developed sensory side effects after thalamotomy persisting 3 months after the procedure. These side effects were categorized into four groups based on the location of the disturbance: face/mouth/tongue numbness/paresthesia, hand-only paresthesia, hemi-body/limb paresthesia, and dysgeusia. Then, areas of significant risk (ASR) for each category were defined using voxel-wise mass univariate analysis and overlaid on corresponding odds ratio maps. The ASR area associated with the maximum risk was used as a region-of-interest in a normative functional connectome to determine side-effect specific functional connectivity. Finally, each ASR was overlaid on the medial lemniscus derived from normative template.

Results: Thalamotomies producing sensory side effects extended posteriorly into the principle sensory nucleus of the thalamus. Thalamic regions associated with significant risk of the specific sensory side effects were distributed according to the somatotopy of the sensory thalamus, with the dysguesia ASR being located the most medial. ML fibers touched by ASRs were found to be organized according to the known somatotopic organization of the ML below the thalamus and at the level of the midbrain. Positive functional connectivity was found between each of the sensory-specific thalamic seeds and the primary somatosensory cortex and insular cortex.

Discussion: Distinct regions in the sensory thalamus may give rise to specific side effects when included in a thalamotomy lesion. These findings demonstrate the relationship between the sensory thalamus, ML, and bilateral sensory cortex. The functional connectivity patterns found between the sensory-specific thalamic seed regions and the insular cortex support the role of the insula in primary processing of gustatory information and also in multi-sensory integration.
 


Michelle PAFF (Orange, CA, Canada), Alexandre BOUTET, Jurgen GERMANN, Gavin ELIAS, Clement CHOW, Aaron LOH, Walter KUCHARCZYK, Alfonso FASANO, Michael SCHWARTZ, Andres LOZANO
16:50 - 17:00 #23927 - Surgery-related 30-day morbidity of functional stereotactic neurosurgery in a large cohort of 600 operations.
Surgery-related 30-day morbidity of functional stereotactic neurosurgery in a large cohort of 600 operations.

Objective:

In this retrospective study we analyzed the surgery and hardwarerelated morbidity of deep brain stimulation within 30 days after surgery.

Methods:

600 functional stereotactic operations (DBS electrode implantation or radiofrequency lesioning) were performed from 1997 to 2018. All procedures were performed or supervised by the senior neurosurgeon in three different centers using the same technique. The target was determined with CT-stereotactic surgery supplemented by MR imaging and approached via a guiding cannula. MER was performed in 2/3 of the cases via a single channel technique, supplemented by additional trajectories if decided necessary. Surgery was performed while patient was awake in 531 instances. Postoperative CT scans obtained within 24 hours after surgery were searched for haemorrhage of any size at any site. Hardware- or other surgery-related complications within 30 days after surgery were documented.

Results:

A total of 251 women and 349 men with a median age of 55 years were operated. The majority of patients underwent DBS (580), while a subset had radiofrequency lesioning procedures (20). Overall in 19 (3.25 %) procedures an intracranial haemorrhage was detected, which was asymptomatic in all patients except in 1 patient (0,16 %), who had a persistent mild hemiparesis on the right side. Early infections were noticed in 3 patients (0,53 %), 1 at the site of the IPG, 2 at the site of the cranial skin incision. Four patient (0,7 %)  had an intraoperative seizure, and 2 (0,3 %) had a seizure one day after surgery. Three patients (0,53 %) had clinically relevant intraoperative air embolism, and in 1 patient (0,16 %) pulmonary embolism occurred. One patient (0,16 %) had an acute coronary syndrome during IPG implantation, in four patients (0,7 %) surgery terminated because of cardiac coronary syndromes were suspected, which however, weren’t confirmed later.

Conclusions:

Stereotactic functional surgery is a generally safe procedure with low morbidity and no mortality when performed by an experienced team. Intraoperative haemorrhage constitutes the highest surgically related complication. Awake surgery is tolerated without relevant problems by the majority of patients. Infections within 30 days after surgery are rare.


Joachim RUNGE (Hannover, Germany), Assel SARYYEVA, Marc WOLF, Christian BLAHAK, Christoph SCHRADER, Holger H. CAPELLE, Hansjörg BÄZNER, Mahmoud ABDALLAT, Joachim K. KRAUSS
17:00 - 17:10 #23933 - Globus pallidus stimulation as treatment for camptocormia in Parkinson’s disease.
Globus pallidus stimulation as treatment for camptocormia in Parkinson’s disease.

Objective: Camptocormia is a common and often debilitating postural deformity in Parkinson's disease (PD). Few treatments are currently effective. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) shows potential in treating camptocormia, but evidence remian limited to case reports. We here report the effect of GPi-DBS in the treatment of camptocormia in a retrospective cohort of PD patients.

 

Methods: Video recordings of patients who recieved GPi-DBS were retrospectively reviewed. The total and upper camptocormia angles (TCC angle and UCC angle), were used to compare camptocormia alterations. The Unified Parkinson’s Disease RatingAssessment Scale Part III (UPDRS-III) was used to assess the patients’ motor symptoms.

 

Results: Thirty-six consecutive patients with advanced PD who underwent GPi-DBS were reviewed. Twelve patients manifested per-operative camptocormia: eight had lower camptocormia (TCC >30°; TCC-camptocormia), four had upper camptocormia (UCC >45°; UCC-camptocormia). Mean follow-up time was 7.3 ± 3.3 months. GPi-DBS improved TCC-camptocormia by 40.4% (angle from 39.1° ± 10.1° to 23.3° ± 8.1°, p=0.017) and UCC-camptocormia by 22.8% (angle from 50.5° ± 2.6° to 39.0° ± 6.7°, p=0.012) (Fig.1).Larger improvement was seen in patients with a larger pre-surgical TCC angle. No significant outliers among the leads were identified through the location analysis (Fig.2).

 

Conclusion: Our study demonstrates the potential effectiveness of GPi-DBS for treating camptocormia in PD patients. Controlled studies with larger numbers of unselected camptocormia patients should extend our findings.

Figure Legends

Fig. 1. Pre- and post-surgical total- (A) and upper (B) camptocormia angles (TCC/UCC angles) in patients with lower camptocormia (blue symbols and lines), upper camptocormia (red symbols and lines) and without camptocormia (green symbols and lines). *p < 0.05; ns: not significant. 

Fig. 2. The DBS leads of all patients with TCC-camptocormia (A) and UCC-camptorcormia (B) were merged on the T2-weighted (upper) and T1-weighted (lower) Montreal Neurological Institute (MNI) templates, with active contacts marked in red. Masses with yellow described the location of the STN, red for the red nucleus, green for the GPi, blue for the globus pallidus externus (GPe).


Yijie LAI, Yunhai SONG (Shangahi, China), Daoqin SU, Linbin WANG, Chencheng ZHANG, Jorik NONNEKES, Bastiaan BLOEM, Dianyou LI
17:10 - 17:20 #23943 - Subthalamic nucleus and EEG signatures underlyingleg force modulation in patients with Parkinson's disease.
Subthalamic nucleus and EEG signatures underlyingleg force modulation in patients with Parkinson's disease.

Impairments of gait and balance are amongst the most disabling and least well-understood symptoms of Parkinson's disease (PD). Well-established neuromodulation therapies for PD are highly effective for the treatment of upper-limb motor symptoms such as tremor or bradykinesia. However, these approaches exhibit modest results for alleviating locomotor deficits, presumably because the control of gait involves additional pathways governed by different neural dynamics.

A key limitation holding back the design of novel therapies is the lack of mechanistic readouts that may help understand and capture pathological neural activity patterns related to leg dysfunction. Here, we sought to identify the cortical and subcortical neural signatures underlying leg movements in PD. We recorded the local field potentials from deep brain stimulation electrodes implanted in the subthalamic nucleus (STN) in conjunction with 64-channel cortical electroencephalographic (EEG) in patients with advanced Parkinson's disease, as they performed a well-controlled leg motor task requiring single-joint modulations of force (high and low force).

We found distinct modulations in STN and EEG frequency bands that strongly correlate with leg motor effort, predominantly in the low beta (~13-20Hz), high beta (~20-35Hz) and gamma (35-90Hz) bands. In particular, high beta desynchronization was time-locked to leg muscle recruitment and maintained throughout force production with amplitudes that correlated with effort, both in STN and EEG (predominantly central sensorimotor electrodes) signals. Low beta and low gamma (35-50Hz) bands also exhibited modulations with leg movements, but with behaviors that differed across patients and between EEG and STN. Interestingly, force-related correlates were identified in STN and EEG regardless of the mobilized leg joint (ankle or knee) or of the direction of movement (flexion or extension), although power differences across force levels varied for each condition.

Our results highlight clear neural patterns underlying effort-related leg movements, both in STN and EEG signals, which hold promises to help clarify the role of such networks during adaptations in gait, initiation and turning, or during episodes of shuffling steps or freezing. Our results additionally emphasize differences across patients in specific frequency bands, which may be related to the pathology of each subject, and which may critically need to be accounted for when developing therapies that address leg-related disorders in PD.


Yohann THENAISIE, Andrea GALVEZ, Kyuhwa LEE, Charlotte MOERMAN, Mayte CASTRO-JIMENEZ, Elvira PIRONDINI, Grégoire COURTINE, Jocelyne BLOCH, Eduardo MARTIN MORAUD (Lausanne, Switzerland)
17:20 - 17:30 #23944 - Subthalamic nucleus activity patterns correlate with modulations in leg muscle synergies during locomotion in Parkinson’s patients.
Subthalamic nucleus activity patterns correlate with modulations in leg muscle synergies during locomotion in Parkinson’s patients.

Most patients with advanced Parkinson's disease (PD) suffer from disturbances of gait and balance, which severely affect their everyday mobility, independence and quality of life. Unlike upper-limb motor symptoms, these deficits respond poorly to commonly available therapies. A key limitation holding back the design of better focused, evidence-based therapies stems from the lack of biomarkers that correlate pathological neural activity patterns and leg dysfunction during gait. However, this identification is contingent on technologies, concepts and methodologies allowing to simultaneously record and link brain states to whole-body biomechanical features representative of gait deficits.

Here we employed a whole-body gait monitoring platform, operating wirelessly and in real-time, to map the activity of the subthalamic nucleus onto kinematic and muscle activity patterns while patients executed a range of locomotor activities. We contrasted the neural correlates underlying basic walking, turning and precision locomotion in order to uncover the STN involvement in locomotor tasks requiring different levels of muscle recruitment and effort.

Similarly to our previous observations during a single-joint leg motor effort task, we found that STN activity patterns exhibit distinct modulations in low beta (~13-20 Hz), high beta (~20-35 Hz) and low-gamma (~35-50 Hz) power during gait, which were aligned to the recruitment of well-defined leg muscle groups (synergies) during each phase of gait, initiation and turning. Although STN patterns displayed significant differences across patients, they all exhibited clear monotonic modulations with effort that correlated in time with increases in muscle synergy activations related to propulsion. We additionally identified specific modulations in patients suffering from freezing of gait.

These results reinforce the link between STN activity patterns and the modulation of vigor in locomotor networks, and may help predict the signatures that underlie propulsion-related deficits of gait and balance in PD, such as asymmetry, shuffling steps or eventually freezing of gait. Our results additionally emphasize particularities in individuals that exhibit freezing, which may critically need to be accounted for when developing therapies that address leg-related disorders in PD.


Yohann THENAISIE, Charlotte MOERMAN, Kyuhwa LEE, Flavio RASCHELLÀ, Andrea GALVEZ, Mayte CASTRO-JIMENEZ, Elvira PIRONDINI, Grégoire COURTINE, Jocelyne BLOCH, Eduardo MARTIN MORAUD (Lausanne, Switzerland)
17:30 - 17:40 #23978 - Bilateral Subthalamic Nucleus Theta Frequency Stimulation Improves Episodic Verbal Fluency in Patients with Parkinson's Disease: A Double-Blinded Randomized Crossover Trial.
Bilateral Subthalamic Nucleus Theta Frequency Stimulation Improves Episodic Verbal Fluency in Patients with Parkinson's Disease: A Double-Blinded Randomized Crossover Trial.

Cognitive outcomes following deep brain stimulation (DBS) in Parkinson’s disease (PD) have gained much attention with particular concern for verbal fluency. Current stimulation paradigms utilize high (gamma) frequency stimulation for optimal motor benefits; however, little work has been done to optimize stimulation parameters for cognition. Recent evidence implicates a role of subthalamic nucleus (STN) low (theta) frequency oscillations in executive function and suggests that theta frequency stimulation could improve executive function in PD. The aim of this study was to evaluate the acute on/off effects of bilateral gamma frequency STN stimulation on verbal fluency and executive function in PD and compare with the effects of theta frequency stimulation.

Twelve patients (all males, mean age 60.8) with bilateral STN DBS for PD underwent a double-blinded, randomized neuropsychological evaluation during stimulation at (1) 130-135Hz (gamma, baseline), (2) 10Hz (theta) and (3) off. Processing speed, verbal fluency, and executive functions were evaluated using a verbal fluency task (phonemic, episodic, nonepisodic, and switching), color-word interference task, and random number generation task. Performance at each stimulation frequency was compared within subjects. Preoperative (mean 4.7 months) scores were compared with postoperative (mean 11 months) scores.

Theta frequency stimulation significantly improved  compared to gamma frequency stimulation (p=0.02), but not compared to off (p>0.05). There were no significant differences between stimulation frequencies in phonemic or nonepisodic verbal fluency, color-word interference or random number generation (p>0.05). Comparing preoperative to postoperative scores, there were no differences in verbal fluency or color-word interference (p>.05).

Our study is the first to show improved episodic verbal fluency during theta versus gamma frequency stimulation, corroborating a role of theta oscillations in cognition. Further work is needed to explore if theta frequency stimulation can be interleaved with gamma frequency stimulation to concomitantly improve both motor and cognitive outcomes.


Jordan LAM, Justin LEE, Brian LEE, Darrin LEE (Los Angeles, USA)
17:40 - 17:50 #23990 - Does dystonia severity impact deep brain stimulation surgery and related complications?
Does dystonia severity impact deep brain stimulation surgery and related complications?

Background/ AimsDeep brain stimulation (DBS) has demonstrated pronounced benefit in treating dystonic conditions, however adverse events (AE) related to the procedure might impact the outcome. DBS-related AEs have been reported in literature; nevertheless, one unanswered question relates to whether the rate of complications is higher in patients with severe dystonia when compared to patients with less severe forms. 

The aim of this study was to first, determine which features explain the best dystonia severity at baseline and second, whether the frequency of DBS AEs was related to symptom severity.

Methods: A total of 80 patients treated with DBS for dystonia in a single center over 20 years were evaluated. We considered the occurrence of dystonic storm (DS) prior to DBS as a criterion for dystonia severity. We performed a case-control study in order to compare 40 patients who developed at least one DS episode (group 0) with a reference group who did not (group 1), matched for sex, age at first DBS and clinical phenotype. 

Related to DBS complications, we considered infection, hemorrhage, lead fracture, extension cable fracture or tension requesting surgical replacement and skin erosion. All patients were treated for dystonia with initial bilateral pallidal stimulation. 

First, we aimed to explain dystonia severity as expressed by the Burke Fahn Marsden dystonia rating scale (motor section) at baseline previous to DBS administration, based on the following variables: gender, family history, age at symptom onset, type of movement disorders, other neurologic or systemic manifestations, etiology, age at worsening with functional disability, number of SD episodes pre-DBS, disease duration pre-DBS, symptom distribution at onset, abnormal movements and postures at onset, duration of ICU stay pre-DBS, distribution of MRI abnormalities. 

Analysis was performed for n=37 subjects from group 0 and n=32 from group 1, for whom all the variables were available. Several machine learning algorithms have been used such as linear regression as well as models based on decision trees (Random Forest and Xgboost). We tested parameters and hyperparameters to obtain the combination providing the best accuracy. To validate model accuracy, mean absolute error (MAE) and root mean square error (RMSE) have been applied and cross-validation for each algorithm and for each group. 

Second, we assessed complications following DBS surgery for n=35 subjects from group 0, for whom 64 features were available and studied. Machine learning algorithms have been applied with use of Random Forest Classifier and XGBoost Classifier. 

Results: Generalized symptom distribution at disease onset was the most frequent presentation among group 0 (42.5%), vs. focal symptom distribution in group 1 (43.6%), p<0.005. Among group 0, 75% patients presented disability at disease onset (gait disturbance, hand movement or sitting abnormalities, dysarthria, dysphagia or dyspnea) vs. 20.5% of patients in group 1, p<0.005. An independent-sample t-test was conducted to compare the preoperative M-BFMDRS scores for both groups. There was a significant difference in scores for DS-patients (mean 85.15 ± 19.92) and non-DS patients (mean 57.80 ± 19.03), p<0.005.

Surgical revision was performed in 37,5% of subjects from group 0 vs. 25% from group 1 (p>0,05). Infections occurred in 20% of the subjects from group 0 vs. 11,1% from group 1. Lead fracture occurred in 20% vs. 17,1% in groups 0 and 1, respectively. No bleeding occurred in both groups. Revision of lead position was more frequent in group 1.

Based on the correlation matrix and models applied, the main features explaining the dystonia severity scores at baseline for group 0 were the following: age at worsening with functional disability and age at symptom onset, symptom distribution at onset, etiology, disease duration before DBS and MRI abnormalities of cortical distribution and for group 1, disease duration pre-DBS, symptom distribution at onset and age at worsening with functional disability.

The main features explaining hardware related complications were etiology, age and symptom distribution at dystonia onset.

Conclusion: DS prior DBS, generalized symptom distribution and disability at disease onset seem to be surrogates for dystonia severity. DBS-related AEs appear to be higher in severe dystonia, which could be due to the fact that these patients have a poorer clinical condition and hence are more prone to surgical complications.

 


Joana MONTEIRO (Lisboa, Portugal), Emilie CHAN SENG, Gaëtan POULEN, Philippe COUBES, Laura CIF
17:50 - 18:00 #26026 - European Multicentre Probabilistic Stimulation Map for Essential Tremor.
European Multicentre Probabilistic Stimulation Map for Essential Tremor.

Background: Deep Brain Stimulation (DBS) is an established therapy for medication-refractory Essential Tremor (ET). However, predictors of outcome and the optimal stimulation site remain a matter of controversy.

Objective: The objective of this study was to collect clinical and neuroimaging data of a large cohort of patients with DBS for ET from different European centers to identify predictors of outcome and to construct a probabilistic stimulation map and identify an optimal stimulation site.

Methods: This study enrolled 119 ET patients treated chronically with unilateral or bilateral DBS operated at five different European DBS centres for retrospective analysis of data on baseline covariates, pre- and postoperative clinical tremor scores (12-month) as well as individual imaging data to obtain individual electrode positions and stimulation volumes.  We calculated a stimulation map using voxel-wise statistical analysis. We used multiple regression analysis to estimate predictors of tremor reduction.

Results: The mean tremor reduction per patient across all centers was 59.3 % (55.7 – 62.9%, 95% CI). Preoperative tremor severity was the only baseline clinical characteristic that was significantly associated with outcome (r2 = 0.05, p= 0.03). We identified an area of optimal stimulation that extended from the posterior part of the PSA to the Vim and coincided with the area of highest likelihood to contain the DRTT. The anatomical location of stimulation was the overall best predictor of outcome.

Conclusions: Our multicentre ET probabilistic stimulation map identified an area of optimal stimulation along the course of the DRTT. This target may be used to guide surgical planning and for computer-assisted planning and programming of deep brain stimulation to in the future.


Andreas NOWACKI (Bern, Switzerland), Sabry BARLATEY, Bassam AL-FATLY, Till DEMBEK, Maarten BOT, Alexander GREEN, Alba SEGURA-AMIL, Anh Khoa NGUYEN, Lennard LACHENMAYER, Ines DEBOVE, Verle VISSER-VANDEWALLE, Andreas HORN, Richaard SCHUURMAN, Michael BARBE, Tipu AZIZ, Andrea KÜHN, Claudio POLLO
18:10 - 18:20 #24013 - A randomized controlled trial of awake versus asleep microelectrode guided frame-based deep brain stimulation for Parkinson’s disease.
A randomized controlled trial of awake versus asleep microelectrode guided frame-based deep brain stimulation for Parkinson’s disease.

Introduction, objective

It is unknown if there is a difference in outcome in asleep versus awake deep brain stimulation (DBS) of the subthalamic nucleus for advanced Parinson’s disease.

Objective: We hypothesized that there would be a difference in adverse effects concerning cognition, mood and behavior between awake and asleep DBS favoring the asleep arm of the study. We further hypothesized that the motor outcomes would be identical between the groups.

 

Methods

The study was a single-center prospective randomized open-label blinded end-point trial. There were 187 persons with Parkinson’s disease referred for DBS between May 2015 to March 2019 and of those 110 were eligible for participation in the study. The primary outcome follow-up visit was conducted six months following DBS.

Bilateral subthalamic nucleus DBS was performed asleep (under general anesthesia) or awake without sedation. Both arms of the study used a frame-based intraoperative microelectrode recording technique for placement of the DBS leads.

The primary outcome variable was the between group difference in cognitive, mood and behavioral adverse effects as measured by a composite score. The secondary outcomes included the Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), the patient assessment of surgical burden and operative time.

 

Results

The participants were randomized to awake (local anesthesia) (N=56, mean age 60.0 years (SD7.4), 40 male (71%)) or to asleep (general anesthesia) (N=54, mean age 61.3 years (SD7.9), 38 male (70%)) DBS surgery. The six months follow-up visit was completed by 103 participants. The proportion of patients with adverse cognitive, mood and behavioral effects on the composite score was 15 of 52 (29%) after awake and 11 of 51 (22%) after asleep DBS (odds ratio 0.7 (95% CI 0·3-1·7)). There was no difference in improvement in the off-medication MDS-UPDRS Motor Examination scores between groups (local anesthesia -27·3±17·5 points, general anesthesia -25·3±14·3 points, mean difference -2·0 (95% CI -8·1 to 4·2)). Asleep surgery was experienced as less burdensome by the patients and was 26 minutes shorter than awake surgery. 

 

Conclusion

There was no difference in the primary outcome of asleep versus awake DBS. Future large randomized studies should examine some of the newer asleep based DBS technologies as this study was limited to frame-based microelectrode guided procedures.


Rozemarije HOLEWIJN (Amsterdam, The Netherlands), Dagmar VERBAAN, Pepijn MUNCKHOF, VAN DEN, Maarten BOT, Gert GEURTSEN, Rob BIE, DE, Rick SCHUURMAN
18:20 - 18:30 #24082 - Probabilistic tractography aids lead placement in DBS for essential tremor.
Probabilistic tractography aids lead placement in DBS for essential tremor.

Introduction 

Since the first implantation of a deep brain stimulation system carried out by Pollack and Benabid in essential tremor, it became the gold standard treatment in the 30 years in movement disorders. Today, accurate planning and electrophysiological mapping of the target region is still essential to achieve successful results. Since 2017, the introduction of diffusion tensor imaging, tractography and their routine use in our department, the technique provided a valuable tool to non-invasively map and pinpoint the stereotactic target in 42 Parkinson’s disease, 8 dystonia, and 19 tremor patients. This trend steers us further away from awake surgeries even in tremor DBS, where anatomical boundaries of the ventral intermediate nucleus, mainly the closeness of the sensory thalamic nuclei can result in unwanted sensations under stimulation. 

 

Materials and methods

16 patients were enrolled in this study. Each patient underwent a preoperative MRI session under general anesthesia, T1, T2, contrast enhanced T1, and DTI images have been acquired in two different centers (10 patients - Philips Achieva - 32 directions, b0=800; 7 patients - Siemens Magnetom Verio 64 directions, b0=1000). Preoperative DTI analysis and fiber tracking has been carried out using tools available in FSL 6.0 (FMRIB) and Freesurfer 6.0 (Martinos Center for Biomedical Imaging). Reconstruction of diffusion tensors, probabilistic fiber tracking, and visualization of the results has been carried out on a Titan XP GPU based system. Connectivity segmentation of thalamus, to visualize the sensory nuclei and the Vim, the traversing lemniscal and dentate-rubro-thalamic pathways were done preoperatively, results were integrated into a Medtronic Cranial Planning Station. Implantation of DBS leads has been carried out using a Leksell stereotactic G frame and a ROSA stereotactic robot system. Intraoperative electrophysiological mapping and macrosimulation were done to control the imaging results.

 

Results

Of the 32 implanted electrodes patients 29 were within a 1 mm close range of the DRT, 65,63% was placed within the tract. The remaining 3 electrodes were within a 2 mm range. Sufficient tremor control was achieved in all of the implanted patients, no sensory side effect has been observed under implantation or postoperative programming, chronic stimulation. Optimal tremor control was found near the thalamic entry of the DRT. 

 

Discussion

Visualization of the DRT, the sensory nuclei, and the lemniscal pathways provide a patient specific implementation of DBS surgery. Relying only on standard stereotactic coordinates might result in unwanted side effects, sensory activation during stimulation. The described method is not only sufficient to achieve tremor control but can also minimize the possibility of suboptimal lead placement, thus might reduce the requirement of intraoperative electrophysiology and awake surgery.


Loránd ERŐSS (Budapest, Hungary), László HALÁSZ
18:30 - 18:40 #24083 - Pedunculopontine Nucleus Deep Brain Stimulation for Parkinsonian disorders: A Case Series.
Pedunculopontine Nucleus Deep Brain Stimulation for Parkinsonian disorders: A Case Series.

 

Background:

Deep brain stimulation (DBS) of the Pedunculopontine nucleus (PPN) has been investigated for the treatment of levodopa-refractory gait dysfunction in Parkinsonian disorders, with equivocal results so far.

 

Objectives:

To summarise the clinical outcomes of PPN-DBS treated patients at our centre and elicit any patterns that may guide future research.

 

Materials and Methods:

Pre- and post-operative objective overall motor and gait subsection scores as well as patient-reported outcomes were recorded for six PPN-DBS treated patients; three with Parkinson’s disease (PD) and three with Progressive supranuclear palsy (PSP). Electrodes were implanted unilaterally in the first three patients and bilaterally in the latter three, using an MRI-guided MRI-verified technique. Stimulation was initiated at 20-30Hz and optimised in an iterative manner.

 

Results:

Unilaterally treated patients did not demonstrate significant improvements in gait questionnaires, UPDRS-III or PSPRS scores or their respective gait subsections. This contrasted with at least an initial response in bilaterally treated patients. Diurnal cycling of stimulation in a PD patient with habituation to the initial benefit reproduced substantial improvements in FOG 3 years post-operatively. Among the PSP patients, one with a Parkinsonian subtype had a sustained improvement in FOG while another with Richardson syndrome (PSP-RS) did not benefit.

 

Conclusions:

PPN-DBS remains an investigational treatment for levodopa-refractory FOG. This series corroborates some previously reported findings: bilateral stimulation may be more effective than unilateral stimulation, the response in PSP patients may depend on the disease subtype, and diurnal cycling of stimulation to overcome habituation merits further investigation.

 


Viswas DAYAL, Ali RAJABIAN (London Queen Square, United Kingdom), Marjan JAHANSHAHI, Iciar AVILES-OLMOS, Dorothy COWIE, Amy PETERS, Brian DAY, Jonathan HYAM, Harith AKRAM, Patricia LIMOUSIN, Marwan HARIZ, Ludvic ZRINZO, Thomas FOLTYNIE
18:40 - 18:50 #25588 - Stereotactic Targeting in Europe: The European Society of Stereotactic and Functional Neurosurgery Survey.
Stereotactic Targeting in Europe: The European Society of Stereotactic and Functional Neurosurgery Survey.

Deep brain stimulation (DBS) of the subthalamus nucleus (STN) is a highly effective surgical technique for providing relief to patients suffering from Parkinson’s disease (PD). The ventral intermediate nucleus of the thalamus (VIM) target is also very effective for treating essential tremor (ET) with DBS or lesion. Nevertheless, targeting procedures remain controversial and variable. Two main techniques are used to identify the target: (i) the indirect technique, which transforms or wraps atlas or statistical information in a patient-specific space; (ii) the direct technique, which creates direct visualisation of the target on pre-operative magnetic resonance imaging (MR) with the multiplication of complex MR sequences.

With the help of the ESSFN, we wanted to interview European centres for functional and stereotactic neurosurgery to assess the reality of heterogeneous targeting and the difficulties encountered by surgeons.

Method:

Two surveys on STN and VIM targeting were sent to ESSFN members and the French centres of functional and stereotactic neurosurgery.

The first part of the survey focused on targeting, and the second part on difficulties encountered by centres during targeting.

Results: Forty-seven centres responded to the survey (about 40% of the 120 European centres of stereotactic and functional neurosurgery) with 1,548 targeting procedures having been conducted (STN 1000, VIM 548) in 18 countries in 2019.

All STN targeting was performed for DBS. 39% of centres targeted STN for diseases other than PD but these represent only 0.7% of STN targeting.

VIM targeting was performed by centres which practice DBS only (46%), DBS and lesion (31%) or lesion only (23%). VIM targeting was performed for tremors other than ET by 59% of centres, accounting for 18% of VIM targeting procedures.

 

Centres perform a mean of 26 STN targeting procedures per year with a median of 15, and a mean of 13 VIM targeting procedures per year with a median of 8. A significant number of centres carry out less than 10 VIM or STN targeting procedures per year.

Direct STN targeting was performed by 15 centres for 32% of STN targeting procedures without using statistical coordinates. Only 6 centres conducting 17% of targeting procedures did not use per-operative evaluations. Direct VIM targeting was used by 3 centres for 4% of VIM targeting procedures without using statistical coordinates and 10 centres (35% of targeting) did not use per-operative evaluations.

The mean targeting duration was 1 h 40 for STN (median of 2 h) and 1 h 25 for VIM (median of 1 h 00). Targeting is always performed by a neurosurgeon who is sometimes assisted by a neurologist or radiologist.

The two main problems noted by neurosurgeons are the complexity and heterogeneity of practices, followed by the duration of targeting and intra-operative evaluation, and the invasive nature of the latter.

 

 

Conclusions

More VIM targeting procedures are carried out than expected. Per-operative evaluation remains the reference method. Some lesion centres have significant VIM activities. STN targeting for indications other than PD is anecdotal, and the complexity and lack of homogeneity of practices are the main problems encountered by neurosurgeons.


Emmanuel CUNY (bordeaux), Jean REGIS
18:50 - 19:00 #23993 - Paediatric Deep Brain Stimulation: the challenge of secondary dystonia.
Paediatric Deep Brain Stimulation: the challenge of secondary dystonia.

Introduction
Unlike primary dystonias where the results of deep brain stimulation (DBS) can be responsible for an improvement of 70 to 90%, the benefit in secondary dystonias is less significant, on average 30%.
We present our cohort of implanted secondary dystonias, comparing our results to the literature data in terms of efficacy, complications and prognostic factors.

Patients & Methods
Among all the dystonic children implanted in our centre since 2015 (n=42), 18 patients (8-16 years old) with secondary dystonia (8 cerebral palsy, 4 PKAN, 1 glutaric aciduria, 5 without etiology), were implanted in the internal pallidum (GPi) bilateral implantation; One patient received a multi-targeted implantation (4 electrodes > GPI+STN).
All implantations were performed under general anaesthesia with electrophysiological control. Validation of the position of the electrodes was carried out intraoperatively by scanner and then again by scanner at 10 days postoperatively. The target chosen was the ventral posterolateral part of the GPi corrected according to the anatomical variability associated with the pallidal lesions induced by the pathology.
All indications were validated in RCP or Multidisciplinary Consultation for paediatric movement disorders. The expected benefits of DBS ranged from a reduction in painful attacks to functional improvement, depending on the initial pathology.

Results
The results are very heterogeneous, ranging from a spectacular improvement for a progressive, unlabelled disease to a lack of efficacy for 2 children with Cerebral Palsy. There were no additional postoperative complications compared to primary dystonias, including infectious dystonias (2/2 cases).

Discussion
We currently have few prognostic means to evaluate good candidates. Precise electrode placement in the GPi is crucial despite the possible lesions of the GP. Other targets than GPi or multi targets schemes can be a alernative surgical option. Early implantation would ensure better results. 
Patient selection and definition of expectations regarding the benefit to be expected from DBS are particularly important in this population.
DBS may be useful in secondary dystonias, particularly in dyskinetic, painful, and malignant forms. It should be discussed on a case-by-case basis with clear goals to be achieved, as functional gain may not always be the primary goal of DBS in this population.


Vincent D'HARDEMARE (Paris), Nathalie DORISON, Diane DOUMMAR, Marie HULLY, Florence RENALDO, Domitille GRAS, Emmanuel ROZE, Cecilia ALTUZZARA, Aude CHAROLLAIS, Véronique DARMENCY, Alice GIGNOUX, Georg DORFMULLER, Bernard PIDOUX, Julie BONHEUR, Laurent GOETZ
Salle Major

"Thursday 09 September"

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C25
15:30 - 17:00

Parallel Session 3
Radiosurgery - Other

Moderators: Roman LISCAK (head) (PRAGUE, Czech Republic), Roberto MARTINEZ-ALVAREZ (Neurosurgeon) (Madrid, Spain), Piero PICOZZI (Consultant) (Milano, Italy)
15:30 - 15:40 #23675 - Long-term Cognitive Outcome after Radiosurgery in Epileptic Hypothalamic Hamartomas.
Long-term Cognitive Outcome after Radiosurgery in Epileptic Hypothalamic Hamartomas.

Introduction: Epileptic patients with Hypothalamic Hamartoma (HH) are frequently presenting with cognitive impairment. Surgical techniques aiming at the HH can be very efficient for epilepsy relief and cognitive improvement but are also demonstrated to carry a significant risk of additional reduction in memory function in these already disabled patients. Gamma Knife Radiosurgery (GKS) offered efficient non-invasive procedure. We evaluated the effect of stereotactic radiosurgery on cognitive outcome.

Methods: Thirty-nine epileptic patients (median age 17, range 3-50) with HH underwent preoperative and postoperative comprehensive neuropsychological standard testing. All patients were prospectively evaluated and underwent complete pre-surgical and post-surgical clinical, electrophysiological, endocrinal and visual assessment. In all patients the post-operative assessment was performed at least 3 years after radiosurgery. We explored what variables correlate with cognitive outcome. Literature review was done for other surgical techniques and their risks for cognitive complications after surgery. The median dose received by Mammillarybodies (MB) and Fornix (Fx) was respectively 16,5Gy and 8 Gy.

Results: No memory or cognitive decline was observed after GKS. We observed significant improvement (>1SD inz-score) especially in working memory index (46%) and processing speed index (35%)but also inintelligence quotient full scale (24%), verbal comprehension index (11%), perceptual organization index (21%), verbal leaning (20%), visual learning (33%). Before GKS, the probability of seizure cessation was higher in patients with higher cognitive performances. After GKS, the cognitive improvement was significantly higher in the seizure free patients compared to the non-seizure-free.

Conclusion: We found clear cognitive improvement in a high percentage of patients but importantly no significant cognitive worsening in long-term comprehensive neuropsychological assessment and specially memory three years after GKS. GKS is comparing very favorably to the other surgical techniques in term of cognitive outcome with similar seizure freedom.


Hussein HAMDI (Marseille), Faisal ALBADER, Virginie LAGUITTON, Agnes TREBUCHON, Fabrice BARTOLOMEI, Jean REGIS
15:40 - 15:50 #23934 - Gamma Knife Radiosurgery in the treatment of Glomus jugulare tumours - the Vienna series.
Gamma Knife Radiosurgery in the treatment of Glomus jugulare tumours - the Vienna series.

Objective:

A Glomus jugulare tumour (GJT) is considered a slowly growing, benign lesion located in the skull base. The tumour is frequently highly vascular and surgical removal is rarely radical. Consequently, radiosurgery became a relevant role in the treatment of these tumours.

 

Methods:

A retrospective analysis identified 42 patients with GJT treated with Gamma Knife Radiosurgery (GKRS) at the Department of Neurosurgery, Medical University Vienna. Nineteen out of 42 patients underwent surgery before GKRS. Twenty-three patients had GKRS as primary treatment.

 

Results:

Five patients were lost to follow-up (5/42, 12%). The median total follow-up time was 49months (range: 11-212months). The median dose to the tumour margin was 13Gy (range 9-16Gy). The median tumour size was 7.4ccm (1.2-74.0ccm).

In MRI controls 13 tumours decreased (35%), 22 remained stable (60%) and two (5%) showed a progression and were managed conservatively. Treatment failures received a marginal tumour dose of 13 and 15Gy, respectively.

 

Conclusion:

GKRS is an effective treatment option for GJTs even after prior surgical resection and provides a tumour control of nearly 95%.


Brigitte GATTERBAUER (Vienna, Austria), Josa M. FRISCHER
15:50 - 16:00 #23969 - Safety of Gamma Knife ICON Hypo-fractionated treatment for benign peri-optic lesions: preliminary results from a single centre.
Safety of Gamma Knife ICON Hypo-fractionated treatment for benign peri-optic lesions: preliminary results from a single centre.

INTRODUCTION

Traditionally Gamma Knife Radiosurgery (GKRS) has been identified as the gold standard therapy for single-fraction high-dose irradiation of intracranial lesions. The Leksell Gamma Knife Icon (GK Icon) system can utilize cone-beam computed tomography (CBCT) to evaluate motion error and it is currently used in some centers for hypo fractionated GKRS treatment (fGKRS).

In this study, we analyzed the safety of GK Icon hypo-fractionated radiosurgery for the treatment of benign lesions close to the optic apparatus.

MATERIALS AND METHOD

The study was conducted with the approval of our institutional review board. We retrospectively analyzed a prospectively maintained database of patients treated with hypo-fractionated GKRS between September 2017 and December 2019 using the GK Icon system. We included patients harboring benign perioptic lesion, including skull base meningiomas, pituitary adenomas and craniopharyngiomas. Patients had at least 12 months of clinical ophthalmological and radiological follow up.

            RESULTS

We collected a total of 41 patients (29 female and 12 male) with a mean age of 59,8 years (38-85). The most frequent lesion was meningioma, except for nine patients (two craniopharingiomas and seven pituitary adenomas). Tumors were most commonly located in the cavernous sinus, 3 lesions originated from the optic nerve sheath. The average lesion volume at fGKRS was 5,136 cm3 (range 0.608-16.441 median 3.240 cm3). 19 patients manifested neurological symptoms at the time of fGKRS, including diplopia, trigeminal paresthesia, visual disturbance or exopthalmus. Sixteen patients had previous surgery (four adenomas, one craniopharyngioma, two patients with WHO grade II meningioma and nine with WHO grade I meningioma). Three patients had prior radiotherapy or radiosurgery. All patients were treated using the Icon mask system; most patients were treated in 5 fractions, while 2 patients were treated in 3 fractions. The majority (92%) of patients received 25 Gy at a median isodose of 50% with a median conformality index of 1.0. When comparing the CBCT and preoperative CT images, the inter-fractional movement was less than 0.5 mm. Daily difference in intra-fractional movement was 0.1 mm with a maximum error of 0.5 mm in HDMM system. The median follow-up period was 14.3 months (range 6-36).

Among the symptomatic patients, three experienced symptom improvement after fGKRS, and eleven remain stable. 2 patients, presenting large lesion volume (16.473 and 10.632 cm3) complained of subjective diplopia. None of asymptomatic patients became symptomatic. All visual fields and visual acuity of asymptomatic patients remained normal, none of the treated patients experienced a worsening in visual field or visual acuity.

CONCLUSION

Despite the short follow-up doesn’t allow us to assert the results on tumor control, this study reports encouraging preliminary results on the safety of hypo-fractionation with Gamma Knife Icon in peri-optic lesions.


Giorgio SPATOLA (Brescia, Italy), Lodoviga GIUDICE, Karol MIGLIORATI, Bassetti CHIARA, Cesare GIORGI, Oscar VIVALDI, Mario BIGNARDI, Alberto Bernardo FRANZIN
16:00 - 16:10 #24048 - Comparison of dorsal root entry zone and trigeminal nerve fibers adjacent to trigeminal ganglion in targeting of gamma knife radiosurgery for trigeminal neuralgia.
Comparison of dorsal root entry zone and trigeminal nerve fibers adjacent to trigeminal ganglion in targeting of gamma knife radiosurgery for trigeminal neuralgia.

Background: The dorsal root entry zone (DREZ) and trigeminal nerve fibers that are adjacent to the trigeminal ganglion (TFatTG) as a target in Gamma Knife radiosurgery (GKRS) for the treatment of medically refractory TN were compared and evaluated. Special interest was given to the complication rates and effectiveness of these targets. The aim was to determine whether (TFatTG) targeting could be an alternative method to DREZ targeting in medically refractory TN patients with pain in V2 and/or V3 distribution. These selective targeting technique could minimize possible side effects like numbness, especially in V1 distribution. 

 

Methods: Twenty-six medically refractory TN patients were enrolled in this study. The patients were divided into two groups. The DREZ and the TFatTG were selected as a target for GKRS. TN patients with pain in V2 and/or V3 distribution especially with good visualization of the Meckel cavum, ganglia and trigeminal fibers in MRI studies were selected for targeting of this area. Selective targeting of V2 and/or V3 nerve fibers was performed with the help of multiplanar reformatting of high resolution CISS MRI studies. DREZ targeting technique was performed as reported in the relevant literature. The irradiation time, pain control, and treatment related complications like numbness were evaluated. 

 

Results: Chi-square test of homogeneity was used for the evaluation of statistical differences of BNI numbness scores after treatment between groups. Three patients (23.1%) in the TFatTG targeting group and  8 patients in the DREZ targeting group complaints from numbness. Numbness after GKRS was statistically higher in the DREZ targeting group in comparison to TFatTG targeting group (p<0.05). Irradiation time for each targeting group were normally distributed, as assessed by Shapiro-Wilk's test (p > .05). An independent-sample t-test was run to determine if there were differences in irradiation time between DREZ and TFatTG. Irradiation time was significantly longer in DREZ targeting (86.9±19.2 min) in comparison to TFatTG targeting (65.0±2.5 min) (P<0.01).

 

Conclusion: TFatTG is a reasonable target in patients with a distribution of pain to V2 and/or V3 TN, with less collateral effects over brain stem and less side effects like numbness especially in V1 distribution. Hence, shorter irradiation time and equal pain control compared with the DREZ target, the TFatTG may be an effective and functional target in selected patients with pain in V2 and/or V3 distribution. Randomized prospective study evaluating DREZ, TFatTG and cistern targeting in patients with medically refractory TN is in progress. 

 


Mesut Emre YAMAN (Ankara, Turkey), Burak KARAASLAN, Munibe Busra ERDEM, Gökberk EROL, Beste GÜLSUNA, Şükrü AYKOL
16:10 - 16:20 #26276 - Long-term hearing outcome after radiosurgery for vestibular schwannomas: a systematic review and meta-analysis.
Long-term hearing outcome after radiosurgery for vestibular schwannomas: a systematic review and meta-analysis.

INTRODUCTION: Stereotactic radiosurgery (SRS) has emerged over the last thirty years as the main treatment option in the management of small to medium size vestibular schwannomas (VS), due to high tumor control rate and low cranial nerves morbidity. In most series, hearing preservation after SRS is generally reported over 60% at 3-year follow-up. However, series reporting long-term hearing outcome are scarce.

OBJECTIVE: We performed a systematic review of the literature and meta-analysis, with the aim of focusing on the long-term hearing preservation after SRS and related prognostic factors.

METHODS: Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2020 and referenced in PubMed®. Inclusion criteria required that each article be a peer-reviewed clinical study or a case series of VS treated with SRS (single dose), irrespective of the technique, reporting hearing outcome after SRS with a median or mean audiometric follow-up of at least 5 years. Hearing preservation, cranial nerves outcomes, and tumor control were evaluated with separate meta-analyses.

RESULTS: Twenty-three studies were included. Hearing preservation at last follow-up was reported in 58.9% of cases, with a median follow-up of 6.7 years (range: 0.2-23 years; 1,409 patients). The main favorable prognosis factors were young age, good hearing status at SRS (Gardner-Robertson IA), early treatment after diagnosis, small tumor volume, low marginal irradiation dose, and low maximal dose to the cochlea. Tumor control was achieved in 96.1% of patients. Persistent facial palsy and trigeminal neuropathy were reported in 1.1% and 2.6% of patients, respectively. The rates of facial palsy and trigeminal neuropathy were significantly higher in Linear Accelearor (LINAC) series (p<0.05), respectively 0.8% vs 6.4% and 1.7% and 7.1%.

CONCLUSIONS: Long-term hearing preservation remains one of the main issues after SRS, with major impact on health-related quality of life. Our meta-analysis suggests that hearing preservation can be achieved in almost 60% of patients after a median follow-up of 6.7 years, irrespective of the technique. However, Linac series present higher risks of trigeminal and facial nerve neuropathy.


Anne BALOSSIER (Marseille), Constantin TULEASCA, Christine DELSANTI, Lucas TROUDE, Jean-Marc THOMASSIN, Pierre-Hugues ROCHE, Jean RÉGIS
16:30 - 16:40 #23795 - Opening of blood brain barrier (BBB) in the hippocampus and entorhinal cortex in early Alzheimer’s disease with focused ultrasound (FUS).
Opening of blood brain barrier (BBB) in the hippocampus and entorhinal cortex in early Alzheimer’s disease with focused ultrasound (FUS).

Background

There is an urgent need for innovative research addressing Alzheimer’s disease (AD) treatment as no effective therapy exists. Animal models have demonstrated that magnetic resonance (MR)-guided low intensity focused ultrasound (FUS) can reversibly open the blood-brain barrier (BBB), resulting in a reduction of amyloid-beta plaque, improvement of memory, and allowing for targeted drug and stem-cell delivery. We report initial clinical and PET analysis of phase II clinical trial targeting the hippocampus and entorhinal cortex (EC) with FUS in patients with AD.

 

Methods

Patients with early AD and positive amyloid-beta PET underwent MRI-guided FUS sonication of the hippocampus and EC (220 kHz, ExAblate Neuro Type 2 system) with concomitant IV microbubble (Definity®) injection. Treatment areas were selected based upon individual anatomy and amyloid burden. FUS treatment occurred on three separate sessions, each two weeks apart, at the same target sites. Outcome assessments included MRI evaluating BBB opening and closure, safety, changes in amyloid PET scans, and cognitive/behavioral evaluations.

 

Results

Six subjects (5 female and 1 male: ages 55-72 years) were enrolled at two trial participating institutions. All six Subjects completed three separate treatment sessions, each two weeks apart for a total of 18 FUS treatments. FUS sonication of up to five targets of the right (n=2) or left (n=4) hippocampus/EC was performed. The follow-up ranged from 2 to 18 months. All 18 treatment sessions were tolerated well and there were no overt hemorrhages.  Post-FUS contrast MRI in all six subjects revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 hours (Figure). The average opening was 95% of the FUS target volume, corresponding to 29% of the overall hippocampus volume. To date, no neurological adverse events have been noted in any of the 6 subjects. Cognitive and behavioral testing demonstrated no meaningful changes at the 3 months (n=5) follow up since the last treatment. Follow up post-FUS treatment PET analysis (approximately 60-days time interval from the baseline pretreatment PET scan; n=5) showed a decrease in amyloid-beta plaque in all participants in the treated hippocampus (range: 2.7% – 6.2%).

 

Conclusions

This study is the first to demonstrate precise, safe, non-invasive, reversible, and substantial opening of the BBB with FUS in the human hippocampus/EC, with the suggestion of reduction of amyloid-beta plaque, providing a unique translational opportunity to investigate novel therapeutics in AD.


Ali REZAI (Morgantown, USA), Manish RANJAN, Pierre-Francois D’HAESE, Mark HAUT, Jeffrey CARPENTER, Umer NAJIB, Rashi MEHTA, Alexander SONG, Daniel CLAASSEN, J. Levi CHAZEN, Michael LIN, Zion ZIBLY, Gary MARANO, Mor DAYAN, Nathaniel KELM, Sally HODDER, Michael KAPLITT
16:40 - 16:50 #26280 - Deep Brain Stimulation in Disorders of Consciousness: A 10-year institutional experience.
Deep Brain Stimulation in Disorders of Consciousness: A 10-year institutional experience.

Aims: Consciousness disorders, namely vegetative state (VS) and minimally conscious state (MCS), represent serious conditions with mayor consequences for patients and their families. Several studies have described regaining of consciousness in such patients with the use of deep brain stimulation (DBS) of brain or brainstem nuclei. The aim of our study is to present  10 years’ experience results in using DBS as a therapy for VS/ MCS patients.

Methods: Ovrall, our study included 63 patients; entry criteria included neurophysiological and neurological evaluation, as well as neuroimaging examination. DBS system was implanted in 26 patients; 20 patients were in VS and 6 in MCS. The implantation and stimulation target was centromedian-parafascicular complex in the left hemisphere in HI-BI or the one better preserved in TBI patients. The span of the follow up period was 10 to 111 months. 

Results: Level of consciousness was improved in six patients. Two MCS patients substantially improved, regaining the ability to walk, to speak fluently and without need for everyday life assistance. Four patients showed improvements in consciousness in a way of regaining the possibility to communicate non-verbally, but are still dependent on the care of their guardians.

Conclusion: In patients with consciousness disorders, spontaneous recovery to the level of consciousness without assistance is rare. Thus, for such patients who meet neurological, neurophysiological and neuroimaging criteria, DBS of certain thalamic nuclei could be recommended as a treatment option, especially in earlier phases when irreversible changes of musculoskeletal system are still not so drastic.

 


Darko CHUDY (Zagreb, Croatia), Vedran DELETIS, Domagoj DLAKA, Dominik ROMIC, Fadi ALMAHARIQ, Nina PREDRIJEVAC, Darko ORESKOVIC, Andelo KASTELANCIC, Petar MARCINKOVIC, Marina RAGUZ
16:50 - 16:55 #23854 - Awakening the brain with DBS of the intralaminar thalamus after severe brain injury.
Awakening the brain with DBS of the intralaminar thalamus after severe brain injury.

Rationale: Severe brain injury can result in prolonged disorders of consciousness and other hypo-responsive behavioral syndromes associated with severely diminished motivation, such as akinetic mutism. Hypoactivation of intralaminar thalamic outflow tracts to the (pre)frontal cortex has been suggested to be the main cause of such behavioral deficits. DBS of the intralaminar thalamus (centromedian-parafascicular complex, CM-Pf) may increase arousal and restore purposeful behavior in these severely injured patients. 

Objective: To explore the efficacy of CM-Pf DBS in restoring consciousness and purposeful behavior in patients with disorders of consciousness and diminished motivation.

Methods: Six patients with a minimally conscious state (MCS) without improvement >24 months after traumatic brain injury and 1-2 patients with severe akinetic mutism will undergo DBS targeted to the CM-Pf complex of the thalamus. The primary outcome measure for post-TBI MCS patients is the change in the Coma Recovery Scale-Revised (CRS-R) score. Secondary endpoints are changes on a subset of additional behavioral scales for patients recovering from coma (such as the PALOC-S). The primary outcome for akinetic mutism patients is the change in the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) tool. Also, neurophysiological changes will be measured using both EEG and MEG.

Results/conclusion: Preliminary results show that CM-Pf DBS improves arousal in one MCS patient and restores the ability to walk and talk in a previously wheelchair-bounded patient with akinetic mutism. These results will be shown in pre-DBS and post-DBS videos. 


Hisse ARNTS (Amsterdam, The Netherlands), Willemijn VAN ERP, Berno OVERBEEK, Rick SCHUURMAN, Pepijn VAN DEN MUNCKHOF
16:55 - 17:00 #26301 - Entraining human wakefulness: selective, closed-loop stimulation of brainstem arousal circuits.
Entraining human wakefulness: selective, closed-loop stimulation of brainstem arousal circuits.

Background: Deep sleep features slow wave activity (SWA) in cortical areas crucial for decision-making and vigilance. Disorders of Consciousness also share this electrophysiological marker –while remaining challenging to treat. In addition, hypersomnia is a feature of advanced neurodegeneration as well as part of sleep disorders (some, like narcolepsy, also potentially treatment-resistant). Therefore paradigms of targeted SWA modulation, as well as enhancement of cortical rhythms positively associated with attention and cognition (such as cortical gamma oscillations), may help open new treatment avenues of these conditions. The pedunculopontine nucleus of the brainstem (PPN) delivers activating cholinergic afferents, closely linked to wakefulness. Its role in locomotion and autonomic control has made it a target for movement disorders therefore accessible for surgical neuromodulation.


Methods: Four patients underwent bilateral electrode implantation in the PPN (Fig.1C). We allowed for a period of recovery, then applied two closed-loop stimulation protocols over multiple nights. We compared their ability to reduce SWA, entrain cortical gamma activity and increase arousal. We also compared their efficacy against a control -sham stimulation trials, delivered at the same level of pre-stimulation SWA. Sham trials (no stimulation) were 'delivered' on separate nights, not mixed with real trials, to avoid any effect of real stimulation washout.


Results:
Both protocols reliably entrained fast cortical rhythms when compared to sham trials. Overall, stimulation increased gamma power and reduced delta activity (p=0.0000, one-way ANOVA with Bonferroni correction) as measured on the EEG (Fig.1 A,B). When examined separately, both protocols led to statistically significant gamma entrainment compared to sham (P=0.0000 for both protocols, ANOVA with Bonferroni correction). However, one of the two protocols was significantly more efficient at SWA reduction (P= 0.0006, CI: [0.8043 4,8094]).

 

Conclusion:
In a human study, we demonstrated selective modulation of arousal state through deep brain stimulation of brainstem arousal pathways, against a control (sham) paradigm. We show that different stimulation parameters can offer different levels of SWA control –therefore offering us the option of staged, even more tailored interventions featuring gamma entrainment. These findings highlight the importance of investigating brainstem DBS in treatment-refractory hypersomnia and disorders of consciousness.


Alceste DELI, Alceste DELI (Oxford, United Kingdom), Shenghong HE, Yongzhi HUANG, Sean MARTIN, Tipu AZIZ, Timothy DENISON, Alexander GREEN
Espace Vieux-Port

"Thursday 09 September"

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D25
15:30 - 17:00

Parallel Session 4
Epilepsy

Moderators: Claire HAEGELEN (Neurosurgeon) (Lyon, France), Dirk VAN ROOST (Consultant) (Ghent, Belgium)
15:30 - 15:40 #23939 - Network substrates of centromedian DBS in generalized pharmacoresistant epilepsy.
Network substrates of centromedian DBS in generalized pharmacoresistant epilepsy.

Objective: Deep brain stimulation (DBS) of the centromedian (CM) nucleus of the thalamus in

patients with pharmacoresistant epilepsy has yielded first promising results. However, the

structural network substrates of its therapeutic effect remain to be identified. A proper

characterization of the targeted networks could improve DBS efficiency and reduced stimulation

related side-effects. We aim at evaluating the targeted network with the description of structural

connectivity patterns derived from volumes of tissue activated (VTA) and its relationship with

CM-DBS outcomes.

Methods: We retrospectively analyzed magnetic resonance imaging (MRI) and diffusion tensor

imaging (DTI) data from patients with generalized pharmacoresistant epilepsy and CM-DBS (N

= 10, mean age at surgery = 30.8±5.9 years, 4 female). We modelled VTAs according to the

individual stimulation parameters and included these as seeds to reconstruct the targeted network,

as derived from deterministic tractography, for the clinical outcome of CM-DBS.

Results: Out of the 10 patients, nine significantly improved (> 50%) with CM-DBS at 6 months

after implantation and later on. The structural connectivity analysis revealed high connectivity

between VTAs and sensorimotor, premotor, brainstem and cerebellar regions, as well as fiber

projections to frontal and temporal cortices.

Interpretation: The outcome of CM-DBS in pharmacoresistant epilepsy is highly dependent

from individual connectivity profile of the volume-of tissue activation at the implantation site and

targeted network encompassing frontal and central regions, brainstem and cerebellum. The

proposed framework could be implemented in future studies to refine stereotactic implantation or

the parameters of the targeted neuromodulation.


Cristina TORRES (Madrid, Spain), Gabriel GONZALEZ-ESCAMILLA, Dumitru CIOLAC, Marta NAVAS, Paloma PULIDO, Jesus PASTOR, Vega-Zelaya LORENA, Rafael G. SOLA, Sergiu GROPPA
15:40 - 15:50 #25980 - Anterior Nucleus of the Thalamus DBS versus best medical therapy including VNS for pharmaco-resistant epilepsy: results of the FRANCE STUDY, a randomized, open label trial.
Anterior Nucleus of the Thalamus DBS versus best medical therapy including VNS for pharmaco-resistant epilepsy: results of the FRANCE STUDY, a randomized, open label trial.

Deep Brain Stimulation(DBS) is an alternative treatment to treat patients with severe pharmaco- resistant epilepsy. However, there is no randomized control study assessing the effect of ANT-DBS in patients who have failed medical treatment and vagus nerve stimulation.  We aimed to compare the efficacy of ANT-DBS in pharmacoresistant epileptic patients who have failed VNS, to the efficacy of best medical therapy.

 

Mathods. We conducted a randomized controlled trial in 12 french expert centers for epilepsy.  We recruited patients who failed medical and VNS treatment and who experienced at least 4 severe seizures (according to the Chalfont Scale) per months for 3 months during the screening period. 

Enrolled patients were randomised in either a neurostimulation group (DBS group) or a best medical therapy group ( BMT group). VNS therapy was maintained ON in patients in whom it was not stopped at the inclusion.  Patients assigned into the DBS group were stimulated bilaterally using different type of stimulation during 12 months.  

The primary endpoint was the difference in the mean number of severe seizures that occurred during 3 months before the randomization and that occurred during the last 3 months at 1 year follow up, as assessed by a Khi-deux test. We also assessed the side effects occuring in all patients. The trial is registered  with clinicalTrials.gov NCT02076698.

 

Results: We enrolled 67 patients and 61 were randomized, 30 in the neurostimulation group (DBS group) and 31 in the best medical therapy group ( BMT group). For the DBS group, 29 received bilateral implantation of the ANT using the 3389 lead from Medtronic. 59 patients completed the final assessment at 12 months.

In the DBS group, 37,93% of patients achieved 50 % of reduction of all seizures  versus 16.67 % in the BMT group ( p= 0.066), and  51.72 % of patients achieved 40 % of severe seizure reduction, compared to 30 % in the BMT group (p= 0.08). In the DBS group, the mean number of severe seizures per month was reduced by 38 %, and was increased by 4 % in the BMT group.  The Beck depression inventory scored was improved in 88.46% of the patients in the DBS group, versus 55.56 % in the BMT group ( p=0.014). 2 patients died due to SUDEP, one in each group, before having received DBS. 

Conclusion: the result of this randomized study shows that ANT -DBS tend to have an effect on the number of severe seizures and on the total number of seizures  in a population of patients suffering from severe epilepsy and who failed medications and VNS, compared to a control group who received the best medical treatment including VNS. 


Stephan CHABARDÈS (GRENOBLE), Haegelen CLAIRE, Fabrice BARTOLOMEI, Sylvain RHEIMS, Emmanuel CUNY, Sophie COLNAT COLBOIS, Louis MAILLARD, Philippe KAHANE, Stephane CLEMENCEAU, Bertrand DEVAUX, Marc Guenot GUENOT, Guillaume PENCHET, Denys FONTAINE, Anca ANCA, Lorella MINOTTI, Study Group FRANCE, Sandra DAVID-TCHOUDA, Jean REGIS
15:50 - 16:00 #26112 - Surgery for multifocal epilepsy.
Surgery for multifocal epilepsy.

 

        Introduction. Multifocal epilepsy predominantly occurs in childhood and characterises by high incidence of intractable, severe and traumatic seizures. High rates of developmental delay, mental retardation and psyhoemotional disturbances are noted in children with multifocal epilepsy. Patients with such epilepsy are often considered unsuitable for epilepsy surgery. However some surgical procedures, such as multilobar resections, functional hemispherotomy, disconnections, neurostimulation or ablative interventions can stop seizures or significantly reduce their frequency and improve patient’s quality of life.  The purpose of the report is to demonstrate our experience of surgical treatment of multifocal epilepsy.

Material and methods. 48 patients with multifocal epilepsy were enrolled in study, among them there were 37 (77%) children and 11 (23%) adults. Patient’s age ranged from 2 to 44 years (mean – 13 years). Most patients had severe epilepsy, refractory to medications. 14 (29%) patients had repeated epileptic statuses and 18 (38%) had epilepsia partialis continua. Epileptic encephalopathy noted in 15 (31%) cases. Mean duration of epilepsy before surgery was 8.9 years.

Patients underwent the following surgical interventions: microsurgical callosotomy - 15 (31%); stereotactic anterior callosotomy - 12 (25%); multilobar resections – 6 (13%); callosotomy in combination with resective interventions - 3 (6%); peri-insular functional hemispherectomy - 12 (25%). Postoperative long-term follow-up ranged from 6 months to  11 years (mean – 5.8 years).

Results. In 25 (52%) cases multiple epileptic focuses or diffuse structure and electrophysiologic changes were found within one hemisphere and in 19 (40%) patients structure abnormalities were revealed in both hemispheres, 4 (8%) patients had MRI -negative epilepsy with bilateral epileptiform discharges. Causes of epilepsy in our group were:  malformation of cortical development - 12 (25%), Rasmussen encephalitis - 8 (16%), intracerebral hemorrhage - 7 (15%), hypoxic-ischemic encephalopathy - 5 (10%), meningoencephalitis - 5 (10%), neoplastic lesions - 3 (6%), Sturge-Weber syndrome - 2 (4%) and microencephaly - 2 (4%). Cause of epilepsy was unknown in 4 (8%) cases. 

After treatment 23 (48%) patients became seizure-free (Engel 1), 8 (17%) patients had rare short auras (Engel 2), in 11 (23%) cases seizure frequency reduced over 75%, in 6 (13%) cases seizure frequency reduced less then 75% or did not change significantly. Best seizure  control achieved in patients who underwent functional hemispherectomy and multilobar resections - 90%, while after stereotactic callosotomy such result achieved only in 25%. However after both types of callosotomy drop-attacks stoped in 21 from 26 (81%) patients who had it before treatment.

After hemispherectomy one child died because of brain hypoxia. Post-hemispherectomy hydrocephalus occurred in one case and was needed repeated shunt interventions. Overall postoperative mortality was 2%, morbidity was 2%.  

Discussion. Our results may to conclude that multilobar resections, combined resective surgery with callosotomy and functional hemispherectomy can be the valuable treatment approach for multifocal epilepsy because of their effectiveness and safeness. Functional disconnecting interventions, such as callosotomy aimed to blocking epileptiform discharges and are reserved for patients, suffering from severe epilepsy who are not good candidates for resective surgery. Sufficient seizure control, normalisation of brain electrical activity, prevention of secondary epileptogenesis and reduction of adverse effects of antiepileptic drugs allow to stop progressive cognitive decline that can be seen in paediatric epilepsy patients.


Kostiantyn KOSTIUK (KYIV, Ukraine), Varelii CHEBURAKHIN, Maxim SHEVELOV, Yuri MEDVEDEV, Andriy POPOV, Sergii DICHKO, Oleksiy KANAYKIN, Vladyslav BUNYAKIN, David TEVZADZE
16:00 - 16:10 #26153 - Towards refined targeting the anterior nucleus of thalamus in DBS for epilepsy.
Towards refined targeting the anterior nucleus of thalamus in DBS for epilepsy.

Introduction

In Deep Brain Stimulation (DBS) for epilepsy addressing the Anterior Nucleus of the Thalamus (ANT) region, the analysis of pre- and post-operative MRI and CT images shows that the active stimulation electrode position is not the sole discriminator for therapy outcome. Electrodes which have been placed accurately (as evaluated by postop imaging) in the ANT nucleus but also the ones which clearly are outside the intended target region (but still in the ANT region) show both good and bad therapy efficacy outcomes.  This may be due to different brain networks passing through the ANT region, which are important in different types of epilepsies.  This research is tailored to finding anatomical hotspots that correlate to good therapy outcome for different types of focal onset epilepsy.

Material

A total of 179 European MORE study epilepsy patients with bilateral ANT deep brain stimulation were analyzed. For 109 patients active stimulation electrode contact location could be linked to stimulation parameters and therapy outcome, at 2 year follow up.  Patients were grouped as Responders (≥ 50% Seizure Reduction (SR)); Improvers, 50%<SR<0% and No Benefit Patients; SR increase. The ANT connectivity description combined a diffusion weighted imaging data from Human Connectome Project (n = 109) with histological data in a synthetic pathway reconstruction process.

Methods

Our non-rigid registration procedures, aims at accurate transfer of patient images into MNI space. We present extensive analytic and probabilistic mapping data of a large cohort of MORE study patients These data were analyzed to define the optimal stimulation volume and to define parameters yielding optimal results.

The analysis of the outcomes included:

1. ANT optimized automatic registration and reconstruction of the electrodes in the MNI space 

2. automatic neuroanatomical characterization of each lead contact and volumes of tissue activated (VTA) computation for the clinically used stimulation electrode contacts

3. probabilistic mapping of stimulation induced effects were constructed by aggregating individual electrode locations and their VTAs.

4. anatomical fingerprint mapping of stimulation outcome defined VTA groups

5. evaluation of the stimulation focus across the MORE patients with a construction of an ANT-DBS stimulation atlas (DSA)

6. multinomial logistic regression analysis to identify and optimize a set of covariates consisting of neuroanatomical, seizure related features. 

Results

Our analysis revealed hotspots for all three outcome groups (Responders; Improvers and No Benefit Patients) in the ANT region. The volumes of the hotspots showed considerable overlap preventing clear outcome discrimination based on these hotspots. 

The volume of the responders was located inferiorly to that of improvers and No Benefit Patients. The anatomical fingerprinting of the atlas revealed that all three outcome clusters have similar anatomical characteristics (Figure 1). 

The multinomial logistic regression of MORE data identified one anatomical area ventral anterior nucleus (VAM) that significantly contributed to the separation of the responder and No Benefit patient groups. 

The stimulation outcome score maps suggest a different hotspot location for the responder group in the US SANTE study (analysis in progress). The average number of contacts in ANT (MORE left=1.72, right=1.67 ) was comparable between the studies. 

The connectivity of the ANT region was characterized by 10 reconstructed pathways. These pathways constitute main connection sources of the ANT region. 

Conclusion

The considerable overlap of the aggregated maps (stimulation outcome score maps) does not allow for clear definition of discriminative stimulation targets. However, the identified various areas and associate fiber relations modulate the probability of being responder. The analysis shows that even if the VTAs are large small fields in the ANT region can nevertheless be segregated in terms of positive and negative improvement.


Milan MAJTANIK (Düsseldorf, Germany), Juergen MAI, Frans GIELEN, Kai LEHTIMÄKI, Volker COENEN, António José GONÇALVES FERREIRA, Antonio GIL-NAGEL, Jukka PELTOLA, Philippe RYVLIN, Abdallah ABOUIHIA, Thomas BRIONNE, Paul BOON
16:10 - 16:15 #26042 - Cost-Effectiveness Analysis of Responsive Neurostimulation for Drug-Resistant Focal Onset Epilepsy.
Cost-Effectiveness Analysis of Responsive Neurostimulation for Drug-Resistant Focal Onset Epilepsy.

Objective: We evaluated the incremental cost-effectiveness of responsive neurostimulation (RNS System) therapy for management of medically refractory focal onset seizures compared to pharmacotherapy alone. 

 

Methods: We created and analyzed a decision model for treatment with RNS therapy versus pharmacotherapy using a semi-Markov process. We adopted a public payer perspective and used the maximum duration of 9 years in the RNS long-term follow-up study as the time horizon. We used seizure frequency data to model changes in quality of life and estimated the impact of RNS therapy on the annual direct costs of epilepsy care. The model also included expected mortality, adverse events, and costs related to system implantation, programming, and replacement. We interpreted our results against societal willingness-to-pay thresholds of $50,000, $100,000, and $200,000 per quality-adjusted life year (QALY). 

 

Results: Based on 3 different calculated utility value estimates, the incremental cost-effectiveness ratio (ICER) for RNS therapy (with continued pharmacotherapy) compared to pharmacotherapy alone ranged between $34,867-$56,253. Multiple sensitivity analyses yielded ICERs often below $50,000 per QALY but predominantly below $100,000 and consistently below $200,000/QALY.

 

Significance: Modeling based on 9 years of available data demonstrates that RNS therapy for medically refractory epilepsy very likely falls within the range of cost-effectiveness depending on method of utility estimation, variability in model inputs, and willingness-to-pay threshold. Several factors favor improved cost-effectiveness in the future. Given the increasing focus on delivering cost-effective care, we hope that this analysis will help inform clinical decision-making for this surgical option for refractory epilepsy.


Brett YOUNGERMAN, Timothy DYSTER, Shraddha SRINIVASAN, Casey HALPERN, Guy MCKHANN, Sameer SHETH (Houston, USA)
16:15 - 16:20 #26046 - A role for modulation of the mamillothalamic tract in seizure control?
A role for modulation of the mamillothalamic tract in seizure control?

Frédéric L.W.V.J. Schaper, Birgit R. Plantinga, Albert J. Colon, G.
Louis Wagner, Paul Boon, Nadia Blom, Erik Gommer, Govert
Hoogland, Linda Ackermans, Rob P.W. Rouhl, and  
Yasin Temel

Background: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with DRE. Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site. 

Objective: We tested the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control.

Methods:The relationship between seizure control and the location of the active contacts to the ANT-MTT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contact relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat-maps. 

Results: After 1 year of stimulation, patients had a median 46%-reduction in total seizure frequency with a 50% responder rate and 20% of patients were seizure free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r = 0.39, p = 0.01) and is ~30% smaller (p = 0,015) in responders than in non-responders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders whereas non-responders had no evident hot-spot. 

Conclusion: ANT-MTT junction stimulation correlates to increased seizure control. Our findings suggest a relationship between stimulation site and therapy response in DBS for DRE with a potential role for the mammillothalamic tract. DBS directed at white matter merits further exploration for the treatment of epilepsy.


Yasin TEMEL (Maastricht, The Netherlands)
16:20 - 16:25 #26129 - Thalamic deep brain stimulation in refractory epilepsy. Surgical practices and outcomes.
Thalamic deep brain stimulation in refractory epilepsy. Surgical practices and outcomes.

Background: Deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) is a treatment option for drug  resistant focal epilepsy. ANT-DBS has been available in European countries after receiving CE-mark in 2010 based on data from a randomized controlled trial (SANTE) (Fisher et al., 2010) and received FDA approval in 2018. Medtronic Registry for Epilepsy (MORE) is an observational open label registry aiming to collect clinical data about DBS implantation practices in Europe.

 

Objective: The aim of the present study is to report surgical implantation practices in centers participating in MORE registry. Secondly, we studied the potential correlation between surgical technique, active contact localization and outcome using advanced image processing tools to co-register individual patient brain and MNI brain for group analysis.

Patients and methods: A total of 191 patients were enrolled between February 21st 2012 and April 30th 2017 by 25 investigational sites in 13 countries. Implant data was available from 179 patients and full analysis set (FAS) was available from 157 patients that completed two year follow up. DBS surgery was performed by neurosurgeons according to local treatment practices aiming to implant lead contacts bilaterally to ANT. Importantly, surgical method or target definition was not controlled by the study group, but education regarding surgical technique used in the US SANTE trial (transventricular) was provided for participating centers. Lead positions were verified postoperatively with magnetic resonance imaging (MRI) and/or computed tomography (CT). Patient outcome was classified as follows: Responders (≥ 50% Seizure Reduction (SR); Improvers, (50%<SR<0%) and No benefit patients (SR increase). At least two-month baseline seizure diary data was required for participation in the study. Each patient’s imaging data was co-registered to MNI brain and contact locations and volume of tissue activation (VTA) were calculated. Statistical outcome score (SoS) maps were calculated for outcome groups by surgical trajectories.

 

Results: In 129 (76%) of patients Medtronic 3389 leads and in 39 (23%) patients Medtronic 3387 leads were implanted bilaterally (one patient had mixed lead types). One hundred patients (59%) had leads implanted using transventricular trajectory bilaterally and 60 (35%) had leads implanted using extraventricular approach. Ten patients (6%) had mixed trajectories. The statistical analysis resulted in a significant difference in the average number of contacts in ANT between transventricular and extraventricular approach (F(1,334)=49.38, p<0.01), where transventricular approach resulted in an average of twice as many ANT contacts compared to the extraventricular approach. The VTAs in transventricularly implanted leads covered ANT in its slightly anterior and superior aspect, while VTAs in extraventricularly implanted leads were distributed slightly more inferior, posterior and lateral (Figure 1). Interestingly, the distribution of VTAs was almost identical between responders and no benefit patient both in transventricular and extraventricular approaches (Figure 2).

 

Discussion: Due to location of ANT in thalamus bordering to CSF from anterior, superior and medial aspects, two distinct surgical approaches (transventricular and extraventricular) were selected by neurosurgeons. VTAs were distributed slightly differently depending on surgical techniques selected, but no obvious difference in VTA coverage between responders and no benefit patients was observed neither in transventricular trajectory nor extraventricular trajectory groups. More consistent lead contact placement in ANT seems to favor transventricular approach, but no superiority of one surgical approach in terms of efficacy could be demonstrated in this open label multicenter dataset.

 

Conclusions: Structural gray matter anatomy and lead contact locations do not clearly explain differences in therapy outcomes. Yet unidentified patient and/or epilepsy related factors or more complex white matter network effects may predict therapy response more reliably and remain to be explored in future studies.


Kai LEHTIMÄKI (Tampere, Finland), Yasin TEMEL, António José GONÇALVES FERREIRA, Volker COENEN, Juergen MAI, Milan MAJTANIK, Antonio GIL-NAGEL, Jukka PELTOLA, Philippe RYVLIN, Abdallah ABOUIHIA, Thomas BRIONNE, Frans GIELEN, Paul BOON
16:25 - 16:30 #27684 - Deep brain stimulation of anterior nucleus of thalamus for intractable epilepsy: analysis of contacts position.
Deep brain stimulation of anterior nucleus of thalamus for intractable epilepsy: analysis of contacts position.

Anterior nucleus of the thalamus as a target of deep brain stimulation (ANT-DBS) is one of the well-tolerated' safe and promising procedures for treatment of epilepsy based on the data from both the experimental studies and limited clinical trials. These preliminary evidences were encouraging enough to design more comprehensive anatomical and functional analysis to improve the outcome.
Our aim was to create mapping analysis of all contacts potentially stimulated and consequently involved in therapeutic and adverse effects with further analysis of "hot spot" and "cold spot" within the target.
Methods through a prospective randomized multicenter trial in 12 French expert centers, 48 patients have been implanted by Medtronic 3389 lead (348 contacts) and were analysed based on high resolution neuroimaging data of brain anatomy and leads implanted. We did patient-specific comprehensive 3D visualization of lead location and further contact-specific anatomical characterization within the detailed thalamic parcellation and surrounding structures invaded in the all three planes on each side using automatic algorithm and StatMaps working pipeline of MRX-Brain platform in MNI space. Group level and individual level analysis of the coordinates of contacts were conducted in correlation with the clinical results and adverse effects if present.
Better understanding and mapping of ANT based on the functional clinical effect in correlation and detailed precise contact characterisations and location, could help for making decisions better on how to implant, program, and fine tune ANT-DBS therapy.


Hussein HAMDI (Marseille), Milan MAJTANIK, Claire HAEGELEN, Juergen MAI, Stephan CHABARDES, Jean REGIS
16:30 - 16:35 #26730 - A tractography study after bilateral anterior thalamic stimulation in drug-resistant epilepsy.
A tractography study after bilateral anterior thalamic stimulation in drug-resistant epilepsy.

Despite optimal medical treatments, many epilepsy patients have drug-resistant seizures. Even after surgery, only 58% of the patients are free of seizure against 8% of the patients without surgery and with best medical treatments (1). In France, a national protocol called FRANCE has included prospectively 61 patients with refractory partial-onset epilepsy and failure of vagus nerve stimulation to be treated with a bilateral chronic stimulation of the anterior thalamic nucleus (ATN). Previous studies have shown depression and memory impairment as the main stimulation-related adverse effects. The prefontal cortex being involved in depression and memory, the object of the study was to assess the patterns of connectivity between the prefrontal cortex and the ATN in epileptic patients with ATN stimulation.

   In FRANCE, all the patients were assessed preoperatively and at one year postoperatively using psychiatric, neuropsychologic and quality of live assessments. Among the 61 patients, twelve of them had, more than the morphological MRI, a diffusion MRI based on the CUSP (Cube and Sphere) method. We used first the PyDBS template (2) to delineate the ATN and 10 Brodmann’s areas (BA) involved in depression and memory impairments. Our regions of interest were 8 prefrontal areas (BA n°8, 9, 10, 11, 44, 45, 46, 47) and 2 areas from the anterior cingulate gyrus (BA n°24, 32). We used the BRAINResample from 3D Slicer to better segment the areas and we corrected manually the segmentation of the ATN if necessary. We used a deterministic method from the SlicerDMRI project to study the tracts between the ATN and our 10 regions of interest. To compare our patients, we used the data from 12 healthy subjects from the Human Connectome Project and analysed them with the same tools. We analysed the correlations between the fractional anisotropy and the mean diffusivity with the clinical data in the patients with Spearman’s rank test. P values < 0.05 were deemed to be significant.

    In all patients and the healthy subjects, the ATN was connected bilaterally with the BA 11 and 47 (Fig. 1). Only 4 patients had connections between the ATN and the BA 9, 10, 45 and 46. In the patients, the mean diffusivity of the right BA 47 and BA 11 was significantly correlated with the verbal and working memories, and with the trail making test difference. The mean diffusivity of the left BA 47 and BA 11 was significantly correlated with the working memory.  Only the fractional anisotropy of the left BA 11 was significantly correlated with trail making test difference. A significant difference was found between the pre- and the postoperative conditions for the depression score (Beck), which was reduced after ATN stimulation.

   We showed that the ATN seems to have strong connectivity with the areas BA 11 and BA 47, perhaps with a tendency for a right hemisphere dominance. BA 11 belongs to the orbitofrontal cortex involved in the depression. BA 47 is the pars orbitaris of the inferior frontal gyrus involved in the emotional control and the inhibition. These two areas were not impaired in these epileptic patients. Even if our study has several limitations, deterministic tractography appears as a valuable non-invasive tool for the exploration of the thalamocortical connections in epileptic patients.  

 

References

1. Wiebe S, Blume WT, Girvin JP, Eliasziw M (2001) A randomized, controlled trial of surgery for temporal-lobe epilepsy. New England J Med 345(5), 311318.

2. Haegelen C, Coupé P, Fonov V, Guizard N, Jannin P, Morandi X, Collins DL (2013) Automated segmentation of basal ganglia and deep brain structures in MRI of Parkinson’s disease. Int J Comp Assist Radiol Surg 8(1), 99110.


Claire HAEGELEN (Lyon), Mathilde GAUDIAN, Alfonso ESTUDILLO, John BAXTER, Elise BANNIER, Stephan CHABARDES, Anca NICA, Pierre JANNIN
16:40 - 16:45 #26195 - Developing prediction models of SEEG electrode implantation accuracy in epileptic patients.
Developing prediction models of SEEG electrode implantation accuracy in epileptic patients.

Background: 

Resection of the epileptogenic zone (EZ) is a curative treatment option for selected patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) aims to localize the EZ. Accuracy of the implanted intracerebral depth electrodes is of critical importance because it improves the delineation of the EZ leading to more precise resective surgery and higher treatment-gain on the one hand, and it lowers the risk of SEEG-associated complications, such as intracranial hemorrhage, on the other hand. Assessment of the implantation accuracy is measured by calculating entry - and target point localization errors (EPLE and TPLE). Many factors appear to contribute to EPLE and TPLE, which may be considered as predictors of accuracy.

Objective: 

To identify potential predictors of depth electrode implantation accuracy, in order to develop prediction models for EPLE and TPLE. 

Methods: 

Retrospective data retrieval and analysis of 75 patients with focal drug-resistant epilepsy (DRE) in whom S-EEG depth electrode implantation was performed between September 2008 and February 2020. A list of 21 potential accuracy predictors was composed and analyzed retrospectively for all patients. Due to the missing data being scattered across electrode cases, the data set was imputed. The potential predictors were identified based on objectiveness, external validity, and relevance, and subsequently investigated for multicollinearity using bivariate correlations (> 0.9 = eliminated) and Variance Inflation Factor (VIF) (VIF > 10 = eliminated). Additionally, univariable multilevel analysis was performed, followed by multivariable multilevel analysis using stepwise backward elimination, to obtain a prediction model for EPLE and TPLE for all implanted electrodes and specified per implantation direction (orthogonal or oblique). Finally, to check the accuracy of the prediction models, the root mean square error (RMSE) was calculated for all prediction models, which is measured in millimeters (mm). 

Results: 

1725 electrodes were analyzed. No variables were excluded based on multicollinearity. 6 prediction models were obtained. The most accurate prediction model was aimed at predicting the EPLE for the electrode direction orthogonal and had an RMSE of 1.311mm. Moreover, the prediction models aimed at predicting the remaining outcome variables were the following: total EPLE = RMSE 2.102 mm, EPLE oblique = RMSE 2.358 mm, total TPLE = RMSE 2.765 mm, TPLE oblique = 22.818 mm and TPLE orthogonal = RMSE 2.276 mm. 

Discussion: 

The present study was accomplished to develop prediction models aimed at SEEG electrode implantation accuracy. This is the first study ever where prediction models have been obtained at predicting SEEG implantation accuracy. Although it is mentioned that EPLE orthogonal has the most accurate prediction model, it is still considered clinically inaccurate due to the relatively large RMSE value. Therefore, all the 6 models may not be useful in clinical practice; however, it may be a good starting point for neurosurgeons and neuroscientists. The limitations of the study include planning bias of the electrodes, specifically regarding electrode direction. Some valuable information was not analyzed due to external validity, but may affect the predicted outcome variables.

Conclusion: 

Intracerebral depth electrodes implantation accuracy can be predicted based on 21 predictors, of which the outcome variable EPLE, for the subgroep orthogonally implanted electrodes, could be predicted most accurately. 


Cyan KORT (Maastricht, The Netherlands), Janvi KAKADIA, Pieter KUBBEN, Olaf SCHIJNS, Louis WAGNER, Lars VAN DER LOO, Govert HOOGLAND, Jim DINGS, Kim RIJKERS, Sander VAN KUIJK
Salle 120
16:30

"Thursday 09 September"

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A26
16:30 - 19:00

Parallel Session 5
Pain Surgery

Moderators: Konstantin V. SLAVIN (professor) (Chicago, USA), Pawel SOKAL (head of department) (Bydgoszcz, Poland)
16:30 - 16:50 Limbic or sensory disciminative DBS in Neuropathic pain. Joachim K. KRAUSS (Chairman and Director) (Keynote Speaker, Hannover, Germany)
16:50 - 17:10 Renaissance of Peripheral Nerve Stimulation in Treatment of Pain" with possible subheading "Does it really work? Konstantin V. SLAVIN (professor) (Keynote Speaker, Chicago, USA)
17:10 - 17:30 Dorsal root ganglion stimulation. Dirk DE RIDDER (Keynote Speaker, Belgium)
17:30 - 17:50 DBS for Pain. Tipu AZIZ (Professor) (Keynote Speaker, Oxford, United Kingdom)
17:50 - 18:00 Mesencephalotomy: anatomo-clinical correlations based on a brainstem normalized coordinate system. Laurent GOETZ (Chercheur / Neurophysiologiste) (Keynote Speaker, Paris, France)
18:00 - 18:10 #23493 - Effectiveness of Stereotactic Thalamotomy in Patients with Intractable Pain.
Effectiveness of Stereotactic Thalamotomy in Patients with Intractable Pain.

OBJECTIVE Ablative procedures are still useful in the treatment of intractable pain despite the proliferation of neuromodulation techniques. In this study, the authors present the results of stereotactic thermolesion (ST) of the centromedian-parafascicularis (CM/Pf) nucleus in various pain syndromes.

METHODS Between 1999 and 2018, unilateral ST of the CM was performed in 62 patients suffering from various severe pain syndromes, in whom conservative treatment had failed. There were 37 women and 25 men in the study population, with a mean age of 63 years (range 30–85 years). The pain syndromes consisted of 22 patients with treatment-resistant trigeminal neuralgia (TN), 10 with postherpetic TN, 1 with TN related to multiple sclerosis, 12 with thalamic pain, 3 with phantom pain, 11 with facial pain related to surgery and 2 related to trauma. The median follow-up period was 23.5 months (range 1–124 months). Other invasive procedures for pain release preceded in 61.2% of patients. The Leksell stereotactic frame, SurgiPlan software, and T1- and T2-weighted sequences acquired at 1.5 T were used for localization of the targeted centromedian-parafascicularis (CM/Pf) nucleus. A stereotactic procedure with a frontal transdermal approach was performed under local anesthesia. The thermolesion was created by a unipolar 16 gauge electrode and Diros generator. A maximum temperature in the range of 75-80 ° C for 60 seconds was applied. Pain relief before and after ST was evaluated. The effect of the procedure was evaluated in percentage scale of remaining pain.

RESULTS The complete data were analyzed in 46 of 62 patients (74%). Overall pain relief was achieved in 19 (41.3%) patients and the pain intensity decreased to 39.5% on average. In 63% of these patients, the effect was recorded on the first follow-up 3 months after the procedure. Pain recurred only in one patient (4.5%) 5 months after the procedure. In one patient, cortical abscess was observed (1.6%) and treated conservatively, no other adverse events occurred.

CONCLUSIONS Our results suggest that stereotactic thermolesion of the CM/Pf complex in patients suffering from severe pain syndromes is a relatively effective and safe method, which can be used even in severely-affected patients. This work was supported by MH CZ – DRO (NHH, 00023884), IG191201.


Jaromir HANUSKA (Prague, Czech Republic), Dusan URGOSIK, Roman LISCAK
18:10 - 18:20 #23800 - DBS for chronic cluster headache: a clinical and image-based meta-analysis of individual patient data.
DBS for chronic cluster headache: a clinical and image-based meta-analysis of individual patient data.

Background: Deep brain stimulation (DBS) is a treatment alternative for refractory chronic Cluster headache (CCH). Despite several recent prospective case series reporting on good outcome, the effectiveness and the optimal stimulation target of DBS for CCH remain unclear. We aimed to obtain precise estimates and predictors of long-term pain relief in an individual patient data meta-analysis. Further, we aimed to construct a probabilistic stimulation map of effective DBS.

Methods:  We invited investigators of published cohorts of patients undergoing DBS for CCH, identified by a systematic review of MEDLINE from inception to Febuary 15, 2019, to provide individual patient data on baseline covariates, pre- and postoperative headache scores at medium (12-month) and long-term follow-up as well as individual imaging data to obtain individual electrode positions.  We calculated a stimulation map using voxel-wise statistical analysis. We used multiple regression analysis to estimate predictors of pain-relief.

Results: Among 40 patients from four different cohorts representing about 50% of all previously published cases, we found a significant 77% mean reduction in headache attack frequency over a mean follow-up of 44 months (corresponding to 75% responder rate). Positive outcome was not associated with baseline covariates. We identified two hotspots of stimulation covering the ventral tegmental area and the retrorubral midbrain tegmentum.

Conclusion: This study supports that DBS provides long-term pain relief for the majority of CCH patients. Our stimulation map of the region of influence of therapeutic DBS identified an optimal anatomical target site that can help surgeons guide their surgical planning in the future.


Andreas NOWACKI (Bern, Switzerland), Martin SCHOBER, Lydia NADER, Assel SARYYEVA, Anh Khoa NGUYEN, Alexander GREEN, Claudio POLLO, Joachim KRAUSS, Denys FONTAINE
18:20 - 18:30 #23896 - Molecular inflammatory phenotyping in neuropathic pain patients under unilateral L4-dorsal root ganglion stimulation.
Molecular inflammatory phenotyping in neuropathic pain patients under unilateral L4-dorsal root ganglion stimulation.

Introduction: Complex regional pain syndrome (CRPS) has been associated with a pro-inflammatory state driven by different circulating mediators. Conventional spinal cord stimulation (SCS) suppressed CRPS pain levels by 40-50% in the past. Most recently, an approach that appears to have a considerable promise for treating focal neuropathic pain has become available (dorsal root ganglion stimulation; DRGSTIM). Anatomically targeted DRGSTIM was found to be superior to conventional SCS in a Class I study as well as several controlled and uncontrolled observational clinical trials for a variety of pain conditions. Briefly, DRGSTIM may have the capability to restore the distorted filter function of the DRG, thus inhibiting hyperexcitability of DRG neurons and deeper layer compartments (laminae II/III) of the spinal cord. The precise mechanism of DRG-evoked effects on spino-nociceptive neural transmission as yet is not fully established

Dorsal root ganglion stimulation (DRGSTIM) suppressed pain levels and improved functional capacity in intractable CRPS in observational and randomized-controlled studies. However, in-human studies evaluating the impact of selective DRG stimulation on the neuro-immune axis in CRPS patients remains under-investigated. 

Methods/Materials: This observational pilot study enrolled 24 subjects (12 CRPS patients - 12 healthy controls) and performed immunoassays of inflammatory mediators in saliva/serum, gene expression assay (whole transcriptome) of neuroinflammatory genes (PantherTM pathway enrichment analysis) and evaluation of pain, mood and sleep at baseline and after 3 months of selective L4-DRGSTIM.  

Results: After L4-DRGSTIM CRPS pain significantly decreased with improved sleep and mood. Elevated levels were detected pre- and post L4-DRGSTIM for high-mobility group box 1, tumor-necrosis factor α, IL-6 and leptin indicating a pro-inflammatory state in CRPS patients. IL-1β was elevated pre-L4 DRGSTIM, but not post-treatment. IL-10 decreased after 3 months in serum, while saliva oxytocin increased after L4-DRGSTIM (Fig.1). Gene expression sub-group analysis of the CRPS subjects (PantherTM pathway enrichment analysis) revealed changes, which may be associated to the clinical effects observed after unilateral L4-DRGSTIM including up and down regulation of certain inflammatory markers (Figure 2).

Discussion: Although of preliminary character, L4-DRGSTIM evoked pain relief and improved functional impairment in CRPS patients revealing a pro-inflammatory molecular pattern. Serum IL-10 significantly declined, while saliva oxytocin increased after L4-DRGSTIM. Sub-group analysis demonstrated either upregulated or downregulated genes involved in immune host response and neural pain circuits.

Conclusions: Large biobank-based approaches are recommended to re-evaluate genetic phenotyping as a quantitative outcome measure for neurostimulation therapy in CRPS patients. The concept of a personalized and predictive neurostimulation therapy based on a comprehensive, preimplant mapping represents the next pivotal step in clinical neuromodulation research for pain.

 

 

 


Thomas KINFE (Erlangen, Germany), Michael BUCHFELDER, Thomas YEARWOOD
18:30 - 18:40 #24080 - Gasserian ganglion stimulation in neuropathic facial pain.
Gasserian ganglion stimulation in neuropathic facial pain.

Introduction

Neuropathic facial pain is a debilitating disease in its medically intractable form. According to the 3rd Edition of International Classification of Headache Disorders it can be the result of multiple sclerosis, mass effect, or its origin can be associated with posttraumatic, postherpetic nerve injuries. Gasserian ganglion stimulation can provide a reliable tool to decrease neuropathic facial pain.

 

Materials and methods

13 patients suffering from medically intractable neuropathic facial pain were enrolled in this study. Indications were of postherpetic (n=3), posttraumatic (3), iatrogenic (5), and unknown (2) origin. Each patient was implanted with a custom-made Medtronic 3 contact anchored, curved lead, under light sedation and intraoperative trial stimulation. Leads were advanced through the oval foramen under fluoroscopy, lead extension has been tunneled and externalized on the neck. Each patient underwent an at most 3-week-long postoperative testing period with an external neurostimulator to evaluate the results of stimulation. VAS scores were obtained three times a day, stimulation parameters were adjusted accordingly.

 

Results

Of the 13 patients 11 patients completed the trial period successfully. Mean age was 53.84±14.24 years, gender distribution was 8 female and 5 male patients. Years passed since onset of symptoms 8.69±10.15. Mean preoperative VAS 9.15±0.9 decreased to 2.64±1.5 in the first two weeks during testing on an external neurostimulator. At least three months after surgery VAS scores were kept in lower ranges - mean VAS 2.5±2,27. Stimulation amplitude and pulse width were inconsistent in the whole group.

 

Discussion

Gasserian ganglion stimulation can be a reliable therapeutic option in medically intractable neuropathic facial pain, but the underlying mechanism is yet to be uncovered. Due to the need of highly variable, patient specific stimulation parameters sometimes an even 3 week-long trial period is advised before IPG implantation to achieve tailored therapeutic settings. The described method can reliably decrease neuropathic facial pain in the observed patient population. Enrollment of more patients is necessary to uncover specific parameters that can tuned to different indications to provide a disease specific guideline for programming. Implementing new fixation techniques can achieve more control during intraoperative lead positioning.


László HALÁSZ (Budapest, Hungary), Loránd ERŐSS
18:40 - 19:00 Discussion.
Auditorium
17:00

"Thursday 09 September"

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C26
17:00 - 19:15

Parallel Session 7
Psychiatry

Moderators: Patric BLOMSTEDT (Neurosurgeon) (Umeå, Sweden), Jean FARISSE (HOSPITAL PRACTITIONER) (MARSEILLE, France), Kuan Hua KHO (Neurosurgeon) (Enschede, The Netherlands), Mircea POLOSAN (MD, PhD) (Grenoble, France)
17:00 - 17:10 #23609 - Neuropsychological and neuropsychiatric outcome after anterior capsulotomy (including the repeated surgery) for obsessive-compulsive disorder.
Neuropsychological and neuropsychiatric outcome after anterior capsulotomy (including the repeated surgery) for obsessive-compulsive disorder.

Objective: Anterior capsulotomy (AC) is sometimes used as a last resort for treatment-refractory obsessive-compulsive disorder (OCD). Previous studies assessing neuropsychological outcomes in patients with OCD have identified several forms of cognitive dysfunction that are associated with the disease, but only a few have focused on changes in cognitive function in OCD patients who have undergone surgery.

Purpose: In the present study, the authors investigated the effects of AC on the cognitive performance and mood status of patients with treatment-refractory OCD.

Method: The authors presented 12 patients with treatment-refractory OCD who had undergone bilateral AC between 2012 and 2019. Patients (N=12 F:M 5:7 ; mean age 39.7 years; duration more than 5 years) were assessed 6 months after intervention at the Department of Clinical Psychology, Na Homolce Hospital, Prague.  Treatment-refractory OCD diagnosis was based on recommended criteria for surgical treatment. For purpose of this study, patients were examined using WAIS-III – short form, including subtests Block Design, Arithmetic, Similarities, Picture Completion; Digit Span; Digit Symbol; RAVLT; TMT A, B; ROCFT; VFT. Anxiety-depressive symptomatology was assessed through the Czech version of the BDI-II; BAI and MADRS. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to measure OCD symptoms.

Results: We found significant decrease of OCD, anxiety and depressive symptomatology assessed by Y-BOCS scale, BDI-II and BAI (p< .05) 6 months after AC in 7 patients and  partial decrease in 5 patients in whom the satisfactory result was reached after the repeated AC. We found unchanged cognitive performance measured by battery of neuropsychological tests in all patients. We detected better immediate and delayed visual memory performance (p< .05) at 6 months follow-up.

Conclusion: The findings of this study suggest that AC not only reduces OCD and anxiety-depressive symptoms but doesn’t influence cognitive performance of patients, even if they underwent repeated surgery. Supported by MH CZ – DRO (NHH, 00023884), IG 161201


Dusan URGOSIK (Prague, Czech Republic), Lenka KRAMSKA, Jaroslava SKOPOVA, Lucia HRESKOVA, Roman LISCAK
17:10 - 17:20 #23937 - What do we learn from the prefrontal leucotomy undergone for psychiatric disorders in times past? – Study with the combination of tractographic and scalp EEG functional connectivity analysis –.
What do we learn from the prefrontal leucotomy undergone for psychiatric disorders in times past? – Study with the combination of tractographic and scalp EEG functional connectivity analysis –.

Objectives:

    Although prefrontal leucotomy was an obsolete remedy for treatment-refractory mental illness, some patients who have undergone prefrontal leucotomy continue to reside in psychiatric hospitals. The surgery achieved a certain therapeutic response, however, that concomitantly produced several complications, such as personality defect (Miller and Psych, 1967), because this extensive lesion was often associated with impairment of frontal lobe function.

    During the past few years, the research focus in brain imaging moved from localizing functional regions to understanding how different regions interact together. It is now widely accepted that some of the brain functions are not supported by isolated regions but rather by a dense network of nodes interacting in various ways. 

    In view of this, the purpose of this study was aimed to identify fibers and functional connectivities severed by the prefrontal leucotomy.

 

Methods:

    Diffusion tensor imaging (DTI) scans were acquired from 5 schizophrenia patients and from 3 prefrontal leucotomized patients with schizophrenia, group-matched for age, on a 1.5T scanner. All leucotomized patients underwent the surgeries approximately more than 40 years previously. Voxelwise statistical analysis of the fractional anisotropy (FA) data in white matter tracts were carried out to compare between leucotomized schizophrenia group and non-leucotomized schizophrenia patient group.
The other method we adopted is oscillation-based functional connectivity analyzed with lagged non-linear coherence developed by Pascual-Marqui (2011). Routine scalp-EEG (19 electrodes) was recorded in 2 prefrontal lobotomized patients and 5 schizophrenia patients matched for age, while they were at rest with eyes closed. This measures coherence (connectivity) between all pairs of ROIs, for each frequency band, for each group.

 

Results:

    Compared with non-leucotomized schizophrenia group, leucotomized schizophrenia group had lower FA in the white matter of rostral and dorsal region of corpus callosum and the mediodorsal thalamic nucleus (MD). Analysis of EEG functional connectivity for the resting state network in leucotomized schizophrenia patients revealed decreased connectivity between prefrontal regions and the rest of the brain for generally almost frequency bands. In particular, the surgeries decreased connectivity of long distance paths  linking between the prefrontal and other cortical regions for low frequency bands, while that of short distance paths between the frontal areas was reduced for high frequency bands.

 

Conclusions:

    The result indicates that the connectivity sacrificed by the prefrontal leucotomy involves fiber degeneration in MD. This was in accordance with the previous studies that demonstrated the prefrontal cortex has reciprocal relationships with a specific portion of MD. Prefrontal leucotomy covered the therapeutic targets the contemporary psychiatric surgeries use. Prefrontal cortical activities in leucotomized brain remained still active, while they were anatomically isolated from the rest of the brain by disconnection with surgical manipulations. Leucotomies decreased functional connectivity of the long distance paths for lower frequency bands, while that of the short distance paths reduced for high frequency bands.

    The specific relationships between activity patterns over the entire brain within individuals and aberrant emotional states remain to be elucidated for advancement of the surgery for psychiatric diseases.


Katsushige WATANABE (Tokyo, Japan), Shunsuke IKEDA, Yasushi OKAMURA, Makoto TANIGUCHI
17:20 - 17:30 #23955 - Structural MRI analyses in OCD: a review of the literature to set out possible predictive factors in patients candidate to anterior capsulotomy.
Structural MRI analyses in OCD: a review of the literature to set out possible predictive factors in patients candidate to anterior capsulotomy.

We analysed the literature to find out the status of art on structural imaging (MRI) in patients affected from OCD with a particular attention on comparison with health controls and with respect to symptoms.

MRI studies in OCD were initially based on region of interest, and later voxel‑based morphometry (VBM) was used (whole‑brain analysis approach) for studying volumetric differences.

Meta-analyses of the literature comparing OCD patients with health controls on cortical thickness and surface showed lower surface area in the temporal cortex and thinner inferior parietal cortex, in the right dorsolateral prefrontal cortex, left posterior cingulate cortex, and bilateral hippocampi other than those prevalent in the CSTC model.  Other meta‑analysis of VBM studies showed decreased grey matter (GM) in bilateral orbitofrontal cortex and anterior cingulate cortex and increased grey matter in the basal ganglia (caudate, putamen, and pallidum). Also Increase in cerebellar GM was found in one meta‑analysis.

Other meta-analyses showed differences with respect to symptom dimensions:

-        cortical thickness was increased in the left OFC in contamination/ cleaning,

-        right OFC, left cingulate cortex, right parietal cortex, and middle temporal cortex in sexual/religious;

-        right occipital and lingual gyrus in aggression/checking;

-        left insula, lingual, precentral, and postcentral gyrus with decrease in fusiform GM in symmetry/order symptom dimension

Even if many studies had recruited patients across heterogeneous symptom dimensions, contributory to the variability in imaging findings making comparisons difficult. Y‑BOCS severity scores have a positive correlation with increase in left dorsal ACC thickness, decrease in cortical thickness in bilateral occipital gyri, and negative correlation with GM volume of left ventral striatum, left frontal pole volume, right anterior cingulate gyrus volume and surface area, and right OFC gyrification.

Enlarging what literature demonstrated is possible to re-analyse the same regions in patients that underwent neurosurgical procedure to find out some predictive factors.


Giorgio SPATOLA (Brescia, Italy), Raphaelle RICHIERI, Viktor JIRSA, Costantin TULEASCA, Yassine BELTAIFA, Nadine GIRARD, Jean Marie REGIS
17:30 - 17:40 #26011 - Long-term results of deep brain stimulation for schizophrenia: a pilot study.
Long-term results of deep brain stimulation for schizophrenia: a pilot study.

Objective: Deep brain stimulation is spreading its indication within psychiatry. In this pilot study, authors present long-term results of DBS for treatment resistant schizophrenia (TRS) and target selection.

 

Methods: Eight patients with TRS underwent DBS, 4 of them in the accumbens nucleus (AcN) and 4 in the subgenual cingulate gyrus (SCG). Demographic and baseline characteristics were recorded. The Positive and Negative Symptoms Scales (PANSS) and its sub-scales (positive, negative and general symptoms) were used to measure the response to the therapy. Responder were defined as improvement of PANSS > 25% to baseline. The AC/PC coordinates of the active contacts and the total electrical energy delivered (TEED) were calculated and correlated with clinical outcomes. Patient-specific tractography-activation models (TAMs) were performed to identify potential pathways in responders.

 

Results: Five women (62.5%) and three men (37.5%) with a median age of 41 years [34 – 58] were included. Along 4 years follow-up, four patients (50%) improved their positive symptoms (two implanted in SCG and two in AcN), two patients (25%) improved their negative symptoms (two SCG) and three patients (37.5%) improved their general symptoms (two AcN and one SCG). TEED showed no correlation with clinical outcomes. In SCG patients the forceps minor (FM) and the frontopolar fascicle (FPF) were the most frequently stimulated pathway, while the superolateral middle forebrain bundle (slMFB) was frequently stimulated in AcN patients.

 

Conclusions: DBS for TRS is an investigational indication. These initial results show that for chronic schizophrenic patients, DBS in SCG might improve specific psychotic symptoms (positive and negative) while DBS in AcN might improve general symptoms. FM, FPFS and slMFB might be tracts involved in the complex circuitry of this disease. 


Juan Ángel AIBAR DURÁN (BARCELONA, Spain), Alexandra ROLDAN BEJARANO, Iluminada CORRIPIO COLLADO, Ignacio ARACIL BOLANOS, Rodrigo RODRIGUEZ RODRIGUEZ
17:40 - 17:50 #26041 - Dual-target deep brain stimulation for depression informed by intracranial stereo-EEG.
Dual-target deep brain stimulation for depression informed by intracranial stereo-EEG.

Deep brain stimulation (DBS) for treatment-resistant depression (TRD) is investigational, with previous studies demonstrating heterogeneous results. We devised a novel personalized medicine platform for DBS therapy development focused on this essential aspect: the need to achieve an individualized understanding of the specific brain networks contributing to a patient’s particular depressive phenotype and their response to stimulation. To do so, we borrowed from the field of epilepsy surgery the well-established approach of using intracranial EEG to individualize the understanding of epileptic networks.

We report results from the first subject treated with DBS for TRD using this approach. The subject underwent implantation of DBS leads targeting both ventral capsule/ventral striatum (VC/VS) and sub-callosal cingulate (SCC) bilaterally, as well as 10 stereo-EEG (sEEG) electrodes targeting fronto-temporal regions putatively involved in depression-implicated networks. We then performed a series of studies using these externalized electrodes to gain an individual-specific understanding of mood-regulating brain networks and their response to stimulation. These recordings enable derivation of individually optimized stimulation parameters using a novel “inverse solution” approach: we first use this novel dual-target strategy to maximize accessibility to as much of the relevant TRD network as possible. We then use the intracranial sEEG recordings to narrow the possible stimulation parameter space and choose those parameters that engage network sub-regions most effectively for the individual subject. This “sEEG-informed DBS” platform enables therapeutic development with an emphasis on individualized understanding of network (patho-)physiology.We then implemented these customized DBS stimulation parameters in an outpatient trial. During the open-label phase, standard rating scales demonstrated progressive improvement in depression severity leading to remission of symptoms by week 22. The subject then entered the double-blind, randomized discontinuation phase of the trial to distinguish between true and sham response. Over this time, he reported steadily worsening mood and anxiety, and his symptom scores increased during this period until he met rescue criteria. At this point, stimulation was reinstated at pre-discontinuation levels, and his depression symptoms again quickly remitted. 

We envision this platform as one for DBS therapy development and optimization for challenging disorders during a critical period of knowledge acquisition. We do not use this platform primarily to find new stimulation targets, as doing so would potentially require an intracranial search in all future patients. Rather, we use the electrophysiological data to optimize identification of DBS stimulation parameters that engage pathological networks. Our results highlight the feasibility and potential value of doing so using an “inverse solution” approach.

The increased invasiveness of this platform over conventional DBS is meant to be a bridge to future less invasive approaches. This successful case is a critical first demonstration of this novel strategy using direct intracranial measurements. Future work can test the success of substituting non-invasive techniques as readouts of neural activity as they become increasingly reliable. More generally speaking, an important advantage of this platform is that stimulation configurations derived from future analyses can be readily implemented as new sets of stimulation parameters to employ and test. This approach enables repeated iteration between computational analysis and clinical testing, providing a long-term testbed for the neuroscientist and continued hope for symptomatic relief for the patient.

            In summary, our initial results demonstrate the feasibility of this novel platform. We propose that this approach, if consistently demonstrated safe and effective, can be used to develop and improve surgical neuromodulation for a vast array of neurological and psychiatric disorders.

 


Sameer SHETH (Houston, USA), Kelly BIJANKI, Brian METZGER, Anusha ALLAWALA, Victoria PIRTLE, Joshua ADKINSON, John MYERS, Raissa MATHURA, Denise OSWALT, Evangelia TSOLAKI, Jiayang XIAO, Angela NOECKER, Adriana STRUTT, Jeffrey COHN, Cameron MCINTYRE, Sanjay MATHEW, David BORTON, Wayne GOODMAN, Nader POURATIAN
17:50 - 18:00 #26057 - Targeting deep brain stimulation in obsessive-compulsive disorder: lessons learned form 84 consecutive cases.
Targeting deep brain stimulation in obsessive-compulsive disorder: lessons learned form 84 consecutive cases.

We present 84 consecutive patients with therapy-refractory obsessive-compulsive disorder (OCD) who underwent deep brain stimulation (DBS) from 2005-2019, and determined the relationship between the anatomical location of active electrode contacts and the clinical outcome. In the first 28 patients, electrodes were implanted in the nucleus accumbens (NAc), with a lateral angle approximately following the anterior limb of the internal capsule (ALIC): 11 (43%) responded to DBS. In patients 29-72, electrodes were implanted in the ventral part of the ALIC (vALIC), just dorsal of the NAc. Also, five previous non-responding NAc patients underwent repositioning of their electrodes to the vALIC. Twenty-nine patients (59%) responded to DBS. In patients 73-84, electrodes were implanted in the superolateral branch of the medial forebrain bundle (MFB), during its course through the ALIC: 10 (83%) responded to DBS. Five previous non-responding NAc & vALIC patients underwent repositioning of their electrodes to the MFB, and three of them became responders. We also retrospectively identified 8 patients among patients 29-72 in whom both centers of stimulation were in the MFB: 7 responded to DBS. Overall, 20/25 MFB patients (80%) responded to DBS. We therefore conclude that the MFB (during its course through the ALIC) is a better DBS target than vALIC and NAc in treatment-refractory OCD.


Pepijn VAN DEN MUNCKHOF (Amsterdam, The Netherlands), Maarten BOT, Luka LIEBRAND, Pelle DE KONING, Nienke VULINK, Martijn FIGEE, Guido VAN WINGEN, Damiaan DENYS, Rick SCHUURMAN
18:00 - 18:10 #26194 - Globus pallidus internus deep brain stimulation can provide durable benefits in severe Gilles de la Tourette syndrome.
Globus pallidus internus deep brain stimulation can provide durable benefits in severe Gilles de la Tourette syndrome.

Objectives

                                                    

To explore whether bilateral Globus pallidus internus (GPi) deep brain stimulation (DBS) provides sustained symptom and quality of life improvements in Gilles de la Tourette syndrome (GTS).

 

Introduction

 

GTS is defined by the presence of multiple motor and vocal tics which can be associated with psychiatric comorbidities. In medical treatment refractory cases, DBS of the GPi has been shown to result in a broad range of symptom improvements though the durability of this effect remains uncertain. We previously demonstrated short term benefits in a cohort of GTS patients treated with GPi-DBS. In this study we explored long-term outcomes in these patients.

 

Methods

Patients previously implanted between 2010 and 2014 were contacted for reassessment. Those consenting were assessed using the following scales: Yale Global Tic Severity scale (YGTSS) sub scores (motor tics, vocal tics, and impairment); Yale- Brown Obsessive Compulsive Scale (YBOCS); Quality of life (QOL); Beck Depression Index (BDI) and State-Trait Anxiety Inventory (STAI). Total scores in the preoperative, and first available post-operative assessments were compared with the current delayed assessment. Clinical outcomes for continuous values are presented as mean ±standard deviations (SD). The Wilcoxon signed-rank test was used for comparison of non-parametric paired data. An exploratory univariate linear regression analysis was performed to identify if baseline factors contributed to the final YGTSS and QOL scores. A two-side p value of <0.05 was used to judge statistical significance.

 

Results

Of the 21 patients with GTS previously implanted at our centre between 2014 and 2016, 11 consented to participate. A slight male predominance (7/11) was noted. The mean operative age was 37.3±13.6 years and age of symptom onset 8.0±2.6 years. Seven patients were implanted in the anteromedial GPi and 4 in the posteroventral GPi. The first post-operative assessment was performed a mean of 15.7±15.2 months after implantation and the delayed post-operative assessment after 8.5± 1.5 years. The YGTSS score improved post implantation (85.6±12.5 vs 48.2±23.9, p <0.01) and remained unchanged at the delayed assessment (48.2±23.9 vs 46.8±22.2, p=0.85). Similar patterns of improvement were also noted for the total motor and vocal tic burden sub-scores. Patients reported an improvement in mood post-surgery as measured by the BDI (30.6±6.0 vs 17.0±10.2, p=0.04). This effect was sustained at the delayed assessment (17.0±10.2 vs 23.6±10.8, p=0.45). No difference was noted in the YBOCS score at the early post-operative assessment (15.5±8.6 vs 11.0±10.1, p=0.21), nor the delayed assessment (11.0±10.1 vs 19.0±10.8, p=0.09). No changes in the STAI score were noted at either post-operative assessment. Patients reported an improvement in QOL at the first post-operative assessment (74.7±17.4 vs 45.1±28.5, p=0.02). This effect was sustained at the delayed assessment (45.1±28.5 vs 47.6± 20.4, p=0.48). Although no baseline patient characteristics predicted the YGTSS score at the final assessment, the age of onset of the disease predicted the final QOL score noted (β=5.90, 95% CI 2.02-9.79, p=0.01). 

 

Conclusions

The beneficial effects of GPi DBS in Gilles de la Tourette’s syndrome can be sustained. However, we cannot exclude the possibility that the patients who declined to participate may include individuals with lower response rates to DBS.


Olga PARRAS GRANERO (Basque country, Spain), Nirosen VIJIARATNAM, Marjan JAHANSHAHI, Joseph CANDELARIO, Catherine MILABO, Harith AKRAM, Jonathan HYAM, Patricia LIMOUSIN, Marwan HARIZ, Eileen JOYCE, Ludvic ZRINZO, Tom FOLTYNIE
18:10 - 18:20 #26290 - Preliminary Safety and Feasibility Outcomes of Nucleus Accumbens Deep Brain Stimulation (DBS) Clinical Trial for Opioid Use Disorder.
Preliminary Safety and Feasibility Outcomes of Nucleus Accumbens Deep Brain Stimulation (DBS) Clinical Trial for Opioid Use Disorder.

Introduction: Given high relapse rates and the prevalence of opioid overdose deaths, novel treatments for opioid use disorder (OUD) are desperately needed for those who are treatment refractory. We initiated a US National Institute on Drug Abuse (NIDA) sponsored clinical trial to evaluate the safety and feasibility of deep brain stimulation (DBS) of the Nucleus Accumbens (NAc) and ventral anterior internal capsule (VC) for treatment refractory OUD and its effects on substance use, craving, frontal, executive, and emotional functions.

Methods: Participants with at least a 5-year history of severe, treatment-refractory OUD with multiple overdoses were eligible for this study. Participants were implanted with bilateral Medtronic DBS electrodes (3387) within the NAc/VC. Clinical safety and the therapeutic response to DBS, including the effects on substance abstinence, craving, mood, and executive function, were assessed. 18fluoro-Deoxy-Glucose (FDG) PET was performed at 12-week post titration to evaluate metabolic changes following DBS.  Local field potentials (LFP) were assessed using the Medtronic Percept DBS recording and stimulation device.

Results: Two eligible participants underwent NAc/VC DBS. There were no surgical complications. The first participant was a 33-year-old male who has achieved over 600 days of continuous abstinence to date, compared to an average relapse time of approximately 1-2 weeks prior to DBS implantation. Cravings for opioid and other substances decreased significantly post-implantation with the most significant reduction in benzodiazepine craving (53.4±29.5 vs. 1.0±2.2; p<0.001). The DBS therapeutic response was associated with a concomitant increase in glucose metabolism in the dorsolateral prefrontal and medial premotor cortices through the FDG PET analysis. The participant also showed signs of improvement in depression, anxiety, impulsivity, and frontal/executive functioning. Diffusion Tensor Imaging (DTI) revealed that the location of the DBS contact with the most optimal therapeutic response corresponded to strong structural connectivity to the mesial frontal region. Stimulation-related adverse effects were associated with connectivity to the amygdala/temporal lobe.

The second participant was a 22-year-old male who underwent DBS implantation successfully. Due to non-compliance with the study protocol and follow-up treatment regiment, the DBS system was explanted at 15 weeks post-implantation.

Conclusion: In a participant with severe, treatment-refractory opioid and benzodiazepine use disorder, DBS of the NAc/VC is safe, well-tolerated, and can reduce substance use and craving, and improve frontal and executive functions. The use of DTI provides valuable insight to select the optimal target for stimulation.  We will present the latest results of this ongoing clinical trial including LFP data and additional subjects. DBS for addiction is promising but complex and challenging given the nature of the population and disease. 

(This study received funding from NIDA 1UG3DA047714-01; device and technical support from Medtronic)


Ali REZAI (Morgantown, USA), Manish RANJAN, Pierre-Francois D’HAESE, Mark HAUT, Wanhong ZHENG, Laura LANDER, Nicholas BRANDMEIR, Victor FINOMORE, Sally HODDER, Berry JAMES, James MAHONEY
18:20 - 18:30 #26306 - Why subthalamic DBS should not be ignored for refractory OCD: evidence from quality of life study.
Why subthalamic DBS should not be ignored for refractory OCD: evidence from quality of life study.

Background : While Deep Brain Stimulation (DBS) is an established therapy for several neurological disorders, effectiveness and safety of this strategy in refractory Obsessive Compulsive Disorder (OCD) is increasingly reported since first reports in 1999. Randomized sham-controlled short term (3 months) as well as open-label long term follow-up (2y) clinical improvement with subthalamic (STN) DBS have consistently been shown on 2 different cohorts respectively. As OCD may lead to significant disability and altered quality of life, the latter includes subjective self-assessment and represents optimal therapeutical objective beyond clinical outcome. We thus focused on quality of life evolution with long term STN DBS in a cohort of refractory OCD.

 

Methods: Fourteen refractory OCD patients were recruited from Grenoble University Hospital and treated by STN high-frequency stimulation. Patients had at least five years of treatment-resistant, severe, disabling OCD before DBS surgery. Clinical severity and quality of life was evaluated using the YBOCS and SF36 scale, respectively. Patients were evaluated in the pre-op phase (T0), at 2-3 years of stimulation (T1), and at minimum of 5 years of stimulation (T2). Clinical scores were compared between the different end-points using repeated measures ANOVA. 

 

Results : We highlight that STN DBS lead to a significant improvement of mental and physical quality of life as measured by SF36 with a mean improvement of 46,9% and 26% respectively, while the clinical severity improved of 53,1% at 5 years end point compared to pre-op. Among the different dimensions of the mental score of quality of life, social function is the one improving the most ( +29,9 points within the 5y period, p=.0022). Regarding the physical score of quality of life, physical activity and limitations due to physical state (“role physical”) are improving significantly of 20,3 points (p= .0041) and 26,4 points (p=.0016) respectively.

There was any statistically significant difference between quality of life measures at 2y and 5y, suggesting a long-term persistence of the acquired improvement obtained within the initial 2y stimulation.    

Conclusion : STN DBS in refractory OCD leads to persistent clinical and quality of life improvement, fostering its recognition within the therapeutical algorithms in this disabling medical condition. 


Mircea POLOSAN (Grenoble), Pauline MAZE, Brigitte PIALLAT, Julien BASTIN, Eric SEIGNEURET, Alexandre KRAINIK, Paul KRACK, Stephan CHABARDES
18:30 - 18:35 #26146 - Cellular anatomy of the Sano triangle and therapeutic hypothesis for psychosurgery.
Cellular anatomy of the Sano triangle and therapeutic hypothesis for psychosurgery.

Stereotactic lesions of the Sano triangle were successfully performed to treat severe aggressiveness in the 70’s (Sano et al. 1970). This emotional and vegetative brain area, located within the medial subthalamic area, is still a target for deep brain stimulation in rare patients with pathological aggressiveness (Torres et al. 2020) and for resistant cluster headaches (Nowacki et al. 2019). Here, we report our experience of bilateral Sano triangle lesions in a schizophrenic violent patient with a transient improvement, in whom MRI lesions were precisely located on a normal post-mortem human brain obtained from a body donation studied with 11.7T MRI and immunostained histological sections. Our aim was to identify neuronal populations, axon terminals and fiber bundles involved in the lesions in order to better understand the pathophysiology of pathological aggressiveness. A 40-year-old man had a paranoid schizophrenia with persecutory delusions and hallucinations for 25 years. Often, he experienced unpredictable and major episodes of auto- and hetero-aggressiveness. Since 2011, violent outbursts became uncontrollable requiring permanent hospitalization and physical restraints. Treatment failure was due to his allergic reaction to all neuroleptics with recurrent severe malignant syndromes. Electroconvulsive therapy was ineffective. In 2013, the patient’s family consented to psychosurgery, which was approved by a multidisciplinary team in accordance with French law. Bilateral lesions of the Sano triangle were performed in December 2013. The targets were calculated on the patient’s T1 MRI with our histological and deformable YeB atlas (Bardinet et al. 2009). The coordinates were X = 4, Y = 12 and Z = 3.5 mm with respect to the posterior commissure. Intra-operative electrical stimulation was applied at different depths and the lesion was performed (75°C for 60s) at the site where stimulation induced sympathomimetic signs. After surgery, the patient showed mild improvement with less frequent and less intense violent outbursts that lasted only for 6 weeks. He also gained weight moderately. MRI showed a one-millimeter right lesion and no definitive left lesion. We performed a second surgery using the same targets and technique in July 2014. Immediately after, the patient’s status improved and physical restraints were removed. He interacted better with his family and the medical staff. MRI showed bilateral lesions. After three months, nocturnal aggressiveness returned requiring neuroleptic medication. The patient died from a malignant syndrome in October 2014. To localize precisely the lesions, a multimodal map of the Sano triangle was adapted to the postoperative patient MRI. This map was built from a normal human post-mortem brain, whose region of interest was first scanned at 11.7T (anatomical and diffusion sequences), then serially sliced and immuno-stained. Fusion of the post-mortem (control) and post-operative (patient) data was performed manually using linear transformations. Adjacent series of sections were immunostained with orexin, histamine, dopamine, serotonin transporter and vesicular transporter of glutamate 1. We showed that lesions were well located in the Sano triangle within the medial reticular formation and posterior to the posterior hypothalamus (Fig 1 a. and b.). Within both lesion sites, we observed few dopaminergic neurons and scattered neurons without specific labeling. The lesions sites mostly contain a homogeneous distribution of serotoninergic terminals and numerous glutamatergic terminals with an increasing latero-medial gradient (Fig 1 c. to f.). We also identified some orexinergic terminals originating in the hypothalamus and ending on unlabeled cell bodies, and a small dopaminergic bundle passing through the lateral part of the lesions. Our preliminary results suggest that Sano triangle lesions involve scattered reticular neurons and many diverse axonal endings together with dopaminergic projections to the thalamus. The obtained clinical effect could be explained by the interruption / modulation of cortical, serotoninergic and hypothalamic projections in this complex area. The use of DBS instead of lesioning may have permitted a more sustained improvement by delivering continuous stimulation. A targeting based on deformable histological atlas and individualized tractography should be the next step to improve results in psychosurgery.


Marie Des Neiges SANTIN (STRASBOURG), Marion PLAZE, Chantal FRANCOIS, Christophe DESTRIEUX, Eric BARDINET, Marwan HARIZ, Raphaël GAILLARD, Carine KARACHI
18:35 - 18:40 #26015 - Cocaine-induced changes in dopamine levels in nucleus accumbens as a potential biomarker for drug addiction neuromodulation.
Cocaine-induced changes in dopamine levels in nucleus accumbens as a potential biomarker for drug addiction neuromodulation.

Background

To develop novel treatments, it is imperative to be able to measure the effect of drugs of abuse on neurotransmission. Here we present a novel electrochemical method, known as multiple cyclic square wave voltammetry (M-CSWV), which can accurately measure tonic dopamine levels, with temporo-spatial resolution superior to existing methods. Together with fast-scan cyclic voltammetry (FSCV), we utilized these techniques to elucidate changes in phasic and tonic dopamine at nucleus accumbens core (NAcc), after cocaine administration.

 

Methods

Carbon fiber microelectrode (CFM) and stimulating electrode were implanted into NAcc and medial forebrain bundle (MFB) of Sprague-Dawley rats, respectively. Locations were optimized via evoked phasic response by MFB stimulation. In the first group, the phasic response was measured after a dose of i.v. saline or cocaine hydrochloride (3mg/kg). In the second group, tonic levels were measured using M-CSWV after saline and cocaine.

 

Results

Both the phasic (n=4) and tonic (n=5) dopamine responses were augmented by cocaine injection. The phasic and tonic levels changed by approximately x2.4 and x1.9, respectively. The minimal disruption/disturbance of neuronal tissue by CFM may explain why the measured baseline tonic values [134±32 nM] were 10-fold higher compared to conventional microdialysis values.

 

Conclusions

In this study, we elucidated the dopamine dynamics at NAcc with acute cocaine administration. This is the first time this has been explored with such a high temporo-spatial resolution. Our results demonstrated the exciting possibility of M-CSWV as a sensing component of a closed-loop neuromodulation system that could modulate dopamine levels similar to drugs of abuse.


Jason YUEN (Rochester, MN, USA), Abhinav GOYAL, Aaron RUSHEEN, Abbas KOUZANI, Michael BERK, Jee Hyun KIM, Susannah TYE, Charles BLAHA, Dong-Pyo JANG, Kevin BENNET, Hojin SHIN, Yoonbae OH, Kendall LEE
18:40 - 18:45 #23958 - Deep brain stimulation (DBS) of the median forebrain bundle in a rodent model of depression: Interaction between depressive-like phenotypes and estrogen in female rats.
Deep brain stimulation (DBS) of the median forebrain bundle in a rodent model of depression: Interaction between depressive-like phenotypes and estrogen in female rats.

Depression is the leading cause of disability worldwide and a major contributor to the global burden of disease. Women are at a higher risk than men to develop mood disorders and depression. The increased risk is associated with fluctuating estrogen levels that occur during reproductive cycle events. There is compelling scientific evidence indicating the neuromodulatory and neuroprotective effects of estrogen, which are directly relevant to mood symptomatology. Specifically, affective regulation has been linked to neural structures rich in estrogen receptors and estrogenic regulation of neurotransmitters. The limbic system, implicated in depression, is modulated by various neurotransmitters which are influenced by the circulating hormone estrogen. Various studies on deep-brain stimulation (DBS) of the median forebrain bundle (MFB) to treat refractory depression are currently ongoing. The current study is the first in a series addressing the issue of sexual dimorphisms in the Flinders Sensitive Line (FSL) rodent model of depression. The female estrous cycle on anti-depressant effects of DBS and the effect on specific neurotransmitters and hormones are being investigated.

Depressive-like FSLs and non-depressive Sprague Dawley (SD) received 8 days continuous MFB-DBS while monitoring the estrous cycle. Before and after DBS, behavioral comparison was assessed using the forced swim test, the sucrose consumption test and locomotion measurements. Post-mortem expression of neurotransmitters, estrogen and their respective receptors in implicated regions was assessed using qPCR, Western Blot and ELISA.

FSLs exhibited significant differential behaviors compared to controls. After MFB-DBS, a significant reduction in depressive-like phenotypes and a significant increase in serum estradiol concentrations was observed. Significant behavioral changes occurred alongside hormonal fluctuations in the estrous cycle throughout all groups. Behavioral results suggest an impact of estrogen fluctuations on the presence of depressive-like symptoms in both FSL and controls. Further analysis focuses on molecular changes to establish relevant interactions between hormonal cycles and neurotransmitter activity.


Anna TADROS (Freiburg, Germany), Wilf GARDNER, Yixin TONG, Tsvetan SERCHOV, Volker Arnd COENEN, Máté DÖBRÖSSY
18:45 - 18:50 #25945 - Deep Brain Stimulation for psychiatric disorders: long-term surgical management.
Deep Brain Stimulation for psychiatric disorders: long-term surgical management.

Objective:

Deep Brain Stimulation (DBS) has implemented itself as a hallmark in movement disorder therapy and has been explored for psychiatric disorders in clinical trials as an adjunct treatment. Data on how to surgically manage these patients long after the clinical trial has ended is currently lacking.

 

Methods:

A single center database analysis was performed to identify all cases of DBS for psychiatric indications. Epidemiologic data, number and type of follow-up surgeries after initial implantation, rate of complications, success in long-term therapy and documented stimulation parameters were analyzed.

 

Results:

Between 2003 and 2019 n=103 patients were implanted with a DBS system for a psychiatric indication (excluding dementias) with a mean follow-up of 106 months. Mean age was 43.1 years with two thirds being female. Indications were major depression (n=66), bipolar disorder (n=6), obsessive-compulsive disorder (n=6), anorexia nervosa (n=22) and Tourette’s syndrome (n=3). The predominant target structure was the subgenual cingulate gyrus (CG25, 91% for depression, bipolar disorder and anorexia). 48.5% of all patients still had an active DBS system with a mean follow-up of 94 months at the time of the study.  21.4% of patients had the system explanted with lack of efficacy being the most common one (77% of explants). IPG replacements were the most common scheduled surgery with an average of 2.3 replacements per patient. IPGs lasted for an average of 24.0 months with average stimulation parameters of 130Hz, 85µs and 5.3V. N=42 patients were switched to a rechargeable IPG with 24% being switched back to a non-rechargeable IPG later on. 37% of patients had unscheduled surgeries for wound-related complications (15.5% of patients), hardware related issues (10.6%) or suboptimal electrode placement (1.0%).

 

Conclusion:

Patients with DBS for psychiatric disorders represent a separate entity compared to movement disorder patients. The rate of explants and unscheduled surgeries is higher. High stimulation parameters demand frequent IPG replacements generating a considerable rate of wound-related complications. Strategies to reduce the number of IPG replacements (optimization of stimulation parameters, use of rechargeable IPGs) could help to increase the rate of long-term responders in the future. When conceiving trials, strategies on how to enable long-term therapy for these patients should be considered.


Martin JAKOBS (Heidelberg, Germany), David Hernán AGUIRRE-PADILLA, Peter GIACOBBE, Andreas UNTERBERG, Andres LOZANO
18:50 - 18:55 #23953 - Investigation of sleep, behavioural and physiological deficits in the FSL model of depression and the related effects of medial forebrain bundle deep-brain stimulation.
Investigation of sleep, behavioural and physiological deficits in the FSL model of depression and the related effects of medial forebrain bundle deep-brain stimulation.

Depression is a common mental disorder, representing one of the largest health burdens worldwide. Despite its significance, the neurobiology underlying depressive symptoms is poorly understood. There remain no unique physiological biomarkers for the disease, and a significant proportion of patients fail to respond to conventional treatments. Sleep problems are an extremely common symptom in depression, the resolution of which may impact treatment outcomes. Deep Brain Stimulation of the medial forebrain bundle (MFB-DBS) represents a promising treatment for refractory depression. The Flinders Sensitive Line (FSL) rat is an established model for depressive symptoms, several aspects of its phenotype have not been fully examined. In the current study, sleep, behavioral and physiological abnormalities in the FSL are further investigated, to extend characterization of the model. In order to assess the anti-depressant action of MFB-DBS, and to provide insight into potential associated mechanisms of the treatment, the effect of MFB-DBS on various measures was examined in the FSL.

FSL rats and non-depressive Sprague Dawley controls were implanted via stereotactic surgery with electrodes for DBS in the MFB, and for electrophysiological recording in the prefrontal cortex, nucleus accumbens and CA1 hippocampus. Assessments were conducted pre- and post- 24-hour DBS. Behavioural phenotypes were measured by the forced swim and sucrose consumption tests. Post-mortem, tissue was collected and processed for analysis using in situ hybridization, HPLC, qPCR and western blotting.

FSLs exhibited previously unreported changes in slow-wave activity and oscillatory activity during sleep, and depressive-like behaviors including anhedonia. MFB-DBS improved behavioral phenotypes, alongside physiological changes including to pre-frontal extracellular monoamine levels and the expression of receptors of the dopaminergic system. Despite other observed anti-depressant effects, measures of sleep were unaffected.

The presence of previously unreported slow-wave sleep deficits and anhedonic-like phenotypes enhance the validity of the FSL as a model of depression. Improvement of behavioral phenotypes provides evidence of the anti-depressant effect of MFB-DBS, while insight into the biological substrate of these effects, potentially mediated via alterations to dopaminergic functioning, is provided by physiological changes. The lack of influence on sleep symptoms presents a challenge and potential clinical limitation of MFB-DBS, which must be addressed in future clinical and pre-clinical research.


Wilf GARDNER (Strasbourg), Laura DURIEUX, Anna TADROS, Fanny FUCHS, Tsvetan SERCHOV, Chantal MATHIS, Volker Arnd COENEN, Máté DÖBRÖSSY, Lucas LECOURTIER
18:55 - 19:00 #23912 - Longterm deep brain stimulation in treatment-resistant obsessive-compulsive disorder: outcome and quality of life at 4- 8 years follow-up.
Longterm deep brain stimulation in treatment-resistant obsessive-compulsive disorder: outcome and quality of life at 4- 8 years follow-up.

BACKGROUND: Obsessive compulsive disorder (OCD) is a severe disabling disease, and around 10% of patients are considered to be treatment-resistant (tr) in spite of guideline based therapy. Deep brain stimulation (DBS) has been proposed as a promising treatment for patients with trOCD. However, the optimal site for stimulation is still a matter of debate, and clinical longterm follow-up observations including data on quality of life are sparse. We here present six trOCD patients who underwent DBS with electrodes placed in the bed nucleus of the stria terminalis/ anterior limb of the internal capsule (BNST/ALIC), followed for 4-8 years after lead implantation.

METHODS: In this prospective observational study, six patients (four men, two women) aged 32-51 years and suffering from severe to extreme trOCD underwent DBS of the BNST/ALIC. Symptom severity was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and quality of life using the World Health Organization Quality of Life assessment scale (WHO-QoL BREF). Follow-up was obtained at least for 4 years in all patients.

RESULTS: With chronic DBS for 4 - 8 years 4/6 patients had sustained improvement. Two patients remitted, and two patients responded (defined as > 35% symptom reduction), while the other two patients were considered non-responders on longterm. Quality of life markedly improved in remitters and responders. We did not observe periinterventional side effects or adverse effects of chronic stimulation.

CONCLUSIONS: Chronic DBS of BNST/ALIC provides longterm benefit up to 4 - 8 years in trOCD, although not all patients take profit. Quality of life improves in DBS responders, documented by improved QoL scores and, even more important, by regaining of autonomy and improving psychosocial functioning.

 


Assel SARYYEVA, Lotta WINTER, Kerstin SCHWABE, Hans.e HEISSLER, Joachim RUNGE (Hannover, Germany), Mesbach ALAM, Ivo-Aleksander HEITLAND, Kai KAHL, Joachim K. KRAUSS
19:00 - 19:05 #23954 - Medial forebrain bundle DBS differentially modulates dopamine release in the nucleus accumbens in a rodent model of depression.
Medial forebrain bundle DBS differentially modulates dopamine release in the nucleus accumbens in a rodent model of depression.

Medial forebrain bundle (MFB) deep brain stimulation (DBS) has anti-depressant effects clinically and in depression models. Currently, therapeutic mechanisms of MFB DBS or how stimulation parameters acutely impact neurotransmitter release, particularly dopamine, are unknown. Experimentally, MFB DBS has been shown to evoke dopamine response in healthy controls, but not yet in a rodent model of depression.

The study investigated the impact of clinically used stimulation parameters on the dopamine induced response in a validated rodent depression model and in healthy controls. The stimulation-induced dopamine response in Flinders Sensitive Line (FSL, n = 6) rat model of depression was compared with Sprague Dawley (SD, n = 6) rats following MFB DSB, using Fast Scan Cyclic Voltammetry to assess the induced response in the nucleus accumbens. Stimulation parameters were 130 Hz (“clinically” relevant) with pulse widths between 100 and 350 μs. Linear mixed model analysis showed significant impact in both models following MFB DBS both at 130 and 60 Hz with 100 μs pulse width in inducing dopamine response. Furthermore, at 130 Hz the evoked dopamine responses were different across the groups at the different pulse widths.

The differential impact of MFB DBS on the induced dopamine response, including different response patterns at given pulse widths, is suggestive of physiological and anatomical divergence in the MFB in the pathological and healthy state. Studying how varying stimulation parameters affect the physiological outcome will promote a better understanding of the biological substrate of the disease and the possible anti-depressant mechanisms at play in clinical MFB DBS.


Danesh Vajari ASHOURI (Freiburg, Germany), Chockalingam RAMANATHAN, Yixin TONG, Stieglitz THOMAS, Volker Arnd COENEN, Máté DÖBRÖSSY
19:05 - 19:15 #25925 - SURGERY AND RADIOSURGERY IN AUTISM: RETROSPECTIVE STUDY IN 10 PATIENTS.
SURGERY AND RADIOSURGERY IN AUTISM: RETROSPECTIVE STUDY IN 10 PATIENTS.

Introduction: A subgroup of patients with autism spectrum disorder (ASD) show self or heteroaggression, dyscontrol episodes, and others of obsessive-compulsive profile (OCD); some of them are resistant to medical and behavioural treatment. We describe the long-term outcome in a group of these patients, treated with radiofrequency brain lesions or combined stereotactic surgery and Gamma Knife (GK) radiosurgery.

Methods: We reviewed the medical records of ten ASD patients with pathological aggressiveness and OCD, who had undergone radiofrequency lesions and/or radiosurgery with GK in our institution.

Results: The ten patients had a significant reduction of their symptoms (PCQ 39.8 and 33.9, OAS 11.8 and 5.4, YBOCS 31.3 and 20.8, preoperatively and in the last follow-up, respectively; p<0.005 in all cases), although all but two needed more than one treatment to maintain this improvement.

Conclusions: We observed a marked improvement in behavior, quality of life and relationship with the environment in all our ten patients after the lesioning treatments, without long-lasting side effects.


 


Cristina TORRES (Madrid, Spain), Nuria MARTINEZ, Monica LARA, Marcos RÍOS-LAGO
Espace Vieux-Port

"Thursday 09 September"

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D26
17:00 - 18:05

Parallel Session 8
Epilepsy

Moderators: Sophie COLNAT-COULBOIS (PU-PH) (Nancy, France), Martin JAKOBS (Consultant) (Heidelberg, Germany), Krassimir MINKIN (Head of Center of Functional Neurosrgery) (Sofia, Bulgaria)
17:00 - 17:10 #23516 - sEEG mapping of basal temporal language area predicts postoperative language outcome.
sEEG mapping of basal temporal language area predicts postoperative language outcome.

sEEG mapping of basal temporal language area predicts postoperative language outcome 

Objective

To evaluate early and late post-operative naming outcome according to the resection status of the Basal Temporal Language Area (BTLA) identified by pre-operative cortical stimulations during Stereo-Electro-Encephalography (SEEG) in patients with intractable temporal lobe epilepsy.

Methods

Twenty patients who underwent SEEG for drug-resistant temporal lobe epilepsy met the inclusion criteria. During language mapping, a positive site was considered when stimulation of 2 contiguous contacts elicited at least one naming impairment during 2 remote sessions. After temporal lobe resection (TLR) ipsilateral to their BTLA, patients were classified as BTLA+ when at least one positive language-site was resected and as BTLA- when positive language sites were preserved. Outcomes in naming and verbal fluency tests were assessed using pre- postoperative (7 and 24 months after surgery) score changes and reliable change indices for clinically meaningful changes. Naming decline predictors were finally investigated using binary regression.

Results

BTLA+ patients had significant greater naming score change compared to BTLA- patients. However, this difference was found only 6 months postoperatively. No difference in verbal fluency tests was observed. When RCI was used, 25% of patients had naming decline 6 months postoperatively (80% of them were BTLA+). A significant correlation was found between resection of the BTLA and this naming decline. In particular, a rate superior to 15% of resected positive language-sites predicted this decline.

Conclusion

Resection of the BTLA is associated with a specific and early naming decline. Even if this decline is transient, BTLA+ patients tend to keep lower naming scores compared to their baseline. SEEG mapping might help in the prediction of postoperative language outcome in dominant TLR. Removing visual naming sites identified by SEEG language mapping is possible but should be considered with caution.

 


Chifaou ABDALLAH, Helene BRISSART, Ludovic PIERSON, Olivier ARON, Natacha FORTHOFFER, Jean Pierre VIGNAL, Louise TYVAERT, Jacques JONAS, Louis MAILLARD, Sophie COLNAT-COULBOIS (Nancy)
17:10 - 17:20 #23666 - Distant Cortical Abnormalities in Epileptic Hypothalamic Hamartoma Patients.
Distant Cortical Abnormalities in Epileptic Hypothalamic Hamartoma Patients.

Background: We hypothesize that developmental or acquired cortical abnormalities could explain failure of surgery aiming at hypothalamic hamartomas (HH).

Objective: Our aim was to do quantitative surface-based MR study to detect distant cortical anomalies in HH epilepsy patients treated by Gamma Knife Surgery (GKS) and correlate it with the GKS response.

Methods: Forty-two HH epileptic patients were compared for sulcus-specific morphometry difference with closely matched controls. All patients weretreated by GKS and followed for at least 3 years with high quality MR studies before and after GKS. We used“surface-based”quantitative MR analysis using Brainvista/Morphologist pipeline (sulcal root/meridian parallel model).

Results (Key Findings):Non-responders comparison to control displayed bilateral multilobar cortical thinning in “pre-central” (marginal) and “frontal” (median and superior), and “ascending ramus” of Sylvian and unilateral thinning in left “insula”, and “pre-central” (superior).More specific thinning was observed in “collateral” (r>l) and “pre-central” (marginal) sulci (l) in non-responders than in responders. No thinning was found in the responders’ group. Pre-motor areas “pre-central” and limbic “collateral” sulcus (l) thinning was the most response-related significant and frequent cortical anomalies.

Conclusion: This is the first quantitative MR study in HH epilepsy patients, which is cross-sectional and controlled.We found distant cortical abnormalities related to the epilepsy response after GKS. Diffuse multilobar thinning was observed in non-responders HH in bilateral “pre-central” (marginal), “frontal” (median and superior), and “ascending ramus” of Sylvian and unilateral thinning in left “insula”. Pre-motor areas “pre-central” and limbic “collateral” sulcus (l) thinning was the most response-related significant and frequent cortical anomalies. There are different patterns of distant cortical abnormalities between GKS responders and non-responders suggesting different epilepsy networks involved in each group.


Hussein HAMDI ABOUELGHEIT (Marseille), Guillaume AUZIAS, Olivier COULON, Nadine GIRARD, Fabrice BARTOLOMEI, Jean REGIS
17:20 - 17:30 #23962 - Long term follow-up in VNS for resistant epilepsy.
Long term follow-up in VNS for resistant epilepsy.

Long term follow-up in VNS for resistant epilepsy

 

Freri E^, Marotta G ^, Porto E*, Tringali G*, Visani E°, Casazza M.°

Department of Neurosurgery*, Neuropediatrics^, Epileptology°

Istituto Neurologico C.Besta, IRCCS, Milan, Italy

 

          Speaker: Casazza M.

          Topic: Epilepsy

          Key words: VNS, pharmacoresistant epilepsy, long term follow-up

 

Vagal nerve stimulation (VNS) is a largely used palliative technique for treating pharmacoresistant focal epilepsy in adults and children. Reported results are encouraging, with a reduction  of seizure frequency higher than 50% in more than half of patients. Side effects are usually well tolerated. Unfortunately no data indicate in which seizure types and syndromes VNS is more effective.

Our results are worse than those published, but our follow-up is very long, more than 15 yrs for 12 patients. Mean follow up lasts 11.6 yrs (range 2-24): 8  died during follow-up, in 3 cases related to epilepsy.

We present a series of 61 patients (32 males and 29 females, affected by pharmacoresistant focal epilepsy, implanted with VNS at a mean age of 30.1years (range 3 to 62).

For four patients we miss many data, so we consider only 57 of the implanted patients of our Institute.

All patients had severe, long lasting epilepsy (mean disease duration 24.6 yrs, range 3-51), in 40 out of 57 cases associated with cognitive impairment, in 26 with neurological deficits.

Epilepsy had unknown etiology in 17 cases, was associated with cortical malformations (10), progressive genetically determined encephalopathy (8), perinatal hypoxia (6), vascular malformations (4), inflammatory diseases (7), tuberous sclerosis (2), other causes (3). 

Seizures had focal onset, mostly with impaired awareness, in 40 patients they determined falls, usually tonic, and often with trauma.

Seizure frequency was daily or more in 68 % of cases. Patients were all treated polypharmacologically: 10 with 2, the other with 3 or more AEDs.

Seizures were recorded in most patients (50); in 8 cases a focal onset was not recognizable. In 28 patients recurrent focal stati or seizure clusters were present.

Interictal EEG was focal or multifocal in all patients, with rapid synchronism in 25.

Seventeen patients were excluded from resective epilepsy surgery , 3 refused it, 11 were operated on before implantation of VNS without results on seizure frequency.

After VNS, one patient underwent hemispherotomy, one anterior callosotomy, one deep brain stimulation and one coagulation of nodular periventricular heterotopia.

Seizure frequency was unchanged in 16 patients, in 21 cases seizures were reduced more than 50% and in 21 of them we observed a marked reduction of falls.

AEDs were added or modified during the years of VNS. Therefore we waited for some months after VNS depletion to verify seizure frequency. If there was an increase in number, VNS was replaced. This happened in 24 patients. In 15 patients no seizure frequency increase was observed after second VNS depletion, so that they were not reimplanted. In 9 patients a third implant was made for marked increase of seizures.

Side effects include stimulation adverse effects, as hoarseness, voice change and cough, differently present in most patients. Surgical side effects are rare, including infections (2). In 3 patients we observed electrode rupture, probably due to fall at least in one case: they requested a reimplantation.

We project to better analyze and discuss the reasons for the bad outcome of our patients at a long distance focusing on seizure type and epileptic syndrome, in order to try the identification of better candidates to VNS.

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Elena FRERI, Marina CASAZZA, Guia MAROTTA, Edoardo PORTO (Milan, Italy), Giovanni Umberto TRINGALI, Elisa VISANI
17:30 - 17:35 #23917 - Awake epilepsy surgery.
Awake epilepsy surgery.

Awake epilepsy surgery

Minkin Krasimir, Gabrovski Kaloyan, Karazapryanov Petar, Dimova Petya, Karakostov Vasil

 

Introduction:

Awake craniotomy (AC) and direct electrical stimulation (DES) emerged together with epilepsy surgery more than 80 years ago in the seminal work of Wilder Penfield. In recent years AC gained important role in glioma surgery, but it is rarely used and reported in modern epilepsy surgery. Contemporary epilepsy surgeons rely more on functional MRI, transcranial magnetic stimulations and extraoperative brain mapping through invasive EEG than on awake surgery. The goal of our study was to investigate a series of awake epilepsy surgeries in patients investigated and operated on in an epilepsy center.

 

 

Material and Methods:

Our clinical material included 23 patients operated on for drug-resistant epilepsy using asleep-awake-asleep technique of AC with DES during a 10-year period. We investigate the following variables: age distribution, indications, brain mapping success rate, epilepsy surgery success rate, intraoperative complications, postoperative complications and intraoperative change of the preoperative resection plan according to the information obtained during the brain mapping using DES.

Results:

The mean age at surgery was 29 years (16- 47 years) with 4 patients under 18 years of age. The epileptogenic zone was localized in the frontal lobe in 12 patients, in the temporal lobe in 7 patients and in the frontotemporoinsullar region in 2 patients. The remaining 2 patients has had epileptogenic zones in the supramarginal gyrus and in the temporoparietoocipital region. Surgery was in the left hemisphere in all but 2 cases. The most frequent indication for AC was language mapping – 19 patients ( 83%). The most frequent histopathological findings were focal cortical dysplasia (14 patients) and ischemic or posttraumatic  gliosis (6 patients). We achieved satisfactory functional mapping in all patients. Intraoperative seizures were observed in 6 patients (23%) without further intraoperative complications and permanent loss of cooperativeness. Transient mild neurological deficit was observed in 5 patients. There were no persistent neurological deficits, hematomas or infections. Our preoperative plan based on preoperative fMRI was changed because of functional constraints in 8 patients (35%). The most striking finding was the localization of eloquent speech areas in the most anterior part of the superior temporal gyrus.

Conclusions:

Awake craniotomy provides additional functional information which may change the preoperative plan based on preoperative fMRI, lower the incidence of persistent functional impairment, making it a useful but forgotten tool in epilepsy surgery.


Krasimir MINKIN (Sofia, Bulgaria), Kaloyan GABROVSKI, Petar KARAZAPRYANOV, Petya DIMOVA, Vasil KARAKOSTOV
17:40 - 17:45 #23972 - Single-center experience with frameless personalized stereotaxy for SEEG.
Single-center experience with frameless personalized stereotaxy for SEEG.

Drug resistant epileptic patients are a complex challenge for modern functional neurosurgeons. The optimal resection limits are planed on more criteria, including Stereo EEG recordings and analysis. StarFix microTargeting Platform (FHC Inc., Bowdoin, ME, USA),  is a frameless patient customized device. It is a lightweight fixture, incorporates guides aligned with all electrode trajectories, simplifying the entire surgical workflow.

 

Patients and method

A total of 23 patients were implanted. Age was ranging 3 to 46 yrs. All patients were on general anesthesia during procedure. Targets were placed in both hemispheres in different structures of the brain.  A vascular safety index, characterizing the proximity of the planned trajectories to the blood vessels was calculated for each trajectory. Number of implanted electrodes (DIXI Medical, Chaudefontaine France), varied between 8 to 20 and the number of contacts 92 to 258. The procedure will be presented in detail during presentation. A post-implantation CT was performed to check for the accuracy of electrode positioning and for possible complications.

Results

All  electrodes reached their intended targets. There were no intracranial hemorrhages or other implantation-related complications. The implantation errors were less then2 mm. Time in the OR was represented by the average time per implanted electrode which was about 7 minutes; this value is shorter than 21 minutes reported for past frame-based implantation procedures. The patients underwent a  3 to 14-days monitoring sessions, during which we managed to record multiple habitual seizures.  No periprocedural adverse events were recorded.  All patients tolerated the implanted electrodes well. The patients who underwent surgery, with the resection of the epileptogenic zone as discussed in the multidisciplinary meeting, presented a good outcome, without any discernable neurological postoperative deficits. The histopathological analysis of the resected tissue showed different types of pathology which will be detailed. All patients presented Engel IA except one who was III.

Discussion

StarFix microTargeting Platform have several advantages over classical, frame-based systems for epilepsy surgery patients. It is easy to use, light weight and does need frame reconfigure  for each electrode trajectory, excluding any possibility of human error. The total OR time is shorter then with metallic frame. StarFix greatly simplifies the implantation workflow. The accuracy of electrode positioning is comparable with the other methods. The flexibility of intraoperative trajectory adjustments available in classical frame is solved by planning additional backup trajectories in case an unexpected event prevents an electrode from being implanted. The anchors are not removed until the end of the SEEG implantation, to allow repositioning of the electrodes following the postoperative CT scan, in case they have not reached their intended targets due to incorrect depth setting or excessive curvature. Re-attaching the platform can be performed in a matter of minutes without any additional CT scan. Another advantage of StarFix is for young patients presenting a thinner cranium, there is an added risk of skull fracture, especially when using a general-purpose, rather heavy, metal frame.

 

Conclusions

Patient-customized stereotactic fixtures that scale to the patient’s anatomy is a safe and accurate option for SEEG exploration in subjects diagnosed with drug-resistant epilepsy.

 

 

     

 

 


Andrei BARBORICA, Jean CIUREA, Ioana MANDRUTZA, Rasina ALIN, Tatiana CIUREA, Costi PISTOL, Felix BREHAR (Bucharest, Romania)
17:45 - 17:50 #26142 - Reduction of penicillin-induced seizure in a non-human primate mesio- temporal lobe epilepsy model by deep brain cooling.
Reduction of penicillin-induced seizure in a non-human primate mesio- temporal lobe epilepsy model by deep brain cooling.

I

Introduction: It is estimated that 1% of the world population suffers from epilepsy and 30% of epileptic patients are resistant to all pharmacological therapies. For medication resistant patients that are not candidates for resective or ablative procedures, there is a great need of far better therapies that could lead to high rates of patients becoming free of seizures without side effects. In order to help this group of patients, we propose to develop an innovative implantable medical device that allows the cooling of deep epileptogenic area. Cooling effect on epilepsy attenuation is known since decades. Rothman et al. [1]  have shown suppression of epileptic discharges when rapid cooling is applied in brain neocortical surface.  Nevertheless, no antiepileptic medical device based on cooling for deep-seated areas is currently available. There is real technical difficulty in transporting the cooling effect to deep-seated areas, so, it has been difficult to study the effect of cooling at the hippocampal level.  Here we present the preliminary results of a prototype of implantable device capable to deliver the cooling effect to hippocampal areas in mesial temporal lobe seizures epilepsy (MTLE) in non-human primates model².Methods: Study was performed in a female Macaca fascicularis. The animal was implanted unilaterally with a deep cooling lead   and sEEG electrodes in the hippocampus. After post-operative recovery, penicillin was injected (10 min at 2µl/min, 1000UI/ml) into the hippocampus and animal was recorded during 5-7 hours periods. After a 45 min-period of seizure stabilization, focal cooling was applied and temperature and seizures frequency and duration were monitored. Injections were repeated once a week over a period of 203 days. To evaluate cooling safety and   characterize the changes occurring within the hippocampus, we performed a histological analysis, including neuronal nuclei and glial fibrillary acid protein immunostaining. Results: After each penicillin injection, we observed that seizure characteristics were reproducible between experiments as already reported by our group².Seizures duration was stable (58.5± 11 s) and the frequency of seizures reached a plateau with at least two seizures each 20 min per trial. MLTE seizures were reproduced similar to the ones observed in similar previous experiments and patients[2]. Sixteen trials were analyzed and seizures were detected by visual analysis of SEEG allowing electro-clinical correlation. We divided the trials in cooling sessions at 20°C, 24°C and no cooling (control). A reduction in the number of hippocampal seizures was seen at temperatures of 20°C when compared with control (32-34°C). There was no change in seizure duration during focal cooling.  Hippocampal sclerosis similar to that encountered in epileptic patients was found at the end of the study after 16 penicillin injections without additional damage.  Conclusions: Our results suggest for the first time, that focal cooling in deep areas of the brain can reduce the number of focal hippocampal seizures induced by penicillin. Deep brain cooling could be an alternative for control of focal seizures, lowering the risk of irreversible functional loss of the resective surgery and with potentially better efficacy than neuromodulation. The study suggest that this approach could be a safe and effective alternative for drug resistance epilepsy.

[1] Rothman SM., Smyth MD., Yang X-F., Peterson GP. Focal cooling for epilepsy: An alternative therapy that might actually work. Epilepsy Behav. 2005; 7: 214–221.

[2] Sherdil A, Chabardès S, Guillemain I, Michallat S, Prabhu S, Pernet-Gallay K, et al. An on demand macaque model of mesial temporal lobe seizures induced by unilateral intra hippocampal injection of penicillin. Epilepsy Res. 2018; 142: 20–28.

 


Napoleon TORRES (GRENOBLE), Quentin BORNTRAGER, Nicolas AUBERT, Fabien SAUTER, Claude CHABROL, David RATEL, Jenny MOLET, Brigitte PIALLAT, Stephan CHABARDES
Salle 120
18:05

"Thursday 09 September"

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D27
18:05 - 19:05

Parallel Session 10
Flash - Movement disorders

Moderators: Harith AKRAM (Associate Professor) (London, United Kingdom), Carine KARACHI (MEDECIN) (PARIS, France), Oystein TVEITEN (Neurosurgeon) (Bergen, Norway)
18:05 - 18:15 #23359 - Long-term motor function and quality of life outcomes from a prospective, international DBS registry.
Long-term motor function and quality of life outcomes from a prospective, international DBS registry.

Objective: Here we report the collected outcomes from a large-scale registry of a Deep Brain Stimulation (DBS) system capable of Multiple Independent Current Source Control (MICC) in the management of symptoms of levodopa-responsive Parkinson's disease (PD).

Background: The effectiveness of Deep Brain Stimulation (DBS) for reducing motor complications of Parkinson's disease (PD) has been substantiated by randomized controlled trials (Schuepbach et al., 2013). Additionally, motor improvement is sustained for up to 10 years (Deuschl et al. 2013). Large patient data registries may facilitate insights regarding real world, clinical use of DBS. Furthermore, no registry database currently exists for a multiple-source, constant current DBS system.

Methods: The Vercise DBS Registry is a prospective, on-label, multi-center, international registry sponsored by Boston Scientific Corporation. The Vercise DBS system (Boston Scientific) is a multiple-source, constant-current system. Subjects were followed up to 3 years post-implantation where their overall improvement in quality of life and PD motor symptoms was evaluated. Clinical endpoints evaluated at baseline and during study follow included Unified Parkinson's disease Rating Scale (UPDRS), MDS-UPDRS, Parkinson's disease Questionnaire (PDQ-39), and Global Impression of Change. Subjects underwent either sleep or awake DBS implantation procedures. 

Results: To date, 822 patients have been enrolled (752 implanted). Improvement in quality of life (QoL), as assessed by PDQ-39,demonstrated improvement following implant at 6-months (-6.1-point change, p<0.0001) and up to 2-years (-2.4-point change) as compared with Baseline. Higher improvement in QoL (-15.7-point change) was noted in patients with worse QoLat Baseline (PDQ-39 SI >45). This trend was also noted in subjects with worse disease state at Baseline (Hoehn & Yahr ≥3) who reported a greater improvement in PDQ-39 summary index. At 1-year post-implant (n=272), a 32% improvement in MDS-UPDRS III scores (stim on/meds off) compared with baseline was reported and sustained up to 2-years (n=51). Stable neuropsychometric status (BDI-II, MoCA) was also reported. The safety profile was comparable to other published reports. Additional data collection and analysis is ongoing and will be presented. Data from those undergoing sleep versus awake DBS-implantation procedures will be presented. 

Conclusions: This DBS registry represents the first comprehensive, large scale collection of real-world outcomes and evaluation of safety and effectiveness of a multiple-source, constant-current DBS system.


Jan VESPER (Duesseldorf, Germany), Roshini JAIN, Heleen SCHOLTES, Alex WANG, Michael T. BARBE, Steffen PASCHEN, Jens VOLKMANN, Chong-Sik LEE, Andrea KÜHN, Monika PÖTTER-NERGER, Günther DEUSCHL
18:15 - 18:25 #23412 - Directional versus Omnidirectional Deep Brain Stimulation: Results of a Multicenter Prospective Blinded Crossover Study.
Directional versus Omnidirectional Deep Brain Stimulation: Results of a Multicenter Prospective Blinded Crossover Study.

Introduction: Published reports on directional DBS have been limited to small single-center investigations. Therapeutic window (TW) has been introduced in DBS to describe the range of stimulation amplitudes achieving symptom relief without side effects. The PROGRESS study evaluated whether directional DBS provides a wider TW in a large prospective trial.

Methods: Participants receiving STN DBS for Parkinson’s disease were programmed with omnidirectional stimulation for 3 months, followed by directional stimulation for 3 months. The subject was blinded to stimulation type and a blinded evaluator assessed TW and motor symptoms. The primary endpoint was based on blinded off-medication evaluation of TW for directional vs. conventional stimulation at 3 months. Additional endpoints at 3, 6 and 12 months included adverse events, subject and clinician stimulation preference, therapeutic current strength (TCS), medication reduction, quality of life and UPDRS part III motor score.

Results: A directional DBS system was implanted in 234 subjects (62±8 years, 33% female). At 3 months, TW was wider using directional stimulation in 90.6% of subjects, satisfying the primary endpoint for superiority (p<0.001). The mean increase in TW with directional stimulation was 41% (2.98±1.38mA, compared to 2.11±1.33mA for omnidirectional, p<0.001). UPDRS part III motor score on medication was improved with either stimulation at each time point (p<0.001). After 6 months, 53% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, 26% (50/193) preferred the omnidirectional period and 21% (41/193) had no preference. The directional period was preferred by 59% of clinicians (113/193) vs. 21% (41/193) who preferred the omnidirectional period. Additional results including 12-month data will be available.

Conclusion: A double-blind randomized comparison of directional and omnidirectional stimulation found that 90.6% of subjects had a wider TW using directional stimulation at 3 months and 89.3% at 12 months. There were improvements in the minimum amplitude required to achieve therapeutic benefit and the side effect threshold, leading to a 40% wider TW at 3 months and 32% at 12 months. For the first time, we demonstrated superiority of TW for directional stimulation over omnidirectional stimulation with sustained UPDRS III motor scores and quality of life improvements.


Alfons SCHNITZLER, Pablo MIR, Matthew BRODSKY, Leonard VERHAGEN, Sergiu GROPPA, Ramiro ALVAREZ, Andrew EVANS, Marta BLAZQUEZ, Sean NAGEL, Witold LIBIONKA, Julie PILITSIS, Monika POETTER-NERGER, Winona TSE, Leonardo ALMEIDA, Nestor TOMYCZ, Joohi JIMENEZ-SHAHED, Fatima CARRILLO, Christian J HARTMANN, Stefan Jun GROISS, Florence DEFRESNE, Edward KARST, Bin CHEERAN, Jan VESPER (Duesseldorf, Germany)
18:25 - 18:30 #23360 - Real-world clinical outcomes using a novel directional lead from a multicenter registry of deep brain stimulation for Parkinson's disease.
Real-world clinical outcomes using a novel directional lead from a multicenter registry of deep brain stimulation for Parkinson's disease.

Objective: In this report, initial real-world outcomes using a directional lead with a Deep Brain Stimulation (DBS) system capable of multiple independent current source control (MICC) for use in managing symptoms of levodopa-responsive Parkinson's disease (PD) are reported.

Background: Early Deep Brain Stimulation (DBS) systems used ring-shaped electrodes to achieve axial selectivity in stimulation of targettissue. However, directional current steering allows for rotational selectivity (in addition to axial) and has the potential tofurther improve patient outcomes by avoiding off-target stimulation due to the ability to create a well-defined field around the intended target. Several pilot studies have corroborated the use of directionality and its impact on therapeutic window and adverse effects.

Methods: The Vercise DBS Registry (ClinicalTrials.gov Identifier: NCT02071134) is a prospective, on-label, multi-center, international registry sponsored by Boston Scientific. Subjects were implanted with a directional lead included as part of a multiplesource, constant-current directional DBS system (Vercise Cartesia, Boston Scientific). Subjects were followed up to 3-years post-implantation where their overall improvement in quality of life and PD motor symptoms was evaluated. Clinical endpoints evaluated at baseline and during study follow-up included Unified Parkinson's disease Rating Scale (UPDRS), MDS-UPDRS, Parkinson's disease Questionnaire (PDQ-39), and Global Impression of Change.

Results: As of February 2021, 627 patients (mean age: 60.9 years, 68.4% male) included were implanted with a DBS directionallead. Improved Quality of Life, as assessed by PDQ-39 (p<0.001) following implant was noted up to 1-year post-implant(n=368). Improvements in motor function (change in MDS-UPDRS III scores-meds off condition) versus baseline were alsonoted (31% at 1-year (n=200), p<0.001). Over 80% of subjects, physicians reported an improvement in PD symptoms during long-term follow-up. Additional data collection and analysis is ongoing and will be presented.

Conclusions: This on-going registry represents the first comprehensive, large scale collection of real-world, long-term outcomes using a directional lead and an MICC-based DBS system. Using directional stimulation, it may be possible to achieve a bigger therapeutic window, thereby facilitating enhanced programming flexibility when optimizing for efficacy, while decreasing the likelihood of surpassing the adverse effect threshold.


Jan VESPER (Duesseldorf, Germany), Roshini JAIN, Heleen SCHOLTES, Alex WANG, Michael T. BARBE, Jens VOLKMANN, Steffen PASCHEN, Chong-Sik LEE, Andrea KÜHN, Monika PÖTTER-NERGER, Günther DEUSCHL
18:30 - 18:35 #23392 - Directional DBS leads implanted under general anesthesia vs. sedation: Findings from an international prospective study.
Directional DBS leads implanted under general anesthesia vs. sedation: Findings from an international prospective study.

Introduction: Traditionally, deep brain stimulation (DBS) leads are implanted under local anesthesia or conscious sedation to allow intraoperative testing for effects (awake procedure). There are also two distinct approaches to perform lead implantation under general anesthesia with intubation (asleep procedure): 1) using intraoperative image-guided targeting only and 2) reducing anesthesia to allow for microelectrode recording.

Methods: A total of 234 subjects were enrolled in PROGRESS between January 2017 and January 2019 in 37 different sites located in Europe, North America and Australia. PROGRESS compared therapeutic window (TW), the difference in amplitude between side effect threshold and minimum therapeutic current, for directional vs. omnidirectional stimulation in STN DBS for Parkinson’s disease. This post-hoc analysis compares therapeutic window and UPDRS motor scores at 3 and 6 months in subjects with awake vs. asleep procedures. Both approaches of intraoperative image-guided targeting and microelectrode recording were integrated in the asleep group for this analysis.

Results: The PROGRESS met its primary endpoint of superiority with 90.6% of subjects (183/202) having a wider TW using directional stimulation. Leads were implanted in an awake procedure for 163 subjects and asleep procedure for 69 subjects. In Europe, 70% of subjects (90/129) were implanted with an awake procedure; in the United States, 73% (64/88) and in Australia, 60% (9/15). Three months after initial programming, directional stimulation increased TW by 0.84 mA for the awake implants (2.18±1.36 mA for omnidirectional stimulation; 3.02±1.30 mA for directional; p<0.001)) and 0.88 mA for the asleep implants (1.92±1.22 mA for omnidirectional stimulation; 2.83±1.53 mA for directional; p<0.001). The increase of TW between awake and asleep procedure was not statistically significant (p=0.57). At baseline, off medication UPDRS scores were 34.6±12.6 for awake subjects and 31.9±12.5 for asleep subjects. At the 6-month follow-up visit, on-medication UPDRS III motor scores improved by 44% in awake subjects (from 31.6±14.0 with DBS off to 17.7±10.4 with DBS on) and 42% in asleep subjects (29.2±13.5 to 16.8±8.5).

Conclusion: In a large international study, directional stimulation was associated with a similar increase in therapeutic window, regardless if the DBS system was implanted using an asleep versus awake procedure. UPDRS motor score improved similarly in both groups.


Jan VESPER (Duesseldorf, Germany), Kim BURCHIEL, Matthew BRODSKY, Brian KOPELL, Julie PILITSIS, Nestor TOMYCZ, Leonard VERHAGEN, Girish NAIR, Andrew EVANS, Wolfgang HAMEL, Pablo MIR, Monika POETTER-NERGER, Joohi JIMENEZ-SHAHED, Philipp SLOTTY, Sergiu GROPPA, Sean NAGEL, Florence DEFRESNE, Edward KARST, Bin CHEERAN, Alfons SCHNITZLER
18:35 - 18:40 #23544 - Primary Cell IPG survival analysis and modelling in Directional Deep Brain Stimulation.
Primary Cell IPG survival analysis and modelling in Directional Deep Brain Stimulation.

Objective: To use explant data from a single center to generate survival plot and model survival curves for Abbott SJM Infinity 7 primary cell IPG.

Background: Primary cell IPGs have distinct advantages in patients with Movement or Neuropsychiatric disorders. However, shortened survival times, less than manufacturer guidance, have been reported for at least one primary cell IPG model. Modelling based on real world explant rates can support manufacturer guidance on IPG lifespan for new primary cell DBS systems.

Methods:  Case records for all Abbott SJM Infinity 7 IPGs implanted prior to 06/2019, at a single expert center, were reviewed. Implanted targets include STN, VIM and GPi, for Dystonia, Tremor and Parkinson’s Disease. Explants due to IPGs reaching end of service were included. Explants due to other causes, infection, or medical complications requiring explant were excluded. A Kaplan-Meier plot of time to explant (IPG survival) was done. Additionally, modelling fitting was done using JMP™ Life Distribution platform. The most conservative distribution model for survival rate is reported.

Results: 105 Infinity 7 IPGs were implanted between 04/2016 and 05/2019. 3 IPGs were replaced due to IPG depletion and included in the analysis. IPGs replaced due to failure other than IPG depletion (known CAPA) (n=2), due to pocket site infection (n=2) and 1 system explant for medical reasons were excluded. Maximum duration of implant at time of analysis was 3 years 10 months. Due to the low number of explants within the duration of follow up, KM survival plot is unable to define mean survival times. The SEV distribution model (BIC=38) estimates mean survival time of 5.201 years (SE±1.0), 95% CI [3.1, 7.2](most conservative estimate at time of analysis). 

Conclusions: With advancements in technology, programming tools and programming technique, real world evidence is necessary to monitor lifespan of primary cell DBS systems. For newer DBS systems, modelling based on real world explant data can provide additional confidence to manufacturer guidance on estimated IPG lifespan. Data and analysis will be updated prior to poster presentation to include validation of best model fit.


Philipp SLOTTY, Binith CHEERAN, Phyllis Sarah MCPHILLIPS, Jan VESPER (Duesseldorf, Germany)
18:40 - 18:45 #23634 - Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease: ADAPT-PD Trial: a prospective single-blind, randomized crossover, multi-center trial of deep brain stimulation adaptive algorithms in subjects with Parkinson’s disease.
Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease: ADAPT-PD Trial: a prospective single-blind, randomized crossover, multi-center trial of deep brain stimulation adaptive algorithms in subjects with Parkinson’s disease.

Objective: To demonstrate safety and effectiveness of adaptive deep brain stimulation (aDBS) algorithms in subjects with Parkinson’s disease (PD).

Background: DBS is an effective therapy for PD symptoms, though opportunities exist to improve the efficiency and efficacy. Commercially approved DBS is programmed to run continuously (cDBS) at specified programming parameters. In contrast, adaptive DBS (aDBS) algorithms may individualize and optimize PD therapy by adjusting stimulation based on objective signals. The algorithm technology used in this study is uniquely embedded in the device, which allows for out-of-clinic assessments. Local field potentials (LFPs) represent population-level neuronal oscillations surrounding the DBS electrode and can be used as aDBS control signals. This study will evaluate the safety and effectiveness of aDBS in PD subjects with stable cDBS therapy.

Methods: Subjects will have been implanted with DBS leads either in the GPi or STN connected to a commercial DBS system capable of sensing LFPs. An investigational feature will be unlocked to allow programming of two different aDBS modes using low frequency (8-30 Hz) LFP control signals. Subjects will enter a 30-day Baseline Phase in their current cDBS programming configuration, followed by an aDBS Set-up and Adjustment Phase. Subjects tolerating both aDBS modes will then enter a 2-period randomized crossover Evaluation Phase and receive each aDBS mode over 30-day periods, followed by a Long-Term Follow-up Phase over 10 months. The aDBS evaluations will involve measures of On time, quality of life, speech, movement, sleep, patient preference and satisfaction, and total electrical energy delivered (TEED).

Results: The primary effectiveness endpoint will measure On time without troublesome dyskinesias from the motor diary. Other endpoints will include TEED, output from a wearable device, Voice Handicap Index, UPDRS, EQ-5D-5L, PDSS-2, PDQ-39, and patient preference and satisfaction. Safety will include evaluation of stimulation-related adverse events (AEs), AEs, and device deficiencies.

Conclusions: This international, multi-center, chronic aDBS study is expected to generate data to support safety and effectiveness for both aDBS modes in PD subjects.


Andrea KUHN (Berlin, Germany), Lisa TONDER, Robert RAIKE, Scott STANSLASKI, Kassa LYNCH, Helen BRONTE-STEWART
18:45 - 18:50 #23641 - Directional DBS is associated with fewer surgical revisions than traditional DBS: a nationwide real-world study.
Directional DBS is associated with fewer surgical revisions than traditional DBS: a nationwide real-world study.

Objective: To investigate the relative occurrence of complications necessitating surgical revision after de novo implantation of a directional deep brain stimulation (DBS) system compared to traditional omni-directional DBS systems in US patients with movement disorders.

Background: Real-world complication rates from DBS implantation have been poorly characterized and have yet to consider the impact of modern systems. These newer systems include significant advancements in the design of both the intracranial electrode and the lead extension. Specifically, modern systems offer directional shaping of the stimulation field that increases flexibility in delivering therapy while avoiding side effects. We therefore aimed to assess if these advancements resulted in fewer complications necessitating revisions.

Methods: Medicare fee for service claims were used to identify patients undergoing DBS implantation for Parkinson’s Disease or Essential Tremor between Jan 1, 2016 - Dec 31, 2018. Claims records were linked to manufacturer device registration data to identify which patients been implanted with Abbott Infinity, at the time the only commercially available system in the US with directional stimulation capability; linked patients were assigned to the Treatment group. Records that did not uniquely link were classified as omni-directional, non-Abbott and assigned to the Control group. ICD-9/10 diagnosis and procedure codes were used to identify reason for implant and to assess comorbidities. Patients were excluded if they had less than 1 year of enrollment prior to or less than 3 months enrollment after the index implant, and if they had evidence of prior DBS implant. Patients younger than 18 years old were excluded. Patients enrolled in Medicare Health Maintenance Organization (HMO) were also excluded because of the lack of necessary data for those patients in the Medicare database. Over a pre-specified maximum 2-year follow up and with a pre-specified 3-month acute period, device-related complication rates resulting in lead or implantable pulse generator (IPG) revision/removal were compared using the Andersen-Gill modification to Cox-proportional hazard model with correction for age, gender, year of implant, indication, number of leads, number of generators, and staged vs. non-staged implant procedure.

Results: A total of 7,788 patients were identified in the Medicare database, of which 5,188 fulfilled the aforementioned inclusion criteria. 603 patients (71 ± 7 years old, 40% female) implanted with Abbott Infinity systems were assigned to the Treatment group, and 4,585 (71 ± 7 years, 38% female) with traditional omni-directional implants were assigned to the Control group. Patients were followed to a maximum of 2 years, with a mean follow-up of 611 ± 160 days.  The cumulative rate of lead revision/removal over the follow up was 7% in the Treatment group versus 12% in the Control group (hazard ratio [HR] 0.5 [95% CI 0.4 - 0.7], p < 0.001).  The cumulative rate of IPG revision/removal over the follow up was 5% in the Treatment group versus 7% in the Control group (HR 0.6 [95% CI 0.4 - 1.0], p = 0.05). The overall revision/removal rate for leads or IPGs was 9% in the Treatment group versus 15% in the Control group (HR 0.5 [95% CI 0.4 - 0.7], p < 0.001). [Figure]

Conclusions: These findings represent the first real-world report of device-related complications in directional DBS. Using US insurance claims linked with manufacturer device registration data, we found that complication rates in patients implanted with Infinity directional DBS system were nearly half of those compared to those with traditional omni-directional DBS systems. Although both significantly lower, the magnitude of the difference in lead revisions was greater than that for IPG revisions, which may be attributable to the benefits of segmented electrodes and electrical field shaping capabilities. Further investigation and analysis are required to better understand the relationships between DBS system implanted, complication rates, and patient comorbidities.


Chengyuan WU (Philadelphia, PA, USA, USA), Monika PÖTTER-NERGER, Rahul AGARWAL, Stuart ROSENBERG, Allison CONNOLLY, Binith CHEERAN, Wolfgang HAMEL, Ashwini SHARAN
18:50 - 18:55 #23945 - Peak characteristics in the beta band of the human subthalamic nucleus: a case for low and high beta activity.
Peak characteristics in the beta band of the human subthalamic nucleus: a case for low and high beta activity.

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients suffering Parkinson’s disease allows for the recording of local field potentials (LFPs) in this part of the basal ganglia. Such recordings are of great interest since they may serve as possible biomarkers for the current physiological ”status” of the patient and thus might be used for “brain-sensing” and consecutive adaptive stimulation (“closed-loop DBS”).

Methods: 38 Parkinson-patients (mean age 60.1 years (range 47-71), 11 female/27 male, mean disease duration 11.6 years (range 7-20) having undergone STN-DBS were included. LFP-recordings were performed via externalized leads in all patients and additionally with a Medtronic ACTIVA PC+S™ INS in 10 of these 38 patients. Recordings (both with and without stimulation) were done with the patient in a recumbent position during rest (awake patient, eyes open), during right/ left hand opening and closing (frequency 2/s; 5 min.), during standing for 3-5 min, slow walking 30 m and fast walking 30 m. LFPs were amplified, recorded and digitally stored (resolution 0.1 µV, sampling rate 2000 Hz, filter 0.1 Hz – 500 Hz). Raw data were high-pass filtered (3rd order Butterworth, 1 Hz) and resampled to a sampling frequency of 422 Hz. The fast Fourier algorithm of Malta and averaging the resulting spectra were used to compute the frequency spectrum of all data

Results: Fifty-one of 76 (67.1%) recordings had one peak, eight (10.5%) recordings showed two peaks, and 17 (22.4%) recordings showed no peak. Movement of either hand did not reliably suppress beta peaks. Walking reduced the peaks in the high beta band (above 20.2 Hz) but not the peaks in the low beta band. Stimulation caused a stimulation-strength dependent suppression of most, but not all peaks. 

Conclusion: Beta-peaks can be detected in a high percentage of LFP-recordings using DBS-electrodes. Beta suppression caused by movement is dependent on the type of movement and the frequency of the peak. Further studies should consider the fact that the beta frequency band may host different physiological processes - that might be suitable biomarkers for “adaptive DBS”.


Jan MEHRKENS (München, Germany), Franz HELL, Thomas KÖGLSPERGER, Bovet AYSE, Scot STANSLASKI, Annika PLATE, Kai BÖTZEL
18:55 - 19:00 #26030 - Programming time using a novel visualization tool in a deep brain stimulation registry.
Programming time using a novel visualization tool in a deep brain stimulation registry.

Objective: We describe utilization of newly available visualization software for use as a Deep Brain Stimulation (DBS) planning toolduring initial programming of patients with Parkinson’s disease (PD) as part of an ongoing device registry.

Background: Optimization of DBS programming consists of a trial-and-error process involving appraisal of various stimulation parametersin which both clinician assessment and patient reporting of clinical benefit are required. However, this can be an inefficientand lengthy undertaking. The use of a visualization tool that illustrates location of the DBS lead in the patient’s own-segmented anatomy may help improve efficiency of achieving programming optimization and outcomes specific to theindividual patient.

Methods: This is a sub-study of ongoing prospective, multicenter, registry (NCT02071134) in which novel DBS visualization software(GUIDE XT, Boston Scientific) is utilized during initial device programming of patients implanted with a multiple-source,constant-current DBS System (Vercise, Boston Scientific). The software uses pre-op MRI and post-op CT to create patient-specific anatomy enabling visualization based-programming and identification of the lead relative to anatomical targets. The time duration to reach effective stimulation settings at the conclusion of initial programming (e.g. monopolar review)using this visualization tool is collected and assessed. All participating patients must hold anti-parkinsonian medicationsovernight per standard of care (meds OFF).

Results: To date, 19 subjects have consented to participate in this ongoing sub-study where settings suggested by the novel visualization software provided a starting point for initial programming post-DBS implant. Initial programming sessions (post-implant), where the visualization software was utilized to provide initial settings, lasted a mean 22.9 ± 6.0 minutes (n = 12). Additional data to be presented.

Conclusions: Preliminary results suggest shorter initial programming sessions are possible using a visualization software tool compared to traditional trial-and-error approach as reported in the published literature. Shorter and more efficient programmingsessions may lead to reduced programming visit time and improve resource utilization.


Jason ALDRED (Spokane, USA), Yarema BEZCHLIBNYK, Jonathan CARLSON, Kelly FOOTE, Sepher SANI, Alexander PAPANASTASSIOU, Jonathan JAGID, David WEINTRAUB, Theresa ZESIEWICZ, Michael OKUN, Leo VERHAGEN MEHTMAN, Juan RAMIREZ-CASTANEDA, Corneliu LUCA, Ritesh RAMDHANI, Lilly CHEN, Roshini JAIN
19:00 - 19:05 #26031 - Real-world deep brain stimulation outcomes using directional DBS systems with multiple independent current control.
Real-world deep brain stimulation outcomes using directional DBS systems with multiple independent current control.

Objective: Here, we report the real-world clinical outcomes associated with the use of DBS systems capable of directionality and Multiple Independent Current Control (MICC) in overall quality of life and the use of medications. 

Background: Deep Brain Stimulation (DBS) is an established treatment for motor signs and fluctuations associated with Parkinson's disease (PD). Retrospective studies can provide a relatively quick and cost-effective means to obtain data regarding various types of patient outcomes when devices are being used per standard-of-care in the real-world clinical setting, thereby contributing to real-world evidence (RWE). Here, we report clinical outcomes associated with the use of DBS systems capable of directionality and Multiple Independent Current Control (MICC). 

Methods: This is an international, multi-center observational study of DBS patient outcomes (NCT03664609) based on retrospective chart review. Patients assessed were implanted with a DBS system (Vercise, Boston Scientific) capable of MICC and/or directionality for use in the treatment of motor symptoms of Parkinson's disease. Data related to disease state, motor function, and overall quality of life are collected. Additionally, reduction in anti-parkinsonian medications usage is also assessed. 

Results: To date, data from 206 patients have been collected (mean age 65.0 ± 9.2 years, 68.9% male). Of the patient data currently available (n = 59), 75% (n=44) of patients reported a reduction in anti-parkinsonian medications at 12-months post-implant. A significant improvement in Quality of Life was noted among patients up to 12-months post-implant (p = 0.015). Cognitive health as measured by multiple relevant assessment scales (e.g. BDI, MOCA, MMSE) indicates stable mental status in most patients out to 12-months post-implant. Additional data will be presented. 

Conclusions: Preliminary RWE obtained from this multicenter, observational case-series demonstrates improved quality of life, decreased medication intake and overall stable mental/cognitive status in Parkinson's disease patients at up to 12-months post-implant using a DBS system capable of directionality and Multiple Independent Current Control (MICC). 


Corneliu LUCA (Miami, USA), Theresa ZESIEWICZ, Michael T. BARBE, Jens VOLKMANN, Frederik CLEMENT, Francisco PONCE, Chris VAN DER LINDEN, Cong ZHAO, Mustafa SIDDIQUI, Nestor TOMYCZ, Tino PRELL, Lilly CHEN, Roshini JAIN
Salle 120
Friday 10 September
08:30

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A31
08:30 - 10:00

Plenary Session 4
Psychiatry

Moderators: Raphaëlle RICHIERI (marseille, France), Rick SCHUURMAN (neurosurgeon) (Amsterdam, The Netherlands), Veerle VISSER-VANDEWALLE (Head of Dep. of Ster. and Funct. NS) (Cologne, Germany)
08:30 - 08:50 Dementia and nucleus basalis of meynert. Ludvic ZRINZO (Professor of Neurosurgery) (Keynote Speaker, London, UK, United Kingdom)
08:50 - 09:10 OCD. Rick SCHUURMAN (neurosurgeon) (Keynote Speaker, Amsterdam, The Netherlands)
09:10 - 09:30 #24089 - Surgery for addiction: animal models suggest to target the subthalamic nucleus.
Surgery for addiction: animal models suggest to target the subthalamic nucleus.

Addiction remains a public health issue with few options for treatment. With the development of deep brain stimulation (DBS) for psychiatric disorders such as treatment-resistant depression, obsessive compulsive disorders, a few groups have started to consider DBS as a possible treatment for addiction. Most of them have suggested that the Nucleus Accumbens (NAc) could be the target. However, manipulating the activity of the NAc may reduce the motivation to take drugs but may also reduce any form of motivation. In contrast, lesion or DBS of the subthalamic nucleus (STN) can reduce motivation for cocaine without reducing motivation for food reward in both rats and monkeys. STN DBS has been shown to be beneficial on various criteria of addiction (loss of control over drug intake, compulsive drug seeking) in rats and these effects can be generalized for cocaine, but also heroin and alcohol. STN DBS seems thus to be an interesting strategy to treat addiction.


Christelle BAUNEZ (Marseille)
09:30 - 09:50 Novelty in Psychiatric Surgery. Volker COENEN (Head of Department) (Keynote Speaker, Freiburg, Germany)
09:50 - 10:00 Discussion.
Auditorium
10:00 COFFEE BREAK & VISIT OF POSTERS AND EXHIBITION
10:30

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A32
10:30 - 12:00

Plenary Session 5
Brain Prediction

Moderators: Linda ACKERMANS (Neurosurgeon) (Maastricht, The Netherlands), Lorand EROSS (Director of the institute) (Budapest, Hungary), Maxime GUYE (Neurologist) (Marseille, France), Viktor JIRSA (Aix-Marseille University, Local Host, EBRAINS AISBL) (Marseille, France)
10:30 - 10:50 Predicting surgery outcome using patient-specfic virtual brain models in epilepsy. Viktor JIRSA (Aix-Marseille University, Local Host, EBRAINS AISBL) (Keynote Speaker, Marseille, France)
10:50 - 11:10 Augmenting diagnosis, inferring mechanisms, and predicting intervention outcomes in neurodegenerative disease through personalized Virtual Brain Cloud simulations. Petra RITTER (Charité University Hospital Berlin) (Keynote Speaker, Berlin, Germany)
11:10 - 11:30 Diagnosis and prognosis of epilepsy using predictive mathematical models. John TERRY (University of Birmingham) (Keynote Speaker, London, United Kingdom)
11:30 - 11:55 Mapping brain response patterns to DBS with fMRi. Andres LOZANO (Alan & Susan Hudson Cornerstone Chair in Neurosurgery, University Health Network) (Keynote Speaker, Toronto, Canada)
11:55 - 12:00 Discussion.
Auditorium

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B32
10:30 - 12:00

Parallel Session 9b
Movement disorders

Moderators: Nicolas REYNS (Professor of Neurosurgery) (LILLE, France), Giorgio SPATOLA (Neurosurgeon) (Brescia, Italy), Pepijn VAN DEN MUNCKHOF (Neurosurgeon) (Amsterdam, The Netherlands)
10:30 - 10:35 #23973 - Evaluating and optimizing Dentato-Rubro-Thalamic-Tract Deterministic Tractography in DBS for Essential Tremor.
Evaluating and optimizing Dentato-Rubro-Thalamic-Tract Deterministic Tractography in DBS for Essential Tremor.

Background: Dentato-rubro-thalamic tract (DRT) deep brain stimulation  (DBS) suppresses tremor in essential tremor (ET) patients. However, DRT depiction through tractography can vary depending on the included brain regions. Moreover, it is unclear which section of the DRT is optimal for DBS.

Objective: Evaluating  deterministic DRT tractography and tremor control in DBS for ET.

Methods: After DBS surgery, DRT tractography was conducted in 37 trajectories (20 ET patients). Per trajectory, 5 different DRT depictions with various regions of interest (ROI) were constructed. Comparison resulted in an DRT depiction with highest correspondence to intraoperative tremor control. This DRT depiction was subsequently used for evaluation of short term postoperative adverse and beneficial effects.

Results: Postoperative optimized DRT tractography employing the ROIs motor cortex, posterior subthalamic area and ipsilateral superior cerebellar peduncle and dentate nucleus best corresponded with intraoperative trajectories (92%) and active DBS contacts (93%) showing optimal tremor control. DRT tractography employing a red nucleus or ventral intermediate nucleus of the thalamus ROI often resulted in a more medial course. Optimal stimulation was located in the section between VIM and PSA.

Conclusion: This optimized deterministic DRT tractography determination strongly correlates with optimal tremor control and shows limited side-effects. This technique is readily implementable for DBS target planning in ET. 

Figure legend

The panels A to G show the different possible depictions of DRTs which are used for comparison. The above panel shows an axial, the bottom a coronal view on a 3-Tesla T2 MRI of the thalamic and subthalamic area (commissural aligned imaging). The green DRT is depicted with ROIs in the ipsilateral motor area, ipsilateral PSA, ipsilateral cerebellar peduncle and dentate nucleus (DRT-PSA). The DRT-VIM (purple) is depicted after adding VIM (depicted by the software) as a ROI. The DRT-RN (orange) is depicted with ROIs in ipsilateral motor area, ipsilateral red nucleus, ipsilateral cerebellar peduncle and dentate nucleus (DRT-RN). The crossing DRT-RN (red) crosses the midline at the level of the red nucleus, and is depicted with ROIs in the ipsilateral motor area, and RN, contralateral cerebellar peduncle and dentate nucleus. The definite DBS electrode (yellow) is displayed. Panel A is located 2 mm above the commissural line, panel B at the commissural line, panel C is located 2 mm below the commissural line, panel D is located 4 mm below, panel E is located 6 mm below, panel F is located 8 mm below and panel G is located 10 mm below.


Maarten BOT (Amsterdam, The Netherlands), Fleur ROOTSELAAR, Vincent ODEKERKEN, Joke DIJK, Rob DE BIE, Pepijn VAN DEN MUNCKHOF, Rick SCHUURMAN
10:40 - 10:45 #23983 - Utilising 7-Tesla Subthalamic Nucleus Connectivity in Deep Brain Stimulation for Parkinson’s Disease.
Utilising 7-Tesla Subthalamic Nucleus Connectivity in Deep Brain Stimulation for Parkinson’s Disease.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective surgical treatment for patients with advanced Parkinson’s disease (PD). Combining 7.0-Tesla (7T)  T2 and diffusion weighted (DWI) sequences allows for segmenting the motor part of the STN and possible optimisation of DBS.

 

Methods: 7T T2 and DWI sequences were obtained and probabilistic segmentation of motor, associative and limbic STN subdivisions was performed. Left and right sided motor outcome (MDS-UPDRS) scores were used for evaluating the correspondence between segmented location of stimulation and DBS effect. The Bejjani line was reviewed for crossing of segments.

 

Results: A total of 50 STNs were segmented in 25 patients. Due to the high resolution of the sequences, segmentation was well feasible using 7T T2 and DWI. Although the highest density of motor connections was situated in the dorsolateral STN for all, exact partitioning of subdivisions differed considerably. For all the active electrode contacts situated within the predominantly motor-connected segment of the STN, the average hemi-body UPDRS motor improvement was 80%, outside this segment 52%. The Bejjani line was situated in the motor segment for 32 STNs.  

 

Conclusion: The implementation of 7T T2 and DWI for STN segmentation in DBS for PD is feasible and offers insight in location of the motor segment. Segment guided electrode placement, instead of classical targeting, is likely to further improve motor response in DBS for PD. However, for full exploitation commercially available DBS software would have to allow for post-processing imaging.  

 


Varvara MATHIOPOULOU, Niels RIJKS, Matthan CAAN, Luka LIEBRAND, Rob DE BIE, Pepijn VAN DEN MUNCKHOF, Richard SCHUURMAN, Maarten BOT (Amsterdam, The Netherlands)
10:45 - 10:50 #23989 - Conventional and directional stimulation of subthalamic nucleus in Parkinson’s disease.
Conventional and directional stimulation of subthalamic nucleus in Parkinson’s disease.

Background: Subthalamic deep brain stimulation (DBS STN) became established as an effective treatment for advanced Parkinson's disease (PD). A new era in DBS appeared to be the introduction of segmented electrodes, which allow steering electric field in a certain direction horizontally. In view of ongoing discussion about the optimal stimulation spot within the STN in individual patients, directionality seems to be particularly relevant. Experimental modeling of directional stimulation suggests a possibility to increase the therapeutic window, reduce the appearance of stimulation-induced side effects, and enhance the efficiency of DBS. However, growing complexity of postoperative programming and patient management should be considered. There is still insufficient clinical data on eventual benefits of using segmented electrodes for outcome.

Objective: To assess efficacy and programming features of DBS STN using segmented directional electrodes compared to conventional omnidirectional leads in PD-patients with motor fluctuations.

Patients and methods: The study included 40 patients with advanced PD who underwent bilateral DBS STN surgery at our center in the last 3 years. In 20 patients (40 DBS-leads), segmented 8-contact electrodes were implanted (mean age at surgery 54.9±9.5 years, disease duration 13.2±4.3 years, Hoehn&Yahr stage 3.2±0.5). In the other 20 patients operated in the same timeframe (40 leads implanted), conventional 4-contact electrodes were used (mean age at surgery 57.4±9.0 years, disease duration 11.4±4.7 years, Hoehn&Yahr stage 3.2 ± 0.5). Groups did not differ significantly in baseline characteristics. All patients were operated by the same surgeon according to the uniform surgical technique including intraoperative microelectrode recording of neural activity (MER) and test stimulation. Neurological examination was standardized and performed preoperatively and at the 6-month follow-up in OFF- and ON-medication conditions (UPDRS, Schwab&England scale, PDQ39, levodopa equivalent daily doze/LEDD scoring). We analyzed intraoperative strategy, primary and following adjustments of the settings, and clinical outcome in each patient.

Results: Final trajectory of electrode implantation confirmed by MER and intraoperative stimulation coincided with central image-calculated trajectory in 67.5% of cases. In 32.5% of electrodes, correction of trajectory was performed (mainly in the medial direction). For MER, 1 to 3 microelectrodes were used (mean 1.5).

At the time of 6 months following continuous DBS STN, all patients experienced amelioration of parkinsonian symptoms and daily life activity in OFF-medication state with no significant difference between two groups. In patients with segmented leads implanted, mean OFF-state UPDRS-3 decreased from 51.3 to 16.7 points (66.3%) and UPDRS-2 from 23.0 to 8.7 (59.8%) compared to from 50.5 to 12.3 (73.9%) and from 22.9 to 9.8 (55.7%), respectively, in patients with conventional electrodes. In both groups, motor symptoms in ON-state also improved (mean UPDRS-3 changed from 13.0 to 7.9). Mean LEDD reduced from 1700 to 735 mg and from 1759 to 581 mg, respectively (p>0.05). Quality of life improvement comprised 19.3% for the whole group.

During initial setup, all leads were carefully screened for the best stimulation level, and then segmented ones were checked for the best direction of stimulation. Directional stimulation was preferentially used if better efficacy or minimization of DBS-induced side effects could be achieved. At the 3-month follow-up, in patients with segmented electrodes, directionality was employed in 9 patients (45%, 15 leads), To the 6-month follow-up, 14 leads were programmed directionally (9 patients). In 7 cases (17.5%), the most efficient electrode contact appeared to be outside the segmented level.

Conclusion: According to our data, efficacy of DBS STN via segmented electrodes is comparable to traditional omnipolar stimulation in short-term follow-up. Directional stimulation provides additional possibilities for programming and optimizing the clinical outcome of DBS STN. At the same time, high precision electrode placement is still required. Considering the increased complexity and time of selecting individual stimulation settings, systematic approach and development of new automated programming algorithms are desirable. We need studies in a larger patient population with long-term follow-up in order to evaluate potential benefits of directional DBS STN.


Alexey TOMSKIY, Anna GAMALEYA (Moscow, Russia), Svetlana ASRIANTS, Valentin POPOV, Anna PODDUBSKAYA, Sabina OMAROVA, Alexey SEDOV
10:50 - 10:55 #23998 - Power demand and battery longevity: 5-year results from a multi-center global registry.
Power demand and battery longevity: 5-year results from a multi-center global registry.

Objective: To characterize electrical features of long-term DBS settings for PD and ET patients, and how these features impact primary cell internal pulse generator (IPG) longevity derived from a global, multi-center registry.

Background: Several recent articles have been published on the impact of programmed settings and impedance on total electrical energy delivered (TEED) and consequently, battery longevity in DBS patients implanted with Activa PC have been compared with predecessor Kinetra IPGs.1-2 However, Activa PC contains hardware and programming capabilities that expand features beyond those available with Kinetra to provide physicians with more choices and greater flexibility in managing patient symptoms. The difference in battery longevity between Activa PC and Kinetra may be due to a number of design improvements which include size reduction for patient comfort and additional device features valuable in therapy optimization. In addition, sample size, diagnosis and duration of disease, stimulation settings including longitudinal impedance changes, and length of follow-up vary widely in these studies. The effect of these electrical parameters is better understood when a standardized approach across diverse centers and patient populations is used, such as a global registry.

Methods: The Product Surveillance Registry (PSR) was established in 2009, as a prospective long-term, multi-center global registry to monitor the reliability and safety of DBS systems. The stimulation settings were analyzed for 612 patients at 35 centers in 11 countries; 452 were first-time implanted IPGs and 215 were replacement IPGs. Electrical parameters were noted after stable programmed settings were achieved (6 months in de novo patients, 1 month in replacement patients). IPG longevity was estimated as the time to replacement due to battery depletion.  TEED (µJ) per lead was estimated from the actual device reported stimulation parameters and impedances over the lifetime of the battery. Statistical analysis was completed using Cox Proportional Hazards regression and Kaplan-Meier methods. 

Results:  The median IPG longevity for first-time implanted devices was 4.7 and 4.5 years, in PD and ET patients, respectively and device longevity was significantly longer in the first-time implanted group compared to the IPG replacement group. The IPG replacement group had higher TEED per lead for both PD and ET patients resulting in reduced battery life (Table 1), likely due to higher stimulation settings. Therapy impedance was significantly higher in first-time IPG devices compared to replacement devices in PD patients (p<0.0001); but not in ET patients (p=0.174).  Also, monopolar stimulation was used more frequently (78 % in PD vs 70% in ET) and 82% of devices had lead placed in STN target site in PD patients. The analysis of different stimulation targets revealed significant reduction of TEED in STN-DBS compared to GPi-DBS in first-time implanted PD patients (p<0.0001).

TEED increased significantly over time in PD patients (p<0.0001 in first-time implanted IPGs, but change was not significant in ET patients (p=0.386). With respect to therapy impedance, there was  evidence of significant downward trend in first-time implanted  PD and ET patients (p<0.0001, Figure 1). Overall, a significant inverse correlation was observed between IPG longevity and TEED in both PD (HR=1.009, p<0.0001) and ET (HR=1.011, p<0.0001) patients. 

Conclusion: The present analyses represent battery longevity from a real-world global patient population and reflect standard practice patterns at most DBS centers without protocol constraints regarding the management of these patients.  IPG longevity was quite similar in PD and ET patients but shorter in replacement IPGs, likely due to  higher energy demand in replacement IPGs compared to first-time implanted systems. The increase in TEED over time and higher TEED in replacement IPG may reflect changes in stimulation settings, usage patterns, or local tissue impedance fluctuations. Overall this analysis demonstrated the expected performance of 3-5 years of primary cell battery longevity for DBS therapy from a multi-center global registry in PD and ET patients.

References

1.              Helmers AK, Lubbing I, Deuschl G, et al. Neuromodulation. 2018;21(6):593-596.

2.              Niemann M, Schneider GH, Kuhn A, Vajkoczy P, Faust K. Neuromodulation. 2018;21(6):597-603.


Stephane PALFI (PARIS), Joachim K. KRAUSS, Peter KONRAD, George PLOTKIN, Emmanuel CUNY, Jean-Philippe AZULAY, Thomas WITT, Tom THEYS, Yesin TEMEL, Gayle JOHNSON, Kulwant BHATIA, Todd WEAVER
10:55 - 11:00 #24003 - Comparison of clinical outcomes and accuracy of electrode placement between robot-assisted and conventional deep brain stimulation of the subthalamic nucleus: a single-center study.
Comparison of clinical outcomes and accuracy of electrode placement between robot-assisted and conventional deep brain stimulation of the subthalamic nucleus: a single-center study.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has demonstrated major improvement of motor and non-motor manifestations and quality of life in Parkinson"s disease (PD) despite various surgical approaches. This single-center study aims to compare clinical outcomes and electrode placement accuracy in patients who underwent robot-assisted versus conventional frame-based stereotactic STN DBS surgery for PD.

Methods

This retrospective study included 48 PD patients, enrolled between October 2016 and December 2018 in the University hospital of Neurology and Neurosurgery of Lyon. They underwent either robot-assisted surgery (RAS) (Neuromate®, Renishaw) (n=20) or conventional frame-based stereotactic surgery (FSS) (n=28) with the same principles of STN targeting on MRI. ES performed RAS surgery, while GP performed FSS. Patients were evaluated before and 1 year after surgery. Electrode contacts within the STN was determined using merge of post-operative CT- and pre-op MRI with Brainlab® GUIDE™ XT software (Fig1).

Results

Median age at surgery was the same (62.5 years old) in both groups. 1 year after surgery, with stimulation on and pharmaceutical treatment, there was no difference in the evolution of MDS-UPDRS III (p=0.29) and IV (p=0,80) between groups, the evolution of the quality of life (p=0.25), the evolution of levodopa treatment (p=0.94). The rate of complications was not different between both groups (p=0.99). Surgery duration was significantly longer in the RAS group (479 min, Q1-Q3: 460— 490) cmpared to the FSS group (351 min, Q1-Q3 317-392) (p=0.0001). There was no difference in electrode placement accuracy in both groups (table1).

Discussion

This is the first study comparing clinical outcomes between robot-assisted and conventional surgery for DBS in PD in the same surgical center. We showed no difference in motor results, quality of life improvement, evolution of Levodopa treatment, complications of the surgery or electrode placement accuracy. The duration of surgery was increased in the RAS group. Prospective randomized study including a larger sample is required to determine best surgical approach, keeping in mind that the most important remains surgeon’s experience with the technique used.

Fig.1 : electrode placement accuracy 

Table 1: Results 


Shams RIBAULT, Emile SIMON (Lyon), Julien BERTHILLER, Gustavo POLO, Patrick MERTENS, Teodor DANAILA, Stéphane THOBOIS, Chloe LAURENCIN
11:00 - 11:05 #24020 - Optimization of the stimulation parameters settings of directional leads with a patient-specific imaging software in implanted parkinsonian patients.
Optimization of the stimulation parameters settings of directional leads with a patient-specific imaging software in implanted parkinsonian patients.

Optimization of the stimulation parameters settings of directional leads with a patient-specific imaging software in implanted parkinsonian patients

Gustavo Touzet MD3, Anne-Sophie Rolland PhD 1, Nicolas Carrière MD2, Bastien Gouges3, Luc Defebvre MD PhD2, David Devos MD PhD1,2, Caroline Moreau MD PhD2, Nicolas Reyns MD PhD3

1Department of Medical Pharmacology, Lille University, INSERM UMRS_1171, University Hospital Center, LICEND COEN Center, Lille, France; 2Department of Neurology, Lille University, INSERM UMRS_1171, University Hospital Center, LICEND COEN Center, Lille, France; 3Department of Neurosurgery, CHU LILLE University Hospital, France

Objectives: Deep brain stimulation in the subthalamic nucleus (STN) is routinely proposed to parkinsonian patients. Introduction of directional leads offers more flexibility for programming but may also increase the complexity and duration of the procedure. Here we assess whether Guide XTR, a new patient-specific imaging software, is helpful to refine stimulation parameters and to simplify the time consuming programming process.

 

Background: Clinical examination of the stimulation effect for each contact is the empirical method to set up stimulation parameters. Guide XTR models the volume of activated tissue and provides semi-automatic lead localization and segmentation of deep brain structures in order to visualize leads position and anatomical structures relative to putative stimulation fields.

 

Methods: We evaluated all parkinsonian patients who were implanted with bilateral directional leads in the STN. After surgery, patients were programmed and followed by the neurological team while blinded from anatomical data. All parameters were reviewed (ring or directional mode) and optimized based on standard clinical evaluation. After surgery, Guide XT was used to analyze imaging data by the neurosurgical team to choose the best stimulation configuration and parameters blinded from clinical data. Clinically determined parameters were then compared to imaging-based parameters.

 

Results: Twenty-eight patients were included in the study (19 males, 9 females, 59.1 ± 5.5 years old, disease duration 12.3 ± 7.4 years). The stimulation depth was similar between imaging and clinical settings in 75% of cases. Stimulation direction was similar between imaging and clinical settings in 18.75% of cases. Ring mode was selected in 62.5% with the clinical procedure and in 25% with the imaging procedure.

 

Conclusion: Predicted depth of stimulation using imaging data and empirically determined stimulation using clinical effects showed good concordance. Clinician used mainly ring mode stimulation despite imaging data suggesting a potentially better stimulation configuration using directional mode, possibly due to the complexity of the clinical evaluation. Imaging-guided parameters settings refined with clinical evaluation could therefore help to optimize parameters and limit non-motor side effects and need to be further evaluated.

 

Keywords: Parkinson’s disease, stimulation parameters, directional leads

 


Gustavo TOUZET (LILLE), Anne Sophie ROLLAND, Nicolas CARRIERE, Bastien GOUGES, Luc DEFEBVRE, David DEVOS, Caroline MOREAU, Nicolas REYNS
11:05 - 11:10 #25903 - Effects of unilateral stimulation in Parkinson’s disease: a randomized double-blind crossover trial.
Effects of unilateral stimulation in Parkinson’s disease: a randomized double-blind crossover trial.

Trials based on individual parallel designs have demonstrated that deep brain stimulation (DBS) treatments targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi) are both effective for the motor symptoms of Parkinson’s disease. However, few studies have compared the motor effects of STN and GPi DBS in individual patients. We compared the acute effects of unilateral STN and unilateral GPi DBS on motor function in individual patients with Parkinson’s disease treated with continuous DBS of both unilateral targets.

This prospective, double-blind, randomized crossover study assessed eight patients with idiopathic Parkinson’s disease who had been treated with continuous DBS of the unilateral STN and contralateral GPi for 2 years. Motor symptom severity, quantified by the Movement Disorder Society-Unified Parkinson Disease Rating Scale part III (MDS UPDRS-III), was assessed preoperatively and at 2-year follow-up in four randomized, double-blinded conditions: 1) Med−STN+GPi−, 2) Med−STN−GPi+, 3) Med+STN+GPi−, and 4) Med+STN−GPi+. The MDS UPDRS-III total score and subscale scores, including scores for axial and bilateral limb symptoms, served as the dependent variables.

Of the eight participants, seven completed the assessments in all four conditions, while one missed two postsurgical Med+ conditions. At the 2-year follow-up, compared with the preoperative Med− state, in the Med−STN+GPi− condition, the cardinal symptoms in both limbs were all improved, although the axial symptoms had deteriorated, except in the context of arising from a chair. In the Med−STN−GPi+ state, symptoms of the GPi-stim limb were improved significantly, while only tremor was improved on the ipsilateral side. The axial symptoms in the Med−STN−GPi+ state significantly worsened, and all sub-scores showed aggravation. Compared with the preoperative Med+ state, in the Med+STN+GPi− state, cardinal symptoms were improved on both sides, except for the tremor on the STN-stim side. The axial symptoms were more serious and the only improved axial symptom was arising from a chair. In the Med+STN−GPi+ state, the overall motor symptoms were aggravated, and the treatment effect was only reflected in the symptoms of tremor and rigidity on the GPi-stim side. The axial symptoms of the Med+ states were all worsened, except in the context of arising from a chair.

In conclusion, improvement of motor symptoms was significantly increased in all sub-scores favoring STN, except for the worsening degree of gait, in which Med+STN−GPi+ was slightly lower than Med+STN+GPi−. We also noted the effects of STN+ acting on both limbs, in contrast to the effects of GPi+, which mainly acted on the contralateral side. 


Zhitong ZENG, Linbin WANG, Weikun SHI, Lu XU, Zhengyu LIN, Xinmeng XU, Peng HUANG, Yixin PAN, Zhonglue CHEN, Yun LING, Kang REN, Bomin SUN, Dianyou LI, Chengcheng ZHANG (Shanghai, China)
11:10 - 11:15 #26047 - Biphasic anode-first pulses increase the therapeutic window.
Biphasic anode-first pulses increase the therapeutic window.

Objective – To investigate the use of biphasic anode-first pulses on the therapeutic window in essential tremor (ET) patients treated with ventral intermediate nucleus deep brain stimulation (DBS). Figure 1.

Background – Since the inception of DBS, cathodic pulses have been used1. Modelling studies suggest that biphasic pulses may influence the therapeutic window2.

Methods – Stimulation was delivered on the most ventral contact, unless this elicited unbearable paresthesias. In that case, one level more dorsally was stimulated. The non-tested hemisphere was turned OFF. Three thresholds were acutely defined for both cathodic and biphasic anode-first pulses: lowest amplitude inducing tremor arrest while performing a finger-to-nose test contralaterally (LowerTW),  lowest amplitude inducing upper limb ataxia contralaterally (AtaxicTW) and lowest amplitude causing non-transient stimulation-induced side effects contralaterally, other than limb ataxia (UpperTW). The thresholds were defined twice in all hemispheres and average results per hemisphere were analyzed. Wilcoxon signed rank test was used to compare the thresholds.

Results – Four ET patients (8 hemispheres) participated in this study. LowerTW was not significantly different between cathode versus biphasic pulse (1.82 ± 0.69 mA versus 2.11 ± 0.62 mA, p = 0.25). The amplitude that elicited limb ataxia was however significantly higher in the biphasic anode-first pulse (2.74 ± 0.96 mA versus 3.75 ± 1.41 mA, p = 0.0078). Also, non-ataxic side effect was only evoked at higher stimulation amplitudes when compared to biphasic pulses (3.69 ± 1.84 mA versus 4.78 ± 1.97 mA, p = 0.0078). Figure 2.

Conclusions – Biphasic pulses elicit stimulation-induced side effects at higher amplitudes, therefore increasing the therapeutic window. Further work is needed to determine if these pulses can bring clinical benefit compared to standard cathodic pulses.

References

1.          Benabid AL, Pollak P, Hoffmann D, et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991;337(8738):403-406. doi:10.1016/0140-6736(91)91175-T

2.          Wongsarnpigoon A, Grill W. Energy-efficient waveform shapes for neural stimulation revealed with a genetic algorithm. J Neural Eng. 2010;7(4):1-20. doi:10.1088/1741-2560/7/4/046009.Energy-efficient


Alexandra BOOGERS (Toronto, Canada), Jana PEETERS, Tine VAN BOGAERT, Wim VANDENBERGHE, Bart NUTTIN, Myles MC LAUGHLIN
11:15 - 11:20 #26102 - Directional subthalamic deep brain stimulation in Parkinson’s disease: Better clinical results with directional stimulation.
Directional subthalamic deep brain stimulation in Parkinson’s disease: Better clinical results with directional stimulation.

Directional subthalamic nucleus deep brain stimulation in Parkinson’s disease allows for a better therapeutic window, with increased motor effects and less stimulation side effects. In our study, we aimed to determine the preferred type of stimulation (omnidirectional or directional) on last-follow-up in patients who were all implanted with directional leads. We then correlated the results of choice of type of stimulation with the anatomical electrode position in the subthalamic nucleus.

From April 2018 to August 2020, 17 patients received directional leads (Boston Scientific) for severe Parkinson’s disease implanted bilaterally into the subthalamic nucleus. The neurologists of the team had all freedom to change the mode of stimulation, but were at that time blinded to the exact lead position of the contacts as revealed by the guide XT software. DBS stimulation status (omnidirectional vs directional) and its evolution was compared post-operatively (when the patient was discharged) and at last follow-up with at least 1 year of follow up.  This mode of stimulation was then correlated to the evolution of the MDS UPDRS scores, to the side effects and to the anatomical position of the implanted electrodes. 1 patient was followed in another centre and data were not available.

6 and 10 patients were stimulated with directional (37%) or omnidirectional mode (63%) respectively at discharge. At last follow up, 11 out of 16 (69%) had a directional mode of stimulation, 7 switching from omnidirectional to directional mode, and 2 switching from directional to omnidirectional mode. Reasons for change included better efficacy and the need to reduce the side-effects. Anatomical correlations will be discussed according to those findings.

In conclusion, there was a great tendency to stimulate preferentially a majority of patients using directional mode for different reasons discussed in the paper.


Mazen KALLEL (Grenoble), Emmanuel DE SCHLICHTING, Eric SEIGNEURET, Anna CASTRIOTO, Valerie FRAIX, Elena MORO, Stephan CHABARDES
11:20 - 11:25 #26138 - Pedunculopontine and Cuneiform nuclei deep brain stimulation for severe gait and balance disorders in Parkinson’s disease: a randomised double-blind clinical trial.
Pedunculopontine and Cuneiform nuclei deep brain stimulation for severe gait and balance disorders in Parkinson’s disease: a randomised double-blind clinical trial.

Doparesistant Freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced  Parkinson’s disease (PD). Their pathophysiology is poorly understood, but imaging and post-mortem studies suggest a causal role of cholinergic dysfunction within the pedunculopontine nucleus (PPN), located in the mesencephalic locomotor region (MLR), also including the cuneiform nucleus (CuN) dorsally. We herein investigate the effects of deep brain stimulation (DBS) of the PPN and CuN nuclei, for treating gait and balance disorders in Parkinson’s disease (PD) patients in a randomized double-blind cross-over clinical trial. Six PD patients with dopa-resistant freezing of gait (FOG) and/or falls were included and operated for bilateral MLR-DBS. Patients each received three DBS conditions, PPN, CuN or sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in anteroposterior anticipatory postural adjustments (APAs) during gait initiation on a force platform at the end of each DBS condition. Secondary outcomes included safety and differences in gait kinetics, and clinical gait, cognitive and quality of life scales between DBS conditions. During the randomized period, we found that the anteroposterior APA were not significantly different between the DBS conditions (median displacement [1st_3rd quartile] of 3.07 [3.12_4.62] mm with sham-DBS, 1.95 [2.29_3.85] mm with PPN-DBS and 2.78 [1.66_4.04] mm with CuN-DBS; p=0.25). Step length and velocity were significantly higher with CuN-DBS vs both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs inclusion. We also found no significant differences in the clinical scales including  the parkinsonian disability, gait and balance scales, and assessment of cognition or psychiatric troubles. Lastly, we observed 3 serious adverse events with one electrode displacement in one patient, one patient had a subdural hematoma following recurrent falls that did not necessitated surgery. Our study suggests a better effect of CuN-DBS relative to PPN-DBS on walking ability in advanced PD patients. However, the absence of significant clinical benefit with 2 months of DBS with no aggravation in FOG or falls one year after surgery would suggest that optimized DBS and for longer period might be beneficial. Further research is needed to better understand the role of the MLR in gait and balance control in humans using new imaging or neurophysiological approaches.

 


Julie BOURILHON, Claire OLIVIER, You HANA, Antoine COLLOMB-CLERC, David GRABLI, Hayat BELAID, Yannick MULLIE, Chantal FRANÇOIS, Virginie CZERNECKI, Brian LAU, Fernando PÉREZ-GARCÍA, Eric BARDINET, Sara FERNANDEZ-VIDAL, Carine KARACHI, Marie-Laure WELTER (Paris)
11:25 - 11:30 #26181 - Deep brain stimulation (DBS) of Subthalamic nucleus and Substancia nigra (SN) for the treatment of gait affection in Parkinson´s disease.
Deep brain stimulation (DBS) of Subthalamic nucleus and Substancia nigra (SN) for the treatment of gait affection in Parkinson´s disease.

Objetive:

Deep brain stimulation (DBS) has been shown to be effective and safe for treating the cardinal symptoms of Parkinson's disease.

Some aspects of the disease, such as gait disorders, respond worse to DBS. Various publications suggest the efficacy of combined DBS in the subthalamic nucleus (STN) and the substantia nigra (SN) for refractory gait disorder in PD. The objectives of our study are to confirm these previous findings. Material and methods:We present data from our randomized, crossover, double-blind, single-center study conducted in 10 patients with advanced PD.
Octopolar deep brain stimulation electrodes were placed bilaterally at STN, leaving the most distal contacts at SN. To perform the quantitative gait analysis, the Step 32 system was used. Clinical and neurophysiological parameters were compared after 4 weeks of STN stimulation versus 4 weeks of combined STN and SN stimulation. Side effects and patient preferences were reported. Results:
There were no complications associated with surgery Postoperative improvement was observed in the cardinal symptoms of PD and in gait parameters. The number of normal gait cycles increased significantly after surgery in both forms of stimulation.
The greatest increase in normal gait cycles occurred in combined STN and SN stimulation (0.57 preoperative, 0.71 STN, 0.79 STN + SN). Coclusion: The combined STN and SN DBS is a safe and effective technique to improve the axial motor disorders of PD, such as gait blocks and postural instability. Studies with a larger number of patients and long-term follow-up would be very useful to confirm the evidence of our work.

 


Marta DEL ÁLAMO DE PEDRO (Madrid, Spain), Iziar AVILÉS-OLMOS, Lidia CABAÑES, Marta VILLADONIGA, Ignacio REGIDOR
11:30 - 11:35 #26193 - Unilateral delivery of autologous injury-activated peripheral nerve graft tissue to the substantia nigra in patients with Parkinson’s disease.
Unilateral delivery of autologous injury-activated peripheral nerve graft tissue to the substantia nigra in patients with Parkinson’s disease.

Background: Both the FDA, under 21 CFR 1271.15(b), and the EU, under Art 2§2(a) and Preamble 8 of Dir. 2004/23/EC, allow for a Same Surgical Procedure Exemption for the grafting of autologous tissue during a same surgical procedure. With a goal of providing support to sick or dying cells, we have previously used this Exemption to deliver autologous injury-activated peripheral nerve graft tissue (APNG) to the substantia nigra in patients with Parkinson’s disease who are undergoing deep brain stimulation (DBS) surgery (van Horne et al. 2018). Following injury, the peripheral nervous system, activates a reparative response that generates a host of neurotrophic and cell-survival factors.

Objective: As part of an open-label Phase I clinical trial (NCT02369003) to expand the utility of this approach and examine dose escalation, we unilaterally implanted APNG to the substantia nigra under two different dosing regimens: a single deployment of APNG or two deployments of APNG.

Methods: As part of the standard of care, participants underwent a two-staged DBS procedure. At the time of stage I, the sural nerve was transected and the incision was closed. Later (3 to 14 days later) at stage II, the injured sural nerve was identified, and an about 1 cm section was excised. The fascicles were identified, diced, and deposited in the substantia nigra with one deployment or a deployment both to the anterior and to the posterior substantia nigra. Participants were followed for 12 months and the motor component of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) was used to assess for changes in Parkinson’s disease severity.

Results: Across our previous trial (van Horne et al. 2018) and this one, a total of 37 participants have received only unilateral grafts to the substantia nigra with a mean age of 62 years (95% Confidence Interval: 60 to 65 years). Adverse event profiles were comparable to standard DBS with the most common study-related events being paresthesias of the lateral foot distal to the sural nerve tissue harvest site.  For the single deployment, off-state motor MDS-UPDRS mean scores were 45.3 points (40.2 to 50.5; n=28) at screening and 36.6 points (30.5 to 42.7; n=24) at 12 months. For participants receiving two deployments: 42.8 points (30.7 to 54.9; n=9) at screening and 35.8 points (21.5 to 50.0; n=8) at 12 months. Overall for unilateral APNG delivery, pooling both groups, the mean decrease in scores at 12 months was -8.4 points (-4.1 to -12.6; n=32). When we analyzed the lateral components of the MDS-UPDRS, the mean difference in scores at 12 months for the body side contralateral to the APNG deployment was -4.6 points (-2.8 to -6.6) and for the side ipsilateral to the APNG deployment it was -0.8 (-2.0 to + 0.5).

Conclusions: Further examination of the approach is merited to further establish the safety profile for this procedure and to investigate the potential for this strategy for disease modification.


Jorge QUINTERO (Lexington, USA), John SLEVIN, Julie GURWELL, Zain GUDURU, Tritia YAMASAKI, Eglė SUKOCKIENĖ, Thomas HINES, Greg GERHARDT, Craig VAN HORNE
11:35 - 11:40 #26201 - Clinical outcome of magnetic resonance guided focused ultrasound thalamotomy for essential tremor: results at 6 months follow-up.
Clinical outcome of magnetic resonance guided focused ultrasound thalamotomy for essential tremor: results at 6 months follow-up.

Introduction

Essential tremor (ET) is one of the most common neurological disorders with a prevalence of 4.6% in people aged 65 years or older. Medical management is generally initiated when the tremor begins to interfere with the patient’s ability to undertake daily activities, but the effectiveness of drugs for this disorder is limited.

Stereotactic radiofrequency (RF) thalamotomy and deep brain stimulation (DBS), targeted to the ventralis intermedius nucleus of the thalamus (Vim), have proven effective for treating ET and other tremors. These interventions, although highly effective, have risks associated with an open neurosurgical operation.  Radiosurgical Vim thalamotomy with Gamma Knife has been used as a non-invasive alternative treatment. However, the lack of immediate clinical improvement and the possibility of extension of the lesion beyond the initially targeted region over time inducing permanent neurological deficits have limited the use of this technique.1

For the last decade, MRgFUS has been raising a lot of interest, as an incisionless and low-risk therapeutic option. This type of treatment creates a coagulation lesion via high-intensity ultrasound beams that converge in a selected target, with great accuracy and with neither need of incising the skin nor opening the skull. Vim-MRgFUS has been used to treat tremor associated with Parkinson´s disease, Essential Tremor, Multiple Sclerosis and Fragile X-associated ataxia.

In the present study, the durability of tremor relief in patients followed for 6 months after MRgFUS thalamotomy was evaluated to confirm the durability of efficacy and safety of MRgFUS thalamotomy for the treatment of medically refractory ET.

 

Methods

One hundred twenty-three ET patients treated with unilateral MRgFUS VIM between 2018 and 2021 were evaluated using the Clinical Rating Scale for Tremor (CRST) score at month, three months, and 6 months. Lesion characteristics were assessed on routine MRI sequences at 6 months in 44 patients. Relationships between imaging appearance in Brainlab Sotware (BrainLAB AG, Munich, Alemania), details of thalamotomy procedure (Insightec Inc, Tirat Carmel, Israel) and clinical outcome were investigated.

 

Results

Mean hand tremor score section A and B at baseline (20.77 ± 5.81; 123 patients) improved by 83.33% ± 22.10% (Section A), 73.51% ± 28.40% (Section B) and 75.74% ± 33.53% (Section C;) at 6 months. This improvements difference was significant (p= 0.05). Paresthesias and gait disturbances were the most common adverse effects at 1 months and at 6 months only 28% patients presented soft adverse effects.

On T2-weighted images the most lesion was hyperintense, the mean relative volume at 6 months was 0,037 ± 0.026cm3 (IQR 0.31– 0.058cm3), some lesions were no longer discernable in T2-weighted images. Mean AC-PC line length was 25.98 ± 1.87 mm (IQR 24.63– 27.45mm). Clinically determined centers of Vim lesion placement differed from the assumed position of the nucleus as suggested in the literature. On the right-left axis, mean lesion position was 14.33 ± 1.95 mm (range 13.37 – 14.93mm) from third wall and 6.75 ± 1.19mm (IQR 5.76 ± 7.45mm) distance from the posterior commissure on the AC-PC line, what represents 26.01 ± 4.21% (IQR 23.55- 27.76%) of AC-PC line. On the dorso- ventral axis, mean lesion position was 3.01 ± 1.21mm (IQR 2.13-3.75). The mean of III ventricle measured on T2-weighted images was 6.81 ± 2.02 mm (IQR 5.63 – 8.35mm). The median patient SDR was 0.52 (IQR 0.44 -0.57). MRgFUS thalamotomies were performed using a median of 3.4 ± 1.4 sonications over maximal mean temperature of 55°C (IQR 2-4), delivering a median of 16243 ± 8640 joules (IQR 8655- 24154). The median of seconds over 55° was 29.85 ± 12.5 seconds (IQR 21 -37.5 seconds). The median median maximal mean temperature of 58 ± 2.14°C (IQR 57-60°C). There was no significant correlation between lesion volume at 6 months and clinical improvement (p =0.13) for tremor reduction on the treated side. The technical parameters were no significant correlation with clinical improvement, nevertheless, III ventricle size was significant correlation with tremor reduction (p=0,046), the greater ventricular size the clinical improvement decrease. 

Conclusion

MRgFUS thalamotomy for ET is an effective and safe procedure that provides long-term tremor relief and improvement in quality of life even in patients with medication-resistant disabling tremor.


Alana ARCADI (Pamplona, Spain), Iciar AVILES, María GOROSPE, Lain GONZALEZ-QUARANTE, Antonio MARTIN, Laura ARMENGOU, María Cruz RODRÍGUEZ, Jorge GURIDI
11:40 - 11:45 #26288 - MRI-guided Laser Interstitial Thermal Therapy thalamotomy for essential tremor: a proof-of-concept study.
MRI-guided Laser Interstitial Thermal Therapy thalamotomy for essential tremor: a proof-of-concept study.

Introduction

Management of drug-resistant essential tremor (ET) is a challenge for clinicians. Thalamic deep brain stimulation (DBS) has proven to be effective in ET patients with drug-resistant tremor. However, for various reasons some patients are not eligible or refuse these DBS procedures. For these reasons, less invasive neurosurgical procedures have emerged in these second-line indications to create thalamic lesions using radiation or MRI-guided focused ultrasound. Recently a new technology has emerged allowing realization of brain lesion by laser with real-time guided MRI imaging: MRI-guided Laser Interstitial Thermal Therapy (MRIg-LITT). MRIg-LITT is increasingly used in neurosurgery thanks to its promising clinical results in treatment of epilepsy and tumors. Here, we report early data of MRIg-LITT thalamotomy in drug-resistant ET patients.

Methods

Briefly, MRIg-LITT thalamotomy consisted of stereotaxically placing a laser probe (Medtronic) in the ventral intermediate (VIM) nucleus of the thalamus using the ROSA robot system (Zimmer Biomet) under general anesthesia. Targeting and trajectory planning were established on the dedicated ROSANA planning software (Zimmer Biomet) separate from the robotic platform, allowing automatic image fusion between preoperative MRI and CT scan images. Intraoperative guidance by CT scans obtained with the O-Arm system (Medtronic) and microelectrode recording (FHC) allowed assisted laser probe placement. Once the probe was in place, patient was transported to MRI still under general anesthesia. A single MRIg-LITT thalamotomy in a 1.5T MRI (GE Optima MR 450w) was performed using the Visualase system (Medtronic) equipped with a diode laser (max power of 15W and 985 nm wavelength). MRIg-LITT protocol was carried out in stepwise, increasing deliveries of 10%, 15%, 20%, and 25% laser power sessions. The overall heating time was 9 min 50 s, alternating with rest periods of 1-2 min (laser power range of 1-2.5W). Then, the laser probe was removed and patient was awakened.

Improvement of upper limb tremor contralateral to the thalamotomy on Fahn-Tolosa-Marin (FTM) scale was evaluated at 3 months postoperative blindly by video by an external expert neurologist. Quality of life was assessed on the Quality of Life in Essential Tremor Questionnaire (QUEST) at 3 months postoperative. All patients gave their consent for the study

Quantitative variables are presented with their mean and standard deviation, qualitative variables with their percentages and numbers. Comparisons of quantitative variables are made using a Wilcoxon test.

Results

Unilateral MRIg-LITT thalamotomy was performed in 5 patients with ET drug-resistant tremor. Mean age was 73.00 (7.07) years, 3/5 were male, 4/5 were right handed and mean duration of the tremor was 441.60 (263.24) months. Preoperative mean FTM score of upper limb contralateral to the thalamotomy was 14.60 (0.89) (rest tremor 0.40 (0.55), postural tremor 3.00 (0.71), action tremor 2.20 (1.09), drawings and writing 9.00 (2.00)). Preoperative mean QUEST Summary Index was 49.55 (11.68). Postoperative mean FTM score of upper limb contralateral to the thalamotomy was 3.80 (1.09) (rest tremor 0 (0), postural tremor 0.20 (0.45), action tremor 0 (0), drawings and writing 3.60 (0.89)). Postoperative mean QUEST Summary Index was 21.77 (11.86). Postoperative mean FTM score of upper limb contralateral to the thalamotomy was improved by 73.98% (p=0.098) and QUEST Summary Index by 56.07% (p=0.043). No serious adverse events have been reported. 5/5 patients report only transient motor weakness and proprioceptive disorders on the upper limb contralateral to the thalamotomy during 1 to 2 weeks post procedure. Persistence of long-term efficacy is currently being assessed, as is cognitive security.

Discussion

Unilateral MRIg-LITT thalamotomy seems to be an effective and safe technique to treat upper limb drug-resistant ET when thalamic DBS is impossible or refused by the patient. It could be an alternative to radiosurgery or MRI-guided focused ultrasound to perform stereotaxic VIM thalamotomy. However, other studies with a larger number of patients and a longer follow-up period are necessary to validate the use of this technique in current practice. To our knowledge, only one study involving 13 patients reports use of MRIg-LITT thalamotomy for drug-resistant tremors in the literature.


Mickael AUBIGNAT (Amiens), Melissa TIR, Felix POTTECHER, Salem BOUSSIDA, Jean-Marc CONSTANS, Michel LEFRANC
11:45 - 11:50 #26296 - Ipsilateral effects of unilateral Deep Brain Stimulation for Essential Tremor.
Ipsilateral effects of unilateral Deep Brain Stimulation for Essential Tremor.

Ipsilateral effects of unilateral Deep Brain Stimulation for Essential Tremor


Background: Essential tremor (ET) is the most common adult movement disorder. For the relatively large group of patients which do not respond adequately to pharmacological therapy, deep brain stimulation (DBS) might constitute an alternative. Most ET patients will have bilateral symptoms and many of them receive bilateral DBS. Even so, unilateral DBS is still the most common procedure and some papers suggest an ipsilateral effect in these patients. 


Objectives: To analyze if we could find an ipsilateral effect of DBS for essential tremor.


Method: We retrospectively analyzed our patient cohort with DBS surgery from 1996 to 2017, selecting patients with ET that underwent surgery with unilateral DBS without previous DBS or lesional surgery. A total number of 68 patients (39 males, 29 females) were identified. The patients were evaluated at a mean time of 12 and 49 months after surgery using Essential tremor rating scale (ETRS).


Results: Total ETRS score was reduced from 49.5 points at baseline before surgery to 20.2 (p<0.001) at short term and 28.3 (p<0.001) at long term follow up. Contralateral tremor was reduced from 6.1 to 0.4 (p<0.001) and 1.2 (p<0.001) respectively. Contralateral hand function was reduced from 11.5 to 2.6 (p<0.001) and 4.6 (p<0.001), respectively. Ipsilateral hand function was reduced from 9 to 8.3 (p<0.05) but this was not maintained at long term follow up (9.4. p>0.05). Ipsilateral tremor was reduced from 4.0 at baseline to 3.7 (p<0.05) but not maintained at long term follow up (4.3. p>0.05).


Discussion:

In this study, we found a small but significant improvement on ipsilateral hand function (items 11-14 on the ETRS) and hand tremor (item 5/6) on short term follow up. But the effect was lost on long term follow up. Although we could see a larger improvement in a few of our study objects, on the group level this improvement was very modest (8% improvement). Furthermore, the effect was not maintained on the long-term evaluation.The situation is similar in the literature. Often a minor reduction is seen regarding hand tremor (item 5/6) which sometimes reaches significance. However, at the group level the improvement is always modest. It has been suggested that ipsilateral effects are caused by ipsilateral connections in this are . However, it is possible that other factors might contribute.

Conclusions:

We observed a significant improvement on ipsilateral hand function and tremor in our material, but the effect was small and transient. Hence, we consider this question to merit limited consideration regarding decision making or patient counseling on DBS for ET.


Erik ÖSTERLUND (Stockholm Sweden, Sweden), Patric BLOMSTEDT, Anders FYTAGORIDIS
11:50 - 11:55 #26304 - Further refinement of the stimulation hotspot in subthalamic deep brain stimulation for parkinson’s disease.
Further refinement of the stimulation hotspot in subthalamic deep brain stimulation for parkinson’s disease.

INTRODUCTION: Individual improvement in motor symptoms can vary considerably after subthalamic deep brain stimulation (STN DBS). Through evaluating this, we have been able to define an optimal theoretic location for STN DBS by introducing a patient-specific reference point: the medial STN border. We aimed to evaluate the implementation of the medial STN border as a patient-specific reference point and its consistency for correlation with lateralized motor improvement using a larger and more recent cohort of PD patients who underwent STN DBS surgery at our institution. METHODS: Patients were selected from a single-center randomized controlled trial comparing bilateral STN DBS surgery under general versus local anesthesia, that included PD patients between May 2016 and November 2018. Body-sides were categorized into three groups, based on percentual MDS-UPDRS-III improvement: (1) non-responding (<30%), (2) responding (between 30% and 70%) and (3) optimally responding (>70%). A theoretic ‘hotspot’ was calculated by averaging X, Y, and Z coordinates of the ‘optimally responding’ group, relative to the medial STN border as well as to the MCP. The Euclidean distance from each active contact to both defined hotspots were calculated separately. RESULTS: 218 DBS electrodes were implanted in 109 patients with PD. Thirty-seven corresponding body-sides were categorized as non-responding body-sides (18%), whereas 108 as responding body-sides (51%) and 67 as optimally responding body-sides (32%). Average percentual UPDRS change of the non-responding body-side group were significantly higher in the current study population compared to the previous population (Bot et al. 2018; independent T(52) = 2.14, P = 0.037), whereas the responding body-side group had less average percentual UPDRS change in the current population (independent T(136) = 2.74, P = 0.007). Using the medial STN border as a patient-specific reference point, difference in mean Euclidean distances between non-responders and responders were statistically significant (independent t(143) = 2.25, P = 0.026), as well as between non-responders and optimal responders (independent t(102) = 3.22, P = 0.002). We found a significant negative correlation (Pearson’s correlation -0.23; P = 0.001) between percentage MDS-UPDRS-III Lateralized scores change and Euclidean distance from active contact to the refined ‘hotspot’ defined relative to the medial STN border. CONCLUSION: We evaluated the implementation of the medial STN border as a patient-specific reference point and its consistency for correlation with lateralized motor improvement using a larger and more recent cohort of PD patients who underwent STN DBS surgery at our institution. We reaffirmed the significance of the medial STN border as patient-specific reference point for DBS location and motor improvement in patients with PD in a larger and highly recent cohort. This refined optimal location for DBS in PD can be used for optimizing lateralized motor outcome scores and was defined at 2.8 mm lateral, 1.1 mm anterior, and 2.2 mm superior to the medial STN border.


Erik BOLIER (Amsterdam, The Netherlands), Maarten BOT, Pepijn VAN DEN MUNCKHOF, Rick SCHUURMAN
Salle Major
12:00

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EXCOM
12:00 - 13:30

ESSFN Executive Committee meeting

Salle 50
INDUSTRIAL LUNCH WORKSHOPS
13:30

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A34
13:30 - 14:30

Plenary Session 6
Epilepsy Surgery

Moderators: Hans CLUSMANN (Department of Neurosurgery) (Aachen, Germany), Michel LEFRANC (MEDECIN) (AMIENS, France), István VALÁLIK (head of department) (Budapest, Hungary)
13:30 - 14:00 Refractory epilepsies: strategies for the surgical management. Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (Keynote Speaker, LISBON, Portugal)
14:00 - 14:30 LITT achievement in Epilepsy Surgery. Robert GROSS (Neurosurgeon, MD/PhD Dir, eNTICE Chair, SOM Faculty) (Keynote Speaker, Atlanta, USA)
Auditorium
14:30 COFFEE BREAK & VISIT OF POSTERS AND EXHIBITION
15:00

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A35
15:00 - 17:00

Parallel Session 11
Movement disorders

Moderators: Alexandre EUSEBIO (Professor) (Marseille, France), Miroslav GALANDA (Kosice, Slovakia), Claudio POLLO (Deputy Chief Doctor) (Bern, Switzerland)
15:00 - 15:10 #26104 - Pallido-putaminal connectivity predicts outcomes of deep brain stimulation for cervical dystonia.
Pallido-putaminal connectivity predicts outcomes of deep brain stimulation for cervical dystonia.

Background

Cervical dystonia is a non-degenerative movement disorder characterised by dysfunction of both motor and sensory cortico-basal ganglia networks. Deep brain stimulation targeted to the internal pallidum (GPi) is an established treatment, but its specific mechanisms remain elusive, and response to therapy is highly variable. Modulation of key dysfunctional networks via axonal connections is likely important.

Methods

Fifteen patients underwent pre-operative diffusion-MRI acquisitions and then progressed to bilateral DBS targeting the posterior GPi. Severity of disease was assessed pre-operatively and later at follow-up. Scans were used to generate tractography-derived connectivity estimates between the bilateral regions of stimulation and relevant structures, namely the thalamus, subthalamic nucleus, and the putamen.

Results

Connectivity to the putamen correlated with clinical improvement, and a series of cortical connectivity-based putaminal parcellations identified the primary motor (M1) putamen as the key node (r=0.70, p=0.004). A forward regression model with this connectivity and electrode coordinates explained 68% of variance in outcomes (r= 0.83, p=0.001), with both as significant explanatory variables (connectivity: p=0.01, coordinates:  p=0.02).

Conclusions

We conclude that modulation of the M1 putamen – posterior GPi limb of the cortico-basal ganglia loop is characteristic of successful DBS treatment of cervical dystonia. Pre-operative diffusion imaging contains additional information that predicts outcomes, implying utility for patient selection and/or individualised targeting.  


Ashley RAGHU (Atlanta, USA), John ERAIFEJ, John STEIN, Stephen PAYNE, Tipu AZIZ, Alex GREEN
15:10 - 15:20 #26119 - Clinical outcome after MRI-connectivity-guided radiofrequency thalamotomy for tremor.
Clinical outcome after MRI-connectivity-guided radiofrequency thalamotomy for tremor.

Clinical outcome after MRI-connectivity-guided radiofrequency thalamotomy for tremor

Thomas Wirth1, Ali Rajabian1, Viswas Dayal1, Abuhusain Hazem1, Nirosen Vijiaratnam1, Dilan Athauda1, Marwan Hariz1,2, Thomas Foltynie1, Patricia Limousin1, Harith Akram1*, Ludvic Zrinzo1*

 

1. Unit of Functional Neurosurgery, National Hospital for Neurology and Neurosurgery (UCLH) -Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, United Kingdom

2. Department of Clinical Science, Neuroscience, Umeå University, Umeå, Sweden

 

*These authors equally contributed and should be considered as co-supervising authors.

 

Background: Historic published outcome data for radiofrequency thalamotomy for severe tremor do not reflect advances in stereotactic targeting using MR connectivity guided surgery

Objective: To evaluate the efficacy and tolerability of contemporary unilateral radiofrequency-thalamotomy procedures in severe tremor.

Material and Methods: Twenty-one consecutive patients (14 essential tremor, 7 Parkinson’s disease) with severe, medically refractory tremor underwent awake radiofrequency thalamotomy procedures in a single institute between 2016 and 2019. Connectivity derived segmentation of the ventro-intermedial (Vim), the anterior ventrolateral (VL / Voa+Vop) and the ventroposterior (VPM/ VPL) nuclei was used to guide targeting. Changes in the Fahn-Tolosa-Martin rating scale (FTMRS) and tremor and disability scores were recorded in treated and non-treated hands as well as procedure related side effects

Results: Twenty-three thalamotomies were performed (with two patients receiving two interventions). The mean (SD) postoperative assessment timepoint was 14.1 (9.7) months. Treated-hand tremor scores improved by 63.8% whereas non-treated hand scores deteriorated by 10.13% (p<0.01). Treated hand tremor disability scores were also significantly lower at follow-up compared to baseline (7.55 vs 13; p<0.01) as were total FTMRS scores (34.7 vs 51.65; p=0.016). Baseline treated-hand tremor severity (r=0.786; p<0.01) and total FTMRS score (r=0.786; p<0.01) best correlated with tremor improvements. No significant correlation was noted between outcomes and gender, age at surgery, tremor etiology, lesion size and location, or previous Vim-DBS failure. 

The most reported side effect was mild, transient gait ataxia (38.1%). Other transient side effects included paresthesia (9.5%), mild dysarthria (19%), and mild motor or sensory deficits (4.7% each). Persistent side effects included mild gait ataxia (14.2%), mild sensory deficit (4.7%) and paresthesia (9.5%). No correlation was noted between lesion size or location and side effects.

Conclusion: Unilateral radiofrequency Vim thalamotomy guided by connectivity-derived segmentation is a safe and efficacious option for severe tremor in both PD and essential tremor


Thomas WIRTH, Ali RAJABIAN, Viswas DAYAL, Abuhusain HAZEM, Nirosen VIJIARATNAM, Dilan ATHAUDA, Marwan HARIZ, Tom FOLTYNIE, Patricia LIMOUSIN, Harith AKRAM (London, United Kingdom), Ludvic ZRINZO
15:20 - 15:30 #26126 - The effect of electric field weighting in improvement maps for deep brain stimulation.
The effect of electric field weighting in improvement maps for deep brain stimulation.

Background

Electric field simulation is a common method to estimate the spatial extent of deep brain stimulation (DBS) effect. Recently, several studies have been focusing on establishing probabilistic improvement maps. These are often based on a volume of activated tissue estimated by an electric field threshold. This method generates a binary volume where voxels with electric field higher than the threshold is judged as activated and those with lower values are not activated. However, since higher magnitude of the electric field will increase the probability of stimulating more neurons, the electric field strength should be taken into consideration. In this study we present the impact of using the magnitude of the electric field as a weighting function to the improvement compared to using binary volume of activation.

Materials and Methods

This study includes clinical data from 87 patients with essential tremor (ET) with DBS lead 3389/3387 (Medtronic Inc, USA) implanted in the caudal Zona incerta (Ethics, Dnr 122-31). Parts of this dataset have previously been published [1]. Each patient underwent a monopolar review where the best improvement for each contact was noted based on the essential tremor rating scale item 5/6 and 11-14. Based on the review data, electric field simulations were performed for each patient and contact using the finite element method (FEM)(COMSOL Multiphysics 5.5, COMSOL AB Sweden) [2]. The simulation results were exported to a group constructed template space based on a nonlinear normalization of the patient’s brain images, similar to what was presented by Vogel et. al [3]. After the transform, the electric field was voxelized to template space resolution (0.5x0.5x0.5 mm) and thresholded at 0.2 V/mm since lower electric field values are judged to not impact the axons. For the total dataset, a mean improvement map weighted with the magnitude of the electric field in each voxel was created. Also, voxelwise statistics were computed comparing the weighted mean improvement in each voxel with the mean improvement in the cohort by using a t-test. Voxels with a p-value < 0.05 were judged as significant. After this, the electric field data was converted to binary label maps with 1 for all voxels above 0.2 V/mm and 0 elsewhere. For these binary volumes of activation, the mean improvement map and voxelwise statistics were repeated.

Results

Comparing the mean improvement maps, they are similar and have corresponding trends of areas with higher or lower improvement. However, the generation of mean improvement maps are sensitive to low occurrence level, i.e. few volumes of activation overlapping in a voxel, which is more evident when created with a binary volume of activation. Comparing the methods shows that the estimated improvement in percentage differ by less than 10 percentage points in most voxels. When evaluating the voxels with higher deviation, it is clear that those voxels are mostly located near a DBS lead where the electric field is as highest. These voxels can deviate in estimated improvement up to 40 percentage points.

For the voxelwise statistics, the significant voxels are located in similar areas when using the electric field as weighting function as for using a binary volume of activation. However, the weighted test generates more significant voxels, which can be seen as larger clusters of significant voxels.

Conclusions

Weighting the improvement with the magnitude of the electric field gives similar results as for using binary volumes of activation. However, the weighted computation can be more sensitive to difference in the dataset especially at high electric field strengths and generate larger clusters of significant improvement.  

*Research supported by the Swedish Foundation for Strategic Research (BD15-0032) and Swedish Research Council (2016-03564)

[1] M. Åström et al., Prediction of Electrode Contacts for Clinically Effective Deep Brain Stimulation in Essential Tremor, Stereotactic and Functional Neurosurgery  (2018).

[2] M. Åström et al., Method for patient-specific finite element modeling and simulation of deep brain stimulation, Medical & Biological Engineering & Computing 47(1) (2009) 21-28.

[3] D. Vogel et al., Anatomical brain structures normalization for deep brain stimulation in movement disorders, NeuroImage: Clinical 27 (2020) 102271.


Teresa NORDIN (Linköping, Sweden), Dorian VOGEL, Erik ÖSTERLUND, Johannes JOHANSSON, Anders FYTAGORIDIS, Simone HEMM, Karin WÅRDELL
15:30 - 15:40 #26136 - Prefrontal network recruitment by STN-DBS is associated with freezing of gait after surgery in PD patients.
Prefrontal network recruitment by STN-DBS is associated with freezing of gait after surgery in PD patients.

Subthalamic deep brain stimulation (STN-DBS) is highly effective for treating dopasensitive motor symptoms of Parkinson’s disease (PD). The benefit of STN-DBS on gait disorders is variable and can result in worsened freezing of gait (FOG) in about 30% of PD patients. Factors contributing to this negative outcome are not understood. Here, we search for clinical and diffusion MRI factors that could predict this impairment. For this, we assessed the link between cortico-subthalamo-peduncolopontine tracts included in the volumes of activated tissue (VATs) by STN-DBS and the severity of gait disorders after STN-DBS at an individual level. Gait disorders were evaluated before (Off and On-dopa) and after STN-DBS using validated clinical scales (axial score, FOG-questionnaire, Gait and Balance scale) and gait recordings on a force platform in 19 PD patients (4F/15M; mean ± SD age: 59 ± 9 years; mean ± SD disease duration: 12 ± 4 years). For each patient, we localized the therapeutic DBS contacts and modeled the VAT using individual current settings [1]. 

In order to corelate cortico-subthalamo-peduncolopontine tracts included in STN-DBS VATs with the severity of gait disorders, we developed a whole brain tractography template [2] using diffusion weighted images (DWI) with 1.76 iso-voxel resolution from a cohort of preoperative PD patients (n=33) previously scanned in our center on a 3 Tesla MRI. An anatomical image template (0.9 iso-voxel resolution) was also reconstructed in the same space for the segmentation of the regions of interests. We segmented the cortex into 39 cortical Brodmann areas (BA) using MRIcro, adapting this segmentation to the cortical ribbon with Freesurfer. We visualized and segmented the pedonculopontine nucleus (PPN) using a 3D histological atlas containing a density map of cholinergic PPN neurons [3] and registered the PPN to the template space. Each individual VAT was registered to the template space as well. The cortical and PPN connectivity of each VAT was extracted from the whole brain tractography template. 

Correlations between connectivity of each VAT with the 39 Brodmann areas revealed that VAT connectivity grouped into two clusters: one prefrontal cluster (predominant connectivity with BA 8, 9, 10, 11, 32) and one sensorimotor cluster (predominant connectivity with BA 1-2-3, 4, 6) (Fig part A). We summed the connectivity for each VAT within these clusters, leaving connectivity with the PPN isolated as the only descending pathway. We then examined the correlations between the effects of STN-DBS on gait and the cortical and mesencephalic fibers contained in each individual VAT using linear regression t-test. In these 19 PD patients, we found that before surgery, gait disorders were significantly improved On-dopa (relative to Off-dopa) with a mean of 71% decrease in the axial score (range: 25-100%), and the presence of FOG Off dopa in 17 patients (mean [SD] FOG-Q: 17.5 [12.2]). With STN-DBS (Off-dopa), we observed various effects on gait ranging from a 100% improvement to a 135% worsening of the axial score, with a mean of 24% decrease in FOG severity (mean [SD] FOG-Q: 11.2 [8.4]). In this cohort, we found that FOG severity after surgery was significantly correlated with increased VAT connectivity with the right prefrontal cluster (p<0.05, Fig part B). By contrast, we observed a non-significant negative association between FOG-Q score after surgery and VAT connectivity with the sensorimotor cluster (p > 0.10, Fig part B). These data suggest that PD patients with post-operative FOG could benefit from avoiding the modulation of the prefrontal cortex-STN networks using individual DWI and directional leads, especially for the right hemisphere.

 

[1] Butson et al., Journal of Clinical Neurophysiology, 116.10, 2490-2500, 2005.

[2] Raffelt et al., Magnetic Resonance in Medicine, 67.3, 844-855, 2012.

[3] Sébille et al., Journal of Neuroscience Methods, 311, 222-234, 2019


Gizem TEMIZ (Paris), Angèle VAN HAMME, Claire OLIVIER, Antoine COLLOMB-CLERC, Sara FERNANDEZ-VIDAL, Elodie HAINQUE, Brian LAU, Carine KARACHI, Marie-Laure WELTER
15:50 - 16:00 #26298 - Could the individual cortico-subthalamic tractography improve surgical targeting in Parkinson's patients receiving deep brain stimulation?
Could the individual cortico-subthalamic tractography improve surgical targeting in Parkinson's patients receiving deep brain stimulation?

Deep brain stimulation of the subthalamic nucleus (STN-DBS) dramatically improves motor symptoms of patients with Parkinson's disease (PD). The mechanism of action of STN-DBS is not fully understood but the clinical effect is possibly due to both the inhibition of the STN cell bodies and the modulation of the cortico-subthalamic fibers that constitute the hyperdirect pathway. Axonal tracing in monkeys and recent studies using probabilistic tractography based on diffusion-weighted imaging (DWI) in humans showed that motor and premotor cortices provide the major input to the STN occupying mostly its posterolateral part. Conversely, limbic cortices projected to the antero-medial part of the STN whereas only few projections of associative cortices are found in between. Our aim was to determine whether mapping at an individual level the hyperdirect pathway could predict intraoperative outcomes in order to refine individual targeting.

Between December 2016 and January 2021, 30 patients with PD (18M/12F; mean age: 57± 11 years, disease duration: 10 years) and eligible for STN-DBS were prospectively included according to usual operability criteria and operated under sedation and local anesthesia. All patients had a severe parkinsonian motor disability with a mean of 71% improvement with levodopa (mean UPDRS part 3 scores Off/On- dopa: 48/13) and disabling levodopa-motor complications (mean UPDRS part 4 score: 10.3). Preoperative anatomical (0.9 iso-voxel resolution) and multi-shell DW (1.76 iso-voxel resolution) were acquired for each patient in a 3 Tesla MR. During surgery, motor disability was assessed using a simplified version of the MDS-UPDRS part 3 to assess rigidity, tremor and akinesia for the contralateral upper limb, including items 3.3 (rigidity), 3.4 (finger tapping), 3.5 and 3.6 (hand movements), and 3.15 (tremor) for each side during STN stimulation using 1 to 3 microelectrodes. We tested 3 different sites inside the STN to stimulate along 1, 2 or 3 different trajectories using 2 to 4 mAmp on each hemisphere, with 60 µs pulse width and 130 Hz pulse frequency. The benefit and side effects were noted for each stimulation site. We modeled the volume of activated tissue (VAT) for each stimulation site according to the amplitude and the impedance of each micro-electrode. We obtained a mean of 17 VATs (+/-5) for each patient. The intraoperative VATs were reconstructed in the pre-operative anatomical images space. On each patient MRI, we segmented the cortex into 39 Brodmann areas (BA) using MRIcro and performed a whole brain probabilistic tractography (with MRTrix) to constructed an individual whole brain tractogram. The streamlines between each BA and a total of 521 VATs were then extracted. We modeled the relationship between clinical changes ON stimulation and the connectivity of the VATs. Since multiple scores associated with different VATs were available for each patient, we used mixed-effects models to patient-level correlations. The repeated measure design also allowed us to separate between-patient effects from within-patient effects. 

We found that VAT connectivity with Brodmann areas 8 (frontal eye field), 9 (dorsal prefrontal cortex), and 32 (dorsal anterior cingulate cortex) were significantly associated with clinical changes (p < 0.05). Increased connectivity with BA9 was associated with clinical improvement, but only at the between-patient level. At the within-patient level, increased connectivity with BA8 was associated with clinical improvement, whereas increased connectivity with BA32 was associated with clinical worsening. Moreover, we found that patients for whom the cortico-subthalamic hyperdirect pathway deviates the most from the group contributed most to the within-patient results, suggesting that individual-level tractography can be effectively used to refine DBS electrode targeting of the STN for these patients.


Marie Des Neiges SANTIN (STRASBOURG), Gizem TEMIZ, Sara FERNANDEZ VIDAL, Marie-Laure WELTER, Elodie HAINQUE, Eric BARDINET, Brian LAU, Carine KARACHI
16:00 - 16:10 #26308 - Structural covariance analysis to probe alterations in cortical thickness induced by essential tremor, and their renormalisation following stereotactic radiosurgical thalamotomy.
Structural covariance analysis to probe alterations in cortical thickness induced by essential tremor, and their renormalisation following stereotactic radiosurgical thalamotomy.

Essential Tremor (ET) is the most common movement disorder in the elderly, and its neurophysiological underpinnings remain to be fully elucidated. Here, we used structural magnetic resonance imaging to extract morphometric data reflective of regional cortical thickness, in right-sided drug-resistant patients suffering from ET (NET=34) and in matched healthy controls (HCs; NHC=29). Patients were scanned both before and after left unilateral stereotactic radiosurgical thalamotomy (SRS-T) of the ventral intermediate nucleus of the thalamus (see [1] for details).

Structural images were processed with Freesurfer [2] to extract values reflective of local cortical thickness, which were then averaged into the 68 parcels of the Desikan-Killiany anatomical atlas [3]. Eventually, the obtained measures were regressed out for age, gender, and total gray matter volume. From this data, we aimed at contrasting cortical thickness between (1) ET patients before surgery and matched healthy controls (to gain insight into the morphometric changes induced by ET), and (2) ET patients before and after surgery (to address the impact of SRS-T). 

For this purpose, we resorted to the computation of structural covariance (SC), in which Pearson's correlation coefficient between regional cortical thicknesses in a given pair of brain areas is computed across subjects, in group-wise fashion [4]. Structural covariance indicates to what extent two brain areas share similar morphometric properties, is influenced by genetic, cognitive and behavioral factors, and is tied to both structural and functional brain features. Group-wise SC computation yields a group difference statistic, which can be compared to a non-parametrically generated null distribution upon random shuffling of individual subjects across groups.

We considered a total of 2'278 individual edges (i.e., pairs of brain regions), and generated 100'000 null realizations. The multiple comparison problem was accounted for by a hard-thresholding screening-filtering approach that enables to take into account the positive dependence between different edges, thus strongly controlling for type I errors [5]. As this method requires an a priori classification of connections into sub-groups, we considered a sub-group as the set of connections between two given lateralised lobes of the brain, as defined in [6].

103 connections differed significantly between ET subjects before and after surgery, linking the left temporal and right frontal, left frontal and right parietal, and right parietal and right frontal lobes. The 5 most significant connections were (using the Desikan-Killiany atlas terminology, and reporting corrected p-values): R Precentral R Postcentral (p=0), L Inferior Temporal R Pars Orbitalis (p=2.35·10-4), R Inferior Parietal L Frontal Pole (p=2.51·10-4), R Supramarginal L Frontal Pole (p=4.58·10-4), and R Frontal Pole L Middle Temporal (p=6.57·10-4).

ET patients pre-surgically and HCs showed 284 significantly different connections, between the left temporal and left frontal, left and right temporal, left temporal and right frontal, left frontal and right temporal, left and right frontal lobes, and within the left frontal lobe. The top 5 most significant connections were: R Middle Temporal L Pars Orbitalis (p=4.19·10-5), R Superior Temporal L Pars Orbitalis (p=8.1·10-5), R Pars Opercularis - L Middle Temporal (p=8.94·10-5), R Superior Temporal - L Inferior Temporal (p=1.06·10-4), and R Banks STS - L Entorhinal (p=1.43·10-4).

In sum, our results point to marked group differences in the cross-regional dependence of cortical thickness. Compared to HCs, ET induced broad differences within, and across, the bilateral temporal and frontal lobes. SRS-T partly enabled the renormalisation of such interactions, while at the same time triggering additional readjustments involving parietal brain structures. Our results thus support the effectiveness of SRS-T to alleviate ET, and open up novel perspectives to comprehend its pathophysiology and its post-surgical evolution.

 

References: 

[1] Tuleasca C.*, Bolton T.A.W.* et al (2019) Journal of neurosurgery132(6), 1792-1801.

[2] Fischl B. (2012) Neuroimage62(2), 774-781.

[3] Desikan R.S. et al. (2006) Neuroimage31(3), 968-980.

[4] Alexander-Bloch A. et al. (2013) Nature Reviews Neuroscience14(5), 322-336.

[5] Meskaldji D. E. et al. (2015) NeuroImage108, 251-264. 

[6] Klein A. and Tourville J. (2012) Frontiers in neuroscience6, 171.


Thomas BOLTON (Lausanne, Switzerland), Dimitri VAN DE VILLE, Jean RÉGIS, Tatiana WITJAS, Nadine GIRARD, Marc LEVIVIER, Constantin TULEASCA
16:10 - 16:20 #23975 - Combining 7-Tesla T2 and 3T FGATIR Sequences for STN Identification.
Combining 7-Tesla T2 and 3T FGATIR Sequences for STN Identification.

Background: In deep-brain stimulation, new 3-Tesla (3T) and 7-Tesla (7T) MRI sequences could improve the visual identification of the borders of the subthalamic nucleus (STN).

 

Objective: To study the usefulness of 7T T2 MRI and 3T FGATIR MRI in identifying the borders of the STN in patients undergoing DBS for Parkinson’s disease.

 

Methods: STN borders identified by pre-operative 7T T2 and 3T FGATIR MRI were compared with STN-borders obtained intraoperatively by micro-electrode recording. Electrode localization was done using intraoperative cone beam CT.

 

Results: Sixty-four microelectrode tracks were evaluated, all but one showing activity typical for STN. The average difference between border determination on MRI and MER was 0.4 millimeter for the dorsal border and 0.2 millimeter for the ventral border.

 

Conclusion: Combining the 7T T2 and 3T FGATIR sequences provides an accurate representation of the electrophysiological STN activity as measured by MER, thereby providing reliable anatomical identification for surgical planning.

 

 

Figure legend

Overview of the mesencephalic area showing subthalamic nucleus and substantia nigra on 7T T2 and 3T FGATIR MR and corresponding MER.

 


Niels RIJKS (Amsterdam, The Netherlands), Wouter POTTERS, José BILAI, Rob DE BIE, Wietske VAN DER ZWAAG, Rick SCHUURMAN, Pepijn VAN DEN MUNCKHOF, Maarten BOT
16:25 - 16:30 #23823 - Turn’em off – to identify stimulation-induced cerebellar syndrome in VIM/DRT-DBS for essential tremor.
Turn’em off – to identify stimulation-induced cerebellar syndrome in VIM/DRT-DBS for essential tremor.

Objective

Up to 20 % of patients with DBS of the VIM/dentato-rubro-thalamic bundle (DRT) for essential tremor develop a stimulation-induced cerebellar syndrome, which is difficult to treat and has effects on the quality of life. It emerges gradually over years and is often difficult to detect in the early time course. While the exact cause is elusive, different theories have been discussed. Among them is the (supratherapeutic) co-stimulation of further cerebellar output pathways in addition to the DRT (Gropppa et al., Brain 2014) and antidromic stimulation of the cerebellum (Reich et al., Brain 2016). A thorough diagnostic work up was performed in affected patients and multi-modal data were retrospectively analyzed to identify common symptom patterns and potential causes.

Methods

In eight patients who complained about recurrent tremor and cerebellar symptoms after VIM/DRT-DBS a cerebral [18F]FDG PET, a tremor (accelerometer & EMG) and gait (video-based markerless motion capture system) analyses were performed with activated DBS (DBSON) and 72 hours after deactivation (DBSOFF_72h); gait and tremor were also analyzed directly after deactivation (DBSOFF). Exploratory PET analyses (categorical comparisons and correlations) were done with SPM.

Results

Across all patients, we found a significantly increased metabolism of the thalamus and dentate nucleus and a decreased metabolism of the cerebellar hemispheres with DBSON (p < 0.01). Thalamic metabolism correlated positively with the metabolism of the dentate nucleus (both conditions pooled, p < 0.01). The coefficient of variation (CoV) of step length (a marker of gait ataxia) with DBSON correlated negatively with the change in metabolism of the right cerebellar hemisphere (DBSON – DBSOFF_72h; p < 0.01). The drop of frequency of postural tremor of the right hand upon deactivation of DBS (DBSOFF– DBSON) correlated with gait ataxia (CoVsteplength) with DBSON (p < 0.05).  The frequency of postural tremor on the right showed a differential course across patients.

Conclusions

We observed differential changes of neuronal activity in the dentate nucleus and cerebellar hemispheres according to stimulation state (DBSON vs. DBSOFF_72h). Increased neuronal activity of the thalamus with DBSON correlated positively with the increase of neuronal activity of the dentate nucleus, supporting the theory of antidromic stimulation, while reduced activity of the cerebellar hemispheres correlated with gait ataxia. The course of tremor frequency before and after deactivation of DBS may help to identify patients developing a stimulation induced cerebellar syndrome.


Bastian Elmar Alexander SAJONZ (Freiburg, Germany), Ganna BLAZHENETS, Marvin Lucas FROMMER, Isabelle WALZ, Johannes THUROW, Christoph MAURER, Michel RIJNTJES, Philipp Tobias MEYER, Volker Arnd COENEN
16:30 - 16:35 #23828 - Impaired movement-related beta band modulation precedes freezing episodes: hypothesis from upper limb freezing for novel STN sensing technology.
Impaired movement-related beta band modulation precedes freezing episodes: hypothesis from upper limb freezing for novel STN sensing technology.

Abstract

Objective: Freezing phenomena in Parkinson’s disease (PD) constitute an important unaddressed therapeutic need. Changes in cortical neurophysiological signatures may precede a single freezing episode and indicate the evolution of abnormal motor network processes. Here, we hypothesized that the movement-related power modulation in the beta-band observed during regular finger tapping deteriorates in the transition period between regular tapping and upper limb freezing (ULF).

Methods: We analyzed a 36-channel EEG of 13 patients with idiopathic PD during self-paced repetitive tapping of the right index finger. In offline analysis, we identified ULF episodes and compared the period immediately before ULF (‘transition’) with regular tapping regarding movement-related cortical frequency domain activity and cortico-cortical phase synchronization.

Results: From time-frequency analyses, we observed that the tap cycle related beta-band power modulation over the contralateral sensorimotor area was diminished in the transition period before ULF. Furthermore, increased beta-band power was observed in the transition period compared to regular tapping centered over the contralateral centro-parietal and ipsilateral frontal areas.

Conclusion: Here, we demonstrate that impaired beta power modulation precedes freezing in upper limb movement. From this work, we generate the hypothesis that beta band related power modulations may also precede freezing of gait episodes. We will translate this finding to freezing of gait by analyzing local field potentials (LFPs) of the subthalamic nucleus in patients with next generation impulse generators with available sensing technology (Medtronic, Percept™ PC) Deterioration of beta power modulation prior to freezing has potential to evolve as biomarker in order to treat and prevent freezing of gait episodes with adaptive stimulation.

Significance: We demonstrate that impaired beta power modulation represents the transition phase from regular tapping to freezing of upper limb movement.


Maria-Sophie BREU, Marlieke SCHOLTEN, Alireza GHARABAGHI, Daniel WEIß (Tuebingen, Germany)
16:35 - 16:40 #23903 - The Multi Recharge Trial: A multicenter, open-label, controlled trial on acceptance, convenience, and complications of rechargeable internal pulse generators for deep brain stimulation.
The Multi Recharge Trial: A multicenter, open-label, controlled trial on acceptance, convenience, and complications of rechargeable internal pulse generators for deep brain stimulation.

Objective:

Rechargeable neurostimulators for deep brain stimulation have been available since 2008, promising longer battery life and fewer replacement surgeries compared to non-rechargeable systems. Long-term data on how recharging affects movement disorder patients is sparse. This is the first multicenter, patient-focused, industry-independent study on rechargeable neurostimulators.

 

Methods:

Four neurosurgical centers sent a questionnaire to all adult movement disorder patients with a rechargeable neurostimulator implanted at the time of the trial. The primary endpoint was the convenience of the recharging process rated on an ordinal scale from very hard (1) to very easy (5). Secondary endpoints were charge burden (time spent per week on recharging), user confidence, and complication rates. Endpoints were compared for several subgroups (age, type of movement disorder, type of IPG, timepoint of rechargeable IPG implantation, person performing the  recharging, user confidence, drivers).

 

Results:

Datasets of 195 movement disorder patients (66.1% of sent questionnaires) with Parkinson’s disease (PD), tremor, or dystonia were returned and included in the analysis. Patients had a mean age of 61.3 years and the device was implanted for a mean of 40.3 months. The overall convenience of recharging was rated as easy (4). The mean charge burden was 122 min/wk and showed a positive correlation with duration of therapy; 93.8% of users felt confident recharging the device. The rate of surgical revisions was 4.1%, and the infection rate was 2.1%. Failed recharges occurred in 8.7% of patients, and 3.6% of patients experienced an interruption of therapy because of a failed recharge. Convenience ratings by PD patients were significantly worse than ratings by dystonia patients. Caregivers recharged the device for the patient in 12.3% of cases. Patients who switched from a non-rechargeable to a rechargeable neurostimulator found recharging to be significantly less convenient at a higher charge burden than did patients whose primary implant was rechargeable. Age did not have a significant impact on any endpoint.

 

Conclusion:

Patients with movement disorders rated recharging as easy, with low complication rates and acceptable charge burden.


Martin JAKOBS (Heidelberg, Germany), Ann-Kristin HELMERS, Philipp SLOTTY, Jürgen SCHLAIER, Karl KIENING, Andreas UNTERBERG
16:40 - 16:45 #23906 - Deep brain stimulation in patients with chronic antithrombotic or anticoagulation treatment: a series of 34 patients.
Deep brain stimulation in patients with chronic antithrombotic or anticoagulation treatment: a series of 34 patients.

Background:  In the aging society many patients with movement disorders, pain syndromes or psychiatric disorders who are candidates for deep brain stimulation (DBS) surgery suffer also from cardiovascular co-morbidities that require chronic antithrombotic or anticoagulation treatment. Because of a presumed increased risk of intracranial hemorrhage during or after surgery and limited knowledge about perioperative management chronic antithrombotic or anticoagulation treatment usually has been considered a contraindication for DBS.

Objective: To determine whether or not there is an increased risk for intracranial hemorrhage or for thromboembolic complications in patients under chronic antithrombotic or anticoagulation treatment (paused for surgery or bridged with subcutaneous heparin) as compared for those without.

Methods: Out of a series of 465 patients undergoing functional stereotactic neurosurgery, 34 patients were identified who were under chronic antithrombotic or anticoagulation treatment before and after receiving DBS. In patients with antiplatelet treatment medication was stopped in the perioperative period. In patients with vitamin K antagonists or NOACs, heparin was used for bridging. All patients had postoperative stereotactic CT scans, and were followed-up for 1 year after surgery.

Results: In patients with chronic antithrombotic or anticoagulation treatment intracranial hemorrhage occurred in 2/ 34 (5.9%) DBS surgeries whereas without the rate of intracranial hemorrhage was 15/ 431 (3.5%) which was statistically not significant. Implantable pulse generator pocket hematomas were seen in 2/ 34 (5.9%) surgeries in patients with chronic antithrombotic or anticoagulation treatment and in 4/ 426 (0.9%) without. There were only 2 instances of thromboembolic complications which both occurred in patients without chronic antithrombotic or anticoagulation treatment. There were no hemorrhagic complications during the follow-up for 1 year.

Conclusion: DBS surgery in patients with chronic antithrombotic or anticoagulation treatment is feasible. Appropriate patient selection and standardized perioperative management are necessary to reduce the risk of intracranial hemorrhage and thromboembolic complications. Furthermore, we could not identify an increased risk of hemorrhage in the first year of follow-up after DBS surgery.


Luisa CASSINI ASCENCAO, Joachim RUNGE (Hannover, Germany), Thomas KINFE, Christian BLAHAK, Christoph SCHRADER, Marc WOLF, Assel SARYYEVA, Joachim KRAUSS
16:45 - 16:50 #23932 - High frequency stimulation of the subthalamic nucleus restores sensorimotor and motor cortical oscillatory activity in a free-moving rat model of Parkinson's disease.
High frequency stimulation of the subthalamic nucleus restores sensorimotor and motor cortical oscillatory activity in a free-moving rat model of Parkinson's disease.

Background: Altered oscillatory activity in cortical-basal ganglia thalamic circuitries, especially enhanced activity in the beta band, have been linked to motor symptoms in Parkinson`s disease (PD). The subthalamic nucleus (STN) is targeted for deep brain stimulation (DBS) in PD and chronic stimulation has been shown to reduce beta band activity.

Objective: The effect of STN DBS on spectral power of oscillatory activity in the commonly used frequency bands in the motor cortex (MCtx) and sensorimotor cortex (SMCtx) was investigated by recording oscillatory activity via cortical electrode grids in free-moving 6-hydroxydopamine (6-OHDA) lesioned hemiparkinsonian (HP) rats and sham-lesioned controls.

Methods: Fifteen male Sprague Dawley rats (250-350g) were either rendered HP by unilateral injection of 6-OHDA (n=8), or by injection of saline (sham-lesioned; n=7) in the right medial forebrain bundle. After three weeks of surgical recovery, a DBS electrode was implanted in the STN, and an electrocortigram (ECoG) recording array was placed under the dura above the MCtx and SMCtx areas of the right hemisphere. All surgeries were performed under chloral hydrate (360 mg/kg; i.p.) anesthesia. Six days after surgery, free-moving rats were individually recorded in three conditions: (1) basal activity, (2) during STN DBS (130Hz, biphasic square pulse width of 80 µs, individual current intensity threshold (100 µA - 400 µA)), and (3) directly 300 seconds after STN DBS. Spectral power of oscillatory activity of theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz) and gamma (30-100 Hz) were analyzed in the MCtx and SMCtx areas and compared between HP and sham-lesioned rats.

Results: In HP rats, the relative power of theta band activity was lower, and beta and gamma activity were higher in MCtx and SMCtx. This was reverted towards control level by STN DBS during stimulation and in the first 300 seconds after stimulation. No differences were found between MCtx and SMCtx.

Conclusion: Our results provide evidence that loss of nigrostriatal dopamine leads to increased beta and gamma, and reduced theta oscillatory activity in motor and sensorimotor cortical areas, which is compensated by STN stimulation both during and directly after stimulation.


Arif ABDULBAKI, Theodor DOLL, Joachim K. KRAUSS, Kerstin SCHWABE (Hannover, Germany), Mesbah ALAM
16:50 - 16:55 #23948 - Adoption of focused ultrasound thalamotomy for essential tremor: why so much fuss about FUS?
Adoption of focused ultrasound thalamotomy for essential tremor: why so much fuss about FUS?

Background

Focused ultrasound (FUS) was approved as a new treatment modality for Essential Tremor (ET) in 2016. The goal of this study was to quantify FUS adoption for ET and understand its drivers.

 

Methods

The adoption of the various surgical options for ET was estimated using 3 measures: the number of presentations on the various surgical treatments for ET at specialized international meetings, the number of original papers published as identified by literature searches and the number of thalamotomy procedures performed worldwide for ET as provided by device manufacturers’ registries.   

 

Results

First, we found that the number of presentations related to lesioning procedures are increasing relative to DBS at international meetings. Second, there are already more publications on FUS (93) than SRS (68) or radiofrequency (43) for ET, although they still lag behind DBS papers (750). Third, the number of annual FUS thalamotomies performed for ET (n > 1200 in 2019) in 44 centers, has surpassed the annual procedures across 342 GK units (n < 400, 2018) but is yet to reach the number of DBS cases for ET estimated at over 2400 per year. FUS adoption over GK cannot be explained by efficacy, safety, patient experience or cost factors. We hypothesize that the ability to perform intraoperative clinical assessments, the manufacturers’ interest in functional neurosurgery and functional neurosurgery’s key opinion leaders’ involvement in the technology are currently the real drivers of FUS uptake. 

 

Conclusion

FUS is being rapidly adopted for the treatment of ET.  We hypothesize that its minimally invasive nature coupled with the ability to perform intraoperative clinical assessments, its immediate effects and active marketing efforts are contributing factors. As lesioning modalities for the treatment of ET are reappraised, the superior popularity of FUS over SRS appears to arise for reasons other than differences in clinical outcomes.


Christian IORIO-MORIN (Sherbrooke, Canada, Canada), Mojgan HODAIE, Andres LOZANO
16:55 - 17:00 #23679 - Tremor and quality of life in patients with advanced essential tremor before and after replacing their standard deep brain stimulation with a directional system.
Tremor and quality of life in patients with advanced essential tremor before and after replacing their standard deep brain stimulation with a directional system.

Introduction:

Patients with essential tremor (ET) treated with thalamic deep brain stimulation (DBS) may experience increased tremor with the progression of their disease. Initially, this can be counteracted with increased stimulation. Eventually, however, this increased stimulation may cause unwanted side-effects as the circumferential effects of stimulation from a standard ring contact spreads into adjacent regions. Directional DBS leads may offer a solution to this clinical problem.

Objective:

We compared the ability of a standard and a directional DBS system to reduce tremor without side-effects and to improve the quality of life for patients with advanced ET.

Methods:

Six advanced ET patients with bilateral thalamic DBS had their standard DBS system replaced with a directional DBS system. Tremor rating scale scores were prospectively evaluated before and after the replacement surgery. Secondary analyses of quality of life related to tremor, voice, and general health were assessed.

Results:

There was a significantly greater reduction in tremor without side-effects (p=0.017) when using the directional DBS system compared to the standard system. There were improvements in tremor (p=0.031) and voice (p=0.037) related quality of life but not in general health for patients using optimized stimulation settings with the directional DBS system compared to the standard system.

Conclusions:

In this cohort of advanced essential tremor patients who no longer had ideal tremor reduction with a standard DBS system, replacing their DBS with a directional system significantly improved their tremor and quality of life. Up-front implantation of directional DBS leads may provide better tremor control in those patients who progress at a later time point.


 


Marie T. KRÜGER (London, United Kingdom), Josue M. AVECILLAS-CHASIN, Mini K. SANDHU, Nancy E. POLYHRONOPOULOS, Natasha SARAI, Christopher R. HONEY
Auditorium

"Friday 10 September"

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B35
15:00 - 17:00

Parallel Session 12
Young Functional NS Session

Moderators: Attilio DELLA TORRE (Neurosurgeon) (CATANZARO, Italy), Emmanuel DE SCHLICHTING (PHC) (Grenoble, France)
15:00 - 15:10 #23792 - Development of Diffusion Tensor Imaging and Tractography for Spinal Cord.
Development of Diffusion Tensor Imaging and Tractography for Spinal Cord.

Introduction: In vivo spinal cord fiber tracts have never been described precisely in humans. Current knowledge corresponds to the results of animal dissections, cyto-histological findings and electrophysiological approaches. Advances in brain MRI have recently made it possible, via Diffusion Tensor Imaging (DTI), to highlight the tracts of the brain's white matter. To date, no study has been able to differentiate clearly spinal cord tracts using tractography.

 

Methods: 1) Using the MEDLINE database, a systematic review was carried out to try to define the optimal DTI parameters used until now for spinal cord tractography studies. 2) From MRI of the EMISEP (healthy subject cohort database), starting with the parameters previously defined, evaluate the effect of patient geometry (sagittal balance) and acquisition geometry on the quality of the tractography rendering, before and after distortion correction (with DSIStudio software). 3) From previous data, develop an original DTI protocol to distinguish different spinal tracts.

 

Results :

1)      Best DTI parameters coming from literature have been defined.

2)      Distortion corrections had a direct impact on the tractography according to the patient's sagittal balance. Moreover, the geometry of the acquisition had a direct impact on the quality of the tractography rendering, since adaptations had to be performed at each vertebral level.

3)      Performing a stitching process between encephalic and spinal cord DTI data, and a meticulous placement of region of interest are both keys to distinguish different fiber tracts inside the spinal cord. By performing these post-processing distorsions, the corticospinal tract, can be distinguish from the spinal cord disease (tumor for example) and allows new advances neuro-anatomy, and spinal cord neurosurgery.

 

Conclusion: The differentiation of spinal tracts with tractography seems to be possible. This imaging would be useful to improve human neuroanatomical and physiological knowledges. When will become usable in routine, spinal DTI will allow to analyze the consequences of intraspinal deseases on fiber tracts and could help the neurosurgeon to define their surgical approaches to intraspinal lesions.


Corentin DAULEAC (LYON), Patrick MERTENS, Carole FRINDEL, Francois COTTON
15:10 - 15:20 #23905 - SPECTRE - A dMRI visualization technique for the display of cerebral connectivity.
SPECTRE - A dMRI visualization technique for the display of cerebral connectivity.

Objective: The analysis and visualization of brain's white matter structures by diffusion magnetic resonance imaging (dMRI) is becoming an important prerequisite during planning of neurosurgical interventions (1). In this work, we propose a rather simple approach to visualize structural connectivity information in certain target regions (Spectre - Subject sPEcific brain Connectivity display in Target REgion). Our idea is closely related to track-weighted imaging (2), where dMRI streamlines are used to aggregate distal information, however we use normative geometric information as the underlying contrast for aggregation. For example, if we want to know whether a voxel in the brain is rather connected to the frontal or to the posterior region, we could just compute the mean of the y-coordinate (in MNI space) along each fiber emitted in this voxel. To realize this concept in a way, which is more suitable for visualization, we assigned cortical regions certain colors in a continuous fashion.

Methods: The concept is demonstrated on a group of subjects from the human connectome project (HCP). The used coloring scheme and target area is shown in Figure A. The rationale of the coloring scheme was developed in appreciation of deep brain stimulation (DBS) planning especially for the subthalamic nucleus (STN). STN anatomy typically is interpreted as follows: Medial and anterior parts of the nucleus are regarded as “limbic” and connect to prefrontal and frontopolar parts of the cortex. Adjacent and more posterior regions are the prefrontal association regions followed on the  posterior and lateral by motor parts (3). With this idea in mind the STN was color-coded in a ‘fronto-polar to motor’ gradient (green to blue) by its mere connectivity pattern.  For warping the coloring scheme to native space of the subject, SPM’s CAT12 is applied on the provided T1 images and the corresponding warping fields are used for warping.  For tract/fiber orientation distributions (FODs) were determined by (4). Then, ordinary probabilistic streamline tractography similar to FSL’s probtrax is used to generate the SPECTRE contrast. Seeds were placed in the area to be colored (here the midbrain) and during propagation of the streamlines the underlying coloring is accumulated. In every voxel (we use a supersolution of 0.5mm isotropic), 500 streamline were seeded to get a robust color value in each voxel.  We applied this procedure on 200 HCP subjects, normalized to group space (MNI) and averaged the SPECTRE maps. 

Results: In Figure B a transversal slice for an example subject together with outlines of deep nuclei is given, while in Figure C several transversal slices of the group average in MNI space are displayed. SPECTRE shows how the fronto-parietal-occipital cortical gradient experiences a twist by 90° while proceeding ventrally towards the midbrain, where the gradient becomes mostly medial-lateral with an interruption at the interface between RN and SNR. The interpretation of the fronto-parietal gradient as limbic-associative-sensori/motor is quite intuitive, in particular when focusing on the STN. In the tripartite descriptions (5) medial/anterior and inferior parts are regarded as limbic and connect prefrontally, especially to frontopolar and orbitofrontal regions. More posterior regions are the prefrontal association regions of the dorsolateral and prefrontal cortex followed laterally by motor parts (3). This agrees mostly with the segmentation used by Ewert et al (6). In Figure D Ewert’s STN subsegmentation is shown, in E the STN overlaid by the group SPECTRE maps. 

Discussion: With the aim of giving neuroscientists a comprehensive view of structural connectivity patterns we have proposed a novel imaging principle, which joins individual tractographic information with normative anatomical information.  SPECTRE allows us to appreciate the fronto-occipital connectivity gradient on the individual level and thereby helps to understand the amount of frontopolar contribution of connectivity to the STN and the region just adjacent to it. Preliminary experiments (not shown) suggest that robust and repeatable SPECTRE maps can be computed, even on clinically feasible dMRI data.

References: (1) Essayed et al. NeuroImage Clin. 2017;15:659–672.  (2) Calamante et al. Neuroimage. 2010;53(4):1233–1243. (3) Haynes et al. J Neurosci. 2013;33(11):4804–4814. (4) Alkemade et al. Brain Struct Funct. 2015;220(6):3075–3086. (5) Ewert et al. Neuroimage. 2018;170:271–282.


Marco REISERT, Christoph KALLER, Horst URBACH, Bastian SAJONZ (Freiburg, Germany), Marvin REUTER, Peter C. REINACHER, Volker Arnd COENEN
15:20 - 15:30 #23994 - Accuracy, precision and safety of stereotactic, frame-based, intraoperative MRI-guided and MRI-verified deep brain stimulation in 650 consecutive procedures.
Accuracy, precision and safety of stereotactic, frame-based, intraoperative MRI-guided and MRI-verified deep brain stimulation in 650 consecutive procedures.

ABSTRACT

Introduction and Aims

Ensuring a safe and accurate approach is fundamental in stereotactic functional neurosurgery. Reliance on anatomical targeting and dispensing with awake surgery is growing in popularity but can be vulnerable to suboptimal targeting. Despite the use of traditional techniques such as microelectrode recording (MER), suboptimal lead placement is currently one of the commonest indications for revision DBS procedures. This can be avoided by confirming lead placement in relation to the visible anatomical target with dedicated imaging during the procedure. Here, the accuracy, precision and safety of using intraoperative-MRI (iMRI) to both guide and verify lead placement during frame-based stereotactic surgery is examined.

Materials and methods

A 1.5 T MRI machine was installed in our surgical theatre in August 2011. Retrospective analysis of 1201 DBS leads implanted in 650 consecutive procedures over an 8-year period (Aug 2011 to Aug 2019) was performed for targeting accuracy, precision and perioperative complications. All patients underwent frame-based lead placement adjacent to the MRI machine with image verification before removing the stereotactic frame, allowing immediate lead re-implantation when necessary and systematic analysis of the targeting error. Fisher Exact test was used for statistical significance when relevant (p value set at 0.01)

Results

Verification with stereotactic MRI was performed in 643 procedures and with stereotactic CT in 7.  The mean final targeting error was 0.85 mm, +/- 0.29 mm SD (range 0.05-2.29). Accuracy was submillimetre in 68 %, within the diameter of the implanted lead (1.27mm) in 80 % and within 1.5 mm in 92 % of analysed leads. Anatomically acceptable lead placement was achieved with a single brain-pass in 97% (n = 1164) of leads; immediate intraoperative relocation was performed in 37 of 1201 leads (3 %) to obtain satisfactory anatomical placement. General Anaesthesia was used in 91% (n=593) of procedures.

Four patients suffered a haemorrhage (0.6%), three presenting with transient neurological symptoms (0.4%), one associated with delayed cognitive decline [Figure]. We do not think that any of the haemorrhages led directly to long term deficits. Two of the bleeds coincided with immediate retargeting (2 of 37 leads, 5.4%). This contrasts with haemorrhage in 2 of 1164 leads implanted on first-pass. (0.17%) (p-value 0.0053)

Transient behavioural changes were noted in 27 patients (4.2%), while 2 suffered from moderate cognitive decline following surgery despite no radiological evidence of haemorrhage. Three patients had transient seizures in the postoperative period, two of which coincided with haemorrhage and one with immediate lead retargeting.

There were 21 infections leading to hardware removal (3.2% of patients), seven of which commenced cranially. Fourteen patients presenting with infection around the neurostimulator were initially treated by removal of the neurostimulator and cables plus appropriate antibiotic therapy; however, 12 of these ultimately progressed to total removal of hardware.

Delayed (>3 months) retargeting of 6 leads (0.5% of 1201) in four patients (0.6%) was performed following suboptimal stimulation benefit. Delayed distal maintenance procedures were performed in 20 patients (3.1%) due to hardware failure (n=10), discomfort or erosion (n=10). There were no MRI related hardware issues, no motor deficits and mortality was zero.

Conclusion

To our knowledge, this is the largest series reporting on the use of iMRI as a tool to both guide and verify lead location during DBS surgery. It demonstrates a high level of accuracy, precision and safety across targets, patients and surgeons. Although numbers are small, a significantly higher rate of haemorrhage was encountered when multiple brain passes were required for lead implantation. Thankfully, all of the haemorrhages were small and did not lead to permanent deficit. Nevertheless, this emphasises the importance of meticulous accuracy, perpetual audit and calibration to improve precision and maximise the safety of stereotactic functional neurosurgery.


Ali RAJABIAN (London Queen Square, United Kingdom), Saman VINKE, Joseph CANDELARIO, Catherine MILABO, Maricel SALAZAR, Karim NIZAM, Nadia SALLOUM, Jonathan HYAM, Harith AKRAM, Eileen JOYCE, Thomas FOLTYNIE, Patricia LIMOUSIN, Marwan HARIZ, Ludvic ZRINZO
15:35 - 15:40 #23902 - Portable magnetic resonance imaging for intensive care unit patients.
Portable magnetic resonance imaging for intensive care unit patients.

Introduction

Patients in an intensive care unit (ICU) often require neuroimaging to rule out a wide variety of intracranial problems. Computed tomography (CT) may be available in the ICU itself, but magnetic resonance imaging (MRI) has greater sensitivity for many conditions that affect the brain. However, transporting patients who are on ventilators and other life-sustaining devices is a labor intensive process and involves placing the patient at risk for adverse events. This is the first report of portable MRI in a clinical setting. 

Methods  

This is a prospective, non-randomized, observational study at one institution utilizing portable MRI in patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients selected for imaging had any of the following: 1) unexplained encephalopathy or coma, 2) seizures, 3) focal neurologic deficit, 4) abnormal head CT. Imaging was performed in each patient’s ICU room with a portable, self-shielding, 0.064 Tesla (T) MRI.  

Results  

Among 19 patients, a total of 20 MRI scans in seven ICUs were acquired between April 20 and May 1, 2020. No adverse events to patients or staff from MRI acquisition were reported. In 12 patients, abnormal findings were seen, which included increased fluid attenuated inversion recovery (FLAIR) signal (n=12), hemorrhage (n=3), and diffusion-weighted imaging (DWI) positivity (n=3). Imaging led to a change in clinical management in 5 patients. 

Conclusion

Portable MRI is safe, feasible, and leads to changes in clinical management. This technique can be applied to any ICU patient whose care requires imaging of the brain. This novel technology offers a path towards new modalities for bedside stereotaxis and intraoperative imaging.


Justin TURPIN (New York City, USA), Prashin UNADKAT, Justin THOMAS, Nick KLEINER, Shahab KHAZANEHDARI, Sheshali WANCHOO, Kenia SAMUEL, Moclair BETSY, Karen BLACK, Amir DEHDASHTI, Raj NARAYAN, Richard TEMES, Michael SCHULDER
15:40 - 15:45 #23935 - Perfusion MRI findings in motor cortex and basal ganlions in Parkinson's disease patients resistant to medical treatment: single centre experiment.
Perfusion MRI findings in motor cortex and basal ganlions in Parkinson's disease patients resistant to medical treatment: single centre experiment.

Background: Parkinson's disease (PD), is a neurodegenerative disease characterized by, the loss of dopaminergic neurons in substantia nigra.

Objective: To contribute to the pathogenesis of the disease by comparing Diffusion tensor (DTI) and contrast perfusion MRI (PWI) findings in medical treatment resistant PD cases.

Material and Methods: 19 control and 18 medical treatment-resistant PD cases, who are candidates for deep brain stimulation, were included in our study. DTI and PWI examination were performed on all cases. Cerebral blood flow (rCBF), mean transit time (MTT) and fractional anisotropy (FA) values were measured in both hemispheres; on primary motor cortex (M1), supplementary motor cortex (SMA), putamen (P), external and internal globus pallidus (GPe / GPi), ventrolateral nucleus (T) of the thalamus, substantia nigra(SN).

Results: The average age of our control group cases was 59.2 ± 13.2 (31-79) and the median was 60 years. The average age of PD patient group was 56.7 ± 16 (42-77) and the median was 60.5 years. The duration of the disease was 12.4 ± 7.1 (5-30) years on average. In PD group, FA values were significantly lower (p ˂ 0.05) than the control group, in all regions. In the case group, rCBF-SMA values on both sides were significantly higher than the control group (p˂ 0.05). In the case group, MTT-GPi value on the left and MTT-M1, MTT-SMA, MTT-GPe and MTT-T values on both sides were significantly higher than the control group (p ˂ 0.05).

Conclusion: It is thought that decrease in FA compared to the control group in all regions except the motor cortex may be secondary to cell loss. In PWI, on the other hand, in medical treatment resistant PD cases, rCBF, increases in the supplementary motor and motor cortex. MTT, moreover, is prolonged in all regions, evident in left GPi. Perfusion differences may be due to increased blood brain barrier permeability, endothelial degeneration, and abnormal angiogenesis, and may contribute to dopa-resistant symptoms in PD cases. More research is needed to improve measurement techniques and standardize research protocols, not only to improve diagnostic accuracy, but also to monitor treatment effectiveness in clinical trials.


Halime CENKERI, Atilla YILMAZ (Istanbul, Turkey), Sadik Ahmet UYANIK, Eray ATLI, Umut OGUSLU, Birnur YILMAZ, Burçak GÜMÜŞ
15:45 - 15:50 #25834 - Feasibility of burr hole ultrasound to improve deep brain structure visualization for neuromodulation.
Feasibility of burr hole ultrasound to improve deep brain structure visualization for neuromodulation.

Introduction

Deep brain stimulation (DBS) relies on precise electrode targeting and stimulation of small, deep structures within the brain to effectively treat various movement disorders. Target accuracy is contingent upon an assumed rigid alignment between the preoperative imaging data and intraoperative patient anatomy. However, this assumption can be compromised by intraoperative brain shift. Although gold-standard microelectrode recording (MER) effectively accounts for brain shift, it requires patients to remain unmedicated and awake in addition to potentially introducing intracranial bleeding due to multiple lead passes. Intraoperative magnetic resonance (MR) imaging is an effective alternative, but the associated image distortion from the implant as well as encumbrance and cost hinder widespread adoption. Considering that shift only occurs in approximately 10-20% of implants, we propose the use of low-cost burr hole ultrasound (US) during DBS to better visualize brain subsurface structures, and to potentially account for deleterious instances of brain shift during surgery. In this work, we aim to demonstrate initial feasibility of using burr hole US registered to preop MR as an additional intraoperative guidance tool for DBS.

 

Methods

A BK5000 ultrasound system and N11C5 burr hole transducer were used to acquire coronal and sagittal ultrasound images during N=6 DBS procedures. Ultrasound images were acquired prior to the placing of the stereotactic frame and implanting of electrodes for each case. The probe was sterilized prior to the start of each procedure. Corresponding MR slice views were selected using CRAVE-registered pre-op MR and post-op CT scans with lead placement confirmation. Regions of interest (ROIs) corresponding to the ventricles were manually generated on the US and MR slices using MATLAB. An iterative closest point (ICP) algorithm was used to map the US ROI to the MR ROI, and the corresponding transformation matrix was used to register the US image to the MR image. The percent of overlap between the US and MR ROIs was computed for each case and slice view. Additionally, a root mean square error (RMSE) was computed on the areas of the ROIs for each slice view.

 

Results

The coronal and sagittal US ventricle ROIs resulted in 89.3% and 83.0% overlap, respectively, with the MR ventricle ROIs. The RMSE between the US and MR areas of the coronal and sagittal ROIs were 0.42cm2 and 1.77cm2, respectively. Fig. 1 shows example coronal US and MR ventricle ROIs before and after ICP registration.

 

Conclusion

The results in this work demonstrate that burr hole US can be used intraoperatively to better visualize deep brain structures that align well with preoperative imaging data. Although intraoperative US by itself can be difficult to interpret, we have demonstrated in this work that it has the potential to be an invaluable real-time guidance tool when registered to preoperative MR. Moreover, we hypothesize that, once optical tracking is incorporated, burr hole US can be used to drive biomechanical models of brain shift that normally rely on sparse intraoperative surface data, which is otherwise difficult to obtain within a small burr hole.


Jaime TIERNEY (Nashville, USA), Hamid SHAH, Michael MIGA
15:50 - 15:55 #25963 - Evaluating functional connectivity differences between DBS ON/OFF states in essential tremor patients.
Evaluating functional connectivity differences between DBS ON/OFF states in essential tremor patients.

Introduction: Essential tremor (ET) is a debilitating disease affecting millions. DBS targeting the ventral intermediate (Vim) nucleus of the thalamus has been an effective treatment modality for years. Yet, it is unclear which functional connections in the brain are most modulated by DBS to effect tremor control, and in fact, are most influential in tremor production.

 

Objective: We studied ET patients undergoing DBS of a major input/output tract of the Vim, the dentato-rubro-thalamic tract (DRTt), using resting state functional MRI (rsfMRI). By collecting rsfMRI scans with DBS ON at parameters for optimal tremor control, and then again with DBS OFF, our goal was to evaluate functional connectivity differences between the two states in the hopes of elucidating which regions connected to the motor cortex might be most involved in tremor regulation.

 

Methods: We enrolled five ET patients who had previously undergone DBS of the DRTt. Tremor severity using The Essential Tremor Rating and Assessment Scale (TETRAS) was scored with DBS ON at optimal stimulation parameters and with DBS OFF. Anatomical (gradient echo FFE 3D T1 sequence sagittal acquisition; voxel size = 1.2x0.94x0.94 mm3; TR 8.5 ms; TE 4.0 ms; Flip Angle 8) and functional (fMRI BOLD EPI sequence axial acquisition; voxel size 2x2x2 mm3; TR 3113 ms; TE 30 ms; 450 dynamics) 1.5T MRIs were acquired and replicated for the two DBS states; (scan time 24 minutes for each DBS state). Anatomical 3D T1 segmentation was performed using Freesurfer. Regions of interest (ROI) were pre-defined as the bilateral pre-central gyrus, superior and inferior parietal lobules (SPL/IPL), dentate nucleus (DN), and cerebellar nodule. fMRI data was preprocessed (slice timing, motion correction, despiking, linear detrending, nuisance regression, bandpass filtering (0.01-0.08 Hz) and smoothing were all performed). After the T1 data was registered with the fMRI data using FSL, these ROIs were transformed to fMRI space. All patients had their electrode-extension connections placed on the left parietal location; the EPI distortion and susceptibility artifact from these implants resulted in signal loss, to which a mask was applied to exclude from analysis. Timeseries for each ROI was extracted from the fMRI data; the Pearson correlation coefficient for each timeseries pair was calculated. A connectivity matrix was generated with threshold criteria to include only p-value < 0.05 and R-value > 0.40 for each DBS state. Comparison of DBS ON/OFF was then performed for each patient and a connectivity rank difference matrix was calculated with the following values for each cell: 1 = ON>OFF, 0 = ON=OFF, -1 = ON<OFF. Group analysis was performed by adding up the connectivity rank matrix per cell for all 5 patients.

 

Results: Of the five patients, 2 were male and 3 female; all were RH. Mean age was 74 years and disease duration was 28 years. Mean bilateral appendicular TETRAS with DBS ON was 1.3; DBS OFF was 6.5. Difference in tremor severity with DBS ON/OFF was highly significant (TETRAS p<0.001). The regions where most decreases in connectivity were seen between DBS OFF and ON  were the left and right IPL, right pre-central gyrus and right SPL, right pre-central gyrus and left SPL, and left and right SPL. Left and right SPL had the greatest connectivity differences relative to other regions, namely the left and right pre-central gyri, with decreased connectivity in the DBS ON state vs. DBS OFF. Group analysis revealed that overall, all ROIs except the left precentral gyrus had less connectivity with other ROIs when DBS was ON relative to OFF.  The cerebellar nodule had no significant connectivity. Please review Figure 1.

 

Conclusion: Stimulation of the DRTt and concordant improvement of tremor resulted in connectivity decreases seen in multiple regions thought to be involved with tremor pathology. The SPL and IPL were the ROIs displaying the greatest connectivity changes between DBS states. Parallel structural and electrophysiological connectivity analyses performed confirm that the SPL and IPL are critical regions that are involved in tremor modulation. Further work to characterize the correlation of clinical response to stimulation evoked functional changes could improve DBS for tremor. 


Albert FENOY (Houston, USA), Christopher CONNER, Z. David CHU, Stephen KRALIK
15:55 - 16:00 #26090 - The FGATIR sequence in DBS: Introducing the rubral wing for DRT depiction and tremor control.
The FGATIR sequence in DBS: Introducing the rubral wing for DRT depiction and tremor control.

Background: The dentato-rubro-thalamic tract (DRT) is currently considered as a potential target in Deep Brain Stimulation (DBS) for various types of tremor. However, tractography depiction can vary depending on the included brain regions. The Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) sequence, with excellent delineation of grey and white matter, possibly provides anatomical identification of rubro-thalamic DRT fibers.

Objective: Evaluating the FGATIR sequence by comparison to DRT depiction, electrode localisation and effectiveness of DBS therapy. 

Methods: In patients with DBS therapy due to medication-refractory tremor, the FGATIR sequence was evaluated for depiction of thalamus, red nucleus (RN) and rubro-thalamic connections. Deterministic tractography of the DRT, electrode localisation and tremor control were compared. The Fahn-Tolosa-Marin Clinical Rating Scale for Tremor was used to assess (hand) tremor. Tremor control was considered successful when complete tremor suppression (grade 0) or almost complete suppression (grade 1) was observed. Stimulation-induced side effects, including dysarthria and gait ataxia, were categorized into moderate or severe.

Results: We retrospectively evaluated 14 patients; 12 essential tremor (ET), 1 tremor-dominant Parkinson's disease (PD), 1 multiple sclerosis (MS); representing 24 trajectories. Mean follow-up was 11.3 months (range 6-19 months). Two patients (PD and ET) were operated under general anesthesia. In all twelve awake electrode placements, a single trajectory was needed for complete intraoperative tremor control. The FGATIR sequence provided a clear delineation of the hyperintense thalamus in the hypointense surrounding internal capsule. A hypointense white matter tract within the thalamus, generally visible from the level of the posterior commissure, was distinguishable in both axial and coronal projections. In coronal plane this tract was most readily recognizable as a 'rubral wing', with the round RN as base and lateral triangular convergence. The deterministic DRT depiction was consistently situated within the rubral wing as visualized by the FGATIR sequence. The number of active contacts located within the DRT (and rubral wing) was 22 (92%), of which 16 (73%) showed successful tremor control. The two active contact points outside the DRT depiction were closely located at 0.5 (within rubral wing) and 2.0 (outside rubral wing) millimeters, and both showed good tremor control. The 6 active contact points located within the DRT with suboptimal tremor response represent 4 patients (1 MS, and 3 ET). Three patients (21%) experienced gait disturbances. Two patients (14%) experienced stimulation-induced dysarthria. 

Conclusion: The FGATIR sequence offers visualisation of rubro-thalamic connections which form the DRT, most readily recognizable as a 'rubral wing' in coronal plane. This sequence contributes to tractographic depiction of DRT and provides a direct anatomical DBS target area for tremor control. 


Maarten BOT, Rik PAUWELS (Amsterdam, The Netherlands), Pepijn VAN DEN MUNCKHOF, Maartje DE WIN, Vincent ODEKERKEN, Martijn BEUDEL, Joke DIJK, Rob DE BIE, Richard SCHUURMAN
16:00 - 16:05 #26149 - Distinguishing the motor subthalamic nucleus: a comparison between 7 Tesla MRI and intraoperative microelectrode recordings.
Distinguishing the motor subthalamic nucleus: a comparison between 7 Tesla MRI and intraoperative microelectrode recordings.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective surgical treatment for patients with advanced Parkinson’s disease (PD). Combining 7.0-Tesla (7T) T2 and diffusion weighted (DWI) MRI sequences allows for segmenting the motor part of the STN. It is unclear whether STN microelectrode recordings (MER) differ in signal power depending on the location relative to the segmented motor part.

 

Methods: 7T T2 and DWI MRI sequences were obtained and probabilistic segmentation of motor STN subdivisions was performed in the postoperative phase in a total of 50 STNs in 25 PD patients, using FSL. A voxel connectivity threshold of 20% was applied, enabling visualising an area within 7T T2 STN representation with the highest density of connections to the motor cortices (motor and supplementary motor area). Intraoperative CT was used for DBS electrode localization and the coordinates of the center of the active electrode contact used for stimulation were determined. The active electrode contacts and corresponding MER were evaluated for being located inside (motor STN group) or outside (STN group) the segmented part with the highest density of motor connections. Subsequently, mean power and mean sigma (standard deviation) of the MER were compared between the two groups.

 

Results: There were no significant differences between motor STN and STN MER for mean signal power (p = 0.72) and mean signal variation (p = 0.72).

 

Conclusions: No differences between MER signal power inside or outside the segmented part with the highest density of motor connections were found. The MER signal power could not be used for distinguishing the motor part of the STN.


Naomi KREMER (Amsterdam, The Netherlands), Wouter POTTERS, José DILAI, Varvara MATHIOPOULOU, Rob DE BIE, Pepijn VAN DEN MUNCKHOF, Richard SCHUURMAN, Maarten BOT
16:05 - 16:10 #26180 - Additional imaging to guide surgical implantation of an electrode to relieve poststroke action tremor.
Additional imaging to guide surgical implantation of an electrode to relieve poststroke action tremor.

Introduction: We report the case of a now 49-year old woman who had an ischemic stroke in 2000. This caused right-sided low-frequency action tremor in the proximal upper limb, rigidity in the right shoulder and slight paresthesia and dysesthesia in the right hand. Cerebral imaging showed a thalamic cavity with a volume of approximately 154mm³.  Medication (Propranolol, Primidone, Gabapentin) did not alleviate the symptoms. Therefore, she requested deep brain stimulation (DBS).

Methods: To implant the DBS lead at an optimal target, an fMRI was performed comparing the resting state (upper arm supported; In this position there was no tremor) to a tremorous state, where the patient was asked to hold the right arm in a wing-beating position. Secondly, a fluorodeoxyglucose (F18) position emission tomography (FDG-PET) was acquired to investigate the metabolic state of the thalamic cavity. To evaluate the clinical effectiveness of DBS on the tremor, A Fahn-Tolosa-Marin (FTM) tremor rating scale (part A and B of the right upper extremity) was performed prior to surgery as a baseline, as well as one month after surgery with DBS off and on. Next, a randomized, double-blinded monopolar review was performed, where the therapeutic window (TW) of every individual DBS-contact was defined, as well as from the two directional levels as omnidirectional contact. Bottom of TW was defined as the lowest amplitude at which tremor arrest occurred in the right arm when performing a finger-to-nose test. Top of TW was defined as the lowest amplitude where non-transient stimulation-induced side effects appeared. To investigate a possible relationship between the distance from each DBS-contact to the fMRI activity to the TW, we first calculated the Euclidian distances between the center of each DBS-contact and the elevated fMRI signal. Thereafter, we correlated these distances to the TW calculated from each DBS-contact.

Results: Imaging (Fig. 1A) showed the cavity just anterior to the indirectly targeted ventral intermediate nucleus of the thalamus (VIM; targeted at 75% to posterior of the AC-PC line, at 14.26mm to lateral left, at the height of the AC-PC line), an increased fMRI signal during tremor anterior to the cavity and intersecting the dentatorubrothalamic (DRT) tract. Furthermore, the DRT on the affected side showed a decreased fiber density. Lastly, FDG-PET showed decreased tracer uptake at the left thalamus. Taken all of the above together, surgical planning proceeded with the hypothesis that the areas with increased fMRI signal on fMRI are expected to be most effective in reducing the tremor when electrically stimulated. For surgery, a directional lead was chosen. Fusion of the preoperative MRI scan to the postoperative CT scan showed that the lead was positioned immediately anterior to the cavity, where the most dorsal DBS-contacts were closest to the elevated fMRI signal and the largest part of the DBS lead intersected the DRT tract. When comparing the clinical measures, the FTM tremor rating scale indicated an 84.6% decrease in tremor before versus after surgery with DBS-on.

Conclusion: We report the case of a 49-year old woman in whom DBS was implanted due to a post-stroke low-frequency action tremor in her upper right arm. A single directional lead was implanted based on information gathered via diffusion MRI, fMRI and FDG-PET immediately anterior from the cavity, thereby intersecting the elevated BOLD signal and the DRT tract. After surgery, the tremor had disappeared, with only a minor tremorous trend when drawing a spiral. We propose that, in rare cases such as the one described here, additional imaging may provide the necessary information to guide the surgery, which could optimize the patients’ chances for a successful implantation.


Jana PEETERS (Leuven, Belgium), Evanthia THEODORU, Alexandra BOOGERS, Myles MC LAUGHLIN, Koen VAN LAERE, Stefan SUNAERT, Bart NUTTIN
16:10 - 16:15 #26273 - Using functional Ultrasound (fUS) for real-time functional and vascular delineation of brain structures with micrometer-millisecond precision: Towards a new, fully integrated, depth-resolved image-guided neurosurgical tool with multimodal potential.
Using functional Ultrasound (fUS) for real-time functional and vascular delineation of brain structures with micrometer-millisecond precision: Towards a new, fully integrated, depth-resolved image-guided neurosurgical tool with multimodal potential.

Background

Neurosurgical practice still relies heavily on pre-operatively acquired images to guide intra-operative decision-making during procedures such as tumor resection and DBS electrode placement. This practice comes with inherent pitfalls such as registration inaccuracy due to brain shift, and lack of real-time functional or morphological feedback. Exploiting the opportunity for real-time imaging of the exposed brain can improve intra-operative decision-making, neurosurgical safety and patient outcomes. Previously, we described functional Ultrasound (fUS) as a high-resolution, depth-resolved imaging technique able to detect functional regions and vascular morphology during awake tumor resections [1]. Here, we describe our recent progress towards fUS as a fully integrated, MRI/CT-registered imaging modality in the Operating Room (OR) (Figure 1A).

 

Materials and Methods

fUS relies on high-frame-rate (HFR) ultrasound, making the technique sensitive to very small motions caused by vascular dynamics (µDoppler) and allowing measurements of changes in cerebral blood volume (CBV) with micrometer-millisecond precision. This opens up the possibility to 1) detect functional response, as CBV-changes reflect changes in metabolism of activated neurons through neurovascular coupling, and 2) visualize in-vivo vascular morphology of pathological and healthy tissue with high resolution at unprecedented depths. During a range of anesthetized and awake neurosurgical procedures we acquired images of brain and spinal cord using conventional linear ultrasound probes connected to a research acquisition system. The ultrasound probes were either handheld for dynamic scans of tissue volumes (Figure 1B) or stabilized over regions of interest using an intra-operative arm developed in-house (Figure 1C). During conventional awake craniotomy procedures, we asked patients to perform functional tasks to elicit cortical responses following the Electrocortical Stimulation Mapping (ESM)-procedure. During all procedures, our research system recorded real-time vital signs data of the patient (arterial pressure and EKG), which can be used to improve image quality in post-processing. Building on Brainlab’s Cranial Navigation and Intra-Operative Ultrasound modules, we co-registered our intra-operative Power Doppler Images (PDIs) to patient-registered MRI/CT-data in real-time. Using the IGTLink research interface, we were able to access and store real-time tracking data for informed volume reconstructions in post-processing.

 

Results

Intra-operative fUS was registered to MRI/CT-images in real-time within the Brainlab interface, showing overlays of PDIs over the conventional neuro-navigation volume including pre-operatively drawn regions of interest and tumor borders (Brainlab Elements Smartbrush) (Figure 1D). During meningioma and glioma resections, these co-registered PDIs revealed fUS’ ability to visualize the tumor’s feeding vessels and surrounding vasculature, with a level of detail unprecedented by conventional MRI-sequences (Figure 1E-F). Using the intra-operatively recorded tracking data facilitated through the IGTLink, we made MRI-registered 3D-reconstructions of the 2D-PDIs post-operatively, which revealed unique vascular details such as the presumed middle cerebral artery originating from the circle of Willis (white arrow, Figure 1G). Imaging of deep brain nuclei (Figure 1H) reveals potential for vascular-guided DBS electrode placements, both in terms of improving morphological delineation as well as increasing safety by avoiding vital vascular structures during electrode implantation. During awake resections, fUS was able to detect distinct, ESM-confirmed functional areas as activated during conventional motor and language tasks (Figure 1I). In all cases, images were acquired with micrometer-millisecond (300 µm, 1.5-2.0 ms) precision at imaging depths exceeding 5 cm.

 

Conclusion

fUS is a new real-time, high-resolution and depth-resolved imaging technique, combining favorable imaging specifications with characteristics such as mobility and ease of use which are uniquely beneficial for a potential image-guided neurosurgical tool. The successful integration of fUS in the neurosurgical OR demonstrated by our team is an essential step towards clinical integration of fUS, as well as the technique’s validation against modalities such as MRI and CT.

 

References

[1] Soloukey, S. et al. Functional Ultrasound (fUS) During Awake Brain Surgery. Front. Neurosci. (2020)


Sadaf SOLOUKEY (Rotterdam, The Netherlands), Luuk VERHOEF, Frits MASTIK, Bastian GENEROWICZ, Eelke BOS, Joost SCHOUTEN, Biswadjiet HARHANGI, Ellen COLLÉE, Djaina SATOER, Marion SMITS, Clemens DIRVEN, Chris DE ZEEUW, Sebastiaan KOEKKOEK, Arnaud VINCENT, Pieter KRUIZINGA
16:15 - 16:20 #26281 - Structural changes in brains of patients with disorders of consciousness treated with deep brain stimulation.
Structural changes in brains of patients with disorders of consciousness treated with deep brain stimulation.

 

Aims: Disorders of consciousness (DOC) are one of the major consequences after anoxic or traumatic brain injury. So far, several studies have described the regaining of consciousness in DOC patients using

deep brain stimulation (DBS). However, these studies often lack detailed data on the structural and functional cerebral changes after such treatment. The aim of this study was to conduct a volumetric analysis of specific cortical and subcortical structures to determine the impact of DBS after functional recovery of DOC patients.

Methods: Five DOC patients underwent unilateral DBS electrode implantation into the centromedian parafascicular complex of the thalamic intralaminar nuclei. Consciousness recovery was confirmed using the Rappaport Disability Rating and the Coma/Near Coma scale. Brain MRI volumetric measurements were done prior to the procedure, then approximately a year after, and finally 7 years after the implementation of the electrode. The volumetric analysis included changes in regional cortical volumes and thickness, as well as in subcortical structures.

Results: Limbic cortices (parahippocampal and cingulate gyrus) and paralimbic cortices (insula) regions showed a significant volume increase and presented a trend of regional cortical thickness increase 1 and 7 years after DBS. The volumes of related subcortical structures, namely the caudate, the hippocampus as well as the amygdala, were significantly increased 1 and 7 years after DBS, while the putamen and nucleus accumbens presented with volume increase.

Conclusion: Volume increase after DBS could be a result of direct DBS effects, or a result of functional recovery. Our findings are in accordance with the results of very few human studies connecting DBS and brain volume increase. Which mechanisms are behind the observed brain changes and whether structural changes are caused by consciousness recovery or DBS in patients with DOC is still a matter of debate.


Marina RAGUŽ (Zagreb, Croatia), Nina PREDRIJEVAC, Domagoj DLAKA, Darko ORESKOVIC, Ante ROTIM, Dominik ROMIC, Fadi ALMAHARIQ, Petar MARCINKOVIC, Vedran DELETIS, Kostovic IVICA, Darko CHUDY
16:20 - 16:25 #26289 - Evaluation of the short- and long-term rotational stability of directional deep brain stimulation leads.
Evaluation of the short- and long-term rotational stability of directional deep brain stimulation leads.

Introduction: The two middle contacts of directional leads for deep brain stimulation are split into three segments, allowing current steering toward desired axial directions. To facilitate programming, their final orientation needs to be reliably determined. Moreover, the rotational stability of directional leads is a major prerequisite for sustained clinical effects. Thus, it is of major importance to determine if and for how long directional leads rotate after their implantation. We here aimed to evaluate the short- and long-term rotational stability of directional leads.

Methods: We retrospectively evaluated the orientation of directional leads in a consecutive series of 33 patients implanted with a total of 63 directional electrodes at different time points. In all cases a postoperative CT scan on the day of surgery (T1) and CT or rotational fluoroscopy at a second time point (T2) were available. In 32 directional leads, which had been implanted with an anterior intention (=0°) their intraoperative X-rays (T0) were evaluated.

Results: Sixty-three leads were evaluated. The mean follow-up between T1 and T2 was 409 (4–1171) days. The difference in rotation between T1 and T2 was 2.4° (0°-9.0°) indicating stable orientation. The difference between T0 and T1 was 155 minutes (108-189 minutes). In nine of the 32 d-leads with intraoperative X-ray, an iron-sight ( ISi; indicating 0° +/- 6° orientation) was visible at T0. In these electrodes median orientation was 1.5° (range 0.5-6.0°) at T1, confirming anterior orientation. In directional leads without ISi or where ISi was not evaluable, the median rotation was 15.5° (9.5–35.0°) and 26.5° (5.5-62.0°), respectively.

Conclusion: Directional lead orientation remains stable both in the short- or long-term. Postoperative images can thus be used at any postoperative time point to reliably determine their orientation. Intraoperative determination of lead orientation using marker-based X-ray alone is too imprecise, which explains the large deviations from the intended anterior (=0°) orientation at implantation in most leads; adding the ISi method can increase the accuracy and permits to define the orientation of directional leads intraoperatively.

 


Marie T. KRÜGER (London, United Kingdom), Fabian CAVALLONI, Yashar NASERI, Oliver BOZINOV, Georg KÄGI, Hägele-Link STEFAN, Florian BRUGGER
16:35 - 16:40 #23400 - Frameless robot-assisted stereotactic biopsies for lesions of the brainstem – a series of 106 consecutive cases.
Frameless robot-assisted stereotactic biopsies for lesions of the brainstem – a series of 106 consecutive cases.

Introduction

Targeted treatment for lesions presenting with a brainstem location requires above all a precise histopathological diagnosis. In the current technological era, robot-assisted stereotactic biopsies represent an accurate and safe procedure for tissue diagnosis. We present our center’s experience in performing frameless robot-assisted biopsies for lesions of the brainstem. 

Material and methods

We performed a retrospective analysis of all patients benefitting from a frameless robot-guided stereotactic biopsy at the University Hospital in Lille (France), from 2001 to 2018. The NeuroMate robot (Renishaw, UK) was used in all cases. We report on lesion location, trajectory choice, histopathological diagnosis and follow-up. 

Results

Our series encompasses 106 patients treated during an 18 years period, presenting with various anatomopathological diagnoses. Mean age at biopsy was 35.4 years (range 1-78). Most common location was pontine region (71.4%). A transcerebellar approach was used in 66 patients (62.2%). Various diagnoses are described, most commonly being diffuse glioma (65.7%), metastases (7.6%) and lymphoma (4.8%). Non conclusive diagnosis was found in 13 cases (12.6%). After second biopsy this decreased to 6 cases (5.8%). Transitory complications were recorded in 16% of cases (17 patients). The most common was oculomotor transitory disorder (5 patients). Permanent disability was seen in 5.6% (6 patients). Adjuvant targeted treatment was performed in 71% of patients. Surgery for debulking was possible in only 5 patients (after adjuvant therapy in two cases). Mean postoperative follow-up in the Neurosurgery Department was 2.2 years. 

Conclusion

Frameless robot-assisted stereotactic biopsies can provide the initial platform towards a safe and accurate management for brainstem lesions. To our best knowledge, we report on the largest case series for frameless robot-assisted stereotactic biopsies, with high diagnostic precision and low morbidity.    


Iulia PECIU-FLORIANU, Victor LEGRAND, Apolline MONFILLIETTE-DJELAD, Claude-Alain MAURAGE, Gustavo TOUZET (LILLE), Nicolas REYNS
16:40 - 16:45 #23984 - INTRAOPERATIVE FLOW CYTOMETRY FOR DETECTING MALIGNANCY DURING STEREOTACTIC BRAIN TUMOR BIOPSIES. FIRST RESULTS.
INTRAOPERATIVE FLOW CYTOMETRY FOR DETECTING MALIGNANCY DURING STEREOTACTIC BRAIN TUMOR BIOPSIES. FIRST RESULTS.

Objective: Rapid and accurate diagnostic confirmation of brain tumor tissue during stereotactic biopsies is of major importance. Frozen section analysis is the gold standard, nevertheless in cases of multiple samples analysis it may be time consuming. Intraoperative flow cytometry is a novel technique that permits differentiation of low from high-grade tumors, brain tumor margins assessment and diagnosis of central nervous system lymphoma within 6 minutes. The technique is based on the evaluation of tumor’s cell cycle phases, ploidy status and cluster differentiation (CD) markers.  Major advantages of flow cytometry are the evaluation of multiple samples, minimal tissue requirements and there is no need to administer any substance to the patient.  In the present pilot study we assessed the value of intraoperative flow cytometry during brain tumor biopsies.

Material-Method: Four patients (3 males, 1 female, mean age 63.2 years) that underwent a stereotactic biopsy for a suspected neoplastic lesion were included in the study. Upon sample receipt fast flow cytometric analysis (Ioannina Protocol) was performed  and the results were compared to standard pathology.

Results: The final diagnosis were three glioblastoma cases and one case of metastatic cancer. Presence of neoplastic tissue was readily identified in all cases based on ploidy status, decreased G0/G1 and increased S and G2/M phase fractions. The exclusion of central nervous system lymphoma was performed within 6 minutes of sample receipt based on CD markers analysis. Histopathology verified the results in all cases.  

Conclusions: Intraoperative flow cytometry might be a novel promising technique for the rapid identification of neoplastic tissue during stereotactic brain lesion biopsies.

 


George ALEXIOU (IOANNINA, Greece), George VARTHOLOMATOS, Spyridon VOULGARIS
16:45 - 16:50 #23790 - Connectivity profile of deep brain stimulation targets in Tourette syndrome.
Connectivity profile of deep brain stimulation targets in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychological disorder characterized by vocal and motoric tics, mainly affecting children and young adults. The pathophysiology of this disorder is not yet completely understood. Nevertheless, studies have shown a delayed neurodevelopment with abnormal connectivity patterns in the cortico-striatal-thalamic-cortical (CSTC) loops. While in most patients, symptoms either cease or considerably diminish in early adulthood, about 20% of the patients continue having symptoms their whole life, with the same or increased intensity. For adult patients with severe treatment-refractory TS, deep brain stimulation (DBS) is a safe and effective therapy option. So far numerous anatomical structures have been researched as DBS targets along the CSTC loops, including the centromedian nucleus- ventrooralis internus (CM-Voi), the CM-parafascicular complex (CM-Pf), the anteromedial (amGPi) and posteroventral globus pallidus internus (pvGPi), the globus pallidus externus (GPe) and the nucleus accumbens (Nacc). According to a recent review, the average improvement for all targets in the Yale Global Tic Severity Scale was about 47%, with none of them showing a greater benefit than the others. Studies on small cohorts showed that some patients responded better to stimulation of amGPi than CM-Pf while in others there was no significant difference. Furthermore, patients with additional obsessive-compulsive disorder seem to profit more from amGPi or Nacc DBS. The aim of this study is to correlate cortical connectivity patterns of patients stimulated in CM-Voi with clinical results, and to compare connectivity patterns of DBS targets for TS in order to elucidate if specific targets are better suited for patients with specific clinical phenotypes.

To establish relevant cortical areas in TS, we investigated diffusion tensor imaging (DTI) in seven Tourette patients who underwent CM-Voi DBS at our clinic. We analyzed the connectivity between the tissue activated by the electrodes and individual cortical areas. Connectivity profiles more specific to the motor cortex (M1, SMA, preSMA) were associated with a reduction of motor and vocal tics.  In poor responders the cortical connectivity was more widespread, mainly projecting to the prefrontal cortex.

Based on these results, we examined the connectivity profile of all DBS targets for TS namely CM, Voi, Pf, amGPi, pvGPi, GPe and Nacc, using a normative connectome. We compared the connectivity of each structure to the motor cortex (M1, SMA, preSMA), the primary sensory cortex, the amygdala and the hippocampus.

The connectivity profile of these targets was remarkably different. While pvGPi and GPe showed the strongest connection to the motor cortex, most fibers from Voi, CM, amGPi and Nacc connected to the prefrontal cortex, and Pf mainly to the amygdala. The connectivity profiles of the thalamic structures, Nacc and amGpi were more specific to single areas, while fiber tracts from pvGPi and GPe were more scattered.  Notably, neither CM nor Voi showed a particularly strong connection to the motor cortex, other than the individual tractography of our patients might have suggested.

In summary, we found that a better clinical outcome after TS DBS targeting CM-Voi correlated with a more specific connectivity of the tissue activated by the electrodes to the motor cortex based on individual tractography. Furthermore, the connectivity profiles of different TS DBS targets were highly variable based on the normative connectome. Further research is necessary to assess whether clinical outcome in TS patients with other DBS targets is also correlated with similar connectivity patterns.


Petra HEIDEN, Moritz HOEVELS, Juan BALDERMANN, Veerle VISSER-VANDEWALLE, Pablo ANDRADE (Cologne, Germany)
Salle Major

"Friday 10 September"

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C35
15:00 - 17:00

Parallel Session 13
Pain

Moderators: Anne BALOSSIER (Dr) (Marseille, France), Ivano DONES (MILANO, Italy), Ioannis PANOURIAS (DOCTOR) (ATHENS, Greece)
15:00 - 15:10 #26190 - Trigeminal microvascular decompression for refractory chronic short-lasting unilateral neuralgiform headache attacks.
Trigeminal microvascular decompression for refractory chronic short-lasting unilateral neuralgiform headache attacks.

BACKGROUNDA significant proportion of patients suffering from short-lasting unilateral neuralgiform headache attacks (SUNHA) are refractory to medical treatment. A recent structural neuroimaging study suggests a pivotal role of ipsilateral trigeminal neurovascular conflict (NVC) in their aetiology. Moreover, a small case series suggests that trigeminal microvascular decompression (MVD) may be an effective surgical treatment. We aimed to determine whether trigeminal MVD is a safe and effective surgical option for medically refractory chronic SUNHA patients in whom there is radiological evidence of NVC. 

 

DESIGN, SETTING AND PARTICIPANTS: An uncontrolled open-label prospective single centre study was conducted between Jan 2013 and Dec 2020. Consecutive patients with refractory chronic SUNHA and MRI evidence of trigeminal NVC ipsilateral to the pain side were enrolled in the study. 

 

INTERVENTION: All patients had high-resolution MRI sequences of the trigeminal nerves. Trigeminal MVD with the modified Jannetta technique was performed in this study.

 

MAIN OUTCOMES AND MEASURES: Responders were those who achieved 90-100% reduction in attack frequency (excellent response), or between 75% and 89% frequency reduction (“good response”), at final follow-up. Secondary efficacy and disability-related outcomes and surgical adverse events were collected.

 

RESULTS: The study included 47 chronic SUNHA patients: 31 with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and 16 with short-lasting unilateral neuralgiform headache attacks with autonomic features (SUNA) (25 females, mean age 55.4 years ± 14.9). The vast majority of patients (89.4%) experienced both spontaneous and triggered attacks by cutaneous and/or intraoral stimulation. The mean number of medical treatments failed at the time of the surgery was 8.1(±2.7). Two patients also had an incomplete response to neuromodulation (occipital nerve or deep brain stimulation). At the time of surgery, all patients were taking preventive treatments. The mean baseline HIT-6 score was 67.7 (± 6.7); 38 patients (80.9%) had baseline HIT-6 scores within the severe disability range.

 

All patients had NVC ipsilateral to the pain side. Of 47 patients, 50 symptomatic nerves were analysed (three patients had side alternating attacks). Arterial conflict, by the superior cerebellar artery (SCA) (n=47), by the anterior inferior cerebellar artery (AICA) (n=2) or by both arteries (n=1) was found with all symptomatic nerves. NVC with morphological changes was found in 72% (n=36/50) and without in 28% (n=14/50) of symptomatic nerves. 

 

Post-operatively, 38 patients (80.8%) were responders. Of these, 34 (72.3%) obtained an excellent and four (8.5%) a good response. The majority of patients responded to MVD immediately (n=36, 94.7%), whereas two obtained an excellent response after three and four months respectively. Nine patients (19.1%, SUNCT=7, SUNA=2) reported no post-operative improvement. Mean follow-up was 49.0±25.7 months (range 7-96). At final follow-up, 32 patients (68.0%) remained excellent/good responders; six had recurrence of SUNHA symptoms (SUNCT=3, SUNA=3): two within the first six months, one within the first 12 months, two within the second year and one patient at month 38 post-surgery. Three of these patients obtained meaningful control of recurrent symptoms with lamotrigine and carbamazepine, two with occipital nerve stimulation and one with ventral tegmental area deep brain stimulation. All but one patient who obtained an immediate excellent response discontinued their preventive medications. Two patients underwent MVD on the other side due to worsening/onset of attacks on the contralateral side of the first operation. The outcome of the second MVD was similar to the first one. 

 

The HIT-6 score was reduced from 67.7 (± 6.7) at baseline to 45.0 (± 13.8) at final follow-up. Furthermore, the percentage of patients with severe disability was reduced from 80.9% (n=38) to 21.3% (n=10), with most patients’ HIT-6 scores showing no further impact of the headache condition in their life.

 

No serious surgical complications were noticed. Twenty-two post-surgery adverse events occurred in 18 patients. 

 

CONCLUSIONS: This study provides Class IV evidence that trigeminal MVD may be a safe and effective treatment for refractory chronic SUNHA patients.


Giorgio LAMBRU, Susie LAGRATA, Sanjay CHEEMA, Andrew LEVY, Indran DAVAGNANAM, Neil KITCHEN, Manjit MATHARU, Ludvic ZRINZO (London, UK, United Kingdom)
15:10 - 15:20 #26252 - Prospective Quality-of-Life Assessment and Meta-Analysis of Microvascular Decompression for Elderly Patients with Trigeminal Neuralgia.
Prospective Quality-of-Life Assessment and Meta-Analysis of Microvascular Decompression for Elderly Patients with Trigeminal Neuralgia.

Abstract

Objective: The incidence of trigeminal neuralgia (TN) increases with age. Elderly patients with severe trigeminal neuralgia may choose microvascular decompression (MVD) for their treatment. This study aims to investigate the impact of MVD for trigeminal neuralgia on health-related quality of life (hr-QoL) in the elderly. Additionally, the authors update a systematic review and meta-analysis of age-stratified MVD outcomes for the trigeminal neuralgia.

Methods: The authors prospectively studied 40 consecutive patients who underwent MVD for the trigeminal neuralgia between 2018 and 2019. The hr-QoL of the elderly (65 years or older) and non-elderly (less than 65 years) patients was assessed using the 36-Item Short Form Health Survey (SF-36) before and 6 months after MVD. Preoperative and postoperative SF-36 score and pertinent clinical data were compared between elderly and non-elderly groups using paired t-tests and repeated-measures analysis of variance (ANOVA).

The authors also conducted a systematic review of the English literature providing age-stratified MVD outcomes for the trigeminal neuralgia. The search included articles published prior to December 2020 to update the previously published meta-analysis. Pooled data for the rates of excellent outcome, death, complication from stroke and thromboembolism, and recurrence were analyzed.

Results: The two cohorts were composed of 22 elderly (mean 76 years, range 65–89) and of 18 non-elderly patients (mean 57, range 38–64). SF-36 score of all domains improved significantly after the operation in both the age groups (p < 0.001). The physical functioning (PF) domain improved significantly less in the elderly compared to non-elderly patients (p = 0.018). In those 80 years or older, SF-36 score also improved significantly after the operation (p = 0.03), except for the PF and vitality domains.

Twenty-one studies met the inclusion criteria for the systematic review and meta-analysis. The updated meta-analysis demonstrated that the elderly had better pain control (risk ratio [RR], 1.05; 95% confidence interval [CI], 1.01–1.10; p = 0.02) and similar risk of recurrence (RR, 0.86; 95%CI 0.71–1.14, p = 0.12) compared to the non-elderly patients. A trend of declining risk of mortality and morbidity was illustrated in both the age group, although the preoperative comorbidity was commonly present in the elderly (RR, 2.90; 95%CI 1.75–4.79, p < 0.01).

Conclusions: MVD can improve the hr-QoL of the elderly with trigeminal neuralgia. Recent advances of perioperative management may control the morbidity and mortality risk. MVD can be a reasonable treatment of choice for the elderly with refractory trigeminal neuralgia.

 


Hiroki TODA (Osaka, Japan)
15:20 - 15:30 #23999 - Neuromodulation in treating complex regional pain syndrome.
Neuromodulation in treating complex regional pain syndrome.

Introduction: CRPS describes an array of painful conditions that are characterized by a continuing (spontaneous and/or evoked) regional pain that is disproportionate in time or degree to the usual course of any know lesion. The pain is regional (not in specific nerve territory or dermatome) and usually has a distal predominance of abnormal sensory, motor, sudomotor, vasomotor, and/or trophic findings. Neurostimulation is an intervention that has been studied extensively in a variety of pain syndromes, demonstrating both safety and efficacy. Spinal cord stimulation (SCS) an effective therapy in the management of patients with CRPS type I (Level A evidence) and type II (Level D evidence). Deep brain stimulation (DBS), motor cortex stimulation (MCS), peripheral nerve stimulation (PNS) and their combinations can use in treatment too. 

Methods: The study was conducted among 24 patients (10 male and 14 female, median age: 48), with an average 9-year history of severe intractable pain. Criteria for inclusion: CRPS I (n=5; 21%), II (n=17; 71%) and III (n=2; 8%); drug-resistant or inefficient medical therapy; ages ≥18. The patients were followed up by the VAS (Visual Analog Scale) and the PCS (Pain Catastrophizing Scale).

Preoperatively all patients had a VAS 6-10. Seven patients had pain attacks every month from 150 to 10000 (150 per hour). All patient have successful test (7 days), after which was implanting systems for chronic neurostimulation: SCS (n = 15; 62.5%), MCS (n = 2; 8.3%), DBS (n = 2; 8, 3%), PNS (n = 2; 8.3%), and also hybrid neurostimulation - SCS + MCS (1), MCS + PNFS (1) and DBS + PNS (1) - 12.6%.

Results: The catamnesis 6 years. The average VAS value decreased by 4.6. The average improvement PCS 2.76. The removal of the implanted system was seven patients (29,2%) for reasons: infection (2 – 28,6%), decrease in efficiency (3 - 42,8%), system breakdown (1 - 14,3%) and one of patients (14,3%) had a uncomfortable sensation in stimulation area. Although the removal of the implanted system, 2 patients have complete regression of attacks pain, 2 have 50% decrease intensity and frequency attacks of pain, 3 have 50% decrease in intensity pain.

Conclusions: In carefully selected patients neurostimulation can reduce pain and improve the health-related quality of life.


Emil ISAGULYAN (Moscow, Russia), Alexey TOMSKY, Elizaveta MAKASHOVA, Valentina MIKHAILOVA, Eugeny DOROCHOV, Ekaterina SALOVA
15:30 - 15:40 #23920 - Operative findings and outcome of microvascular decompression/ adhesiolysis for trigeminal neuralgia in multiple sclerosis.
Operative findings and outcome of microvascular decompression/ adhesiolysis for trigeminal neuralgia in multiple sclerosis.

Objective: Trigeminal neuralgia (TN) in multiple sclerosis (MS) poses several challenges for treatment. Although these patients often have typical attacks, they may not be considered as candidates for microvascular decompression (MVD). Optimal treatment in this group of patients is still unclear. Here we report on surgical findings and the results of MVD/ adhesiolysis in a series of patients with multiple sclerosis.

 

Methods: Fifteen patients with typical trigeminal neuralgia and MS underwent MVD. All patients had preoperative magnetic resonance imaging (MRI) to exclude mass lesion in cerebellopontine angle. The trigeminal neuralgia was refractory to the medication in all patients preoperatively.  All patients were available for follow-up. The outcome of intervention was graded according to the Barrow Neurological Institute (BNI) Pain intensity score. The 3, 12, 24 months follow-up and long-term follow-up (mean 41,2 months) were analysed.

Results: For the 15 patients, a total of 19 MVDs were performed. Intraoperative findings indicated scar tissue at the trigeminal entry zone (15/19 instances), arterial contact (8/19 instances) and vein contact (11/19 instances). A complete pain relief was achieved in all patients directly after surgery. From these 15 patients 4 patients underwent second MVD because of pain recurrence and on the 12 months follow-up all benefited from re-surgery. For 14 patients we were able to show 24 months follow up; 8 patients BNI I (complete pain relief), 2 patients BNI II (occasional pain, but no medications required), 2 patients BNI IIIa (no pain but continued taking medication for fear of stopping) and 2 patients BNI IV (limited benefit).

 

Conclusion: On the long-term follow-up, 13/15 patients had pain relief (including the patients who underwent a second MVD). These findings show that MVD provides good outcome for TN in patients with MS. These necessities, however, a careful patient selection and meticulous surgical decompression/ adhesiolysis.


Gökce HATIPOGLU MAJERNIK (Hannover, Germany), Shadi AL-AFIF, Hans E. HEISSLER, Joachim K. KRAUSS
15:40 - 15:45 #23879 - Sub-perception and supra-perception spinal cord stimulation in chronic pain syndrome: a randomised, semi-double-blind, crossover, placebo-controlled trial.
Sub-perception and supra-perception spinal cord stimulation in chronic pain syndrome: a randomised, semi-double-blind, crossover, placebo-controlled trial.

Objective: The introduction of modern sub-perception modalities has improved the efficacy of spinal cord stimulation (SCS) in refractory pain syndromes of the trunk and lower limbs. The objective of this study was to evaluate the effectiveness of low frequency, high frequency, and burst SCS among patients with chronic pain.

Material and methods: A randomised, semi-double-blind, placebo controlled, four period (4×2 weeks) crossover trial was conducted from August 2018 to January 2020. Eighteen patients with SCS due to failed back surgery syndrome and/or complex regional pain syndrome were randomised to four treatment arms without washout periods: (1) low frequency (40-60 Hz), (2) high frequency (1 kHz), (3) burst, and (4) sham SCS (i.e., placebo). The primary outcome was pain scores measured by visual analogue scale (VAS) preoperatively and during subsequent treatment arms. Results: Pain scores (VAS) reported during the preoperative period was M [SD] = 8.19 (0.98). There was a 49.67% reduction in pain reported in the low frequency treatment group (M [SD] = 4.18 [1.76]), a 38.32% reduction in the high frequency treatment group (M [SD] = 5.13 [1.36]), a 34.2% reduction in the burst settings group (M [SD] = 5.27 [1.33]), and a 36.23% reduction in the sham stimulation group (M [SD] = 5.23 [1.38]). The reduction in pain from the preoperative period to the treatment period was significant in each treatment group (p < 0.001). Overall, these reductions were of comparable magnitude between treatments, including the sham (placebo) treatment. Average pain did not significantly differ between treatment arms and was relatively stable across treatment periods. However, the modality most preferred by patients was low frequency (55% or 10 patients). 

Discussion

One of the main advantages of this study was the double-blind setting in sub-perception modes and the placebo control. These settings were made possible by paraesthesia-free stimulation that was applied in this trial. No sensory perceptions were observed during the three allocated treatment arms (i.e., burst stimulation, 1 kHz stimulation, and sham stimulation). Furthermore, the crossover design allowed for each subject to be exposed to each modality, which allowed for individual subjects to serve as their own control. 

The primary goal of the study was to establish the type of stimulation was the most effective for relieving pain and to establish which type was the most preferred in long-term stimulation.  Patients were not aware of the type of stimulation that had been programmed and were not aware of whether the stimulation was on or off because they were informed that they could not perceive any sensations. There were no washout periods between subsequent treatment arms. The design of this cross-over study could be burdened by carry-over effects, but the analysis revealed that average pain was relatively stable through the entire study periods. In present study, average values of pain intensity after each type of stimulation were not shown to be superior to sub-perception stimulation. The observed reduction in pain was modest across all modalities. During the sham arm, devices showed that the IPG was on. LF tonic SCS had, however, the most robust analgesic effect of greater than 49.7%. At the end of the randomised phase, the majority of subjects (55%) chose tonic stimulation as their preferred mode for SCS. Further, we found that LF tonic SCS was associated with the highest level of relative pain relief and the lowest use of NSAIDs and anticonvulsants. 

In contrast to prior studies, we did not find burst stimulation to be superior to other forms of stimulation, although 3 people (14.7%) in the present study reported this modality to be the most satisfactory. In our study, we applied clustered tonic stimulation. We did not observe higher efficiency of HF stimulation as compared to other forms of stimulation. This observation is in agreement with conclusions drawn from a prior review of HF stimulation clinical trials, which showed a lack of high-quality evidence on the superiority of HF SCS. Conclusions: SCS was effective in pain relief. Sub-perception stimulation was not superior to supra-perception. SCS was characterised by a high degree of placebo effect. No carryover effect was observed between subsequent treatments with different frequencies. Contemporary neuromodulation procedures should be tailored to the individual preferences of patients.


Paweł SOKAL (Bydgoszcz, Poland), Sara KIEROŃSKA, Agnieszka MALUKIEWICZ, Marcin RUDAŚ, Marcin RUSINEK
15:45 - 15:50 #23907 - SOMATOTOPY OF THE SOMATOSENSORY THALAMUS: CONTRIBUTION FROM DIRECTIONAL DEEP BRAIN STIMULATION IN PATIENTS TREATED FOR REFRACTORY NEUROPATHIC PAIN.
SOMATOTOPY OF THE SOMATOSENSORY THALAMUS: CONTRIBUTION FROM DIRECTIONAL DEEP BRAIN STIMULATION IN PATIENTS TREATED FOR REFRACTORY NEUROPATHIC PAIN.

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Introduction: Somatotopic organization of the sensory thalamus has been described using intraoperative data from microelectrodes recordings, location or stimulation-induced paresthesias in patients treated by deep brain stimulation (DBS) for intractable pain. These data suggested a mediolateral somatotopic organization in the contralateral ventroposterior thalamus, the head and the inferior limb being represented respectively medially and laterally. The aim of our study was to explore the somatotopy of the sensory thalamus using the principle of directional DBS.

Methods: Four patients with chronic refractory neuropathic pain were included in a prospective study evaluating combined thalamic and anterior cingulate DBS. DBS directional leads (Infinity, Abbott) were implanted under local anesthesia in the sensory thalamic region corresponding to their contralateral pain. Orientation and location of the leads were assessed by postoperative 3D CT-scan and merged on Schaltenbrand and Wahren atlas according to their AC-PC coordinates. Three months after surgery, bipolar stimulation was delivered in each direction and correlated to location of stimulation-induced paresthesias.

The stimulation specificity was defined as the difference in mA between the stimulation threshold inducing paresthesias in the desired painful area and the threshold inducing paresthesias in undesired body areas.

 

Results: Stimulation-induced paresthesias were perceived in areas of the body that differed according to the stimulation direction, allowing to map the somatotopic organization of the sensory thalamus in each patient. The somatotopy re-constructed using directional DBS in the four patients will be displayed and was globally in accordance with the somatotopy based on previous data.. Compared to the omnidirectional stimulation, the specificity of directional stimulation was 43% wider and the intensity needed to produce paresthesias in the intended body area was 35% lower. There was no complication.

Conclusion: This preliminary study confirmed the somatotopic organization of the sensory thalamus and strengthens the concept and interest of directional DBS. More patients will be include in the study to confirm these findings.



Aurélie LEPLUS (NICE), Michel LANTERI-MINET, Emilie PIQUET, Denys FONTAINE
15:50 - 15:55 #23916 - Spinal cord stimulation in the treatment of ischemic pain: Microcirculation and tissue perfusion improvement.
Spinal cord stimulation in the treatment of ischemic pain: Microcirculation and tissue perfusion improvement.

Introduction. Refractory angina pectoris (RAP) and peripheral vascular disease (PVD) is a chronic pain condition that affects a certain group of patients with systemic atherosclerosis. These diseases have bad control of neither by a combination of medical therapy nor by vascular surgery treatment (angioplasty or bypass surgery). The efficacy of SCS is supported by one placebo-controlled study, two larger randomized controlled trials, and several small controlled studies. According to systematic reviews, there is strong evidence that SCS gives rise to symptomatic benefits and improves functional status in patients with vascular diseases. Spinal cord stimulation (SCS) is an effective and safe treatment for these patients that has an excellent effect on pain relief and microcirculatory function’s improvement.

Methods. Two groups of patients with non-reconstructable RAP (n=22) and PVD (n=75) underwent SCS procedure in our facility. Preoperative and follow-up myocardium perfusion scintigraphy (MPS), transcutaneous oximetry (TCO), and laser-doppler flowmetry (LDF) were performed on admission and in 1 year after the procedure. The lead placement in the RAP group was C7-Th4, in the PVD group - Th11-L1. Pain relief was assessed by a visual analog scale (VAS) in all patients.

Results. The patients showed 8,56±0,13 marks according to VAS before the procedure and pain relief to 2,09±0,09 marks (p<0,01) in the 1-year follow-up. All the patients in the RAP group demonstrated the rise of tolerance to physical activity. MPS detected the decrement of perfusion's defect from 15,72±2,05 to 9,17±1,3 units (increase in coronary reserve up to 24%). TCO detected the microcirculatory improvement (n=75): tissue oxygenation increased from 7,5 to 43,1 mm Hg (p=0,045).

Discussion. The present study has some limitations: the follow-up period was relatively short, leading to a limited evaluation of the outcome of SCS. Measurements were not used to select patients for SCS since we intended to include this indicator as a factor that could potentially influence the clinical dynamics after this procedure. The duration of clinical manifestations of RAP and PVD is associated with the long-term results of SCS. Hence, the approaches to the treatment of these diseases need to be optimized to timely use of surgical and nonsurgical therapy, including SCS, to improve the clinical and cost-effectiveness of non-reconstructable vascular disease treatment.

Conclusions. In summary, patients with non-reconstructable RAP and PVD show a positive clinical dynamic 1 year after SCS. At the same time, the initially low peripheral tissue metabolism, and the significant disturbance of the functional status of peripheral microvasculature is associated with the negative clinical dynamics one year after SCS. Our experience also highlights the importance of preserving the microcirculatory reserve capacity (1), confirms that SCS can reduce the pain (2), and improve quality of life with vascular reserve enhancement (3) in patients with ischemic pain syndrome.


Vladimir MURTAZIN (Novosibirsk, Russia), Roman KISELEV, Martin KILCHUKOV, Asya KLIMKOVA, Kirill ORLOV
15:55 - 16:00 #24032 - Multimodality treatment for pain control in multiple sclerosis-related trigeminal neuralgia.
Multimodality treatment for pain control in multiple sclerosis-related trigeminal neuralgia.

Background: The best surgical choice for MS-related TN (MSrTN) remains controversial. Recent literature express poor pain control and high recurrence rates in surgical interventions of MSrTN compared to classical TN. Our aim was to evaluate the effects of microvascular decompression (MVD), radiofrequency thermocoagulation (RFT) and gamma-knife radiosurgery (GKRS) in patients with MSrTN. The primary outcome measure was the duration of pain-control; in other words, the time until the treatment failure and the factors that are predictive for outcome with different surgical modalities in the treatment of MSrTN.

 

Methods: A total of 31 patients underwent 65 surgical procedures to treat drug-resistant MSrTN in our department from 2003 to 2019. The patients’ demographic characteristics, pain severity scores, pain characteristics, initial symptom of MS, type of MS, the duration between MS and TN diagnosis, the interval between MS and the beginning of TN, location of MS plaques in MRI, duration of pain control after each procedure, and acute pain relief were evaluated. Pain control was determined as BNI scores that are ranging from I-IIIB. 

 

Results: Mann-Whitney U test was performed to analyze probable statistical differences in the duration of pain control (months) and decrease of VAS score between GKRS and RFT. Statistical analyses were not run for the MVD treatment group because of inadequate data. Distribution of the pain control duration and VAS score decrease were not similar, as by visual inspection. VAS scores decrease after RFT (Mean ± SD: 8.28 ±1.93) were statistically significantly higher than after GKRS (Mean ± SD: 5.18±3.71), U= 48.5, z=-2.31, p=0.020. 

Although comparison between pain control duration after RFT (Mean ± SD: 20.11 ±24.3)  and GKRS (Mean ± SD: 9.36±13.7) was not statistically significant, longer pain-free duration has been achieved with RF, U= 57.5, z=-1.88, p=0.061.

 

Conclusion: Pain control in MSrTN patients is challenging and requires multimodal surgical management generally. Patients with MS have a higher risk of disability and morbidity. Our results showed that RFT is a safe and effective surgical procedure for decreasing pain with a favorable longer duration of pain control without adding any morbidity to MS patients

 

 


Şükrü AYKOL, Mesut Emre YAMAN (Ankara, Turkey), Burak KARAASLAN, Munibe Busra ERDEM, Enes KARA, Tolga TÜRKMEN
16:00 - 16:05 #24079 - Dorsal root ganglion stimulation, a salvage therapy in neuropathic pain syndromes.
Dorsal root ganglion stimulation, a salvage therapy in neuropathic pain syndromes.

Introduction 

Medically intractable neuropathic low back and leg pain became manageable in the last two decades since the wide availability of spinal cord stimulation systems. Recent developments of new SCS stimulators and leads, introduction of new waveforms provided a possibility to salvage even those patients, who were not responding to treatment or had residual pain in mainly the low back. Dorsal root ganglion stimulation however provides a possibility to treat even those patients suffering from monoradicular, monodermatomal, or low back pain, who were not responding to spinal cord stimulation therapy.

 

Methods

6 patients, who were implanted with Abbott Proclaim DRG systems were enrolled in this review. 3 patients were suffering from neuropathic low back pain, 2 of these patients were previously implanted with percutaneous SCS systems without any success in the low back area. 1 patient developed bilateral Th5 level after tumor resection, 1 patient was suffering from post-thoracotomy pain, and 1 patient experienced ilioinguinal pain after inguinal hernia surgery. Stimulation parameters were tailored according to postoperative VAS scores and sufficient dermatomal involvement.

 

Results

 

Each patient completed the trial phase successfully lasting at most 3 weeks. Mean age was 57,83±8,93 years, years passed since age onset of symptoms was 9,83±7,03 years. Patients suffering from low back pain received bilateral Th12 Axium Slim Tip leads, the remaining 3 patients received DRG leads according to dermatomal involvement in the bilateral Th5, unilateral L1, and unilateral Th9 dermatomes. Frequency was set between 12-20 Hz, pulse width was in range between 200-340 microseconds, while amplitude showed a mean level 0,52±0,21 mA. Preoperative VAS scores were decreased and maintained from a mean of 7,83±1,17 to 1,50±1,05. No complication has been observed during implantation or follow-up.

 

Discussion

Dorsal root ganglion stimulation provides a valuable option to treat medically intractable neuropathic low back or monoradicaluar, monodermatomal pain. Patients suffering from low back pain can benefit from bilateral Th12 level stimulation. Low amplitudes and frequencies provide an option to prolong battery life in the long run, but it also raises the possibility of the involvement of different underlying neural circuits and regulatory mechanisms in action to achieve pain relief.


László HALÁSZ (Budapest, Hungary), Loránd ERŐSS
16:05 - 16:10 #25933 - Gamma Knife radiosurgery for trigeminal autonomic cephalalgias: preliminary results of a single-center prospective study.
Gamma Knife radiosurgery for trigeminal autonomic cephalalgias: preliminary results of a single-center prospective study.

Background: Gamma Knife radiosurgery (GKRS) was considered as a potential treatment for trigeminal autonomic cephalalgias (TACs). However, it was abandoned after that some authors reported an excessive facial sensory morbidity following GKRS for cluster headache (CH) in small cohorts of patients. Today, data about its efficacy, specific indications and ideal treatment parameters are lacking.

 

Objective: To report on 4 patients who underwent combined GKRS ablation of the cisternal part of the trigeminal nerve and of the sphenopalatine ganglion for TACs.

 

Methods: We have prospectively assessed four patients with TACs who were treated with combined GKRS ablation of the cisternal part of the trigeminal nerve and of the sphenopalatine ganglion. We report on characteristics including facial pain distribution and autonomic features, changes in pain scores and complications. Post-treatment facial numbness was assessed with the Barrow neurological institute (BNI) facial hypesthesia scale.

 

Results: Two patients with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and two patients with chronic cluster headache (CH) were treated with GKRS and followed-up for at least six months. Two patients with SUNCT and one patient with chronic CH had complete pain relief after GKRS and one had partial pain reduction. Two patients had non-bothersome facial numbness after GKRS (BNI facial hypesthesia score II). Three patients met classical criteria for responders (50% decrease in pain scores). Autonomic features were improved or stable in 3 and 1 patients, respectively.

 

Conclusions: GKRS may be an effective treatment in patients with SUNCT or CH. Non-bothersome sensory disturbances is frequent following combined radiosurgery-mediated ablation of the trigeminal nerve and sphenopalatine ganglion. More prospective studies are needed to define the actual safety and efficacy of GKRS for the treatment of TACs.


Andrea FRANZINI, Zefferino ROSSINI, Pierina NAVARRIA, Elena CLERICI, Attuati LUCA, Pessina FEDERICO, Piero PICOZZI (Milano, Italy)
16:10 - 16:15 #26093 - HF-SCS versus LF-SCS in treatment of chronic limb-threatening ischemia (CLTI): results of randomized trial.
HF-SCS versus LF-SCS in treatment of chronic limb-threatening ischemia (CLTI): results of randomized trial.

BACKGROUND

Chronic limb-threatening ischemia (CLTI) is the end stage of peripheral artery disease, which represents the third leading cause of atherosclerotic morbidity, following coronary artery disease and stroke. Considering resistant rest pain, spinal cord stimulation played an important role in the treatment of these patients. Nowadays, different SCS waveform modalities are available for pain management. High-frequency (HF-SCS) and Burst-SCS demonstrated their superiority to conventional SCS in the treatment of back pain and neuropathic leg pain. Despite strong evidence about the efficacy and safety of conventional SCS in the treatment of ischemic pain, any information about an application of high-frequency SCS (HF-SCS) for ischemic conditions is still absent. The objective of the study was to determine whether high-frequency or low-frequency SCS is better for pain relief in CLTI treatment.

 

METHODS

This study was designed as a parallel-group randomized trial with 1:1 allocation ratio. The enrollment of the patients was arranged in Meshalkin National Medical Research Centre from August 2018 till February 2020. Throughout enrollment we examined 56 patients in total, 6 of whom rejected to participate in the trial. In line with the study protocol, the patients were examined in 3 and 12 months by neurosurgeons. To achieve primary (pain relief) and secondary (quality of life, walking ability, limb salvage and tissue blood flow) endpoints we surveyed patients with VAS, short-form-36 (SF-36), Walking Impairment Questionnaire (WIQ) and provided laser-Doppler flowmetry (LDF) before surgery, in 3 and 12 months.

 

RESULTS

Mean VAS scores were 2.84±0.85 for the HF-SCS group and 3.32±0.74 for the LF-SCS in 3 months after treatment (p=0.03) and 2.52±0.51 for HF-SCS and 3.72±0.48 for LF-SCS group in 12 months (p<0.001). Mean overall WIQ score raised from 13.6 (±7.0) to 35.8 (±11.0) in 12 months (p<0.001) defining improvement in pain relief (from 21.6±8.7 to 59.11±13.1, p<0.001), walking distance (from 7.0±2.93 to 39.0±17.14, p<0,001), walking pace (from 9.1±5.5 to 35.9±17.42, p<0.01) and stair climbing (from 8.18±3.5 to 9.2±3.6, p=0.03). Arms comparison revealed HF-SCS superiority over LF-SCS in all WIQ scales. Emotional well-being (p<0.001), role-emotional score (p=0.004), vitality (p=0.07) social functioning (p<0.001) and pain scores (p=0.034) were significantly better in the HF-SCS group in 3 months. All SF-36 scores prevail in the HF-SCS group significantly in 12 months after the operation. LDF revealed significant perfusion improvement in both groups over 12 months period (p<0.001), but an intergroup analysis indicated no difference between HF-SCS and LF-SCS (p=0.5).

CONCLUSION

Despite similar improvements in tissue blood flow, high-frequency spinal cord stimulation grants better pain relief and walking ability in patients with chronic limb threatening ischemia comparing with conventional SCS.


Roman KISELEV (Novosibirsk, Russia), Martin KILCHUKOV, Vladimir MURTAZIN
16:15 - 16:20 #26196 - Occipital nerve stimulation: a promising option for surgically resistant trigeminal neuralgia.
Occipital nerve stimulation: a promising option for surgically resistant trigeminal neuralgia.

INTRODUCTION: Trigeminal neuralgia (TN) is a severe, debilitating pain condition causing physical and emotional distress. Although most patients respond to well conducted medical treatments, some become drug-resistant over time, requiring a surgical procedure. Various surgical techniques can be proposed depending on the medical condition and pain mechanism, with initial success rate of 70-90%. Yet, long-term recurrences are reported in 15-30% of cases irrespective of the technique, leaving patients with intractable pain. Neuromodulation techniques have been scarcely used for refractory TN, with studies reporting only small case series and short-term follow-up.

OBJECTIVE: This study aims at evaluating the long-term safety and efficacy of occipital nerve stimulation (ONS) for refractory TN.

METHODS: We conducted a bicentric (CHU de Nice, AP-HM Timone Marseille, France) retrospective study of patients treated by ONS for TN based on the IHS criteria. The efficacy of the ONS was evaluated using the Barrow Neurological Institute (BNI) pain score and the pain relief (0-100%) at best and at last follow-up. Adverse events were recorded.

RESULTS: Eight patients (6F/2M) suffering from refractory TN were included. Mean age at ONS was 47 years-old (range: 32-75; median: 43). Mean pain duration was 8.3 years (range: 2-14; median: 8). Mean number of medical treatments before ONS was 6.1 (range: 2-10; median: 6). Mean number of surgical treatments was 4.8 (range: 1-8; median: 5.5). A percutaneous trial was performed in 5 out of 8 patients; all responded and 4 out of 5 patients recurred after explantation. Eventually, 7 patients benefited from a permanent implantation. Average BNI pain score before implantation was V. Mean follow-up after implantation was 51 months (range: 2-102; median: 60). All patients reported an improvement after implantation. The average BNI score and mean pain relief at best were IIIa (range: IIIa-IV) and 85.7% (range: 70-100%; median: 80%), respectively. At last follow-up, the average BNI score and mean pain relief were IIIa (range: IIIa-V) and 61.7% (range: 0-100%; median: 65%), respectively, with 3 patients experiencing pain recurrence. Adverse events were reported for 5 patients (71.4%) who required surgical revision for lead breakage (2), erosion (1), migration (1), or hardware-related discomfort (1). This last patient was finally explanted for infection.

CONCLUSIONS: Although ONS is not validated in this indication, these results suggest that it can induce a dramatic improvement in TN patients recurring after several surgical treatments and the benefit of the stimulation can be sustained on the long term.


Anne BALOSSIER (Marseille), Anne DONNET, Jean RÉGIS, Aurélie LEPLUS, Michel LANTÉRI-MINET, Denys FONTAINE
16:20 - 16:25 #26312 - Effects of rate on analgesia in three common use sub-perception SCS: Burst, 1 khz and 10 kHz - 8 months results in double blind, randomized, multicentre study.
Effects of rate on analgesia in three common use sub-perception SCS: Burst, 1 khz and 10 kHz - 8 months results in double blind, randomized, multicentre study.

Introduction

         Spinal Cord Stimulation (SCS) is a commonly recommended procedure to treat several pain syndromes with a focus on pain relief an functionality.Stimulation parameters have been investigated and manipulated for years to optimize pain therapy. A wide range of frequencies used in commercially available SCS devices have been explored for various indications. Shechter et al., reported superior efficacy of high frequency SCS (1 kHz and 10 kHz)  The authors reported no differences in efficacy between 1 kHz and 10 kHz delivered at sub-perception stimulation strength.

The Burst waveform consists of intermittent stimuli delivered at 500 Hz (500-Hz spike mode) 40 times per second (40-Hz burst mode), with a pulse width of 1000 μs. The SUNBURST study shows that burst stimulation is capable of achieving better pain relief in 102 subjects when comparing to conventional low frequency stimulation. PROCO RCT study shows all kilohertz stimulations provide equivalent pain relief, demonstrating that stimulation rate was not meaningful determinants of back pain relief. 

Objective: the study investigated effect of 3 different paradigms rate: 500 hz,  calld burst, 1 kHz called HD (High Density) and 10 kHz, wall known as High Frequency (HF). on analagesia effect in randomized double blind, multi centers  study.

Material and method: on the 59 patients from 5 centres located in Poland consented to the study with implanting SCS wireless micro-stimulator, which can delivered all range of rates devices and all types of waveforms depending on pulse rate, pulse widths dosage configurations before randomization, all subjects received trial stimulation. Eight months observation finished 37 patients. Rate randomization phase where each patient has got 3 programs with 3 different rate paradigms: 500 Hz in Burst mode, 1khz and 10 kHz on personal programmer. Patient didn’t know, the differences between programs. Clinician, patient and data collecting research  were blinded and didn’t knows which program number is related to each rate. All observation last 8 months. During first 3 weeks, each rate was experienced one week. In fourth week, patients return to the most efficient program in own opinion. The first choice of rate and patients preferences were collected after 1 month of observation. Additionaly details about the most sufficient stimulation parameters and sweet spot search.  Pain relief was evaluated by Visual analogy scale, Oswestry Disability Index (ODI), Laitinnen Scale and Mc. Gill Scale.

Six month Follow-up. Patient used frequency from their preferences and change between 3 programs depends on pain level. To deliver the best pain relief, programming session with parameters adjustment was provide depends on patient needs. 6 months evaluation include: patient preferences for the best efficient rate, second and third choice of efficient rate, electric parameters and sweet pot location.  Pain relief was evaluated by Visual analogy scale, Oswestry Disability Index (ODI), Laitinnen Scale and Mc. Gill Scale.

Results: the main overall pain relief scores decreased from base related to back and leg pain. Pain reduction after 8 months of observation was statistically better than after 1 month of stimulation.

Patient preferences related to stimulation rate. All patients feel deference between different paradigms of stimulation, could recognize it and describe it. However, there was now clear corelation between efficacy and rate. After first month: 19 patients choose 1 kHz stimulation as a first choice.  10 patients choose 10 kHz stimulation and 9 patients Burst stimulation. After next 6 months of stimulation, 19 patients use at least 2 stimulation rate paradigms alternately. 16 patients used only one paradigms rate. After 6 months experiences of stimulation the shift from lower to higher rate was observed.

Side effect of stimulation. Especially in first phase of observation 14 patients demonstrating overstimulation effect after 10 kHz stimulation. 13 patients describe Burst stimulation as too week for them.

Conclusion:  the study provide, that is no clear rules in preferences of SCS sub-perception frequencies in Chronic low back and legs pain. All paradigms provide pain relief equivalent. The most stable pain relief effect seams to be during 1 kHz stimulation, however the possibilities of using different rate in different phase disease, could provide better long-term outcomes for chronic pain and required further investigations.

 


Aleksandra MAJ-KESICKA (Bydgoszcz, Poland), Pawel SOKAL, Marek HARAT, Leszek HERBOWSKI, Zennar KHEDER, Jacek NACEWICZ
16:25 - 16:30 #26325 - Occipital nerve stimulation for refractory chronic cluster headache: a cost-effectiveness study.
Occipital nerve stimulation for refractory chronic cluster headache: a cost-effectiveness study.

Introduction: Occipital nerve stimulation (ONS) is proposed to treat refractory chronic cluster headache (rCCH) but its cost-effectiveness has not been evaluated, limiting its diffusion and reimbursement. 

Methods: We performed a before-and-after economic study, from data collected prospectively in a nation-wide registry1. We compared the cost-effectiveness of ONS associated with conventional treatment (intervention and post-intervention period) to conventional treatment alone (pre-intervention period) in the same patients. The analysis was conducted on 76 rCCH patients from the French healthcare perspective at 3 months, then 1 year by extrapolation. Because of the impact of the disease on patient activity, indirect cost, such as sick leave and disability leave, were assessed secondly.

Results: The average total cost for 3 months was €7,602 higher for the ONS strategy compared to conventional strategy with a gain of 0.07 QALY (quality-adjusted life-years), the Incremental Cost-EffectivenessRatio(ICER) was then €109,676/QALY gained. The average extrapolated total cost for 1 year was €1,344 lower for the ONS strategy (p=0.5444) with a gain of 0.28 QALY (p<0.0001), the ICER was then €-4,846/QALY gained. The scatter plot of the probabilistic bootstrapping had 80% of the replications in the bottom right-hand quadrant, indicating that the ONS strategy is dominant(Figure 1). The average indirect cost for 3 months was €377 lower for the ONS strategy (p= 0.1261).

Discussion: This ONS cost-effectiveness study highlighted the limitations of a short time horizon in an economic study that may lead the healthcare authorities to reject an innovative strategy, which is actually cost-effective. 1-year extrapolation was the proposed solution to obtain results on which healthcare authorities can base their decisions. 

Conclusion: Considering the burden of rCCH and the efficacy and safety of ONS, the demonstration that ONS is dominant should help its diffusion, validation and reimbursement by health authorities in this severely disabled population.


Julie BULSEI, Aurelie LEPLUS, Jean REGIS, Donnet ANNE, Nadia BUISSET, Sylvie RAOUL, Stéphane DERREY, Bechir JARRAYA, Jimmy VOIRIN, Stephan CHABARDES, Sophie COLNAT-COULBOIS, Francois CAIRE, Philippe RIGOARD, Eric FONTAS, Michel LANTERI-MINET, Denys FONTAINE (NICE)
16:40 - 16:50 #23506 - Motor improvements after Selective Dorsal Rhizotomy (SDR) for GMFCS III and IV levels cerebral palsy children.
Motor improvements after Selective Dorsal Rhizotomy (SDR) for GMFCS III and IV levels cerebral palsy children.

OBJECTIVE : Until now, SDR have been reported mainly to treat lower limb spasticity for diplegic children with cerebral palsy GMFCS (Gross Motor Function Classification System) levels I and II (=less severe levels). The aim of the study is to evaluate functional motor improvements after SDR in children with cerebral palsy and more severe GMFCS levels: III to IV.

METHOD: Inclusion criteria were diagnosis of spastic cerebral palsy, GMFCS III to IV level, age between 3 to 18 years old at time of surgery. Exclusion criteria were spinal deformities, other pathologies and opting out of the study. Gross Motor GMFCS, Gillette Functional Assessment Questionnaire (FAQ), GMFM Goal Total Score D on standing and E on walking (GMFM GTS DE), and Physical Cost Index (PCI) were recorded. Selective dorsal rhizotomy (SDR) was performed on 33 CP children, 5 to 12 years old. Data analysis are retrospective. Side effects and evolution of other spasticity treatments were noted.

RESULTS: After two years follow-up, significant improvements of GMFCS (IV to III n=9/15) and FAQ (+2 level median) and an average gain of 8% on GMFM Goal total Score (GTS DE) are observed. PCI tends to decrease.

Most of children preoperative goals were obtained: facilitate standing position, nursing facilitation, walking improvements, decrease pain. Botulinum toxin injections were pursued on muscles non targeted by SDR for all children. BACLOFENE was interrupted for 3 patients and introduced for 3 during post-operative hospitalization. 5 years in average after SDR, complementary orthopedic surgeries were necessary for 19 (57%) children. Adverse effects of SDR were transcient urinary retention (n=2), scar infection (n=2).

CONCLUSION: SDR seems to be a valuable therapeutic option to control spasticity for CP children even with severe score of mobility (GMFCS III and IV). Two years after SDR, 47% of GMFCS IV children become GMFCS III. That means improvement of ambulatory capacities. Walking ability progress are in accordance with FAC and PCI improvements. Most functional preoperative goals were obtained.


Patrick MERTENS, Amelie FUSTIER, Andrei BRINZEU (Lyon), Poirot ISABELLE, Emmanuelle CHALEAT VALAYER, Jean Claude BERNARD
16:50 - 17:00 #23649 - Selective microsurgical tibial neurotomy for spastic foot. Effectiveness on Goal Attainment Score (GAS) at one year follow-up.
Selective microsurgical tibial neurotomy for spastic foot. Effectiveness on Goal Attainment Score (GAS) at one year follow-up.

Objective:Evaluation of achievement of individual functional goals for patients who beneficiated from selective tibial neurotomy for spastic foot. 

Goal Attainment Scale (GAS) is used toquantify progress of patients towards their personal goals. This scale have been applied for spastic patients but until now mainly to assess effects of botulin toxin injections. GAS is attracting and growing interest in clinical practice because it enables assessment of a treatment’s efficacy in terms of goals set by the patient him/herself rather than on generic scales, which may not always include the problem that most severely bothers the patient. For the first time, GAS assessment is used to evaluate functional consequences of selective neurotomies,

Method: A retrospective chart review of adult patients admitted to the Department of Functional Neurosurgery - Lyon (France) and selected for microsurgical selective tibial neurotomy was performed from 2011 to 2016. The primary outcome was to assess the Goal Attainment Scale (GAS) at 1 year follow-up. GAS is a formalization of the therapeutic objectives discussed on a daily basis with patients and their families. Determining these goals is relatively easy in routine during preoperative screening of the patient. Then, calculation of the overall attainment score for all the goals is performed at follow-up, with a five-point scale (from initial pretreatment baseline = -2  to  +2 = best possible outcome expected, 0 is the expected level after treatment). The pre and post-operative assessment were also performed for motor function using Medical Research Council (MRC) scale, spasticity using Modified Ashworth Scale (MAS), deformities with angular measures and walking ability with quantified analysis.

Results: Sixty-two selective tibial neurotomies were performed during this period, for patients disabled with different etiologies of spasticity: 56% post-stroke, 18% traumatic brain injury, 16% miscellaneous, 6% spinal cord injury. Preoperative goals defined for surgery were:  increase walking abilities (77%), provide better support and facilitate transfers (59%), make it easier to put on shoes (16%), reduce pain (11%), and allow new sporting activities (6%). One year after the surgery, the mean GAS was 0.42 ± 0.73. 42 patients had expected outcomes, 11 had more than expected outcomes, 6 had much more than expected outcomes, while 3 patients had less than expected outcomes. There was not difference of the motor function of the triceps surae muscle (according to the MRC scale) between the pre and post-operative periods (p >0.5). One year after the surgery, the spasticity of the triceps surae muscle was significantly lower according to the MAS (0.25 ± 0.6) than in the preoperative period (3.1 ± 0.8; p < 0.0001). One year after the surgery, equinus was residual in 16 subjects (25%) due to muscle-tendon shortness. 7 from them underwent associated orthopaedic surgery to correct it. No complication of tibila neurotomy occurred except scar infection in 2 patients (3%).

Conclusion: Studies with GAS-based approaches are now widely used in neurorehabilitation. Using this individual tailored assessment, this study is in favor that microsurgical selective neurotomy provided expected outcomes (or more) at one year follow-up for 95 % of patients with spastic foot.


Corentin DAULEAC (LYON), Jacques LUAUTE, Patrick MERTENS
Espace Vieux-Port
15:15

"Friday 10 September"

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D35
15:15 - 17:00

Parallel Session 14
Basics - Neurophysiology

Moderators: Linda ACKERMANS (Neurosurgeon) (Maastricht, The Netherlands), Christelle BAUNEZ (Director of Research) (Marseille, France)
15:15 - 15:30 #24018 - Electrophysiological correlates of fornix deep brain stimulation in a rat model of memory disorders.
Electrophysiological correlates of fornix deep brain stimulation in a rat model of memory disorders.

Deep Brain Stimulation (DBS) of the fornix is under preclinical and clinical investigations for the treatment of memory impairment in patients presenting with Alzheimer's disease (AD) (Lozano AM et al. 2016, Laxton AL et al. 2010). The fornix is a white matter bundle located in the mesial aspect of the cerebral hemispheres connecting various nodes of a limbic circuitry and believed to play a key role in cognition and episodic memory (Senova S et al. 2020). Optimal target within this circuitry and stimulation parameters to rescue memory deficits in AD and possibly a wider range of memory disorders have yet to be determined (Senova S et al. 2018). Most of preclinical studies investigating fornix DBS action mechanisms focused on molecular effects of prolonged fornix DBS (Mann A et al. 2018, Gondard E et al. 2015, Hescham S et al. 2015). However fornix DBS might acutely modify brain oscillations within the circuit of Papez and thus modulate memory processes (Senova S et al. 2018). In a rat model of acute memory deficit after scopolamine intraperitoneal injection, we started to investigate the effects on hippocampal and thalamic intracerebral local field potentials of precommissural fornix or post-commissural ventral fornix DBS, when performing high frequency (100Hz), low frequency (1Hz) or theta burst stimulation. In freely moving rats (n=6), we found that scopolamine administration decreased both hippocampal theta-gamma coupling as observed in AD and phase locking between hippocampus and anterior thalamic nuclei, which might be two electrophysiological correlates of memory processes. Acute theta burst stimulation of the precommissural fornix restored hippocampal theta-gamma coupling and phase locking between hippocampus and anterior thalamic nuclei. This study paves the way to investigate the behavioral effects of closed-loop precommissural fornix theta burst stimulation during a memory task in rat models of memory disorders associated with hippocampal oscillations disruption as observed in AD.


Yann-Suhan SENOVA (Créteil), Sara MAHALLATI, Elise GONDARD, Andres LOZANO
15:30 - 15:40 #23966 - Online decoding of leg force modulation and locomotor states from STN local field potentials in Parkinson's patients.
Online decoding of leg force modulation and locomotor states from STN local field potentials in Parkinson's patients.

The neural mechanisms that underlie gait and balance deficits in Parkinson's disease (PD) remain unclear. As a result, existing therapies merely rely on neuromodulation approaches optimized for upper-limb motor signs, such as tremor and bradykinesia, which have shown modest results for gait. Biomarkers of leg motor dysfunction are critically missing to help guide the development of novel strategies that specifically target locomotor impairments, for instance using predictions of leg motor dysfunction and locomotor states throughout movement execution.  

Previous studies have shown modulations in basal ganglia activity patterns that align to the timing of gait events, but the way such neural patterns correlate with actual deficits, how they change across locomotor activities, and how they may be employed to help predict impairments and thereby optimize therapies remains unknown.

Here, we aimed to develop real-time decoding algorithms that can predict leg muscle activations and locomotor states from local field potentials recorded from the subthalamic nucleus (STN). We recorded STN LFP signals in conjunction with whole-body kinematics and bilateral leg muscle activity patterns in 10 PD patients, as they performed a variety of locomotor tasks requiring adaptations in muscle recruitment and effort. We developed non-linear classification algorithms (random forest decoders) that automatically identify and extract relevant neural features for each patient in order to classify locomotor states (stand, walk, turn) and the level of bilateral leg motor effort (strong or weak muscle activation).

Despite intrinsic patient differences in STN patterns and locomotor behaviors, our decoder systematically achieved accuracies in the range of ~75%. Feature importance analyses automatically revealed specific frequency bands that contained the highest concentration of information for distinguishing locomotor states. Additionally, in patients exhibiting freezing of gait episodes, our decoder successfully predicted the occurrence of such events.

These results confirm that human STN LFP signals may be leveraged to predict gait states and motor adaptations, which holds promises to help regulate neuromodulation therapies in real time to specifically address deficits of gait and balance, such as asymmetry, freezing or shuffling steps in PD.


Kyuhwa LEE (Geneva, Switzerland), Yohann THENAISIE, Charlotte MOERMAN, Andrea GALVEZ, Flavio RASCHELLÀ, Mayte CASTRO JIMENEZ, Elvira PIRONDINI, Grégoire COURTINE, Jocelyne BLOCH, Eduardo MARTIN MORAUD
15:50 - 15:55 #26279 - Directional deep brain stimulation causes distinct intraoperative local field potentials in Parkinson’s Disease patients.
Directional deep brain stimulation causes distinct intraoperative local field potentials in Parkinson’s Disease patients.

Deep brain stimulation (DBS) is an invasive neuromodulation method used to treat medically refractory Parkinson’s disease (PD). Optimal stimulation effects are obtained by selectively targeting therapeutic brain regions, while avoiding regions causing side effects. The recent introduction of directional leads has made this task easier, with multiple studies showing improved clinical outcomes with directional stimulation, as opposed to omnidirectional stimulation.1 However, research on the effect of directionality on the electrophysiological brain response is limited. A previous study conducted by this lab has already shown a significant effect of stimulation contact direction on evoked response peak amplitude in electroencephalography (EEG) recordings from PD patients. In this study, we want to investigate if similar correlations exist for intraoperative local field potential (LFP) recordings. 

These LFPs were recorded intraoperatively during subthalamic nucleus (STN) implantation in PD patients. Stimulation was delivered from the directional contact level with the largest therapeutic window based on intraoperative clinical measures. For this level, the top of the therapeutic window was determined when stimulating omnidirectionally. This amplitude was used for stimulation to compare the directional contacts. Bipolar DBS stimulation was delivered at 10Hz for 30s from the directional contacts on one ring. One of the contacts served as the cathode, while the other two were used as the anode. For each combination, a differential recording was made between the contact level above and below. The evoked potentials in response to stimulation were calculated by averaging and filtering the individual stimulation epochs. Peaks and troughs were detected and analysed. The peak-to-peak amplitudes were calculated and the number of peaks was determined. The measures were related to the direction of the cathodic contact, which was determined post-operatively using Lead-DBS. The effect of  directionality was investigated with analysis of variance (ANOVA) (α=0.05).

The preliminary data (collection is ongoing) revealed the evoked response to DBS stimulation to be a high frequency under-damped oscillation (Figure 1), consistent with previous research.2 The peak-to-peak amplitude was observed to vary with stimulation direction. This was confirmed by the ANOVA, which showed a clear effect of directionality for the amplitude for the first 3 peaks (Peak 1. F-value: 396.89, p=1.73·10-119 ; Peak 2. F-value: 655.69, p=1.521-167; Peak 3. F-value: 412.56, p=8.02-123). A significant difference between each pair of contacts was confirmed using a post-hoc analysis. Postoperative localization of the implanted lead showed the contact with the highest oscillations to be directed towards the dorsolateral STN. In addition, the number of oscillations seemed to vary with direction, with the highest number of oscillations when stimulating dorsolateral in the STN. However, due to limited number of tested patients, this was not found to be significant. In the literature, the dorsolateral STN has consistently been linked to improved motor outcomes3, indicating that the evoked response could possibly be linked to clinical outcomes. However, more research is needed to confirm these findings.

1.         1 Merola A, Romagnolo A, Krishna V, et al. Current Directions in Deep Brain Stimulation for Parkinson’s Disease—Directing Current to Maximize Clinical Benefit. Neurology and Therapy. 2020;9(1):25-41. doi:10.1007/s40120-020-00181-9

2.         2 Wiest C, Tinkhauser G, Pogosyan A, et al. Local field potential activity dynamics in response to deep brain stimulation of the subthalamic nucleus in Parkinson’s disease. Neurobiology of Disease. 2020;143:105019. doi:10.1016/j.nbd.2020.105019

3.         3 Herzog J, Fietzek U, Hamel W, et al. Most effective stimulation site in subthalamic deep brain stimulation for Parkinson’s disease. Movement Disorders. 2004;19(9):1050-1054. doi:10.1002/mds.20056

 


Tine VAN BOGAERT (Leuven, Belgium), Jana PEETERS, Alexandra BOOGERS, Bart NUTTIN, Philippe DE VLOO, Myles MC LAUGHLIN
15:55 - 16:00 #26092 - Evoked potentials to guide deep brain stimulation programming in Parkinson’s disease.
Evoked potentials to guide deep brain stimulation programming in Parkinson’s disease.

Deep brain stimulation (DBS) is an established therapy to treat movement disorders such as Parkinson’s disease (PD). DBS parameters must carefully be programmed for each patient to deliver the best therapeutic effect. The advent of directional leads as well as current steering provide improved control of the stimulation field towards the target region and away from side effect-causing regions. However, this can extend the time necessary to optimize stimulation settings for individual DBS patients. Better understanding of how each DBS contact relates to its clinical outcome could help shorten the necessary programming time significantly. For this purpose, we propose a neurophysiological approach using electroencephalography (EEG) recordings to investigate how the evoked potential (EP) responses during DBS relate to its clinical outcome. Recent research conducted by our lab has shown that distinct EPs can be evoked by stimulating the different DBS-contacts (Peeters et al. submitted). More specifically, short-latency EPs around 3 ms (P3) had the largest amplitude when stimulating from DBS-contacts closest to dorsolateral subthalamic nucleus (STN) and long-latency EPs around 10 ms (P10) were strongest when stimulating from DBS-contacts closest to the substantia nigra pars compacta (SNr). In literature, P3 is often linked to activation of a corticosubthalamic hyperdirect pathway. It has even been suggested that DBS reaches its therapeutic effect by antidromic activation of this pathway. However, to the autor’s knowledge, no studies have reported a direct connection between EP amplitude recorded from different DBS-contacts and its corresponding clinical effect.

Thus, the aim of this research was to correlate EPs during DBS of the subthalamic nucleus to monopolar review results in PD patients. DBS was delivered at the different DBS-contacts separately and at the segmented contacts in an omnidirectional setting. DBS was delivered at 10 Hz for 50 seconds and EPs were recorded using EEG. For the duration of the experiment, stimulation was only applied in one hemisphere and turned off in the other. A template-matching artifact-reduction method was applied to reduce the stimulation-induced artifact, allowing investigation of short-latency EPs (< 10 ms). A monopolar review was performed to determine the therapeutic window (TW) of each DBS-contact. Bottom of TW was defined as the lowest stimulation intensity that relieved rigidity in contralateral wrist. Top of TW was defined as the lowest stimulation intensity where non-transient side effects appeared. Correlation analyses were performed between the peak amplitudes measured from each DBS-contact and its corresponding TW.

Four PD patients participated in this study, of which five hemispheres were tested (data collection is ongoing). In all tested hemispheres, we recorded a short-latency peak around 3 ms (P3) and a long-latency peak around 10 ms (P10). On an individual hemispheric level, we found a significant correlation between P3 and TW in 4 out of 5 hemispheres (p < 0.05). Furthermore, a significant correlation between P3 and the bottom of TW was found in 1 out of 5 hemispheres (p = 0.0008). Lastly, a significant correlation was found between P10 and the top of TW in all tested hemispheres (p < 0.05). On the group level, a significant correlation was found between P3 and TW (R² = 0.57; p = 0.0013) and between P10 and the top of TW (R² = 0.70; p < 0.0001). No significant correlation was found between P3 and the bottom of TW on the group level (p = 0.513).

This ongoing study provides preliminary evidence that P3 amplitude is higher in DBS-contacts where the TW is larger. This suggests that P3 might be a good predictor for the TW of each contact and could potentially be used as a biomarker to guide DBS programming of PD patients. Furthermore, P3 amplitude appears higher in DBS-contacts where the top of TW is reached at a lower stimulation intensity. This indicates that P10 is highest in the least optimal DBS-contacts and suggests that P10 might be a good predictor for avoidance of side effects. Future research should confirm the preliminary results presented here in a larger population. Ultimately, an EP biomarker that correlates to the best clinical contact would be highly relevant to guide the programming of DBS patients in a more objective manner.


Jana PEETERS (Leuven, Belgium), Alexandra BOOGERS, Tine VAN BOGAERT, Robin GRANSIER, Jan WOUTERS, Bart NUTTIN, Myles MC LAUGHLIN
16:00 - 16:05 #26121 - Deep brain stimulation and spinal cord stimulation changes iron and calcium-phosphate metabolism.
Deep brain stimulation and spinal cord stimulation changes iron and calcium-phosphate metabolism.

Background: Deep-brain stimulation (DBS) electrically modulates the subcortical brain regions. Under conditions of monopolar cerebral stimulation, electrical current flows between electrode’s contacts and an implantable pulse generator, placed in the subclavicular area. Spinal cord stimulation (SCS) delivers an electrical current to the spinal cord. Epidural electrical stimulation is associated with the leakage of current, which can cause generalized reaction. The aim of our study was to investigate whether the electrical stimulation of the cerebrum and spinal cord could have generalized effects on biochemical parameters. Materials and methodsA total of 25 patients with Parkinson’s disease (PD, n = 21) and dystonia (n = 4), who underwent DBS implantation, and 12 patients with chronic pain, who had SCS, received electrical stimulation. The blood levels of selected biochemical parameters were measured before and after overnight stimulation. Results: After DBSthe mean ± interquartile range (IQR) values for iron (off 15.6±13.53 µmol/L; on: 7.65±10.8 µmol/L; p<0.001), transferrin (off: 2.42±0.88 g/L; on: 1.99±0.59 g/L; p<0.001), transferrin saturation (off: 23.20±14.50%; on: 10.70±11.35%p=0.001), phosphate (off: 1.04±0.2 mmol/L; on: 0.83±0.2 mmol/L; p=0.007), and total calcium (off: 2.39±0.29 mmol/L; on: 2.27 ± 0.19 mmol/L; p=0.016) were significantly reduced, whereas ferritin (off: 112.00±89.00 ng/mL; on: 150.00±89.00 ng/mL; p=0.003) and C-reactive protein (off: 0.90±19.39 mg/L; on: 60.35±35.91mg/L; p=0.002) were significantly increasedAmong patients with SCS, significant differences were observed forferritin (off: 35±63 ng/mL; on: 56±62 ng/mL; p=0.013), transferrin (off: 2.70±0.74 g/L; on: 2.49±0.69 g/L; p=0.048), and C-reactive protein (off: 31.00±36.40 mg/L; on: 36.60±62.030 mg/L; p=0.018) before and after electrical stimulation. No significant changes in the examined parameters were observed among patients after thalamotomy and pallidotomy. Conclusions: Leaking electric current delivered to the subcortical nuclei of the brain and the dorsal column of the spinal cord exposes the rest of the body to a negative charge. The generalized reaction is associated with aninflammatory response and altered iron and calcium-phosphate metabolism. Alterations in iron metabolism due to electrical stimulation may impact the course of PD. Future research should investigate the influence of electric current and electromagnetic field induced by neurostimulators on human metabolism.


Paweł SOKAL (Bydgoszcz, Poland), Sara KIEROŃSKA, Milena ŚWITOŃSKA, Marcin RUDAŚ, Marcin RUSINEK, Marek HARAT
16:05 - 16:10 #26135 - Subthalamic local field potential recordings during gait in patients with Parkinson’s disease: first experiences with the Percept® neurostimulator.
Subthalamic local field potential recordings during gait in patients with Parkinson’s disease: first experiences with the Percept® neurostimulator.

Freezing of gait and falls are the main motor disabilities in patients with advanced Parkinson’s-disease (PD). These signs worsened with time and are not fully improved by the antiparkinsonian treatment or deep brain stimulation of the subthalamic nucleus (STN-DBS) leading to severe disability, increased morbidity and mortality. The link between STN neuronal activity and these episodic axial motor signs is not fully understood. Here, we recorded STN local field potentials (LFP) activity in 3 patients (2F/1M, mean age: 68.6 yrs, mean disease duration: 17.7 yrs, mean delay from STN-DBS surgery: 5.3 yrs) using the Percept neurostimulator (Medtronic, Ind. USA) allowing us to measure neuronal activity together with gait recordings using a force plate and Vicon system. These patients had residual On-dopa freezing of gait and/or falls. Patients were assessed both Off and On-dopa after intake of a suprathreshold dosage of levodopa both before STN-DBS, 6 months after STN-DBS and at the time of the implantation of the Percept neurostimulator. Gait recordings showed that 6 months after surgery, gait improved in all patients with increased step length and velocity with STN-DBS relative to before surgery Off-dopa. Conversely, 5 years after surgery, gait parameters were aggravated with no significant effect of STN-DBS, with moreover an additional aggravation with levodopa treatment in two patients. 

STN LFP recordings performed at the time of STN-DBS surgery in 2/3 patients revealed peak power increases in the alpha (8-12 Hz) and high beta (25-35 Hz) bands during gait initiation Off-dopa, concomitantly with low-beta band power (12-25 Hz) decrease. The high beta band power decreased On-dopa. Five years after surgery, we found the same alpha-beta peak power at rest Off-dopa (8 to 35 Hz). During gait, we found changes in these frequency bands related  to gait events, with alternating increased and decreased peak powers. Off-dopa, we found an increase of the beta power mainly in the high beta band frequency at gait initiation, with  low-beta band power increasing at lift-off of the contralateral foot during straight-ahead gait, and high-beta band power increasing during foot-contact. On-dopa, the alpha-beta power decreased with an increase in the gamma band power (more than 35 Hz). One patient had freezing of gait during recordings. In this patient, we observed concomitant increases in the low and high-beta band powers during FOG episodes. In one patient, we also used the Percept® system to record STN-LFP activity at home during gait, using the “events” recording mode (30 sec recording epochs) allowing us to measure the peak powers in the beta band activity. Looking the differences between “FOG periods” versus “quite normal gait periods” revealed no major differences. In conclusion, these preliminary results indicate that the use of the Percept® system is feasible for recording STN-LFP recordings in PD patients, and can be combined with behavioral tasks such as gait. However, recordings performed On-STN DBS could not be analyzed due to signal corruption by heartbeat-related artifacts. Further studies are needed to be able to specifically and individually correlate STN-LFP neuronal activity and motor or non-motor performance with the aim of developing closed-loop system for these patients.


Claire OLIVIER (Paris), Elodie HAINQUE, Julie BOURILHON, Brian LAU, Carine KARACHI, Marie-Laure WELTER
16:10 - 16:15 #26213 - Mapping of directional motor evoked potentials during the DBS surgery.
Mapping of directional motor evoked potentials during the DBS surgery.

Introduction

One of the main reasons to perform the Deep Brain Stimulation surgery (DBS) in awake patients is the possibility to detect undesired activation of descending motor tracts, since this is a therapy-limiting side effect. The current standard technique to detect motor side effects is based on the visual observation of muscle contraction during stimulation with conventional DBS stimulation parameters. Although directional lead technology can minimize long term stimulation side effects, it is still crucial to define the „optimal contact“ by intraoperative testing of all contacts – which is time consuming and sometimes unpleasant for the patient. The intraoperative mapping of subcortical motor evoked potentials (MEP) to detect motor threshold during DBS surgery is feasible, as already shown in the literature. We investigate the value of directional MEP mapping using segmented leads in basal ganglia as an alternative method to detect motor side effect thresholds during awake and asleep DBS surgery and to evaluate electrophysiological lead orientation.

Patients and methods

This study includes the results of the 44 patients who underwent DBS surgery in the subthalamic nucleus (STN), nucleus ventralis intermedius (VIM) and globus pallidus internus (GPI) in 32 cases as in awake surgery and 12 under general anesthesia (GA). The recording data of 88 trajectories were available. A cathodal stimulation in the stereotactic target was applied first over the macroelectrode tip in the target point using train-of-four pattern in 1 mA steps of 0 to 5 mA. Then we performed conventional 130Hz stimulation to detect muscle contractions. After the test stimulstion, DBS lead was inserted and we performed train-of-four MEP stimulation on all 8 contacts of segmented lead (Cartesia Lead, Boston Scientific). The recordings were obtained using surface electrodes in awake patients and needle electrodes in GA in the projection of m.mentalis, m. flexor dig., m. abductor policis brevis, and m. tibialis anterior on the contralateral side of the stimulation. The visual detection of the motor contraction under 130 Hz 60 μs stimulation in 1 mA steps (0-5 mA) was used as a standard control parameter.

Results

The MEP registration was successful in all stimulation sites. The MEP threshold correlated with visible muscle contraction at 130 Hz stimulation intraoperatively and with postoperatively documented DBS side effects. The recognition of activation of muscle response with MEP was muscle specific, more sensitive than visible muscle contraction, and remained stable under repeated stimulation. Patients described no complaints during the MEP mapping, only minimal contractions of the muscles, as opposed to much more unpleasant, possibly painful muscle contraction under classical detection of the motor capsule threshold with 130Hz-stimulation. The MEPs were easily obtainable in all cases under propofol-remifentanyl GA and showed comparable threshold values as the "tonic" stimulation postoperatively.

Conclusion

The MEP mapping is a safe and robust alternative to the conventional testing of the motor side effects, which can improve the safety and comfort of the DBS operation. The MEP thresholds correlate with capsule activation with 130 Hz stimulation and can be reliably recorded under general anesthesia. Directional MEP during DBS surgery provide information on lead orientation relatively to corticospinal tract independently from imaging methods, which facilitates decision on best stimulation site.


Yaroslav PARPALEY (Bochum, Germany), Manuel MACHADO LEMOS RODRIGUES, Lars SCHÖNLAU, Sabine SKODDA
16:15 - 16:20 #23781 - Evaluating physiologic and structural connectivity of Vim with motor cortex and superior parietal lobule during DBS for tremor.
Evaluating physiologic and structural connectivity of Vim with motor cortex and superior parietal lobule during DBS for tremor.

Introduction: Essential tremor (ET) is a debilitating disease affecting millions. DBS targeting the ventral intermediate (Vim) nucleus of the thalamus has been an effective treatment modality for years. Yet, the optimal methods for and precise effect of stimulation remain elusive. 

 

Objective: We studied ET patients undergoing DBS of a major input/output tract of the Vim, the dentato-rubro-thalamic tract (DRTt), using tractography and intra-operative thalamo-cortical evoked potentials (TCEPs). We performed intra-operative stimulation outside the normal constraints of clinical parameters while recording TCEPs, modifying stimulation amplitude and pulse width while controlling for total charge delivered. Finally, we expanded on results from de Hemptinne et al. (2015) in subthalamic nucleus DBS to show changes in phase-amplitude coupling (PAC) over primary motor cortex (M1) during DRTt DBS.

 

Methods: We enrolled seven ET patients undergoing DBS of the DRTt to undergo intra-operative thalamic stimulation. Diffusion tensor imaging (DTI) was collected pre-operatively for use in directly targeting the DRTt during surgery; the DRTt was reconstructed with probabilistic tractography using the cerebellar dentate nucleus as a seed region. Stimulation studies were carried out after a 12-contact subdural electrode was placed posteriorly from the access burrhole in the skull over M1 and superior parietal lobule (SPL); its position was confirmed with intra-operative 3D imaging prior to recordings. This was only performed unilaterally on the side contralateral to the more significant distal hand tremor. The Medtronic 3387 DBS lead was then placed stereo-tactically into the DRTt just inferior to the Vim; macrostimulation then ensued to evaluate for clinical efficacy, and the optimal contact pair for tremor control was identified. Tremor severity using The Essential Tremor Rating and Assessment Scale (TETRAS) was scored at baseline and at optimal stimulation. The DBS electrode was then connected to a Grass Stimulator, and stimulation was applied as balanced square wave pulses (stimulation amplitude from 1.25 to 10mA, pulse width from 30 to 250us). Amplitude and width were controlled for total charge deposited by calculating standard charge-density isolines (CDIs) for each amplitude-width pair (CDIs of 5,10 and 20 uC/cm2 were used). The impact of stimulation frequency on beta-gamma PAC (12-30Hz phase and 30-100Hz amplitude) was investigated by varying stimulation frequency (1, 2, 5, then 10 to 160Hz in 10Hz increments) with clinical stimulation parameters (pulse width 30us, pulse amplitude 3mA).

 

Results: DBS electrodes were successfully implanted into the DRTt in each of the seven patients; macrostimulation at a specific contact pair under typical parameters (130Hz, 60us, 2mA) significantly reduced contralateral tremor (pre-op/intra-op tremor TETRAS p<0.001). TCEPs were analyzed for N1/P1/N2 peaks (first negative, first positive, and second negative deflections, respectively), with both peak amplitude and area-under-the-curve (AUC) extracted. Upon multi-variate analysis with TCEP amplitude and AUC as dependent variables, and stimulation amplitude, pulse width, and CDI as independent variables, we found that CDI was a significant predictor of TCEP morphology (p<0.001, amplitude and pulse width were not significant). In our stimulation frequency experiment, we found decreased beta-gamma PAC similar to results seen in Parkinson’s patients, but were able to demonstrate that this effect was stimulation frequency dependent (PAC was significantly decreased for stimulation frequencies >80Hz).

 

Conclusion: Stimulation of the DRTt resulted in consistent TCEPs and demonstrates the potential for using intra-operative recordings to test for successful DBS lead placement. The earlier and larger evoked potentials in M1 as compared to SPL correlated well with the pre-operative tractography of the DRTt, which has greater connectivity with M1 than SPL. We found that the most important factor in TCEP morphology was total charge of stimulation (as measured by CDI) and not pulse amplitude or width. Decreased beta-gamma PAC within M1 correlated with clinical efficacy as hypothesized and was specific for stimulation frequencies >80Hz. Further work to characterize the correlation of clinical response to stimulation could improve DBS for tremor. 

 


Christopher CONNER, Kiefer FORSETH, Albert FENOY (Houston, USA)
16:20 - 16:25 #23472 - Injectable nanoelectrodes enable wireless deep brain stimulation in mice.
Injectable nanoelectrodes enable wireless deep brain stimulation in mice.

Devices that electrically modulate the deep brain have enabled important breakthroughs in the management of neurological and psychiatric disorders. Such devices are typically centimeter-scale, requiring surgical implantation and wired-in powering, which increases the risk of hemorrhage, infection, and damage during daily activity.  Recently, several remotely powered devices have emerged that could enable less invasive neuromodulation. The most clinically promising of these do not rely on transgenesis of neural tissue, but instead directly create electric signals to achieve neuromodulation. However, it has not yet been possible to scale down such devices sufficiently to enable complete implantation in the brain while still achieving deep-brain neuromodulation. Herein, we present injectable, magnetoelectric nanoelectrodes that wirelessly transmit electrical signals to the brain in response to an external magnetic field. Importantly, this mechanism of modulation requires no genetic modification of neural tissue and allows animals to freely move during stimulation. Using these nanoelectrodes, we demonstrate neuronal modulation in vitro and in deep brain targets in vivo. We also show that local thalamic modulation promotes modulation in other regions connected via basal ganglia circuitry, leading to behavioral changes in mice. This work demonstrates the potential of magnetoelectric materials as nanoelectrodes for wireless electrical modulation of deep brain targets. Herein, we have shown that we can stimulate Magnetoelectric Nanoparticles (MENPs) with a magnetic field to remotely generate electric polarization of the MENPs. We have shown evidence that non-resonant frequency magnetic stimulation of MENPs locally modulates neuronal activity in vitro and in vivo. We have also demonstrated that this modulation is sufficient to change animal behavior and to modulate other regions of the cortico-basal ganglia-thalamo-cortical circuit. Future work will be key to optimizing magnetoelectricity based neural devices and understanding the abilities and limitations of this technology. Magnetoelectric materials present a versatile platform technology for less invasive, deep brain neuromodulation.


Jahanshahi ALI (Maastricht, The Netherlands), Kristen KOZIELSKI, Hunter GILBERT, Yan YU, Önder ERIN, David FRANCISCO, Faisal ALOSAIMI, Yasin TEMEL
16:25 - 16:30 #23524 - High frequency stimulation of the subthalamic nucleus reveals a functional link between the basal ganglia and midbrain 5-HT system via the lateral habenula nucleus.
High frequency stimulation of the subthalamic nucleus reveals a functional link between the basal ganglia and midbrain 5-HT system via the lateral habenula nucleus.

Introduction

Basal ganglia disorders such as Parkinson’s disease are often co-morbid with psychiatric illness, and evidence that deep brain stimulation of the subthalamic nucleus (STN) can induce depressive behaviour in vulnerable patients identifies this nucleus as a potential neural substrate. Here using deep brain stimulation as a tool to modulate the STN in a ratmodel, we uncover an interaction between the STN and the lateral habenula nucleus (LHb), a controller of motivational and emotive behaviour, and a major source of input to 5-hydroxytryptamine (5-HT; serotonin) neurons in the midbrain raphe nuclei. 

Methods

Electrophysiological and behavioural experiments were performed on male Sprague Dawley rats with bilateral STN electrodes for high frequency stimulation (130Hz, 100uA, 60us). In vivo single unit recording of LHb neurons was performed in chloral hydrate anaesthetised animals. Once a spontaneously active LHb neuron was encountered the STN was stimulated with high frequency for 5 min and recordings continued for another 5 min. Also LHb neurons projecting to the midbrain raphe nuclei were identified by antidromic stimulation and collision testing, for which an additional stimulation electrode was implanted into the dorsal raphe nucleus. Once these LHb neurons projecting to the midbrain raphe were identified similar recording and stimulation was performed. The modulatory effect of STN stimulation on the firing rate of LHb neurons was analysed. The same STN stimulation model was used to evaluate the behavioural changes for motivation in food intake and sucrose intake tests and spontaneous locomotion in an unfamiliar open field. Some animals received discrete neurotoxic lesions of the LHb by bilateral stereotactic injection of quinolinic acid and underwent the same behavioural testing and STN stimulation, to evaluate the role of the LHb in STN related motivation.

Results

We found that electrical stimulation of the STN at clinical parameters consistently modulated the firing of LHb neurons (29% of the total neurons were significantly activated). We identified LHb neurons that project specifically to the midbrain raphe nuclei using antidromic activation and collision testing, and found that these neurons were also frequently modulated by STN stimulation. Juxtacellular labelling indicated that the vast majority of STN-responsive LHb neurons examined were glutamatergic, consistent with the known chemical identity of LHb output neurons including those projecting to raphe 5-HT neurons. Importantly, we found a behavioural correlate for the effects of STN stimulation on LHb neurons. STN stimulation induced a behaviourally selective decrease in food and sucrose intake, consistent with a reduced motivational state. Moreover, these behavioural responses were attenuated by neurotoxic lesion of the LHb, thereby linking STN-evoked behaviours to a LHb-dependent mechanism. 

Conclusion

Collectively, the present data demonstrate a convergence of neural connectivity between a core nucleus of the basal ganglia and the midbrain raphe 5-HT system via the LHb. This connectivity indicates a route by which STN stimulation evokes psychiatric effects in vulnerable patients, and by which dysfunctional basal ganglia circuitry can disturb emotionality more generally.


Sonny TAN (Aachen, Germany), Henrike HARTUNG, Trevor SHARP, Yasin TEMEL
16:30 - 16:35 #23942 - Epigenetic regulation of neurological key factors in rats after fastigial nucleus lesions.
Epigenetic regulation of neurological key factors in rats after fastigial nucleus lesions.

Objective: The cerebellar cognitive affective syndrome may result from various cerebellar injuries. Although it is not exactly known which anatomical structures are involved, the fastigial nucleus has been thought to play a pivotal role according to recent studies. We already showed that bilateral lesions of the cerebellar fastigial nucleus in juvenile rats lead to reduced social interaction during development, as well as to enhanced anxiety and reduced cognitive functions in adulthood together with altered firing patterns and low frequency band oscillations in the prefrontal cortex. Here we investigate whether fastigial nucleus lesions would affect epigenetic regulation of different target genes related to  dopamine, glutamate and oxytocin neurotransmission (DRD2, DAT, GAD1, Grin1, and OXTR) in brain regions with anatomic connections to the fastigial nucleus, i.e., medial prefrontal cortex, nucleus accumbens, striatum, thalamus, sensorimotor cortex.

Methods: The fastigial nucleus was lesioned bilaterally by thermocoagulation via stereotaxically implanted electrodes in 23-day old male Sprague Dawley rats. Sham-lesioned (no application of electrical current) and naïve rats served as controls. To investigate the methylation of the promotor regions of the target genes, DNA was extracted from different brain regions and subjected to Touchdown PCR protocols and Sanger sequencing. All data were validated for quality and subjected to comparative statistical analysis. Important areas of the promoter region were in-silico verified for existing transcription factor motives.

Results: From the five targets analyzed, we identified methylation sites positions that were altered in lesioned rats as compared to control and sham lesioned rats. Differences were mainly shown for OXTR and Gad1, indicating compromised function of the glutamate and oxytocin transmitter systems after fastigial nucleus lesions.

Conclusion: We observed several regulative hotspots for OXTR and GAD1 in brain regions with anatomical connections to the fastigial nucleus, which may contribute to behavioral deficits and altered neuronal activity in lesioned rats as compared to control and sham-lesioned rats. These findings can guide further studies towards prevention of long-lasting non-motor deficits after cerebellar lesions early in life.


Simeon O. A. HELGERS, Marc A. N. MUSCHLER, Alexander GLAHN, Shadi AL-AFIF, Yazeed AL KRINAWE, Elvis J. HERMANN, Joachim K KRAUSS, Helge FRIELING, Kerstin SCHWABE (Hannover, Germany), Mathias RHEIN
16:35 - 16:40 #23977 - Frequency-dependent medial septal nucleus deep brain stimulation modulates hippocampal oscillatory activity and improves spatial working memory in an MK-801 model of schizophrenia.
Frequency-dependent medial septal nucleus deep brain stimulation modulates hippocampal oscillatory activity and improves spatial working memory in an MK-801 model of schizophrenia.

Introduction:

Schizophrenia is a debilitating psychiatric disease characterized by positive, negative and cognitive symptoms.  Pharmacological models targeting glutamate N-methyl-D-aspartate (NMDA) receptor hypofunction (such as MK-801) mimic these symptoms and disrupted neural oscillatory activity, such as decreased hippocampal theta (5-12 Hz) activity.  Here, we studied the effects of MK-801 on neural network oscillations and spatial working memory and the potential for medial septal nucleus (MSN) stimulation to improve these outcomes.

Methods:

44 male Sprague-Dawley rats underwent implantation of hippocampal, prefrontal cortex (PFX) and thalamic recording electrodes and an MSN stimulating electrode.  Rodents underwent sham (n=13) or MK-801 (n=31) intraperitoneal injections 30 minutes prior to baseline recordings and each Barnes maze task.  During the behavioral task, MK-801 rats received no stimulation, theta (7.7 Hz) stimulation or gamma (100 Hz) stimulation. Latency to finding the escape hole was recorded. 

Results:

MK-801 rats had reduced hippocampal theta power (p<0.05) compared to sham animals, but were not different in PFC (p=0.88) or thalamic theta power (p=0.05).  On the Barnes maze, MK-801 animals had longer latencies relative to sham animals on post-surgery days 12-14 (p<0.05).  MK-801 animals without stimulation had a longer latency than sham animals (145.0+/-26.0 vs. 55.3+/-10.9 seconds, p<0.001).  MK-801 animals with theta stimulation had shorter latencies than MK-801 animals without stimulation (48.6+/-14.8 seconds, p<0.001); however, MK-801 animals with gamma stimulation were no different than MK-801 animals without stimulation (182.6+/-33.0 seconds, p=0.39). 

Conclusions:

MK-801 glutamate hypofunction reduced hippocampal theta oscillations and impaired spatial working memory.  MSN theta, but not gamma, stimulation improved spatial working memory following MK-801 administration.


Nancy ZEPEDA, Gengxi LU, Raymond GIFFORD, Darrin LEE (Los Angeles, USA)
Salle 120
17:00

"Friday 10 September"

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A36
17:00 - 18:30

ESSFN General Assembly

Auditorium
Saturday 11 September
08:30

"Saturday 11 September"

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A41
08:30 - 10:30

Plenary Session 7a

Moderators: Christelle BAUNEZ (Director of Research) (Marseille, France), Jean REGIS (PROFESSEUR) (MARSEILLE, France)
08:30 - 09:00 To sleep or not to sleep: that is the question for DBS procedures and Parkinson's disease. Hagai BERGMAN (Prof) (Keynote Speaker, Jerusalem, Israel)
09:00 - 09:30 Immunity in the brain and radiosurgery. Bodo LIPPITZ (Co-Director) (Keynote Speaker, Hamburg, Germany)
09:30 - 10:00 Deciphering the hodology of essential tremor. Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Keynote Speaker, Lausanne, Switzerland)
10:00 - 10:30 The future of Epilepsy Surgery. Hans CLUSMANN (Department of Neurosurgery) (Keynote Speaker, Aachen, Germany)
Auditorium
10:30 COFFEE BREAK & VISIT OF POSTERS AND EXHIBITION
11:00

"Saturday 11 September"

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A42
11:00 - 12:00

Plenary Session 7b

Moderators: Jocelyne BLOCH (Médecin Cadre) (Lausanne, Switzerland), Viktor JIRSA (Aix-Marseille University, Local Host, EBRAINS AISBL) (Marseille, France), Joachim K. KRAUSS (Chairman and Director) (Hannover, Germany)
11:00 - 11:30 Controversies in movement disorders surgery: Should we offer DBS to dystonia patients regardless of etiology? Joachim K. KRAUSS (Chairman and Director) (Keynote Speaker, Hannover, Germany)
11:30 - 11:45 #26205 - Long-term outcomes of ventral tegmental area deep brain stimulation for trigeminal autonomic cephalalgias.
Long-term outcomes of ventral tegmental area deep brain stimulation for trigeminal autonomic cephalalgias.

Objectives

                                                    

To present long-term outcomes of ventral tegmental area (VTA) deep brain stimulation (DBS) for medically refractory, chronic trigeminal autonomic cephalalgias 

 

Introduction

 

VTA DBS has been proven to be a safe and effective therapy for chronic cluster headache (CCH) and short-lasting unilateral neuralgiform headache attacks (SUNHA) in relatively small patient cohorts. The mechanism of action is not fully understood but is likely to involve the neuromodulation of the trigeminal parasympathetic reflex, which is triggered during attacks. To our knowledge, this is the largest series of patients that have undergone this procedure in a single centre.

 

Methods

 

Between 2009 and 2019, 71 patients (39 male and 32 female with an average age of 53 years [SD=13]) were treated with VTA DBS for chronic, medically refractory CCH (n=43) and SUNHA (n=28). Fifty-four patients underwent unilateral implantation (33 right), and 17 underwent bilateral implantations. Patients were assessed pre- and post-operatively by a specialist multidisciplinary team including headache neurologists, specialist nurses and functional neurosurgeons.

 

Results

 

The average follow-up was six years (SD=3.2). Response was set at 50% improvement in attack frequency. Forty-nine patients (69%) were responders with a mean improvement of 78% (SEM=2.7, SD=19.1, CL95%=5.5) and a median of 83%. In responders, headache severity on the verbal rating score (VRS) improved by a mean of 40% (SEM=5.2, SD=36.7, CL95%=10.5) and a median of 30% (3 points out of 10 in the CCH responders and 4.5 points in the SUNHA group). Attack duration in the responders improved by a mean of 37% (SEM=8, SD=56.1, CL95%=16.1) and a median of 50% from 120 to 45 minutes per attack in CCH and from 2 to 0.35 minutes in the SUNHA group. The headache load (HAL); a composite score encompassing frequency, severity, and duration of attacks improved by a mean of 73% (SEM=7.7, SD=52, CL95%=15) and a median of 89% in clinical responders.

 

Two thirds of patients (73% of responders and 48% of non-responders) had a stun effect during the postoperative period, which consisted in either complete symptom relief or in clinically significant reduction of the frequency, duration, or severity of the headaches. The mean length of the stun effect was 28 days (SEM=5.5, S=37.4, CL95%=11) and a median of 17 days. 

 

Four non-responders had the DBS system explanted, two of them secondary to infection and one due to post-surgical neuropathic pain around the head wound site. Two patients had the stimulation turned off due to absence of benefit. Four patients died due to unrelated conditions.

 

Conclusions

 

This open label study provides class IV evidence that VTA-DBS is a safe and effective long-term therapy for CCH and SUNHA.

 

Dr M Matharu and Mr H Akram contributed equally to this submission as co-senior authors


Olga PARRAS GRANERO (Basque country, Spain), Sanjay CHEEMA, Susie LAGRATA, Jonathan HYAM, Ludvic ZRINZO, Manjit MATHARU, Harith AKRAM
11:45 - 12:00 Connectivity Changes in the Salience Network after Cordotomy and Cingulotomy for Cancer Pain. Ido STRAUSS (Neurosurgeon) (Keynote Speaker, Tel Aviv, Israel)
Auditorium
12:00

"Saturday 11 September"

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A43
12:00 - 12:30

ESSFN Search grant and Awards 2021

Moderators: Jocelyne BLOCH (Médecin Cadre) (Lausanne, Switzerland), Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (LISBON, Portugal), Jean REGIS (PROFESSEUR) (MARSEILLE, France)
12:00 - 12:30 3 Best oral communications and 3 best Posters. Niels Anthony VAN DER GAAG (neurosurgeon) (Keynote Speaker, The Hague, The Netherlands), Kuan Hua KHO (Neurosurgeon) (Keynote Speaker, Enschede, The Netherlands), Martin JAKOBS (Consultant) (Keynote Speaker, Heidelberg, Germany)
12:00 - 12:30 Best Publication. Juan Antonio BARCIA (Neurosurgeon) (Keynote Speaker, Barcelona, Spain), Patric BLOMSTEDT (Neurosurgeon) (Keynote Speaker, Umeå, Sweden), Lorand EROSS (Director of the institute) (Keynote Speaker, Budapest, Hungary)
12:00 - 12:30 Best research awards. Jocelyne BLOCH (Médecin Cadre) (Keynote Speaker, Lausanne, Switzerland), Stephan CHABARDÈS (head of the department) (Keynote Speaker, GRENOBLE, France), Bart NUTTIN (Professor) (Keynote Speaker, Leuven, Belgium)
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EP01
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Eposters
BASIC SCIENCE

00:00 - 00:00 #24072 - Changes in the patient’s cognitive status at the spinal cord stimulation.
Changes in the patient’s cognitive status at the spinal cord stimulation.

The high social significance and prevalence of cognitive impairment determines the relevance of the search for new ways to correct these conditions, but existing pharmacological methods that improve the functional state of the central nervous system do not always meet the expectations of both doctors and patients. In clinical practice, a combination of moderate cognitive impairment of vascular origin with chronic pain syndromes is quite often noted.

The aim of the study was to study changes in cognitive status in patients with trial and chronic epidural spinal cord electrical stimulation.

Materials and methods. The study was conducted on 46 patients hospitalized and operated on at the Department of Functional Neurosurgery of the Federal Centre of Neurosurgery (Tyumen) from January 2015 to December 2019. The average age of the patients at the time of the study was 59.5±2.9 years. In all patients the indication for surgical treatment was a severe drug-resistant pain that developed as a result of various surgical interventions on the lumbar spine. Cognitive status was assessed using the SAGE test before the trial stimulation of the spinal cord, on day 5, immediately after the end of the trial period of electrical stimulation and after 3 months after implantation of the chronic epidural spinal cord electrostimulation system (EON C (St. Jude Medical Inc., USA). The study included patients over the age of 50 years with moderate cognitive deficiency of vascular origin (10-16 scores on the SAGE scale). Epidural electrodes in all patients were located at Th9-Th10 level. Stimulation parameters were selected individually and varied from 60 to 80 Hz, pulse widths from 300 to 500 μs, amplitude from 2.5 to 6 mA. The control group was represented by 28 patients of the spinal surgery department with chronic vertebrogenic pain syndromes. The age, gender distribution, and initial cognitive status of these patients corresponded to the main clinical group.

Results. All patients of the main clinical group on the background of electrical stimulation subjectively described improvement in well-being, normalization of sleep, and a decrease in the level of anxiety and depression. On the 5th day of the trial stimulation of the spinal cord in patients of this group, an improvement in cognitive status on the SAGE scale from 13.5±0.8 to 17.1±0.7 scores (P<0.05) was objectively observed. The average test execution time decreased from 18.36±1.18 min to 13.09±1.62 min (P <0.05). These changes significantly differed from the indicators of the control group, where in the postoperative period there was no significant change in cognitive status (except for the time of the repeated test). At the control examination (after 3 months) against the background of chronic epidural electrical stimulation of the spinal cord, the SAGE test scores were 17.4±0.6  (P<0.05 compared with the initial level), the average test time was 13.18±0.79 min (P<0.05 compared to baseline). All patients both in the early and in the distant postoperative period showed an improvement in cerebral circulation according to MRI and CT perfusion of the brain.

Conclusion. Our data show that chronic epidural spinal cord stimulation is accompanied by a persistent improvement in cognitive status in patients with moderate cognitive deficiency of vascular origin.


Andrei SHAPKIN (Tyumen, Russia), Albert SUFIANOV, Galina SUFIANOVA
00:00 - 00:00 #26256 - Effects of high frequency stimulation of the subthalamic nucleus in Parkinsonian mice on the acetylcholinergic system of the pedunculopontine nucleus.
Effects of high frequency stimulation of the subthalamic nucleus in Parkinsonian mice on the acetylcholinergic system of the pedunculopontine nucleus.

Introduction

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is standard care for motor symptoms of Parkinson’s disease. However, a challenge of DBS remains improving gait and balance disturbances. The control of gait and balance has been associated with the acetylcholine system in the pedunculopontine nucleus (PPN). In this study we investigated the effects of STN DBS on the PPN acetylcholine system in a Parkinsonian mouse model by immunohistochemistry.

 

Materials and Methods

Mice received intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline. This was followed by bilateral STN electrode implantation. The animals underwent chronic STN DBS or sham stimulation. Motor behaviour was assessed by the automated Catwalk gait analysis. After transcardial perfusion brains were sectioned and processed for tyrosine hydroxylase (TH), choline acetyltransferase (ChAT) and c-Fos immunohistochemistry. Neuronal expression of these markers was evaluated by stereological analysis.

 

Results

MPTP treated mice showed static and dynamic gait impairments in the Catwalk analysis compared to saline treated animals. These impairments were reversed by STN DBS. MPTP treated mice resulted in a significant reduction of dopaminergic neurons in the substantia nigra pars compacta and PPN acetylcholinergic neurons by TH and ChAT immunohistochemistry respectively. STN DBS did not alter the number of PPN ChAT neurons expressing the neuronal activation marker c-Fos.

 

Conclusion

MPTP injections resulted in motor and gait impairments as well as a degeneration of the PPN acetylcholine system. Although STN DBS improved gait and balance in the automated Catwalk this was not associated with an activation of PPN acetylcholine neurons, as immunohistochemical double labelling for ChAT and c-Fos was not changed by STN DBS. Motor and gait effects of STN DBS are therefore less likely to be mediated by a STN-PPN connection.


Sonny TAN (Aachen, Germany), Victoria WITZIG, Faisal ALOSAIMI, Hans CLUSMANN, Yasin TEMEL, Ali JAHANSHAHI
00:00 - 00:00 #23349 - Influence of DBS-like electric stimulation on inflammatory mediators in-vitro.
Influence of DBS-like electric stimulation on inflammatory mediators in-vitro.

Objective: Deep brain simulation (DBS) is a neurosurgical therapy especially for movement disorders but also psychiatric diseases as depressions with a therapy-refractory course are rising. Even if the therapeutic results are mostly satisfactory, the mechanism of action is not completely understood. Possibly the effect of DBS is partly based on changed cytokine/ chemokine concentrations of the surrounding brain cells. Thus, in this study we established an in vivo adapted in vitro model of DBS and analyzed the influence of an electric stimulation on different brain cells.

Methods: According to conditions used in DBS patients, we established an in vitro model to electrically stimulate SVGA- (Astrocytes), HMC3- (Microglia) and SH-SY5Y-cells (Neurons). To exclude an influence on apoptosis or proliferation rates, cells were stained by TUNEL-Assay and proliferation rates were determined by cell counting compared to control samples, respectively. Additionally, we stimulated brain cells with 2mV for 24 hours and measured the expression of different cytokines and chemokines (CXCL12, CXCL16, CCL2, CCL20, IL1β, IL6) by qrtPCR and verified significant expression differences by fluorescence staining.

Results: The in vivo adapted in vitro DBS-model was established successfully. An influence on cell proliferation and apoptosis rates was not observed. mRNA expression of IL1β in SH-SY5Y-cells and CXCL12 in SVGA-cells were significantly induced, and these results were confirmed by fluorescence staining.  

Conclusion: The mechanism of action of DBS seems to be very complex and its influence on the expression of cytokines and chemokines should be further explored. The establishment of this DBS-model could lead to a better understanding of these effects.


Henri MOLKEWEHRUM, Carolin KUBELT, Michael SYNOWITZ, Janka HELD-FEINDT, Ann-Kristin HELMERS (Kiel, Germany)
00:00 - 00:00 #25856 - Minimising post-op micro-hemorrhages in the milieu of the DBS electrode by using bipolar stimulation – an in-vitro experiment.
Minimising post-op micro-hemorrhages in the milieu of the DBS electrode by using bipolar stimulation – an in-vitro experiment.

Background: Introducing the Deep Brain Stimulation (DBS) Electrode into the target may cause peri-electrode edema which can present from 6 hours to 120 Days postoperatively, with symptoms ranging from confusional states, neurological deficits to seizures and dyskinetic storms.[1-3]  A postulated mechanism of peri-electrode edema is Microhaemorrhages due to lead implantation.[2] In a prospective study by Borellini et al., all patients who underwent DBS implantation showed asymptomatic peri-lead edema on postoperative MRI imaging, with 30% having microhemorrhages.[4] Microhemorrhages and edema around the lead can result in postoperative as well as the long term changes in tissue impedance.[5] Therefore, an ideal Lead-Tissue interface, i.e. one with minimal post-operative edema, is essential to prevent post-operative complications as well as to improve long term outcome of stimulation.

Material and Methods: In our in-vitro experiment, two DBS electrodes were introduced into two test tubes, each containing 5 ml of freshly drawn venous blood. One electrode was turned on with a bipolar pattern of stimulation, and the other acted as a control. Clotting time was observed in both the test tubes.[Fig 1] The experiment was repeated with increasing increments of stimulation voltage from 0.5 to 4.5 Volts. The experiment was conducted at a constant temperature of 25°C.

 

Results: There was a 44.4% decrease in the clotting time with the bipolar stimulation turned on as compared to the control electrode.[Table 1] No change in clotting time was observed after increasing the stimulation voltage beyond 2.0 V. After blood in both test tubes had clotted (at 5 minutes), there was visible clotting on the electrode with the stimulation turned on, while the control electrode was clean. [Fig 2]

 

Conclusions: Turning on the stimulation significantly reduced the clotting time around the DBS electrode in our in-vitro experiment. We believe these findings will prove to be beneficial in an operative setting. Till date, no evidence based guidelines exist on when to begin the stimulation after a DBS surgery, with most centres turning on the stimulation after 4 weeks of the implantation. [6] We hypothesise that turning on the DBS electrodes immediately after implantation would help reduce Microhemorrhages and Edema by expediting the hemostasis. We believe a bipolar stimulation [Fig 3] at 2.0 V for 3 minutes would ensure adequate hemostasis, thereby minimising peri-lead edema. This would ensure a better lead-tissue interface for future stimulation purposes.

 

References:

1.     Lee JJ, Daniels B, Austerman RJ, Dalm BD. Symptomatic, left-sided deep brain stimulation lead edema 6 h after bilateral subthalamic nucleus lead placement. Surg Neurol Int. 2019 Apr;10:68.

2.     Deogaonkar M, Nazzaro JM, Machado A, Rezai A. Transient, symptomatic, post-operative, non-infectious hypodensity around the deep brain stimulation (DBS) electrode. J Clin Neurosci. 2011 Jul;18(7):910–5.

3.     K. Hooper A, M. Ellis T, D. Foote K, Zeilman P, S. Okun M. Dyskinetic Storm Induced by Intra-Operative Deep Brain Stimulator Placement. The Open Neurosurgery Journal. 2009 Feb [cited 2021 Apr 15]. ;2(1). Available from: http://benthamopen.com/contents/pdf/TONEUROSJ/TONEUROSJ-2-1.pdf

4.     Borellini L, Ardolino G, Carrabba G, Locatelli M, Rampini P, Sbaraini S, et al. Peri-lead edema after deep brain stimulation surgery for Parkinson’s disease: a prospective magnetic resonance imaging study. Eur J Neurol. 2019 Mar;26(3):533–9.

5.     Hartmann CJ, Wojtecki L, Vesper J, Volkmann J, Groiss SJ, Schnitzler A, et al. Long-term evaluation of impedance levels and clinical development in subthalamic deep brain stimulation for Parkinson’s disease. Parkinsonism Relat Disord. 2015 Oct;21(10):1247–50.

6.     Picillo M, Lozano AM, Kou N, Puppi Munhoz R, Fasano A. Programming Deep Brain Stimulation for Parkinson’s Disease: The Toronto Western Hospital Algorithms. Brain Stimul. 2016 May;9(3):425–37.


Hargunbir SINGH (Chandigarh, India), Nishit SAWAL, Arnav MITTAL, Divij SINGHAL, Adhish BERI, Gurmehar HUNDAL, Saloni Rani KUMAR, Ansh CHAWLA
00:00 - 00:00 #24071 - Renal hemodynamic and excretory function at spinal cord stimulation.
Renal hemodynamic and excretory function at spinal cord stimulation.

Pain is a strong stressful irritant that has a huge impact on almost all organs and systems of a patient, while a pain reaction through a reflex mechanism can cause impaired renal hemodynamics. Changes in renal blood flow, in turn, is accompanied by impaired homeostasis, disorders of the water-electrolyte balance, impaired neuroendocrine regulation, causing and exacerbating dysfunction of the cardiovascular system. Considering the known peripheral hemodynamic effects of spinal cord stimulation, a similar positive effect of this treatment on blood circulation and kidney function can be assumed.

Purpose of the study. To study the effect of epidural electrical stimulation of the spinal cord on renal blood flow and excretory function.

Materials and methods. We examined 18 male patients aged 50 to 65 years who were treated at the Federal Center of Neurosurgery (Russia,Tyumen). In all patients, regardless of the nature and severity of the clinical picture of the underlying disease, the indication for surgical treatment was a severe drug-resistant pain syndrome that developed as a result of various surgical interventions on the cervical and lumbar spine. Temporary epidural electrodes were implanted in all patients, respectively, at the cervical (C3-C6, N = 8) or lower thoracic (Th9-Th10, N = 10) levels. The stimulation parameters were selected individually, the pulse frequency was 80 Hz, the pulse width was 500 μs, and the amplitude was from 2 to 6 mA. The period of temporary epidural electrical stimulation of the spinal cord was 5-7 days. Assessment of renal blood flow was carried out on an ultrasound machine Toshiba Aplio 500 before implantation of the trial epidural electrode and 5-7 days after surgery. Peak systolic (PSV), end-diastolic blood flow velocities (EDV) and resistance index (RI) were studied in the renal artery, segmental, interlobar and arciform arteries and in the renal veins. To assess the excretory renal function in the concentration of creatinine, urea and residual nitrogen in the blood serum were evaluated.

Results. With spinal cord stimulation at the Th9-Th10 level, all patients showed a statistically significant increase in peak systolic renal blood flow velocity by 20-35%. The greatest hemodynamic changes were recorded in the renal artery and interlobar arteries, where the increase in PSV was 30.8%, respectively (from 0.74±0.01 m/s to 0.98±0.03 m/s, P<0.01) and 39.62% (from 0.32±0.03 m/s to 0.44±0.04 m/s, P<0.05). Peak systolic blood flow velocity in segmental and arciform arteries increased by 24.4%, respectively (from 0.56±0.06 m/s to 0.71±0.07 m/s, P<0.05) and 28% ( from 0.23±0.03 m/s to 0.29±0.02 m/s, P<0.05). Moreover, statistically significant changes in the diameter of the arteries (the diameter of the renal artery was 6.3-6.8 mm) and RI (0.33-0.4) were not observed. In the analysis of biochemical parameters, a decrease in the serum level of urea (from 6.48±0.45 mmol/L to 4.74±0.4 mmol/L, P<0.01), residual nitrogen (from 26.6±1.36 mmol/L to 21.42±1.2 mmol/L, P<0.01) and creatinine (from 76.8±2.3 μmol/L to 72.4±2.2 μmol/L, P<0.05), which indicates an increase in glomerular filtration rate. When stimulating the spinal cord at the level of the cervical thickening, statistically significant changes in the renal hemodynamics and biochemical blood parameters were not observed. In both groups, there was a tendency to a decrease in average daily heart rate and systolic blood pressure.

Conclusion. Spinal cord stimulation is accompanied by an increase in the functional and speed indicators of renal hemodynamics, which is of interest for using this method in cases of impaired renal blood flow and filtration-excretory renal function of various genesis, this study is also promising with the aim of using the method of electrical stimulation of the spinal cord for renal arterial hypertension.


Andrei SHAPKIN (Tyumen, Russia), Albert SUFIANOV, Galina SUFIANOVA, Olga SADYKOVA, Tamara ISHENKO
00:00 - 00:00 #23500 - Stereo-EEG with microelectrodes: Single neurons in human medial temporal lobe encode ego- and allocentric direction during virtual spatial navigation.
Stereo-EEG with microelectrodes: Single neurons in human medial temporal lobe encode ego- and allocentric direction during virtual spatial navigation.

Background: Successful spatial navigation requires a detailed neural representation of the spatial environment. Allocentric representations encode spatial information in a world-centered reference frame, whereas egocentric representations encode spatial variables relative to the observer. 

 

Methods: To demonstrate the coexistence of ego- and allocentric representations of direction in the human brain, we recorded from medial temporal lobe neurons in neurosurgical epilepsy patients performing a virtual navigation task. 498 medial temporal lobe neurons were recorded via 45 stereotactically implanted depth electrodes outfitted with 8 microelectrodes each (Behnke-Fried electrodes). Neurons were extracted using spike sorting and clustering algorithms and their activity was related to the patients' behavioral performance in the virtual environment. 

 

Results: We describe a new class of neurons whose activity varies as a function of egocentric direction towards local reference points of the spatial environment (“anchor cells”), complementary to neurons coding for allocentric location or global direction. Anchor cells were particularly prevalent in parahippocampal cortex and overrepresented the environmental center as a local reference point.

 

Conclusion: Our results provide first evidence for neural codes of egocentric space in the human brain and support the two-system model of parallel egocentric and allocentric representations in spatial memory and navigation.

 

Fig. 1: Task, behavioral performance, and illustration of anchor-cell identification. 

A, Patients performed an object–location memory task in a virtual environment. In each trial, a given object (“cue”) had to be placed at its correct location (“retrieval”). Patients received feedback depending on response accuracy (“feedback”) and re-encoded the object location afterwards (“re-encoding”).

B, Bird’s eye view of the environment. Blue compass, allocentric direction; green compass, egocentric direction (given the patient is facing “northeast”). A (B; L; R), ahead (behind; to the left; to the right) of the subject.

C, Histogram of spatial memory performance values across all trials from all patients (n=1890 trials). Red dotted line, chance level.

D, Change in spatial memory performance between the first and the last trial (n=18 sessions from n=14 patients). Blue line, mean across subjects.

E, Illustration of anchor bearing, which is the angular difference between the allocentric heading angle and the angle of the vector from the subject’s location to the anchor point.

F, Left, candidate anchor points. Right, illustrative tuning curve for one candidate point depicting firing rate as a function of bearing towards this point. Significance of each point is tested via surrogate statistics.

G, Cluster-based permutation testing identifies the largest cluster of significant candidate points (“anchor field”). The “anchor point” is the center of mass of the anchor field.  


Peter C. REINACHER (Freiburg, Germany), Lukas KUNZ, Bernhard P. STARESINA, Armin BRANDT, Nora A. HERWEG, Melina TSITSIKLIS, Michael J. KAHANA, Joshua JACOBS, Andreas SCHULZE-BONHAGE
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EP02
00:00 - 00:00

Eposters
EPILEPSY

00:00 - 00:00 #26155 - Angiocentric Glioma – a case report of a rare entity.
Angiocentric Glioma – a case report of a rare entity.

Introduction

Angiocentric Glioma (AG) was first described in 2005 as a distinct lesion and recently classified as a WHO Grade I tumour. According to the literature and available case reports (around 100 cases described worldwide) these lesions are predominantly seen in children or young adults with intractable or drug-resistant epilepsy.

Case report

A 17 year old boy presented with progressively worsening episodes of sudden leftward rotation of the head, without impaired awareness   He underwent vídeo-EEG monitoring which revealed ictal pattern projection in the right frontal region, and interictal epileptiform discharges in the right fronto-central region and less frequently in the contralateral homologous region. An MRI scan revealed a T2 hyperintense lesion adjacent to the right pre-central gyrus measuring approximately 8mm x 22mm x 6mm. The lesion involved the cortex and subcortical white matter, resembling a focal cortical dyplasia with the transmantle sign but with discrete gadolinium enhancement and a thin ( After a multidisciplinary discussion the patient was indicated for surgery with intraoperative electrocorticography (EcoG) and neurophysiologic motor mapping. The lesion was resected after a right frontal craniotomy and sent for histopathological evaluation. Epileptiform discharges were recorded over the lesional area and the surrounding tissue. The analysis revealed elongated glial cells involving the cortex and subcortical white matter aggregated around blood vessels. The neoplastic cells were positive for Glial fibrillary acidic protein (GFAP) and no Ki-67 or IDH-1 expression identified. 5 months after surgery the patient remains seizure-free (Engel Ia according to the Engel classification).

Conclusion

AG is a slow-growing primary lesion of the central nervous system, usually discovered during the investigation of a drug-resistant epilepsy. The main differential diagnosis includes dysembryoplastic neuroepithelial tumor (DNET), oligodendrogliomas, and gangliogliomas. Being a WHO grade I with excellent prognosis after ressective surgery with minimal or no adjunctive therapy, a prompt evaluation for surgery should be pursued in every case.


António CUCO (Lisbon, Portugal), Alexandra SANTOS, Francisca SÁ, José Paulo MONTEIRO, Nuno CANAS, Jose Carlos FERREIRA, Mrinalini HONAVAR, Pedro CABRAL, Jose CABRAL
00:00 - 00:00 #22509 - Deep brain stimulation of the anterior nuclei of the thalamus relieves basal ganglia dysfunction in monkeys with temporal lobe epilepsy.
Deep brain stimulation of the anterior nuclei of the thalamus relieves basal ganglia dysfunction in monkeys with temporal lobe epilepsy.

Background: Deep brain stimulation of the anterior nuclei of the thalamus (ANT-DBS) is effective in treating temporal lobe epilepsy (TLE). Previous studies have shown that the basal ganglia involved in seizure propagation in TLE, but the effects of ANT-DBS on the basal ganglia have not been clarified.

Methods: Chronic ANT stimulation was applied to monkeys with kainic-acid-induced TLE using a robot-assisted system. Their behavior was monitored continuously. Immunofluorescence analysis and western blotting were used to estimate the basal ganglia and the effects of ANT stimulation. 

Results: The electrodes were accurately implanted into the ANT, and the seizure frequency decreased after ANT-DBS. The expression of the D1 and D2 receptors in the putamen and caudate was higher in the ANT-DBS group than in the epilepsy (EP) model. Neuronal loss and apoptosis were less severe in the ANT-DBS group. Glutamate receptor 1 (GluR1) in the nucleus accumbens (NAc) shell increased in the EP group but decreased after ANT-DBS, and similar changes in GluR1 expression were observed in the globus pallidus internus (GPi). γ-Aminobutyric acid receptor A (GABAA-R) also decreased and glutamate decarboxylase 67 (GAD67) increased in the GPi of the EP group, whereas the reverse tendencies were observed after ANT-DBS.

Conclusion: Chronic ANT-DBS exerts neuroprotective effects on the caudate and putamen and enhances D1 and D2 receptor expression. GPi overactivation was downregulated by ANT-DBS, which enhanced the antiepileptic effect of the basal ganglia in the NHP-TLE model. Our findings provide further insight into the molecular mechanism of ANT-DBS therapy for TLE.


Guanyu ZHU (Beijing, China), Chen YINGCHUAN, Tingting DU, Jianguo ZHANG
00:00 - 00:00 #21777 - First experience of endoscopic transsphenoidal resection of hypothalamic hamartoma.
First experience of endoscopic transsphenoidal resection of hypothalamic hamartoma.

This article discusses two clinical cases of hypothalamic hamartoma (HH) which have not yet been described in any Russian or international papers, and presents the details of endoscopic resection technique with a transsphenoidal approach.

Materials and methods. Patient R., 16 years old male with a 9-year history of epileptic seizures was admitted to a hospital with a complaint of epileptic seizures every 5-6 days.  Magnetic resonance imaging (MRI) showed 1.5 х 1.4 х 1.4 cm HH, focal cortical dysplasia of the right occipital lobe. Three complex partial seizures with secondary generalization were detected during 3-days scalp video-EEG monitoring.

Patient M., 23 years old female with a 16-year history of illness was admitted to a hospital with a complaint of epileptic seizures once in a week.  MRI showed 2.44 х 2.79 х 2.68 cm HH. Two complex partial seizures with secondary generalization were detected during 4-days scalp video-EEG monitoring. In both cases surgical excision by transsphenoidal endoscopic approach was performed.

First patient was discharged in satisfactory condition on the 7th day after surgery, and didn’t have neurological deficit, electrolyte disorders (hypo- or hypernatremia, polyuria, polydipsia), visual disorders ( hemianopsia or reduced visual acuity).

Second patient in the early postoperative period had electrolyte disorders (hyponatremia), which were reversed after using hypo-osmolar solutions and mineralocorticoids. There were no visual impairments (hemianopia or visual acuity reduction). The patient was discharged in satisfactory condition on the 7th day after the surgery. In 18 months after surgery both patients are seizure free (Engel I).

Results. Clinical observation data suggest that transsphenoidal resection of HH in patients with drug-resistant epilepsy is possible.

Conclusion. Our experience shows that refractory epilepsy associated with HH can be safely and effectively treated with transsphenoidal resection of HH, with the possibility of radical cure and disease control.


Vladimir KRYLOV, Igor TRIFONOV (Moscou, Russia), Guekht ALLA, Mikhail SINKIN, Igor KAĬMOVSKIĬ, Andrey GRYGORIEV, Elena GRYGORIEVA
00:00 - 00:00 #23926 - Initial experience of an O-Arm®-based neuronavigated and Vertek®-assisted stereo-electroencephalography for drug-resistant epilepsy.
Initial experience of an O-Arm®-based neuronavigated and Vertek®-assisted stereo-electroencephalography for drug-resistant epilepsy.

Background

Evidence suggests O-Arm®-based neuronavigation assisted by a Vertek® passive articulated arm is an effective strategy for stereo-electroencephalograhy (SEEG) deep brain electrodes implantation and a valid alternative for robotic arm assisted methods.

 

Methods

We retrospectively review our center’s initial experience with O-Arm®-based neuronavigated and Vertek®-assisted sEEG (OV-SEEG).

 

Results

From May 2019 to February 2020 we performed OV-SEEG in 5 cases of adult drug-resistant epilepsy. Mean age at procedure was 39.8 years, varying from 18 to 54. All patients were female. A total of 61 leads were implanted, varying from 10 to 14 per patient. Procedure total duration averaged 24 minutes per lead. Mean intracranial trajectory length was 42.7±13.8mm. Mean trajectory error was 2.7±2.0mm. Trajectory errors were predominantly anterior lead skew (observed in 46% of trajectory errors). No correlation was observed between intracranial trajectory length and trajectory error (Person correlation coefficient of 0.104, p=0.674). Trajectory error was significantly larger in the first procedure when compared to the subsequent four (6.2±0.8mm vs 2.0±1.5mm, p<0.001). 

 

Conclusion

OV-SEEG is a valid tool for the diagnosis of drug-resistant epilepsy and our experience further suggests this is a precise and time-effective SEEG solution.


Vasco PINTO, Sérgio SOUSA, Eduardo CUNHA (Porto, Portugal), Carla SILVA, Rui RANGEL, Alfredo CALHEIROS
00:00 - 00:00 #21775 - Invasive EEG monitoring for presurgical evaluation in patients with drug resistant form of epilepsy.
Invasive EEG monitoring for presurgical evaluation in patients with drug resistant form of epilepsy.

Purpose: resective epilepsy surgery based on an invasive EEG (iEEG), performed with subdural grids or depth electrodes is considered to be the best option towards achieving seizure-free state in drug-resistant epilepsy.
Method: prospective analysis of 79 patients with drug-resistant epilepsy who underwent iEEG monitoring for the presurgical evaluation before resective surgery.
Results: 31 patients (39%) – were MRI negative, 48 (61%) – MRI positive. For all patients were made scalp EEG (sEEG). During sEEG in 55 patients (69%) seizure onset zone (SOZ) was bilateral. In 24 (31%) patients results of MRI and sEEG were not concordance. In patients with bilateral SOZ by sEEG, on iEGG we found: 6 (13%) patients had bilateral SOZ and in 49 (87%) seizure began in one side. In patients, with non-concordance MRI/scalp EEG: 3 patients (9%) didn’t have epileptiphorm activity on sEEG, but had it on iEEG; in 3 patients (9%) – sEEG was not concordance with iEEG and in 18 patients SOZ were detected only by iEEG. For all patients were made resective surgery. Outcomes were evaluated 12 months after surgery in 60 patients (76%): 32 patients (53%) became seizure free: 26 patients (43%) – Engel Ia, 2– Engel Ic, 4 – Engel Id. Eleven (18%) - Engel II: one - Engel IIa, 7 – Engel IIb, one – Engel IIc, 2 – Engel IId. The unsatisfactory result of treatment were noted at 13 patient (21%): 3 – Engel IIIa, one - Engel Iva, 9 – Engel IVb. There was no mortality in our group. The complications developed in 7 (11%) patients: 2 – had intracerebral hematoma in the area of electrode placement (without indications for surgical treatment), 4 patients had status epilepticus and one - wound liquorrhea.

Conclusion: Our results confirmed efficiency and safety of iEEG as presurgical procedure in patients with drug resistant form of epilepsy. 53 % patients become «seizure free» 12 months after surgical treatment.


Vladimir KRYLOV, Igor TRIFONOV (Moscou, Russia), Guekht ALLA, Mikhail SINKIN, Igor KAĬMOVSKIĬ
00:00 - 00:00 #23986 - Neurocognitive outcome after laser interstitial ablation for temporal lobe epilepsy, a systematic review and meta analysis.
Neurocognitive outcome after laser interstitial ablation for temporal lobe epilepsy, a systematic review and meta analysis.

Introduction:

Epilepsy is a common condition that  affects  4 to 10 per 1000 people around the world. About one third of patients with epilepsy become medically refractory. Temporal lobe epilepsy encompass the most common cause of refraction to medication

Anterior temporal lobectomy  (ATL) became the golden standard  after the land mark study by Wiebe et al was published in 2001 and showed clear evidence of superiority of surgical treatment over medical treatment alone for temporal lobe epilepsy. Minimally invasive options such as Laser interstitial laser therapy (LITT) are becoming attractive options particularly in older patients or those with multiple co-morbidities. In this systematic review and meta analysis we aim to summarize the current evidence on neurocognitive outcome after LITT.  We provide a summary estimate of memory and naming outcome. 

 

Methods:

This study was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed and OVID Midline were systematically searched for all indexed publications in the English language up to May 2020. Search was limited to human studies. The search strategy combined the following search terms: (seizure OR epilepsy OR intractable epilepsy OR intractable seizure OR mesial temporal sclerosis ) AND (laser interstitial thermal therapy OR laser-induced thermal therapy OR laser ablation OR laser interstitial thermal OR stereotactic laser OR neuroblate OR visualase OR MRIgLITT OR lesioning) AND (prognosis OR prognostic OR outcome OR follow up OR cognitive OR memory OR IQ). Additional strategies included manual searches of articles that were not included in the electronic search and screening bibliography  of collected studies. 

 

Results:

This meta-analysis included 10  studies with 181 candidates. Regardless of the side of the procedure the rate of verbal memory loss is 50% (CI 19.5%-80.5%). For left sided procedure the rate is 50.3% ( CI 28.5%-71.19%) while for right sides procedure the rare is 23.7% ( CI 6.3%-59%). For visual memory regardless of the laterality, the rate of loss is 47.4% (CI 26.8%-68.9%), while 42.9% (CI 20.6%-68.4%)  and 26.9% (CI 4.1%-75.9%) after left and right sided procedures respectively. 

For naming regardless of procedure laterality the loss rate is 17.8% (CI 7%-38.6%), while 26.5% (CI13.3-45.9%) and 22.8% ( CI 8.7%-47.6%) after left and right sided procedures respectively. 

 

Conclusion: 

Similar to open temporal lobectomy left sided LITT carries higher rate of adverse effect on neurocognitive outcome including, verbal memory, visual memory and naming. The rate of verbal memory loss is more than double after left sided procedure compared to right sided one.

 


Soha A ALOMAR (Jeddah, Saudi Arabia), Rana MOSHREF, Leena MOSHREF, Abdulrahman SABBAGH
00:00 - 00:00 #25795 - Quality of life after deep brain stimulation for epilepsy.
Quality of life after deep brain stimulation for epilepsy.

Quality of life after deep brain stimulation for epilepsy

 

Jacco Smeets, MSc1, Linda Ackermans, MD, PhD2,3,6, Ghislaine van Mastrigt, PhD4, Rob Rouhl, MD, PhD3,5, Louis Wagner, MD3,6, Sander van Kuijk, PhD7, Jeske Nelissen5, Ilse van Straaten, MD, PhD8, Kuan Kho, MD9, Francesca Snoeijen-Schouwenaars, MD, PhD6, Anne-Marthe Meppelink, MD, PhD10, Sylvia Klinkenberg, MD, PhD5,6, Kim Rijkers, MD, PhD2,3,6, Marian Majoie, MD, PhD3,5,6

 

1 Faculty of Health, Medicine and Life Sciences, Maastricht University

2 Department of Neurosurgery, Maastricht University Medical Center

3 School for Mental Health & Neuroscience, Maastricht University Medical Center

4 CAPHRI: Care and Public Health Research Institute, Maastricht University

5 Department of Neurology, Maastricht University Medical Center

6 ACE: Academic Center for Epileptology

7 Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University

   Medical Center

8 Department of Neurology, Amsterdam University Medical Center, location VUmc

9 Department of Neurosurgery, Medisch Spectrum Twente

10 SEIN: Centre of Excellence for Epilepsy and Sleep Medicine

 

Topic: epilepsy

 

Key words: epilepsy, quality of life (QoL), neuromodulation

 

Objective

Epilepsy, one of the most frequently occurring chronic neurological disorders, is associated with reduced quality of life (QoL). Epilepsy is generally treated with anti-epileptic drugs, however, 30% of epilepsy patients are medically refractory, meaning that they continue to have seizures despite adequately dosed medication. For these medically refractory patients, neuromodulation can be an option, especially when resective epilepsy surgery is not an option or did not have a significant effect. Two types of neurosurgical neuromodulation are currently accepted in The Netherlands: Deep Brain Stimulation of the Anterior Nucleus of the Thalamus (ANT-DBS) and Vagus Nerve Stimulation (VNS). VNS has been used for over 20 years in The Netherlands, DBS since 5 years. The effectiveness in terms of seizure control of DBS and VNS are quite similar. Observational studies show that DBS and VNS lead to a seizure reduction of 50% or more after 2 years in respectively 54% and 33% of patients. QoL in epilepsy heavily depends on seizure control. Few small previous studies show that neuromodulation in epilepsy increases QoL. However, there is no data on QoL changes after neuromodulation for epilepsy in the Netherlands. We therefor aim at determining the change in QoL in medically refractory epilepsy patients treated with DBS or VNS.

 

Methods

Included are all adult patients and children above 15 years of age referred for DBS or VNS to one of the three participating hospitals; Maastricht University Medical Center, Amsterdam University Medical Center and Medisch Spectrum Twente. After informed consent they receive the Quality of Life in Epilepsy Inventory (QOLIE-31) questionnaire and the EQ-5D-5L questionnaire on health-related QoL at baseline and after 3, 6, 12, 24, and 60 months.

Data on seizure frequency are derived from the patient charts where treating neurologists record seizure frequency based on seizure diaries.

 

Results

We expect that medically refractory epilepsy patients will report a better QoL after treatment with DBS or VNS. Thus, we expect a clinically relevant increase in QOLIE-31 score, which is an increase of at least 5.19 points, and an increase in EQ-5D-5L score. Treatment with DBS of VNS for epilepsy usually leads to less seizures, instead of a complete disappearance of seizures. When patients report a better QoL after DBS or VNS, even though they still report seizures, the treatment can be seen as useful. This is especially true when patients are able to participate in society again, to a greater extent than before treatment. 

 

Conclusions

Previous research shows that neuromodulation might lead to an increase in QoL in patients with medically refractory epilepsy. We expect that this prospective study will lead to similar results.


Jacco SMEETS, Linda ACKERMANS (Maastricht, The Netherlands), Ghislaine VAN MASTRIGT, Rob ROUHL, Louis WAGNER, Sander VAN KUIJK, Jeske NELISSEN, Ilse VAN STRAATEN, Kuan KHO, Francesca SNOEIJEN-SCHOUWENAARS, Anne-Marthe MEPPELINK, Sylvia KLINKENBERG, Kim RIJKERS, Marian MAJOIE
00:00 - 00:00 #21776 - Types of epileptogenic lesions in patients with drug-resistant forms of epilepsy.
Types of epileptogenic lesions in patients with drug-resistant forms of epilepsy.

Purpose: to evaluate pathomorphological types of epileptogenic lesions in patients with drug-resistant epilepsy.
Method: prospective analysis of 270 patients with drug-resistant epilepsy, who had undergone resective surgery in University Clinic of Moscow State University of Medicine and Dentistry between 01.01.2014 and 12.12.2019.

Results: According to MRI data 49 (18%) patients were MRI negative and 221 patients (82%) – MRI positive.  Data of the pathohistological results were: FCD Ia – 14 patients, FCD Ic – 37, FCD IIa – 34, FCD IIb – 3, FCD IIIa – 117, FCD IIIb – 11, FCD IIIc – 5, FCD IIId – 28, LGG – 10,  HS – 3, AVM – 4,  HH – 3, LGG+HS – 1. Based on the histology data, the main type of pathology was FCD IIIa – 117 patients (43%). In group of patients with FCD IIIa, the accompanying pathology with HS was: FCD Ia – in 12 patients, FCD Ib – 2, FCD Ic – 32, FCD IIa – 52, FCD IIb – 19. In analysis patients with MRI positive and negative forms the following results were obtained: in MRI positive forms the main type of epileptogenic lesion was FCD IIIa – 50%, in MRI negative – FCD Ic – 32% and FCD IIId – 26%. No statistically important relationship between outcomes of surgical treatment and pathomorphology was found in our study.

Conclusion: the results obtained in our series revealed that the main type of epileptogenic lesions were FCD – 43% and in MRI positive forms  - FCD IIIa – 50%, in MRI negative – FCD Ic – 32% and FCD IIId – 26%.


Vladimir KRYLOV, Igor TRIFONOV (Moscou, Russia), Guekht ALLA, Anna LEBEDEVA, Mikhail SINKIN, Igor KAĬMOVSKIĬ
00:00 - 00:00 #21774 - VNS - second chance after failed resective epilepsy surgery.
VNS - second chance after failed resective epilepsy surgery.

Purpose: to evaluate the effectiveness of  vagus nerve stimulation (VNS) after failed resective epilepsy surgery.

Method: All the patients who had persistent seizures after resective surgery who subsequently underwent VNS placement at our institution from 2016 to 2019 were included in the study. Twenty-one consecutive patient (14 women and 7 men) were enrolled and followed for the outcome.  Seizure outcomes were based on modified Engel classification (I: seizure-free/rare simple partial seizures; II: >90% seizure reduction (SR), III: 50-90% SR, IV: <50% SR; classes I to III (>50% SR)=favorable outcome).

Results:  The patient's average year old was – 31,15, the duration of the epilepsy was 17,6 years,

Temporal lobe epilepsy was diagnosed in 5 patients, temporal plus (temporal+frontal) - 8 patients, 6 - patients had bilateral lesions and 2 – multifocal. All patients in this group previously had resective surgery: 20 patients -  anterior medial temporal lobectomy (AMTLE) and one patient – AMTLE plus exTLE.  10 (47%) patients were evaluated 12 months after surgery: 2 (20%) had a modified Engel class I outcome, 4 (40%) had class II, 4 (40%) had class III. Data of the pathohistology results were: FCD Ia – 2, FCD Ic – 4, FCD IIa – 1, FCD IIIa-10, FCD IIId – 4. There was no surgical mortality. Side effects of VNS were detected: hoarseness -10 (47%) patients, cough during stimulation – 3 (14%).

Conclusion: VNS therapy in patients who have failed surgical therapies only provides improvement in seizure control in all 100% patients in our series. We confirmed its efficacy and safety: 20 % patients become «seizure free», 40% - had >90% seizure reduction and 40% - 50-90% SR 12 months after surgical treatment.


Vladimir KRYLOV, Igor TRIFONOV (Moscou, Russia), Guekht ALLA, Mikhail SINKIN, Igor KAĬMOVSKIĬ
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EP03
00:00 - 00:00

Eposters
ETHICS

00:00 - 00:00 #23952 - "e;Utility of volume of tissue activated-modeling for clinical stimulation parameters in DBS patients.
"e;Utility of volume of tissue activated-modeling for clinical stimulation parameters in DBS patients.

Introduction: Deep brain stimulation (DBS) is an established treatment for a number of movement disorders, including Parkinson's disease (PD), essential tremor (ET), and dystonia. DBS surgery is widely recognized as depending essentially on precision for clinical efficacy. There is an inherent difficulty in accurately determining electrode positions post-operatively due to factors such as brain shift and co-registration limitations. Novel methods,
 for visualizing post-operative results on individual- and (importantly) on group-level, include the open-source Lead-DBS suit which uses a custom image-processing pipeline to normalize individual patient images to MNI-space, thereby enabling accurate anatomical electrode visualization. Here, we build onto what other groups have indicated: the potential for using 3D neuro-modeling as a guide to post-operative stimulator programming and anatomical analysis.

Method: 20 patients with 1-2 electrodes each (amounting to 30 electrodes) were included in the analysis. These were a subset in a cohort of patients treated with DBS at Sahlgrenska University Hospital, Sweden, with a diagnosis of either PD or ET. The Lead-DBS pipeline consists of (1) co-registration of pre-operative and post-operative images, (2) normalization to MNI-space, (3) registration of electrode positions, (4) VTA (volume of tissue activated) simulation using clinically stable stimulator parameters (1 year post-op) and finally (5) statistical analysis.

Results: Of the 20 patients included, 11 had PD and 9 had ET. Median distance to the closest voxel within the target structure (STN/VIM) was 1.64, 0.38, 0.53 and 1.11 mm for contacts 0-3 (ventral to dorsal) respectively. Distances smaller than 1 mm were dee med within the target structure. With this definition, 76 of 120 contacts (63,3%) resided within the target structure. Visual 2- and 3-dimensional evaluation revealed a clear difference between the STN and VIM leads: the former most often incorporated either contact 1 (40.0%), 2 (35.0%) or both (60.0%) whereas the latter was most often located above the active contacts suggesting that, at least in part, white matter tracts in the subthalamus may be stimulated in these patients. Indeed, contact 3 was the closest on average (median 0.12 mm to nearest voxel within the VIM). The median VTA/target overlap was 13.9 mm2. Approximately a third (median 28%) of the VTA was occupied by the motor subdivision of the STN in patients with PD.

Conclusion: Neuroimaging-based visual and statistical analysis provides useful data. The present small-sample study suggests utility in facilitating patient-specific programming and in patient-to-patient anatomical comparison.


Linus KOESTER (Gothenburg, Sweden), Thomas SKOGLUND, Johan LJUNQVIST
00:00 - 00:00 #23886 - Assessing the accuracy of intraoperative 3D fluoroscopy to predict correct electrode position during deep brain stimulation surgery.
Assessing the accuracy of intraoperative 3D fluoroscopy to predict correct electrode position during deep brain stimulation surgery.

Background/Goal

The effectiveness of deep brain stimulation (DBS) surgery is critically dependent on accurate electrode position. Microelectode recording and microstimulation are invaluable tools to fine-tune the location to target. However, an anatomical post-implantation confirmation of the true electrode position is required to exclude unwanted shifts during definitive electrode implantation. Intraoperative confirmation of real electrode position is usually performed with lateral 2D fluoroscopy or intraoperative CT/MRI, methods which lack high accuracy or easy accessibility, respectively. The goal of the current work is to assesses the accuracy of intraoperative 3D fluoroscopy (3DF), a quick, inexpensive, radiation-light method, in estimating the final electrode location.

 

Methods 

This study included 28 patients submitted to DBS surgery, and a total of 52 electrodes implanted (24 Parkinson’s disease patients implanted bilaterally in the subthalamic nucleus and 4 chronic pain patients implanted in the left ventral posterolateral thalamic nucleus). All patients underwent intraoperative fluoroscopic imaging acquisition and 3D reconstruction with a C-arm system (Ziehm) after implantation of the definitive electrodes. The acquired 3DF images and 48h post-operative CT images were fused with preoperative MRI using the StealthStation S8 system (Medtronic). The Euclidean coordinates of the electrode tip in the 3DF and CT images were extracted and used to calculate their distance. Radiation exposure from 3D fluoroscopy and post-operative CT was also compared.

 

Results/Discussion

The difference between the electrode position estimated by 3DF and CT was 0.90 mm (p>0.05). The brain shift effect on final electrode position was minimal, possibly because deeper structures are less affected by brain shift. Total radiation exposure was significantly lower with 3D fluoroscopy compared to CT (p<0.05).

 

Conclusion

Intraoperative 3D fluoroscopy accurately predicts final lead position after DBS surgery. We believe its advantages - less expensive, less radiation exposure, opportunity to correct electrode position during the same operative period, shorter operative time and  earlier hospital discharge -  render it a valuable tool to replace post-operative CT imaging.


Manuel PINTO (Porto, Portugal), Clara CHAMADOIRA, Rui VAZ
00:00 - 00:00 #23909 - BrainCubes - MRI histology of the human reward system.
BrainCubes - MRI histology of the human reward system.

Objective: Bridging the gap between the microstructural scale, accessible via optical techniques, and the millimeter scale, observable by modern whole brain imaging techniques, is one of the major challenges of modern neuroscience. Microscopy techniques offer rich detail, however, massive tracing of individual neuronal structures (e.g. sub-bundles) over large distances at this moment is impossible. Full brain imaging techniques like diffusion-weighted MRT can give the full view, but due to the coarse resolution the information content is more of statistical nature and tractographic reconstructions provide rather a sketch than the true picture of whole brain connectivity. In this project we want to contribute to fill this gap by comparing high resolution MR-imaging (including tractography) and histological investigations of cadaver specimens by  building a high-throughput MRT scanning pipeline and applying it in the same coordinate system. Our focus is the human reward system, especially the limbic midbrain.  

 

Methods: Fixed postmortem human brains are cut regularly into cubes such that they can be scanned by small-animal MR-scanners at resolutions of 50µm to 200µm. Here we propose preliminary data acquired at a Bruker Biospec 7T. The specimen (midbrain) was cut to an approx. 60mm, 40mm, 40mm cube, embedded in phosphate buffered saline and scanned with a 3D spinecho scan at a resolution of 200 micron in-plane and slice-thickness of 300 micron. The b-value was chosen to be 4000 s/mm² with 50 gradient directions. The probe was acquired in three slabs using partial excitation and afterwards digitally stitched to achieve full coverage. The scantime of one slab was around 21 hours. For further preprocessing a denoising (1) and Gibbs-artifact correction (2) was applied. Simple tensor analysis revealed diffusion coefficient of around 0.2 µm²/ms and fractional anisotropy values of around 0.3 in highly anisotropic areas, which is sufficient for tractographic approaches. We applied global tractography (3) on the dataset and rendered directional streamline densities, which are shown in the accompanying figure at a closeup around the nucleus ruber. 

 

Results: In a first example specimen we were able to successfully perform fiber tractography at high resolution in a postmortem brain. Comparison between MR-imaging and histological staining of the specimen allowed to discover local topographical anatomy in the human limbic midbrain. Especially the ventral tegmental area (VTA), the retroflex fascicle of Meynert, the superolateral (sl) and inferomedial medial (im) forebrain bundles (MFB) could be differentiated at an unprecedented detail. 

 

Conclusion: The proposed technique might help to understand local connectivity and bridge the gap to classical anatomical methods like histologica workup and staining. It appears to be a valuable adjunct to interpreting the long distance depiction of the human brain’s connectome.

 

References:

  1. Lemberskiy, Gregory, and Dmitry S. Novikov. 2019. “Achieving Sub-Mm Clinical Diffusion MRI Resolution by Removing Noise during Reconstruction Using Random Matrix Theory.” In ISMRM Proceedings 2019.

  2. Kellner, E., B. Dhital, V.G. Kiselev, and M. Reisert. 2015. “Gibbs-Ringing Artifact Removal Based on Local Subvoxel-Shifts.” Magnetic Resonance in Medicine, n/a-n/a. https://doi.org/10.1002/mrm.26054.

  3. Reisert, Marco, Irina Mader, Constantin Anastasopoulos, Matthias Weigel, Susanne Schnell, and Valerij Kiselev. 2011. “Global Fiber Reconstruction Becomes Practical.” Neuroimage 54 (2): 955–962.


Marco REISERT (Freiburg, Germany), Shi Jia TEO, Andrea WESSOLLECK, Máté DÖBRÖSSY, Andreas VLACHOS, Volker Arnd COENEN
00:00 - 00:00 #24000 - C1C2 puncture under FP navigation: a safe and useful procedure.
C1C2 puncture under FP navigation: a safe and useful procedure.

Background and purpose: The C1C2 intrathecal puncture is performed when lumbar puncture is not feasible or usable. Since cervical vertebra are adjacent to the spinal cord and blood vessels, the puncture risk is high and requires high accuracy. We present the FP navigation method with preoperative planning and various indications.

Material and method. The goal of preoperative planning was to accurately localize the target, the high risk structures and an identifiable fixed key point during the planning and the procedure. The CT scan was the most accurate method.

Preoperative imagery allowed to localize VA (vertebral artery) and PICA (postero inferior cerebellar artery) which normally were not located in the C1C2 posterior space.

The key point was the localization of the F point (Peckham “flare“ point), an osseous landmark which represents the triangular “flaring” of the posterior C1 arch at its junction with the anterior arch, corresponding to the VA groove. FP was 0.2 _ 0.5 mm posterior to the dorsal spinal cord margin (Peckham 2018).

The target was located in the high part of the C1C2 space, at the middle between the perpendicular to the F point and the spinous line. Usual navigation procedure was performed in relationship to FP even if the cervical junction position was different.

Results. C1C2 punctures were performed for various procedures, notably to implant intrathecal catheters connected to a subcutaneous pump in pain and spasticity treatment.

Discussion: C1C2 puncture with FP neuronavigation was a safe procedure. Posterior spinal cord piamater and posterior veinous plexus were avoided thanks to an accurate procedure. Development of intrathecal cervical catheter was still ongoing.


Hayat BELAÏD (PARIS), Jean-Baptiste THIÉBAUT, Vincent D'HARDEMARE, Pierre BOURDILLON, Alister ROGERS, Philippe AUTRET, Claire-Marie RANGON, Catherine VIART
00:00 - 00:00 #26262 - DBviS – A visualization tool of DBS research data.
DBviS – A visualization tool of DBS research data.

The most common method for estimating the spatial effect of deep brain stimulation (DBS) is by using electric field simulation. The outputs can be used to evaluate a patient specific response but also on a group level to create probabilistic improvement or side disorder maps for intuitive visualization of the result and possible prediction of new data. Further, several theoretical studies are available showing the impact of different parameters in the simulations. To spread information of the simulation technology and study results we are implementing a visualization tool, DBviS, where the user can look through datasets from studies and compare with own results.

DBviS is a software based on 3DSlicer (https://www.slicer.org/) for visualization of DBS research data. It utilizes all the default 3DSlicer functions for visualization and measurements. In this platform, we have gathered data from several different types of studies. One is an anatomical normalization study of 19 patients, which generated an atlas of substructures in Thalamus and the subthalamic area [1]. Other studies include probabilistic stimulation maps for clinical improvement or side effects in different diseases (Parkinson’s disease, essential tremor, Tourette, OCD etc.) [2, 3]. Further, information from theoretical studies is included to visualize the effect of different modelling choices, like including the brain tissue anisotropy [4, 5]. Other examples are comparisons of the stimulation effect when using microelectrode recording with the implanted DBS lead [6] and electric field simulation related to tractography reconstruction [5].

The plan for future development is that highly skilled users can transform their own simulations to the different scenes and compare their clinical result with published data. This can also be supported by using our other apps, ELMA (based on MATLAB, The Mathworks Inc., USA) for brain conductivity modelling, and DBSim (based on COMSOL Multiphysics, Sweden) for electric field simulations [7]. These are stand-alone applications that can be downloaded for free from the webpage of the Neuroengineering group at Linköping University (https://liu.se/en/research/neuroengineering-lab) for performing patient-specific electric field simulations.

*Research is financially supported by the Swedish Foundation for Strategic Research (BD15-0032)

[1] D. Vogel et al., Anatomical brain structures normalization for deep brain stimulation in movement disorders, NeuroImage. Clinical 27 (2020) 102271.

[2] A. Shah et al., Stimulation maps: visualization of results of quantitative intraoperative testing for deep brain stimulation surgery, Medical & Biological Engineering & Computing 58(4) (2020) 771-784.

[3] R. Stenmark Persson et al., Deep Brain Stimulation of caudal Zona Incerta for Parkinson’s disease; one-year follow-up and electric field simulations, Submitted  (2021).

[4] T. Nordin et al., The Effect of Anisotropy on the Impedance and Electric Field Distribution in Deep Brain Stimulation, in: T. Jarm, A. Cvetkoska, S. Mahnič-Kalamiza, D. Miklavcic (Eds.) 8th European Medical and Biological Engineering Conference, Springer International Publishing, Cham, 2021, pp. 1069-1077.

[5] T. Nordin et al., White matter tracing combined with electric field simulation - A patient-specific approach for deep brain stimulation, Neuroimage Clin 24 (2019) 102026.

[6] F. Alonso et al., Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems-A Simulation Study, Brain sciences 8(2):28 (2018).

[7] J.D. Johansson et al., Patient-Specific Simulations of Deep Brain Stimulation Electric Field with Aid of In-house Software ELMA, 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), IEEE, Berlin, Germany, 2019, pp. 5212-5216.


Teresa NORDIN (Linköping, Sweden), Fabiola ALONSO, Dorian VOGEL, Johannes JOHANSSON, Simone HEMM, Karin WÅRDELL
00:00 - 00:00 #23936 - Does cable-bound stimulation and recording of neuronal activity affect rat`s wellbeing?
Does cable-bound stimulation and recording of neuronal activity affect rat`s wellbeing?

Chronic stimulation and recording of neuronal activity in different rodent models for movement disorders and neuropsychiatric disturbances is carried out via a cable with a swivel that allows relative free movement of the rat without twisting of the cable. Nevertheless, it is still semi-restraining and may therefore impose stress and confound to the animal.

We here subcutaneously implanted transmitters for contactless recording of heart rate and activity of rats during cable-bound stimulation and recording of neuronal activity, which was compared to the perioperative period of intracranial electrode implantation.

Male Sprague Dawley rats (n=8, 180 g) were implanted with electrodes in the subthalamic nucleus (STN) under general anesthesia with local anesthesia and perioperative pain management with non-steroidal anti-inflammatory drugs. Two weeks after the electrode implantation the threshold for stimulation-induced side effects were determined in each rat. Thereafter, a five-day sham-stimulation period started with only the cable connected to the rat’s electrode head stage but no current applied.  Finally, the cables were disconnected and rats were allowed to move freely in their cages for another two days. In addition to continuous monitoring of heart rate and activity via a subcutaneously implanted transmitter, the rats’ well-being and general health condition were monitored by daily body weight measures and clinical scoring.

Clinical scoring and weight measures during the course of the study did not show any substantial alterations. Right after electrode implantation, heart rate was elevated, however, without reaching the level of significance. Only the first two days of cable-bound sham-stimulation resulted in decreased locomotor activity (p<0.05) as compared to pre- and post-stimulation values, whereas heart rate measures were not affected.

Electrode implantation and semi-restraint caused by tethered electrodes had only a transient and mild effect on rat`s activity. Since so far, even advanced and fully implantable devices do not allow flexible switching between recording and electric stimulation with different settings, as e.g., needed for adaptive “closed loop” stimulation, our stimulation/recording setup may be valid and ethically justifiable in neuroscience rat models.


Laura WASSERMANN, Ann-Kristin RIEDESEL, Simeon HELGERS, Mesbah ALAM, Christine HÄGER, Joachim KRAUSS, Kerstin SCHWABE (Hannover, Germany)
00:00 - 00:00 #26087 - Effect of the Trajectory Angle on Idiopathic Delayed Onset Edema in DBS.
Effect of the Trajectory Angle on Idiopathic Delayed Onset Edema in DBS.

Background: Symptomatic idiopathic delayed onset edema (IDE) is a complication which can occur after DBS electrode placement. Due to the potential duration and severity of neurological deficits, it can cause a heavy burden on the patient. The location of the cortical area used for electrode entrance could be related to the development of symptomatic IDE.

Objective: To evaluate possible influence of cortical entry of DBS electrodes on symptomatic IDE occurrence in patients from 2014 until 2021.

Methods: DBS electrode cortical entry in Brodmann areas 6 (divided in pre-supplementary motor area and supplementary motor area, pre-SMA and SMA) and 8. Symptomatic IDE occurred in ten Parkinson's disease (PD) patients, three tremor patients and one pain patient (IDE group, representing 27 trajectories). The cortical entry and edema volume of the trajectories were determined. A group of PD patients after DBS without IDE (non-IDE, 243 trajectories in 122 patients) was used for comparison. Edema volume was measured using CT, Brodmann areas were determined using MRI.

Results: Average edema volume was 9.4 cm³ and 11.8 cm³ for right and left trajectories, respectively. In the IDE group, 74% (20/27) of the electrodes entered the brain in Brodmann area 6 (52% pre-SMA, 22% SMA) and 26% (7/27) in area 8. In the non-IDE group 40% (97/243) of the electrodes had area 6  as entry (30% pre-SMA, 10% SMA) and 60% entered the brain through area 8 (146/243).

Conclusion: In the IDE group, Brodmann area 6 was used more often as DBS entry compared to the non-IDE group. Possibly this area is more susceptible for the development of symptomatic IDE due to its neuronal architecture and its contributions in linking cognition to action. The current analysis will be extended with non-IDE tremor and pain patients that underwent DBS. Adding these patients for analyses could provide more insight in the relation between the occurrence of symptomatic IDE, cortical entry, diagnosis and DBS target.


Patrick O'DONNELL (Amsterdam, The Netherlands), Pepijn VAN DEN MUNCKHOF, Catherine M.k.e DE CUBA, Rob M.a. DE BIE, P. Richard SCHUURMAN, Maarten BOT
00:00 - 00:00 #23904 - Expanding applicability of intraoperative cone beam (O-arm) CT in stereotactic neurosurgery.
Expanding applicability of intraoperative cone beam (O-arm) CT in stereotactic neurosurgery.

Background: Implementation of intraoperative cone beam CT (‘the O-arm system’) for navigation in neurosurgery is expanding. The O-arm is known to enable navigation-guided screw placement in spine surgery and is also increasingly being applied in intracranial procedures, such as deep brain stimulation. In frame-based stereotactic procedures, it has  more potential applications.
Objective: To describe the technical details and advantages of the O-arm in common stereotactic neurosurgical procedures.
Methods: Frame-based stereotaxy using the O-arm was applied in four different neurosurgical procedures: ventricular catheter placement for hydrocephalus in idiopathic intracranial hypertension, catheter placement for cystic suprasellar tumor drainage, pediatric supratentorial, and infratentorial tumor biopsy.
Results: The O-arm enabled fast acquisition, high stereotactic registration accuracy, and direct intraoperative evaluation of probe location.

Conclusion: The O-arm system can be conveniently implemented for both supra- and infratentorial frame-based stereotactic procedures, as well as catheter placement and tumor biopsies, in both pediatric and adult cases, further expanding its applicability in neurosurgery.


Hisse ARNTS (Amsterdam, The Netherlands), Rick SCHUURMAN, Jantien HOOGMOED, Pepijn VAN DEN MUNCKHOF, Maarten BOT
00:00 - 00:00 #26283 - Frameless stereotactic brain biopsy: A prospective study on robot‐assisted brain biopsies performed on 32 patients by using the RONNA G4 system.
Frameless stereotactic brain biopsy: A prospective study on robot‐assisted brain biopsies performed on 32 patients by using the RONNA G4 system.

Aims: We present a novel robotic neuronavigation system, RONNA G4, used for precise preoperative planning and frameless neuronavigation. The system has been developed by a research group from the University of Zagreb and a team of neurosurgeons from the University Hospital Dubrava, Zagreb, Croatia. The aim of this study is to provide a comprehensive error measurement analysis of the system used for brain biopsy procedures.

Methods: Frameless stereotactic robot-assisted biopsies were performed on thirty-two consecutive patients. Post-operative computerized tomography (CT) and magnetic resonance imaging (MRI) scans were assessed to precisely measure the target point error (TPE) and the entry point error (EPE). All clinical data, the learning curve, and the influence of the trajectory angle on targeting accuracy were measured and evaluated.

Results: The application accuracy of the RONNA system for the TPE was 1.95 ± 1.11 mm, while for the EPE was 1.42 ± 0.74 mm. In our cohort, only one pathohistological diagnosis was inconclusive; thus, the total diagnostic yield was 96.87%. Linear regression showed statistical significance between the TPE and EPE and the angle of the trajectory on the bone (p=0.026, p=0.010). The learning curve analysis showed statistical significance, especially for one neurosurgeon who performed most of the procedures (p<0.001). The operation duration was significantly reduced over time, as shown by comparing the first ten procedures with the last ten procedures (p=0.0007).

Conclusion: According to the results of our comprehensive analysis of TPE and EPE, the RONNA G4 robotic system is a precise and highly accurate autonomous neurosurgical assistant in performing frameless brain biopsies. Greater trajectory angles were associated with larger EPE and TPE.


Domagoj DLAKA (Zagreb, Croatia), Švaco MARKO, Darko CHUDY, Jerbić BOJAN, Šekoranja BOJAN, Šuligoj FILIP, Vidaković JOSIP, Dominik ROMIC, Marina RAGUŽ
00:00 - 00:00 #23337 - MRI 3T Multi-channel Radiofrequency Safety Assessment of DBS Systems.
MRI 3T Multi-channel Radiofrequency Safety Assessment of DBS Systems.

Introduction: More than 60% of patients implanted with a deep brain stimulation (DBS) system need an MRI within 10 years after implantation [1]. Furthermore, MRI is an important research tool to develop better understanding of DBS therapy, to improve outcome in existing indications and expand therapy with new indications.

1.5T and 3T MRI scanners comprise 80+% of installed base, with the share of 3T scanners increasing [2]. ISO/TS 10974:2018 “Assessment of the Safety of MRI for Patients with an AIMD” provides detailed guidelines for hazards that can occur with 1.5T MR scanners; however, considerations of hazards for 3T scanners are not currently in scope of the test specification.

Primary challenges at 3T compared to 1.5T stem from the diversity of MRI radiofrequency (RF) fields that can be generated by modern 3T MRI scanners. Traditional circularly-polarized quadrature excitation (CP) may fail to produce uniform image contrast at 3T (128MHz) due to electromagnetic (EM) wave-interference effects, therefore most modern 3T MRI scanners employ radiofrequency (RF) shimming with two-channel whole-body transmit coils (MC-2) to alleviate these artifacts [3]. Impact of MC-2 on RF-field distributions on AIMD need to be accurately evaluated at 3T for evaluation of hazards related to RF-fields.

 

Problem Statement: RF-field distribution and excitation mode optimization procedure may vary depending on the imaging location, subject size, transmit coil design, proprietary algorithms employed by different MR vendors, and future developments in the MRI technology. Therefore, from a neurostimulator manufacturer standpoint, entire RF-field shim space needs to be thoroughly analyzed for both RF lead heating and RF induced voltage levels. If not performed properly, risk of device malfunction, unintended tissue stimulation and risk of thermal injury due to interactions with AIMD and RF-field may be underestimated.

 

Discussion: Two different MC-2 RF excitations that produce similar magnetic-field uniformity may demonstrate distinct E-field distributions (Figure 1). Either one of these two shim solutions might be employed by an MRI scanner depending on vendor-specific 3T shim algorithm selection. Tangential E-field distributions of a DBS system implanted within the annotated region of Figure 1 can be significantly different (Figure 2), and thereby causing more than 10-times higher RF lead heating and 3-times higher RF induced voltage due to Shim A excitation compared to Shim B.

 

Conclusion:  RF shimming introduces complexity to 3T MRI safety assessments.  This type of RF excitation needs to be considered carefully to appropriately evaluate potential RF effects in safety assessments.

 

References:

  1. Falowski et al. Stereotact Func Neurosurg 2016;94:147-153.

  2. IMV Benchmark Report, 2017 MR.

  3. Harvey PR, Hoogeveen RM. Multi transmit parallel RF transmission technology. Philips Healthcare. 2009.


M. Arcan ERTURK, Mark CONROY, Thomas BRIONNE (Tolochenaz, Switzerland), Jacob CHATTERTON, S. Riki BANERJEE
00:00 - 00:00 #26133 - Optical guidance tool for frameless brain tumour needle biopsy.
Optical guidance tool for frameless brain tumour needle biopsy.

Background

Needle brain tumour biopsies are performed to tailor therapy when resection is not an option. Secondary outcomes of the procedure include inconclusive results (5-7% of cases [1-2]), and haemorrhage (5% of cases [2]). 5 aminolaevulinic acid (5-ALA) induced fluorescence has previously been suggested for decreasing the negative biopsy rate in frame-based biopsies [3]. The method demonstrates that fluorescence can indicate tumour tissue and, if combined with laser Doppler flowmetry (LDF), also act as a “vessel alarm” [4]. As a next step the method is transferred to frameless navigation, integrating an updated fluorescence and LDF system with an optical probe into the navigation procedure. The aim of the study is to present the first clinical measurements during brain tumour needle biopsy using the new concept.

 

Methods

The FluoRa 1.0 system [5] consists of four parts: a commercial LDF module, an inhouse fluorescence module, a LabVIEW (National Instruments, USA) software, and an optical probe. The LDF module (PF 5000, 780 nm, Perimed AB, SWE) records tissue perfusion (i.e., microcirculation [6]). The fluorescence module emits blue laser light (405 nm, Z-laser GmbH, DE) that is collected (AVASpect-ULS2048L-EVO, Avantes BV, NL) after tissue interaction. All signals are presented in real time in the FluoRa software, simultaneously with a ratio that illustrates the relation between tissue autofluorescence at 510 nm and fluorescence at 635 nm [7].

The optical probe consists of one sending and one receiving fibre for the fluorescence and LDF module, respectively. Each source fibre transports light from one laser to the tissue, and each detector fibre transports backscattered light to the corresponding module for signal digitization. The outer dimensions of the probe were adapted to the biopsy needle (Passive Biopsy Needle, Medtronic, Inc., USA). To allow for forward-looking measurements of the tissue, the needle was modified with an aperture at the tip. The probe was sterilized using the STERRAD® protocol. The system was tested experimentally and, following risk analysis, approved for use by Linköping University Hospital.

A patient with suspected malignant brain tumour referred for needle biopsy was included in the study (written informed consent, EPM-2020-01404). Preoperative MR images (T1-Gd, 3T Skyra, Siemens Healthcare, DE) were used for planning and optical guidance with the StealthStation® (S8, Medtronic, Inc., USA). An oral dose of 5-ALA (20 mg/kg) was administered 4 hours before intraoperative measurements. The optical probe was inserted in the modified needle. Stepwise insertion along two planned trajectories was combined with LDF (5-10 s) and fluorescence (3x200 ms) measurements presented in real time. When in target position, the probe was removed from the outer part of the needle and the inner biopsy needle was inserted. Biopsies were taken at -6, -3 and 0 mm according to standard clinical protocol.

 

Results and Discussion

Fluorescence and LDF were recorded in 79 points. A temporary increase in perfusion was observed at 2 sites. A fluorescence peak was visible in 15 of the 79 points. Biopsy sites coincided with fluorescence peaks. Intraoperative histopathology confirmed presence of malignant tumour tissue from the marginal zone. The postoperative diagnosis on frozen tissue samples confirmed glioblastoma WHO grade IV IDH wild-type.

Further clinical evaluation is needed to investigate the benefits of the integrated optical probe system for frameless needle biopsies, as well as for resections. The next step is to link the optical measurements to different MRI protocols, including tractography, microdiffusion and 3D visualization of results.

In conclusion, this clinical case illustrates the feasibility of real time identification of malignant tumour tissue through optical guidance, with both fluorescence and LDF, in frameless brain needle biopsy.

The study was financially supported by the Swedish Foundation for Strategic Research (RMX18-0056).

 

Disclosure

JR and KW are inventors of related patents and hold shares in FluoLink AB, Sweden.

 

References

[1] Kesserwan MA, et al, Surg Neurol Int. 2021.

[2] Livermore LJ, et al, Br J Neurosurg. 2014.

[3] Richter JCO, et al, Operative Neurosurgery, Accepted, 2021.

[4] Zsigmond P, et al, Stereotact Func Neurosurg, 2018.

[5] Klint E, et al, 43rd IEEE EMBC, Submitted, 2021.

[6] Wårdell K, et al, Operative Neurosurgery, 2013.

[7] Haj-Hosseini N, et al, Laser in Surgery and Medicine, 2010.


Elisabeth KLINT (Linköping, Sweden), Johan RICHTER, Karin WÅRDELL
00:00 - 00:00 #26260 - Orientation detection of deep brain stimulation electrodes based on neuronavigation with an embedded magnetic sensor.
Orientation detection of deep brain stimulation electrodes based on neuronavigation with an embedded magnetic sensor.

Background: Recently, directional leads (D-leads) have been introduced. The horizontal current steering allows an adaptation of the stimulated volume leading to a reduction of induced side effects. Indeed, the identification of the orientation of the DBS lead and of the position of the different lead segments within the anatomical structures represents an important basis for stimulation parameter tuning. Therefore, the control of their orientation during surgery gains in importance compared to conventional DBS leads.

While the positioning of DBS leads using electromagnetic tracking (EMT) has recently been investigated [1][4], their orientation is still not completely handled. Orientation detection currently relies on postoperative electrode artefact analysis on Computed Tomography (CT) images [3] implying additional radiation dose and remaining time consuming. It has been reported that D-leads can exhibit large deviations from the intended implantation direction [2]. Previous published results with an EMT system under development have shown a mean absolute error (MAE) of 2.46° on the angle of interest (yaw angle) for D-leads detection [5]. The aim of the present work is to evaluate the accuracy of angle detection with a 3D magnetic sensor providing a higher sensitivity than the one reported in [5].

Materials and Methods: A magnetic field generator, which consists of a single coil (3B Scientific GmbH, Germany) arranged sequentially in three orientations, was used to create field changes below 100 uT within the tracking volume. In addition, a single 3D magnetic field sensor (MMC5603NJ, MEMSIC Inc. USA, sensitivity of 6.25 nT per LSB) was integrated at the tip of a carbon tube mimicking the DBS electrode (Fig. A). Due to prototyping constraints, the tip was designed with a 2.5 mm diameter. The tracking algorithm was based on Kuipers’ resolution method. The outcomes of our algorithm were compared to the stereotactic Leksell system (Elekta, Sweden) used as reference to control the rotation over each axis. Each rotation was measured separately with different measuring steps and ranges (Roll rotation: 0-90° by 5° step; Pitch rotation: 0-110° by 10° step; Yaw rotation: 0-280° by 20° step) due to the stereotactic arc dimension.

Results: The rotations over roll, pitch and yaw showed a MAE of respectively 0.24°, 0.86°, and 1.66° (Fig. B) (Root mean square error (RMSE) of 0.29°, 0.99° and 1.85°). The measurement uncertainties varied according to the angles from 0.5° for roll angle to 2° for yaw angle, which corresponds to the uncertainties introduced while reading the true angles on the arc’s graduation.

Discussion and outlook: The results obtained are similar to those obtained through post-CT artefact analysis, which have been reported to be 1.5° [3] (RMSE). In comparison to the previous results, the use of a sensor with higher sensitivity leads to an improvement on the angular resolution. In parallel with the position tracking already put forward in previous works [4], the neuronavigation based on an embedded 3D magnetic sensor could provide a full tracking of DBS leads. The robustness of the system, especially to magnetic perturbations, is under investigation, and the performance obtained in presence of a stereotactic system are encouraging. This system should provide a new approach to intra-operative verification of the DBS electrode orientation and relevant information to tune the stimulation parameters accordingly. Considering the dimensions of the presented magnetic sensor (0.8 x 0.8 x 0.4 mm), further miniaturization steps will allow us to reach the dimension of DBS electrodes (1.27 - 1.4 mm diameter).

References:

[1] Burchiel et al. Verification of the Deep Brain Stimulation Electrode Position Using Intraoperative Electromagnetic Localization. Stereotact Funct Neurosurg. 2020
[2] Dembek et al. Directional DBS leads show large deviations from their intended implantation orientation. Parkinsonism Relat Disord. 2019
[3] Hellerbach et al. DiODe: Directional Orientation Detection of Segmented Deep Brain Stimulation Leads: A Sequential Algorithm Based on CT Imaging. Stereotact Funct Neurosurg. 2018
[4] Quirin, et al. Towards Tracking of Deep Brain Stimulation Electrodes Using an Integrated Magnetometer. Sensors 2021
[5] Vergne et al. Tracking the Orientation of Deep Brain Stimulation Electrodes Using an Embedded Magnetic Sensor. 10th IEEE EMBS Conference on Neural Engineering, online, 2021


Celine VERGNE (Basel, Switzerland), Morgan MADEC, Joris PASCAL, Simone HEMM
00:00 - 00:00 #23971 - Perivascular spaces as a potential risk marker for intracerebral hemorrhage in DBS surgery – a retrospective investigation.
Perivascular spaces as a potential risk marker for intracerebral hemorrhage in DBS surgery – a retrospective investigation.

Objective: Intracerebral hemorrhage (ICH) poses the most devastating complication of DBS surgery and is associated with higher age and the use of microelectrode recording. In the preOP MRI we encountered wide perivascular spaces (PVS) in cases with ICH during electrode implantation at our department. This aspect has not been described in the literature before. However, PVS enlargement is associated with occurrence of spontaneous intracerebral hemorrhage (Raposo et al. 2019, Duperron et al. 2019) and may reflect a general vascular vulnerability. Here we aimed to explore the role of enlarged PVS as a risk indicator for ICH during DBS electrode implantation.

Methods: The data of 330 consecutive patients (01/2013-11/2019) were analysed. Preoperative imaging includes a 3T T1-MPRAGE and T2-Space sequence with 1mm isotropic resolution. Unsuitable MR images were excluded (movement artefacts, <3 Tesla, WMH of non-vascular origin e.g. multiple sclerosis, preexisting DBS, tumor resection), resulting in 242 MRIs. Prior to PVS burden quantification, T1 und T2 images were coregistered using SPM12 and the T1 image was segmented using SPM12’s segmentation algorithm in WM/GM/CSF. For normalization of the T2 contrast a smooth T2 CSF reference image was computed by 1) masking out the all signal non-CSF in the T2 image (using SPM’s CSF-T1 segmentation), and 2) extending the CSF signal to adjacent regions by a broad Gaussian smooth. The raw T2 is then divided by this reference image to obtain comparable contrasts. PVS burden was computed by the commonly used Frangi-filter for tubular structures (smin=0,4mm, smax=2,0mm, scale ratio=2, α=0,1, β=1, c=0,01) on the normalised T2 (Frangi et al. 1998). All responses in non-WM were excluded. Finally, PVS index was computed by a simple summation of all non-negative filter responses within white matter.

A score was set up representing the most invasive implantation method applied in each patient: intraoperative clinical testing with stimulation via blunt tip probe (1) or via macroelectrodes with retracted microelectrodes (2); microelectrode recording (3). Metric data (age and PVS index) were dichotomised using the median.

The Fisher exact test was applied with a level of significance at p < .05 to compare the incidence of ICH in patients with a high and low index of PVS. Further exploratory analyses were conducted (Fisher exact test for known risk factors age, and invasivity; correlation analyses for the metric data age and PVS index).  

Results: 8 intracerebral hemorrhages occurred during implantation of 649 electrodes in 336 operations (2.4 %) in 330 patients. Relevant neurological deficits resolved in all but one of the affected patients. ICHs occurred more often in patients with high PVS enlargement (p = .029, 2-sided).. As expected, exploratory analyses showed a higher incidence of ICH in patients of higher age (p = .019, 2-sided) and with increasing invasivity index (p = .008, 2-sided). As expected, we found significant positive correlations of age and the PVS index.

Discussion: Enlarged PVS may serve as an additional risk indicator for ICH in DBS surgery and help to mitigate invasivity (e.g. avoid microelectrodes) in patients at risk. The presented results are preliminary and further analyses are in preparation to address the sparse data bias (Greenland et al. 2016) due to low incidence of ICH.

 

References:

Nicolas Raposo and others, ‘Enlarged Perivascular Spaces and Florbetapir Uptake in Patients with Intracerebral Hemorrhage’, European Journal of Nuclear Medicine and Molecular Imaging, 46.11 (2019), 2339–47 <https://doi.org/10.1007/s00259-019-04441-1>.

Marie-Gabrielle Duperron and others, ‘High Dilated Perivascular Space Burden: A New MRI Marker for Risk of Intracerebral Hemorrhage’, Neurobiology of Aging, 84 (2019), 158–65 <https://doi.org/10.1016/j.neurobiolaging.2019.08.031>.

Alejandro F. Frangi and others, ‘Multiscale Vessel Enhancement Filtering’, in Medical Image Computing and Computer-Assisted Intervention — MICCAI’98, ed. by William M. Wells, Alan Colchester, and Scott Delp (Berlin, Heidelberg: Springer Berlin Heidelberg, 1998), mcdxcvi, 130–37 <https://doi.org/10.1007/BFb0056195>.

Sander Greenland, Mohammad Ali Mansournia, and Douglas G Altman, ‘Sparse Data Bias: A Problem Hiding in Plain Sight’, BMJ, 2016, i1981 <https://doi.org/10.1136/bmj.i1981>.


Timo Sebastian BRUGGER, Marco REISERT, Christoph KALLER, Egger KARL, Volker Arnd COENEN, Bastian Elmar Alexander SAJONZ (Freiburg, Germany)
00:00 - 00:00 #26250 - StereoSlicer, a plugin for 3DSlicer to handle data from stereotactic surgeries.
StereoSlicer, a plugin for 3DSlicer to handle data from stereotactic surgeries.

Background:

When performing analysis of data related to stereotactic neurosurgery, one of the first operations is to extract image data from the clinical software systems. This step can become quite problematic, due to a gap in 3D reference space between software used in clinical practice and image analysis environment. Leksell arc settings (Leksell G Frame, Elekta AB, Sweden) for trajectories are an example: they are of great importance in functional neurosurgery but importing these to research-oriented software can become a complex task since the reference of the coordinates is based on the N-shaped marker of the Coordinate Frame (Elekta AB, Sweden) embedded in the 3D image. Our aim is to minimize the burden from this gap in an automatic and user-friendly way.

In this paper, StereoSlicer, a plugin easing the use of Leksell arc settings in the medical image visualization and processing software 3DSlicer (slicer.org) is presented.

Method:

The plugin consists of three modules. The first module is responsible for the detection of the N-shaped markers in the images: histogram-based intensity thresholding is used to isolate their contrast band from the background and from the patient. Then the resulting objects are filtered based on their size and position. Once the markers are identified, their 3D representation is generated. An ideal model of the markers in a known orientation can then be generated with the user interface. This orientation corresponds to the marker plates normal to the vectors describing the Right-Anterior-Superior (RAS) space.

The two models (segmented and ideal) are then registered using iterative closest point surface-to-surface registration. The resulting affine transformation describes the position of the Coordinate Frame within the patient images. In the second module, the Leksell arc settings are first converted to an affine transform describing the position of the trajectory in RAS space. By combining it with the previous transform, the Leksell arc settings can be used to place the trajectory in the original patient images. To use trajectories in generic research software, points can also be transformed to voxel indices in image space.

With the third module, the standard slice views from 3DSlicer can be oriented orthogonal to the trajectory rather than the anatomical directions. The result is a “probe view” similar to what is available in clinical software.

The two first modules were validated separately. The segmentation module was tested with CT data from 19 patients originating from the university hospital in Clermont-Ferrand in France (2011-A00774-34/AU905). The segmentation was run for each patient and the proper detection of the marker was checked visually. The validity of the affine transforms calculated was tested with the placement of trajectories at known locations in the Leksell coordinate system, namely along the bars of the marker. Parallel trajectories corresponding to the use of the Ben Gun were added in order to validate conversion from the arc settings to an affine transformation. The transform between Leksell space and the patient space was then tested by checking that the same trajectories indeed align with the markers visible in the CT contrast and the 3D model based on segmentation. Lastly, a fake trajectory was created in Brainlab iPlan Stereotaxy with the anterior commissure (AC) and posterior commissure (PC) labeled by the neurosurgeon as entry and target points. The resulting arc settings were used in StereoSlicer and the position of AC and PC points were calculated and compared to the anatomy.

Results:

In each of the 19 patients, all N-shaped marker were correctly identified, the registration between the surfaces of the segmented and ideal fiducials was successful and allowed to place trajectories with Leksell settings which aligned with the artifacts of the marker in the CT image in patient space. In all the patients, each end of the fake trajectory coincided with AC and PC on the MRI in StereoSlicer with a sub-voxel precision.

Conclusion:

StereoSlicer provides automatic N-shaped marker segmentation and allows to use Leksell arc settings within the popular, open-source 3DSlicer platform. It was tested with CT images from a single center. Further testing is needed with images from other centers and other imaging modalities such as MRI. To that end, the source of the plugin will be open-sourced and submitted to the Slicer Extension Index.


Dorian VOGEL (Basel, Switzerland), Johansson JOHANNES, Nordin TERESA, Karin WÅRDELL, Simone HEMM
00:00 - 00:00 #26123 - Tractography Alterations in the Arcuate and Uncinate Fasciculi in Post-Stroke Aphasia modulated by tDCS.
Tractography Alterations in the Arcuate and Uncinate Fasciculi in Post-Stroke Aphasia modulated by tDCS.

Fiber tractography based on diffuse tensor imaging (DTI) can reveal three-dimensional white matter connectivity of the human brain. Tractography is a non-invasive method of visualizing cerebral white matter structures in vivo, including neural pathways surrounding the ischemic area. DTI may be useful for elucidating alterations in brain connectivity resulting from neuroplasticity after stroke. We present a case of a male patient who developed significant mixed aphasia following ischemic stroke. 

The patient had been treated by mechanical thrombectomy followed by an early rehabilitation, in conjunction with transcranial direct current stimulation (tDCS). DTI was used to examine the arcuate fasciculus and uncinate fasciculus upon admission and again at three months post-stroke.

Results showed an improvement in the patient’s symptoms of aphasia, which was associated with changes in the volume and numbers of tracts in the uncinate fasciculus and the arcuate fasciculus.

This case report demonstrated DTI with tractography as an MRI technique used to detect the microstructural changes and difference in the anatomy and morphology of fiber tracts in patients after ischemic stroke which corresponded with improvement in the patient’s clinical functioning.


Sara KIEROŃSKA (Bydgoszcz, Poland), Milena ŚWITOŃSKA, Paweł SOKAL
00:00 - 00:00 #26122 - Tractography changes in the forceps minor and superior longitudinal fasciculus after cingulotomy in patient with obsessive-compulsive disorder.
Tractography changes in the forceps minor and superior longitudinal fasciculus after cingulotomy in patient with obsessive-compulsive disorder.

After stereotactic procedure, the brain is known to be reorganized especially in the associate cortex. We report a case to show changes in the forceps minor and superior longitudinal fasciculus in a patient with obsessive-compulsive disorder underwent cingulotomy using diffusion tensor imaging. 

A 45-year-old man with obsessive-compulsive disorder history since 12 years in the form of uncontrolled hand washing pharmacologically treated with unsatisfactory effect was qualified to bilateral cingulotomy. 

The anterior part of gyrus cingulum 25 mm above of the frontal horn of lateral ventricles was chosen as the target bilaterally. The procedure of cingulotomy was undertaken without adverse events.

An initial brain magnetic resonance imaging with a diffusion tensor imaging was performed before and 3 months after cingulotomy procedure. After 3-months follow up we observed changes in forceps minor and superior longitudinal fasciculus comparing in increase of tracts volume from 18-22% and increase of numbers of tracts from 15-20% comparing with baseline DTI. Moreover fractional anisotrophy (FA) after 3 months follow up has been increased up to 25% in forceps minor and up to 20% in superior longitudinal fasciculus

At 3-months follow-up, there was also  more than 60 % reduction in OCD symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale.

Results showed an improvement in the patient’s symptoms of OCD, which was associated with changes in the volume and numbers of tracts in the forceps minor and the superior longitudinal fasciculusThis case report suggests that diffusion tensor imaging tractography could be a useful method to understand cortex reorganization after cingulotomy in OCD. 

 


Sara KIEROŃSKA (Bydgoszcz, Poland), Paweł SOKAL, Marcin RUDAŚ, Banasiak ANNA, Marcin RUSINEK
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MOVEMENT DISORDERS

00:00 - 00:00 #26189 - 3T Magnetic Resonance-guided Focused Ultrasound (MRgFUS) unilateral thalamotomy of Vim (ventral intermediate nucleus) in patients with essenzial tremor: three-years clinical experience of a single center.
3T Magnetic Resonance-guided Focused Ultrasound (MRgFUS) unilateral thalamotomy of Vim (ventral intermediate nucleus) in patients with essenzial tremor: three-years clinical experience of a single center.

Background and Aims. Magnetic resonance-guided focused ultrasound (MRgFUS) unilateral thalamotomy of the ventralis intermedius (Vim) nucleus is emerging as a minimally invasive treatment for patients with disabling and medication-refractory essential tremor (ET). We report our preliminary three-year experience on 52 patients with ET treated from January 2018 to December 2020 in a single center (University Hospital of Verona).

Methods. From January 2018 to December 2020, 52 patients (31 men, 21 women, age: 73.5 ± 7.8 years) underwent MRgFUS thalamotomy of the Vim nucleus for disabling and refractory ET (tremor duration: 22.6 ± 12.1 years) with a 3T magnetic resonance scanner (MRgFUS Insightec Exablate 4000) at Verona University Hospital.

Results. At baseline the total Clinical Rating Scale for Tremor (CRST) score was 45.8 ± 15.6, and the Quality of Life in Essential Tremor Questionnaire (QUEST) score was 40.8 ± 13.8. At one-month follow-up, the total CRST score was 12.8 ± 6.3 and the QUEST score was 10.5 ± 4.1. Response persisted in the majority of patients at three-month, six-month, one-year, two-year and three-year follow-up.        Side effects related to Vim nucleus thalamotomy included ataxia, speech disturbances, ballism, paraesthesia, and lower extremity weakness. These side effects were mild and transient in most patients.

Conclusions. Our data confirm that MRgFUS thalamotomy of the Vim nucleus is an effective and safe treatment for disabling and refractory ET and its effects are long-lasting.


Giorgia BULGARELLI (Verona, Italy), Stefano TAMBURIN, Giuseppe Kenneth RICCIARDI, Michele LONGHI, Emanuele ZIVELONGHI, Tommaso BOVI, Stefania MONTEMEZZI, Roberto FORONI, Antonio NICOLATO
00:00 - 00:00 #23965 - ACTIVA systems for deep brain stimulation: an analysis on a prospective, multicenter Product Surveillance Registry (PSR) to meet the reimbursement requirements of the French Haute Autorité de Santé (HAS).
ACTIVA systems for deep brain stimulation: an analysis on a prospective, multicenter Product Surveillance Registry (PSR) to meet the reimbursement requirements of the French Haute Autorité de Santé (HAS).

Following reimbursement of ACTIVATM DBS systems, the French Haute Autorité de Santé (HAS) via the Commission Nationale d’Evaluation des Dispositifs Médicaux et des Technologies de Santé (CNEDiMTS) requested a five-year follow-up registry of implanted DBS patients to maintain the reimbursement of the devices. The aim of the study was to characterize adverse events and quality of life measures by DBS indication.

A prospective, non-randomized, observational, multicenter study was conducted, as part of the Product Surveillance Registry (PSR), an ongoing, prospective, long-term multi-center registry. Patients were enrolled from June 2013 until October 2018. A sampling of patients (n=400) from 7 representative French implanting centers would be pooled with data from other global centers enrolling in the PSR. Testing for homogeneity would be performed to ensure poolability of data. The eligible centers in France were analyzed by quartiles representing implant volume (very large, large, average, and small sites to be representative of real-world use). To limit bias, changes in EQ-5D score were analyzed for therapy-naïve PSR patients who completed both baseline and follow-up questionnaires (matched pairs).

At the time of the final study report in June 2019, 2 537 patients were enrolled at 38 global sites, including 491 (19,4%) from France. The majority of patients were treated for Parkinson’s disease (PD) (64,2%) and Essential Tremor (22,9%). The average length of follow-up time was 31 months (0 – 106,7 months). France enrolled a higher proportion of PD patients (71,1% vs 58,3%; p<0,0001) and patients receiving a replacement device (45,6% vs 36,7%; p<0,0001). There was no statistically significant difference in enrolled patients from France versus patients from other geographies in age and gender. Overall, 1 427 events were reported for 768 patients (30,2%). Of those, 381 events were classified as serious (26,7%) for 294 patients (11,6%). A total of 331 events were reported for 197 French patients (40,1%). Of those, 109 events were classified as serious (32,9%) for 89 patients (18,1%). The rates of adverse events and serious adverse events in France were not significantly different from other European countries. Overall, 693 hospitalizations were reported (376 in France). Of these 221 (31,9%) were due to events. The most common adverse events related to hospitalizations were for medical device site or wound infections, worsening tremors or dyskinesia, high impedance, psychiatric disorders (e.g. depression, anxiety), gait disturbances, and device migrations. There was a difference in hospitalization rates between patients in France and other geographies, that may be attributable to regional variation in care patterns (e.g more hospitalizations in France for device re-programming vs. outpatient care).  Overall, there were 171 deaths (6,7%) and 17 deaths (3,5%) in France. None of deaths were reported as a direct result of a product performance event. Patients from France and other geographies showed a statistically significant improvement in EQ-5D index and VAS scores through first follow-up. For therapy-naïve PD patients from France (N=135), change across time was statistically significant with average improvements between baseline and first follow-up (6 or 12 months) of 0,12 in EQ-5D index score (p<0,0001) and a significant improvement in EQ-5D VAS score of 12,4 units or 22,9% change between baseline and first follow-up.

The results of this five years follow-up study support the continued safety and effectiveness of the DBS systems for their intended use in real world conditions. Thus, HAS approved the renewal of reimbursement of ACTIVATM DBS systems in France.


Stéphane PALFI (PARIS), Emmanuel CUNY, Jean-Philippe AZULAY, Luc DEFEBVRE, Soledad NAVARRO, Philippe COUBES, Franck DURIF, Apolline ADE, Pierre-Antoine GROHARD, Christian AUBLANT, Thomas BRIONNE, Keisha SANDBERG, Todd WEAVER
00:00 - 00:00 #26099 - Awake versus asleep STN-DBS for Parkinson’s disease: asleep as a feasible alternative.
Awake versus asleep STN-DBS for Parkinson’s disease: asleep as a feasible alternative.

Introduction
Bilateral deep brain stimulation (DBS) of the nucleus subthalamicus (STN) has been proven to be a successful treatment for Parkinson’s disease. The success of DBS correlates with the anatomical accuracy of the implanted electrodes. Generally, this procedure is performed under local anesthesia (LA) to enable microelectrode recording (MER) and intraoperative macrostimulation. The correct location of the implanted electrode is verified during the test stimulation. Nowadays, general anesthesia (GA) is a feasible alternative, due to technical improvements in direct targeting employing high field MRI and intraoperative CT imaging (iCT) (Medtronic O-arm). The verification method relies on intraoperative imaging with or without MER. The impact on the patient is less severe while using GA, as it is perceived as more accessible and comfortable. The success of this technique is independent of cooperation of the patient.

Material and Methods
Five patients with Parkinson’s disease were treated with bilateral DBS of the STN under GA. Preoperative 3T MRI T2 and T1 MPRAGE with gadolinium sequences images (Siemens Skyra 3T MRI) were made under GA. Direct targeting through visualization of the STN in T2 images was done. After attachment of a Cosman-Roberts-Wells frame (Integra CRW stereotactic system), CT guided stereotactic images were made and fused with the preoperative MRI. Boston Scientific Vercise Cartesia directional leads were stereotactically implanted and linked to BS Vercise Gevia battery. Intraoperative MER was used to verify the correct electrophysiological location. Intraoperative verification of the anatomical lead positions was done with iCT. There were no postoperative infections or hemorrhages.


Results
All lead positions were within 2mm radius of the planned trajectory. The postoperative motor effect was comparable with STN DBS under LA. Long term follow-up showed a lasting result.

Conclusion
We can confirm similar results on the postoperative improvement between LA and GA for STN DBS.


Sarah HENDRICKX (Ghent, Belgium), Stijn VANDAMME, Frederik CLEMENT, Jeroen VAN LERBEIRGHE, Dimitri VANHAUWAERT, Olivier VAN DAMME
00:00 - 00:00 #23930 - Bilateral deep brain stimulation of the internal globus pallidus for severe refractory tardive syndromes: multicentric experience and evidence-based recommendations.
Bilateral deep brain stimulation of the internal globus pallidus for severe refractory tardive syndromes: multicentric experience and evidence-based recommendations.

TITLE

Bilateral deep brain stimulation of the internal globus pallidus for severe refractory tardive syndromes: multicentric experience and evidence-based recommendations. 

 

 

AUTHORS

Oscar Andrés Escobar Vidarte. MD. FACS.

Associate Professor, Neurosurgery Section, Universidad del Valle, Cali, Colombia.

Professor, Department of Medical Clinics, Pontificia Universidad Javeriana, Cali, Colombia.   

Coordinator Neorosurgery Service, Comfandi Amiga Clinic, Cali, Colombia.

Functional Neurosurgeon, Castellana Clinic, Cali, Colombia.

Functional Neurosurgeon, Latin American Institute of Neurology and the Nervous System (ILANS), Bogotá, Colombia.

First author and speaker.

 

Javier Orozco Mera. MD. FACS.

Professor, Neurosurgery Section, Universidad del Valle, Cali, Colombia. 

Neurosurgeon of Tumors and Skull Base Surgery, Neurosurgery Service, Comfandi Amiga Clinic, Cali. 

 

Gabriel José Arango Uribe. MD.

Movement Disorders Neurologist.

Latin American Institute of Neurology and the Nervous System (ILANS), Bogotá, Colombia. 

Marly Clinic, Bogotá, Colombia. 

 

Juan David Rivera. MD.

Neurosurgery Program Specialization Resident. 

Neurosurgery Section, Universidad del Valle, Cali, Colombia.

 

 

TOPIC

Movement disorders.

 

 

 

KIND OF COMMUNICATION

Poster presentation.

 

 

KEY WORDS

Tardive syndromes, deep brain stimulation, internal globus pallidus.

 

 

INTRODUCTION

Tardive Syndromes (TS) are characterized by the appearance of involuntary dystonic and/or dyskinetic movements after chronic use of some medications (3-6 months). Deep brain stimulation (DBS) of the Internal Globus Pallidus (GPi) has been used to treat severe and refractory cases.

 

OBJECTIVE

To describe and analyze the impact of DBS GPi on the severity of the movements in patients with severe and refractory TS, and to review the available evidence to recommend this procedure.

 

METHODS

Eleven patients with severe and refractory TS were driven to GPi bilateral DBS, the series analysis was performed by results evaluation with a minimum 1-year follow-up using preoperative Burke-Fahn-Marsden Dystonia motor scale (BFM) value and postoperative value during the last follow-up visit.

 

RESULTS

Patients were followed during a period of 1 to 7 years, with an average preoperative score of the BFM scale of 36,7 and postoperative score of 9,3, obtaining an average improvement of 74,7%. An extension cord rupture, a surgical wound infection and a case of persistent moderate dysarthria were documented. When performing a literature review a meta-analysis published in 2018 was found and such work showed an average improvement in the severity of the BFM scale of 76% in patient driven to a DBS because of TS.

 

CONCLUSION

GPi DBS for severe and refractory TS can be considered as a tratment for movement control, being recommended by expert groups as a safe and reproducible procedure.


Oscar ESCOBAR (Cali, Colombia), Javier OROZCO, Gabriel ARANGO, Juan RIVERA
00:00 - 00:00 #23964 - Bilateral double beta peaks in a PD-patient with STN-electrodes and „brainsensing“.
Bilateral double beta peaks in a PD-patient with STN-electrodes and „brainsensing“.

Objective: Subthalamic (STN) local field potentials (LFPs) in the beta band are considered as potential powerful biomarkers for for the current physiological” status” of the patient and might therefore be used for “brainsensing” and consecutive adaptive, closed-loop deep brain stimulation. Our goal was to investigate the subthalamic beta band peak amplitudes in a Parkinson’s disease patient over an extended period of time under various „conditions“ (movement tasks, stim on/stim off, med on/med off) by using a novel and commercially available implantable neurostimulator with permanent sensing capability for the first time.

Methods: We recorded LFPs within the STN using the novel, now commercially available implantable neurostimulator at rest and during physical activity (gait) and the respective response to various stimulation protocols and stim-off. Gait performance was continuously monitored with sensors attached to the shanks, thighs, arms and chest, and step length, cadence and foot clearing were measured. Gait recordings and LFPs were synchronized by detecting the impulses of a transcutaneous electric nerve stimulator (TENS) triggered by the gait recording devices. The exact timing and amplitude of stimulation was recorded by the stimulator and transferred to atablet computer.

Results: We found a double-peaked beta activity on both sides. Increasing stimulation and physical activity (walking) resulted in a decreased beta band amplitude, but was accompanied by the appearance of a second, and previously unrecognized peak at 13 Hz in the right hemisphere.

Conclusion In summary, our results will support the investigation of patient-specific individual LFP patterns (LFP ‘fingerprints’) and aid the development of LFP-based feedback signals. In addition, our exploratory study highlights the potential of dual deep brain stimulation and recording devices (DBS/R) for the study of LFPs.

 


Jan MEHRKENS (München, Germany), Thomas KÖGLSPERGER, Kai BÖTZEL
00:00 - 00:00 #26115 - Cerebellar and sensorimotor cortical connectivity predicts outcomes of pedunculopontine nucleus stimulation in Parkinson's disease.
Cerebellar and sensorimotor cortical connectivity predicts outcomes of pedunculopontine nucleus stimulation in Parkinson's disease.

Background

Deep brain stimulation of the pedunculopontine nucleus is a promising surgical procedure for the treatment of Parkinsonian gait and balance dysfunction. It has, however, produced mixed clinical results that are poorly understood. We used tractography with the aim to rationalise this heterogeneity.

Methods

A cohort of eight patients with postural instability and gait disturbance (Parkinson’s disease subtype) underwent pre-operative structural and diffusion MRI, then progressed to deep brain stimulation targeting the pedunculopontine nucleus. Pre-operative and follow-up assessments were carried out using the Gait and Falls Questionnaire, and Freezing of Gait Questionnaire. Probabilistic diffusion tensor tractography was carried out between the stimulating electrodes and both cortical and cerebellar regions of a priori interest.

Results

Five of eight patients showed improvement at follow-up (median = 12 months, Q1–Q3: 12–16 months). Structural connectivity between stimulating electrode and precentral gyrus (r = 0.81, p = 0.01), Brodmann areas 1 (r = 0.78, p = 0.02) and 2 (r = 0.76, p = 0.03) were correlated with clinical improvement. A negative correlation was also observed for the superior cerebellar peduncle (r = −0.76, p = 0.03). 

Conclusions

Both motor and sensory structural connectivity of the stimulated surgical target characterises the clinical benefit, or lack thereof, from surgery. In what is a challenging region of brainstem to effectively target, these results provide insights into how this can be better achieved. Considering both electrode coordinates and connectivity patterns, we conclude that stimulating the most caudal and lateral part of the pedunculopontine nucleus may offer the best chance of relieving symptoms, whereas, stimulating the superior cerebellar peduncle medially may worsen them. The mechanisms of action remain unclear, but our results support both motor and sensory components, commensurate with the probable nature of the underlying dysfunction.


Ashley RAGHU (Atlanta, USA), Tariq PARKER, John STEIN, Jesper ANDERSSON, Stephen PAYNE, Tipu AZIZ, Alex GREEN
00:00 - 00:00 #23784 - Clinical deep brain stimulation targeting based on an inverse problem approach. The artificial intelligence solution.
Clinical deep brain stimulation targeting based on an inverse problem approach. The artificial intelligence solution.

Targeting in deep brain stimulation (DBS) procedures remains controversial, mainly because research into the relationship between improvement and electrode location requires correction for anatomical variations leading to poorly controlled errors.

Thus, it is difficult to present the following forward problem in simple terms: From a preoperative clinical status, we must define the targets to be reached in order to obtain a good result, the result obtained with the stimulation, the precise location of the electrodes and the correlation between all of these items.

From a mathematical perspective, when it is difficult to solve a forward problem, a solution can be found by considering the inverse problem.

By identifying patients with a good clinical outcome after DBS, we correlated active contacts of electrodes with simple MRI landmarks around this contact. We thus describe the location of the electrode by the Euclidian distance and the vector of each landmark. We produced a metamodel that expresses the position of active and clinically effective contacts depending on the position of MRI landmarks. We applied this metamodel to new patients to predict the effective location of active contacts by identifying MRI landmarks. After verification of the consistency and the robustness of the model, we verified its clinical effectiveness through trials where electrodes were directly inserted at the predicted target without any microrecording or MRI correction.

We first applied this method to the subthalamus nucleus (STN) in Parkinson’s disease (PD). We selected 22 PD patients who dramatically improved with STN DBS. The coordinates of the active contacts were correlated with 12 radiological landmarks around the electrode. We selected the 3 landmarks with the strongest correlation with the active contact and expressed the target coordinates as 3 equations of the corresponding regression line of these landmarks.

xT=0.44xlat hedge of the 3rd ventricle+10.71

yT=0.69ymammilothalamic tract+1.62

zT=0.72zthalamus height -16

In a second cohort of 9 patients, we verified the target accuracy (external validation) by calculating the Euclidian distance between the active contact location and the predicted target. Comparison of the internal error (calculated by leave-one-out cross-validation) of the first cohort and the external error confirmed the model’s coherence and robustness.

We conducted the PARKEO trial (NCT01817088), a prospective phase-2, open-label, single-centre, randomised non-comparative trial with two parallel groups: an asleep group without microrecording (20 patients) and an awake group with microrecording (10 patients). All patients were targeted on the clinical-based STN.

The mean motor improvement rates (mean [95% Confidence Interval]) on the UPDRS III between OFF and ON stimulation without medication was 52.3% [45.4% – 59.2%] and -18.8 [-31.6; -6.0] for the quality-of-life improvement evaluated by the decrease in PDQ39 in the asleep group 6 months after surgery.

We applied this method to the VIM in essential tremor (ET), but the selection of three landmarks, as for the STN target, failed to predict the active contact of the electrodes. We then constructed a learning data base from 15 patients (29 leads) who had undergone surgery with a median tremor improvement of 72% on the Fahn-Tolosa-Marin scale. All the patients underwent pre- and post-operative imaging from which the coordinates of 18 anatomical landmarks per side and of the active contacts were extracted. We used regression and deep learning methods (Artificial Intelligence). The models were statistically and anatomically validated, respectively, according to a leave-one-out cross-validation and the mean distance to VIM structure on the DISTAL atlas in the MNI space. Support Vector Regression (SVR) gave the best results with a mean error of 1.33 +/- 1.64mm between the predicted target and the active contact position.

We conducted the Opti-VIM trial (NCT03760406), a prospective phase-2, open-label, double-centre (Bordeaux and Lyon) single group trial on a group of 20 asleep patients without microrecording. Further preliminary results of stimulation of the optimized VIM target under general anaesthesia and without additional electrophysiological or MRI correction are presented.

Thus, the resolution of the inverse targeting problem by AI simplifies surgery by allowing interventions under general anaesthesia, without MER correction and with good outcomes.


Julien ENGELHARDT, François CAIRE, Nejib ZEMZEMI, Denis FONTAINE, Dominique GUEHL, Pierre BURBAUD, Nathalie DAMON-PERRIERE, Wassilios MEISSNER, Caroline GIORDANA, Michel BORG, Emmanuel CUNY (bordeaux)
00:00 - 00:00 #23992 - Comparison of DBS devices lifespan for the treatment of Parkinson’s disease with corresponding meta-analysis of the literature.
Comparison of DBS devices lifespan for the treatment of Parkinson’s disease with corresponding meta-analysis of the literature.

Technological advances have permitted the manufacture of new generation of devices for deep brain stimulation. These devices need to be tested to demonstrate non inferiority both on clinical effectiveness associated complications and longevity of the device. Several studies have compared the lifespan o such devices using heterogeneous methods. The goal of this study is to determine whether there is a longevity difference between first and second generation of Medtronic© devices.  The second objective is to compare the longevity of the same implanted devices after its first implantation and after its replacement. PRISMA review methods were applied to construct a meta-analysis of similar studies.

 

Methods

60 consecutive patients implanted with DBS for Parkinson’s disease from 2010 to 2013, in whom the device was not later explanted for adverse effect reasons (i.e. infection), were followed and screened for device replacements from 2010 to the current date (01/01/2018). Thirty patients beneficiate from Kinetra® devices and thirty patients beneficiate from new stimulator model (at this time) ActivaPC®. Comparisons were made between the lifespan of these two different models. The longevity of same type of device used both for first implantation and then for replacement in the same patient was also compared and analysed.

 

Results

Average lifespan for the Kinetra® stimulator was 1711±478 days whereas for the ActivaPC® was 1691±289 days. The difference is not statistically significant (p=0,32 student t-test) . Kaplan Meyer statistics were calculated for these two models. Median survival for Kinetra® was 1611 days whereas for ActivaPC® was 1740 days. A log rank test showed this difference to be close to the statistical significance limit p=0.06.

Lifespan comparison between first and second implanted device showed a statistically significant difference in lifespan with a shorter lifespan of the second device (1699 vs 1435 days, p=0.02).

 

Discussion

Four similar studies were found and were candidates for meta-analysis. Using PRISMA review criteria none qualified for inclusion in the meta-analysis. Elements of each study are discussed and compared to the presented original study. .

 

Conclusions

In this study, no significant difference in longevity between the two devices Kinetra® and Activa® was shown. Replaced devices of both type, have shorter lifespan than first implant devices.

This independent study was not supported by any grants.


Andrei BRINZEU (Lyon), Theo BRUSSOLLE, Emile SIMON, Gustavo POLO, Teodor DANAILA, Chloe LAURENCIN, Stephane THOBOIS, Patrick MERTENS
00:00 - 00:00 #25487 - DBS Implantable Pulse Generator Trauma Protection Pad; a novel solution to reduce trauma induced IPG explantation.
DBS Implantable Pulse Generator Trauma Protection Pad; a novel solution to reduce trauma induced IPG explantation.

Background: Our centre is set in a tropical environment where the attire includes thin fabrics

which do not provide any cushioning/protection against trauma to the skin overlying the IPG.

Our study revolves around patients of low socio-economic strata, who preferred the cheaper

but bulkier non rechargeable IPG over its compactor but more expensive counterpart, the

rechargeable IPG. Patients who suffered from accidental trauma to the left infra clavicular

region had severe lacerations, leading to local infections and in some cases a complete loss of

battery function requiring immediate replacement.

Method: Amoldable memory foam embedded in a hydrophobic fabric with cooling properties,

was made to be placed over the IPG. A ferromagnetic catch is placed inside the foam to

articulate with a magnet. A neodymium magnet attached to a large sized button holds the DBS

IPG Trauma Protection Pad in place and it seconds as a brooch.

Result: The DBS IPG Trauma Protection Pad was successfully placed over the IPG and acted

as a shock absorber thereby reducing the chances of accidental trauma causing damage to the

IPG.

Conclusion: The Trauma Protection pad would reduce the damage caused by accidental

trauma and prevent local infection, thereby reducing patient morbidity as well as the rate of

trauma induced DBS battery explantation procedures.


Adhish BERI (Chandigarh, India), Hargunbir SINGH, Nishit SAWAL
00:00 - 00:00 #26127 - Decrease of daytime sleepiness by deep brain stimulation of pedunculopontine nucleus area in parkinsonian non-human primate.
Decrease of daytime sleepiness by deep brain stimulation of pedunculopontine nucleus area in parkinsonian non-human primate.

Introduction:

Less known than motor symptoms, excessive daytime sleepiness (EDS) is one of the most disabling non-motor symptoms reported by parkinsonian patients. EDS seriously affects the patients’s quality of life and is often worsened by current treatments, and justifies to explore new therapies such as deep brain stimulation (DBS). We aimed to evaluate the effect of pedunculopontine nucleus area (PPNa)-DBS, a key area of the brainstem arousal system, on daytime sleepiness in parkinsonian non-human primates (NHPs).

Methods:

Two NHPs (macaca fascicularis) were implanted with a polysomnographic telemetry equipment recording electro-encephalogram, electro-occulogram and electro-myogram signals in freely moving animals, synchronized with a video system to analyze the wake/sleep behavior. In addition, a quadripolar electrode, connected to a stimulator, was implanted into the PPNa to apply the stimulation. After a characterization of wake/sleep behavior by 12h daytime continuous recordings and an evaluation of the level of daytime wakefulness by a modified multiple sleep latency test in healthy and parkinsonian monkeys, the effect of PPNa-DBS at low (LFS) frequency was studied in the same experimentations mentioned previously.

Results:

First, we showed that wakefulness was significantly modified in parkinsonian monkeys resulting in a total disorganization of nap architecture with an increase in daytime sleepiness associated with sleep inertia in the morning. Second, we observed that PPNa-LFS counter-balanced these disturbances by reducing the total sleep duration (158.1 ± 43.18 min in DBS-OFF vs 87.36 ± 15.74 min in DBS-ON; p<0.05) and the sleep inertia (first sleep after wake: 12.64 ± 3.98 min DBS-OFF vs 63.74 ± 25.86 min DBS-ON; p<0.05). 

Conclusion:

Haut du formulaire

Bas du formulaire

Our results show that the PPNa-LFS increases the daytime wakefulness in parkinsonian NHPs. This awakening effect observed in our study appears as an encouraging result which offers new perspectives to treat severe wake/sleep disorders.


Aurélie DAVIN (Grenoble), Stephan CHABARDES, Olivier DAVID, Napoléon TORRES-MARTINEZ, Brigitte PIALLAT
00:00 - 00:00 #22675 - Deep brain stimulation and lesioning surgery – a three year start in Bangladesh.
Deep brain stimulation and lesioning surgery – a three year start in Bangladesh.

Abstract: Idiopathic Parkinson’s Disease ( IPD ) is a chronic neurodegenerative disease results from degeneration of Dopaminergic neurons of substantia nigra  . It’s cardinal features are resting tremor , rigidity , akinesia and postural instability.The role of subthalamic nucleus in the development of Parkinsonian tremor and other cardinal features is not completely understood yet. However, previous studies in monkey, administration of MPTP( 1-methyle-4-phenyl-1.2.3.6.-tetrahydropyridine ) proved that sub thalamic nucleus has a direct role in the development of parkinsonian tremor and other features . Commonly, very disabling dyskinesia develop due to the side effects of dopaminergic drugs used in Parkinson's Disease.  Until recently in Bangladesh had no functional neurosurgery service. We report our very preliminary experience over the last three years.

Surgery is performed awake with image guided (MRI/CT Stereotaxy) assessing the effects of stimulation and lesioning on table. We have so far implanted 5 deep brain stimulators (PINS) and a pallidotomy with good effect. Patients were assessed at 6 weeks and up to one year after surgery. In the cases of STN DBS, the UPDRS was reduced by 63.33%( p<0.001) and dyskinesias by 70% after a pallidotomy.

There have been no infections or hemorrhages in this small pilot series.

Key words: Subthalamic Nucleus(STN), Deep Brain Stimulation(DBS) , Parkinson’s Disease(PD), Globus Pallidus Internus ( Gpi) 

1. *. Md. Zahid Raihan , Associate Professor & Head, Department of Neurosurgery, KuMC, DGHS,Dhaka . 1967zahidraihan.zr@gmail.com

 2. Professor Tipu Zahed Aziz, Professor of Functional Neurosurgery, Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford.

Hospital , University of Oxford , UK


Mohammad ZAHID RAIHAM (Dhaka, Bangladesh)
00:00 - 00:00 #23997 - Deep brain stimulation, subthalamic nucleus with its motor networks.
Deep brain stimulation, subthalamic nucleus with its motor networks.

INTRODUCTION

Deep brain stimulation (DBS) is a widely described technique, and very effective in Parkinson's disease (PD) resistant to drug management. Most authors agree that the target of choice is the subthalamic nucleus (STN) for the control of cardinal symptoms stiffness-tremor-bradykinesia. Advances in radiological imaging, such as the DTI, could play a fundamental role in the surgical planning of the STN.

 

OBJECTIVES

We report a clinical case with DBS at the STN level, and the relevance of tractography in planning.

 

METHODS

46-year-old woman with PD for 7 years, the last year she complain of stiffness, bradykinesia of the upper extremities and freeezing of gait; resistant to pharmacological treatment. L-dopa test (UPDRS III) OFF = 45, ON = 9. We proposed to perform the ECP at the NST level, the patient understood and accepted the consent.

A preoperative brain MRI was performed1.5T that included volumetric sequence T1, T2 and DTI. NST surgical planning was performed directly and adjusted by tractography connecting the dorsolateral region of the NST with the supplemental motor area / lateral premotor cortex (X: 11.7, Y: -2.8, Z: -4).

Under local anesthesia was performed micro-recording and micro-stimulation, was implanted definitive electrodes (Vercise Cartesia-Boston Scientific); Intraoperative CT confirming the correct lead placement, without complications. Immediately after general anesthesia, a pulse generator is implanted (Vercise Gevia-Boston Scientific). On the third day the stimulation was ON, and the fourth day post-surgical the patient was discharge.

 

RESULTS

Seven month after surgery, we observed a significant reduction in the Unified Parkinson Disease Rating Scale part III ON medication-ON stimualtion 8, reduction L-dopa equivalent daily dose in 70%.

Currently, programming stimulation is monopolar with ring (5-6-7) 1.5mA, 60mSec, 130Hz. The volume of tissue activated included the suplementary motor area, lateral premotor cortex, parcially primary motor cortex.

 

CONCLUSIONS

The planning of the STN in the first papers was based on indirect methods, currently with the resolution of the MRI we can perform directly visualizing the nucleus. However, tractography allows us to reconstruct the possible hyperdirect pathway connecting the STN and the motor cortex. This allows us to improve DBS targeting, identify the most effective lead contact, and programming with low intensity.


Luis Mariano ROJAS-MEDINA (Madrid, Spain), Lucía ESTEBAN-FERNÁNDEZ, Daniel LOURIDO-GARCÍA
00:00 - 00:00 #24031 - Deep brain stimulation-electrodes may rotate after implantation – an animal study.
Deep brain stimulation-electrodes may rotate after implantation – an animal study.

Background & Purpose: Directional Deep Brain Stimulation (dDBS) electrodes allow to steer the electrical field in a specific direction. When implanted with torque they may rotate for a certain time after implantation. Aim of this study was to evaluate whether and to which degree leads rotate in the first 24 hours after implantation using a sheep brain model. 

Methods: dDBS electrodes were implanted in 14 sheep heads and 3D rotational fluoroscopy (3D-RF) scans were acquired to visualize the orientation of the electrode leads according to Reinacher et al. 2017. Electrode leads were clockwise rotated just above the burrholes (180° n=6, 360° n=6, 2 controls) and 3D-RF scans were again acquired after three, six, 13, 17 and 24 hours, respectively.

Results: 180° rotated electrodes showed an initial rotation of 83.5° (range: 35.4°-128.3°) and a rotation of 114.0° (range: 57°-162°) after 24 hours. With 360° torsion, mean initial rotation was 201° (range: 3.3°-321.4°) and mean rotation after 24 hours 215.7° (range 31.9°-334.7°), respectively. 

Conclusion: Implantation of dDBS leads with torque (i.e.rotating the lead during implantation) should be avoided. Direct postoperative imaging may not be accurate for determining the rotation of dDBS electrodes if a torque is present.

 

Figure: Rotational deviation of implanted electrodes after applied torsion

180° applied torsion depicted in GREEN, 360° in RED and controls (0°) in BLUE 
A: Initial rotational deviation (timepoint 0h) and in follow-up. B: Absolute deviation in relation to the rotation after applied torsion. 


Peter C. REINACHER (Freiburg, Germany), Volker Arnd COENEN, Horst URBACH, Karl EGGER, Alexander RAU
00:00 - 00:00 #23995 - Deep brain stimulation: Shaving versus not shaving?
Deep brain stimulation: Shaving versus not shaving?

INTRODUCTION

Deep brain stimulation (DBS) is a widely described technique with excellent results for some movement disorders resistant to pharmacological treatment. The reported infection rates are less than 4%. Usually, shaving the scalp is widespread in surgical practice; however, there is conflicting evidence to decrease or increase the risk of infection.

 

OBJECTIVE

We report two cases not shaving all scalp, and we describe the technique step by step.

 

METHODS

We present two cases diagnosed with Parkinson's disease (PD) resistant to pharmacological treatment.

Casse 1. 59-year-old woman with PD for 12 years, the last 3 years worsening of simple motor fluctuations. Currently with Levodopa/Carbidopa, Rasagilene, Amantadine. L-dopa test (UPDRS III) OFF=62, ON=11.

 

Case 2. 46-year-old woman with PD for 7 years, last year worsening of upper limb stiffness, bradykinesia and freezing of gaitCurrently with Levodopa/Benserazide, Levodopa/Carbidopa, Safinamida, Opicapona. L-dopa test (UPDRS III) OFF=45, ON=9.

Taking into account symptoms and poor control with pharmacological treatment, we proposed to perform DBS in the bilateral subthalamic nucleus (STN). Patients understand and accept informed consent.

 

RESULTS

The night before and the morning of the surgery, the head is washed with povidone-iodine, the Leksell stereotaxic frame is placed, the intraoperative CT (AIRO) is obtained, for subsequent fusion with the brain MRI, and we obtained the coordinates. We shave only the incision area, the surgical field and transparent dressing are put on.

Bilateral frontal burr-hole were performed wiht local anesthesia, NST  micro-recording and micro-stimulation was obtened, improvement symptoms and without side effects, definitive electrodes were implanted; Intraoperative CT confirms the correct lead placement, without complications. Immediately after, under general anesthesia, a pulse generator is implanted. Antibiotic prophylaxis with Cefazolin 2gr IV, Vancomycin 500mg diluted in SSF 0.9% 500ml. On the third day the stimulation is ON, and  the fourth post-surgical day the patient is discharge.

During follow-up, mean 10.5 months, wounds in perfect condition, improvement of symptoms UPDRS III ON medication - ON stimulation: 9; Levodopa dose reduction of 70%.

 

CONCLUSIONS

In our hospital, we usually shave the head completely to perform DBS surgery; however, applying this protocol we have obtained very good results, without presenting infections or healing problems, and the patients preferred it for its aesthetic and psychological results in the postoperative period.


Luis Mariano ROJAS-MEDINA (Madrid, Spain), Lucía ESTEBAN-FERNÁNDEZ, Freddy SALGE-ARRIETA
00:00 - 00:00 #23462 - Directional Lead in Deep Brain Stimulation for Parkinson's Disease - Hong Kong Experience.
Directional Lead in Deep Brain Stimulation for Parkinson's Disease - Hong Kong Experience.

Deep Brain Stimulation (DBS) for Parkinson's Disease (PD) was first performed in Hong Kong in 1997.  More than 300 cases had been operated using conventional ring electrodes.  Directional Lead was introduced since March 2018.  Totally 9 patients with 17 directional leads had been implanted.  We reviewed the clinical outcome including UPDRS III moto scores, clinical assessment, system-related complication and drug dosage reduction.


Tak Lap POON (Hong Kong, Hong Kong)
00:00 - 00:00 #23911 - Emergency deep brain stimulation in a girl with dystonic storm due to GNAO1-associated hyperkinetic-dystonic movement disorder.
Emergency deep brain stimulation in a girl with dystonic storm due to GNAO1-associated hyperkinetic-dystonic movement disorder.

Background:

Mutations in the GNAO1 gene, encoding for a G-protein subunit, are associated with a hyperkinetic-dystonic movement disorder and mental retardation as well as an epileptic encephalopathy. Patients with the movement disorder show continuous hyperkinetic movements of variable degree with frequent exacerbations during minor illness, pain or surgery resulting in life-threatening dystonic storms. Various medications such as clonidine and tetrabenazine are used both to prevent exacerbations and as options in the acute treatment of dystonic storms. Sedation, analgesia and relaxation may be required to terminate the crisis. Deep Brain stimulation (DBS) has shown to be effective in preventing exacerbations. We report the case of an adolescent girl with refractory dystonic storm and emergency implantation of DBS.

Case report:

The 16 year old teenager presented repeatedly with dystonic states and rhabdomyolysis (max. CK 100.000 U/ml) requiring ICU treatment. In most events, balanced sedation with continuous hydromorphone, clonidine infusions and midazolam bolus plus oral clobazam and tetrabenazine was sufficient to control the hyperkinetic movements. During the last episode, even maximum doses of this treatment combination were insufficient to control the symptoms. As the patient developed impaired bowel passage and hemorrhagic colitis due to the prolonged dystonic storm, emergency stereotactic implantation of DBS electrodes in the globus pallidus internus (GPI) was performed. Shortly after activating the stimulator (manufacturer?), symptoms resolved and the medication could be tapered to zero over three weeks without recurrence of symptoms. Only low dose dronabinol was added to reduce spasticity.

Conclusion:

Emergency implantation of GPI DBS in dystonic state due to GNAO1 mutation is feasible and may be effective to terminate dystonic storms.


Assel SARYYEVA (Germany, Germany), Jan-Christoph SCHOENE-BAKE, Thomas JACK, Eva BUELTMANN, Hans HARTMANN, Joachim K. KRAUSS
00:00 - 00:00 #26270 - Evidence of possible bias in pre-surgical assessment of Parkinson’s disease using levodopa challenges.
Evidence of possible bias in pre-surgical assessment of Parkinson’s disease using levodopa challenges.

IntroductionParkinson’s disease (PD) patients who no longer reliably respond to medication may be treated with deep brain stimulation (DBS). Whether DBS is appropriate for a given patient is assessed, in part, by a levodopa challenge, in which a patient will undergo the MDS-Unified PD Rating Scale (MDS-UPDRS) part-3 assessments before and after taking levodopa. However, a significant fraction of patients do not benefit sufficiently from DBS to justify the attendant surgical risk and cost of the procedure. This suggests the process of selecting patients for DBS intervention could be improved. 

 

Because motor requires subjective ratings of disease severity, by unblinded clinicians, a rater bias could result in a patient receiving, or being denied, treatment inappropriately. We investigated whether there is an identifiable bias in levodopa challenges when conducted for the purpose of surgical pre-assessment, as compared to levodopa challenges conducted during clinical trials that do not involve patients being considered for surgical treatment. 

 

Method: The dataset consists of 180 levodopa challenges on 146 different patients, conducted at six different sites and by a variety of assessors, collected using the KELVIN-PD™ platform. Of these, 93 were conducted for pre-surgical assessment for DBS, while the remaining 87 were conducted as part of a pharmaceutical clinical trial (see Figure 1). 

 

The null hypothesis was that these two groups would see a similar level of improvement, as measured by the improvement in UPDRS part-3 score between the ‘off levodopa’ and ‘on levodopa’ assessments. We tested this hypothesis by two methods. 

 

Firstly, we considered whether a patient was undergoing pre-surgical assessment as a boolean variable (1 meaning they are, 0 otherwise), alongside the ‘off levodopa’ rating, within a linear regression model to predict the ‘on levodopa’ rating. The coefficient of this boolean being significantly different from zero would be consistent with the hypothesis that there exists a systematic bias when PD patients are assessed for DBS surgery.

 

Secondly, we computed the distribution of percentage improvements for both groups, and performed a Mann-Whitney test for difference in distributions. The Mann-Whitney test was chosen because as a non-parametric method for testing whether one distribution’s mean is significantly greater than another. 

 

For this second analysis we controlled for baseline disease severity (off levodopa UPDRS part-3), because we observed that percentage improvement had a weakly significant correlation with baseline rating (Pearson’s r = -0.149, p-value = 0.046). We controlled for this by conducting the analysis on a subset of 80 levodopa challenges, selected such that the distribution of baseline rating among patients was identical between the surgical and pharmaceutical trial groups (see Figure 2). 

 

Result:

The average improvement in UPDRS part-3 score was 40.9% among the pharmaceutical trial group, and 55.1% among the surgical assessment group. 

 

Our first test found the linear regression model coefficient of the surgical assessment boolean to be significantly different from zero (F1,178 = 10.2 , p < 0.01), with a mean estimated value of -5.3 (see Table 1).

 

Our second test found the difference between the distributions of these percentage improvements to be highly significant (Mann-Whitney’s U = 552, p-value < 0.01).

 

Conclusion:

While further work is required to exclude the possibility of systematic differences between pre-surgical and other patients, these results are consistent with there being a clinically significant bias in levodopa assessments when conducted on patients being considered for DBS, and that this bias equates to approximately a difference of 5.3 on the UPDRS part-3. 

 

Should further work bear this result out, it would suggest that extra care should be given to objectively assess patients who are being considered for DBS. 

 

Blinded rating might go some way towards removing any bias, although this may be logistically challenging. Alternatively, true objectivity may be achieved through algorithmic measurement of motor function. 


Gareth MORINAN, Jonathan O'KEEFFE (London, United Kingdom)
00:00 - 00:00 #23655 - Freezing of Gait as a Complication of Bilateral Pallidal Deep Brain Stimulation in a Patient with Tardive Dystonia.
Freezing of Gait as a Complication of Bilateral Pallidal Deep Brain Stimulation in a Patient with Tardive Dystonia.

Background

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective and well-tolerated treatment for different forms of generalized, focal and segmental dystonia. Impressive results have been reported in patients with tardive dystonia (TD). GPi DBS affects the pallidal outflow on normal limb function causing the bradykinetic symptoms seen often in patients especially in focal and segmental dystonia. The aim of this case report is to present a patient with TD who developed a bradykinetic symptom mainly freezing of gait due to bilateral monopolar GPi stimulation.

Methods

We present a patient who was treated by GPi DBS for TD. The patient underwent staged bilateral implantation of DBS leads (Medtronic, Minneapollis, Minnesota, USA).  The formal objective assessment included Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The patient was assessed preoperatively and at 3, 6, and regular 12 months postoperative visits. The follow-up reached 60 months.

Results

The patient gained significant improvement of his TD till 48 months. The motor part of BFMDRS scores when compared to baseline scores improved by 70 %, 84 % , 25 % at 3, 12 and 48 months, respectively. The functional part of BFMDRS scores when compared to baseline scores improved by 75 %, 82 % , 30 % at 3, 12 and 48 months, respectively. At nearly 48 months follow-up, the patient experienced rapid reoccurrence of TD. Skull, neck and chest  x-rays, as well impendence measurements were within normal range. Changing the stimulation polarity from bipolar to monopolar resulted in nearly complete resolution of TD. After 2 months of continuous bilateral monopolar GPi DBS this patient developed freezing of gait. This bradykinetic symptom is not bothersome to patient over the ensuing 2 years of follow-up. 

Conclusion

Although GPi DBS has shown its efficacy in patients with focal or segmental dystonia, the influence of GPi DBS on nondystonic body regions deserves further investigation. Probably the co-stimulation of pyramidal tracts by monopolar than bipolar stimulation polarity may cause bradykinetic symptoms in patients with focal, segmental dystonia who underwent GPi DBS.


Michał SOBSTYL (Warsaw, Poland), Angelika STAPIŃSKA-SYNIEC, Anna KUPRYJANIUK
00:00 - 00:00 #23960 - Globus pallidus internus deep brain stimulation for the treatment of axial dystonia.
Globus pallidus internus deep brain stimulation for the treatment of axial dystonia.

Introduction

 

Axial dystonia is a rare phenotype of segmental dystonia that predominantly affects the trunk with occasional contiguous spread to the cranio-cervical junction. It is usually medically refractory and poorly controlled with Botulinum toxin injection. The truncal dystonia causes major morbidity and significant impairment of quality of life. Based on the experience with deep brain stimulation (DBS) of the Globus Pallidus internus (GPi) for other forms of dystonia, we report three cases of axial dystonia from different aetiologies that benefited from bilateral GPi DBS

 

Methods

 

Three male adult patients with axial dystonia due to tardive dystonia, dystonia associated with Parkinson’s disease and idiopathic adult-onset axial dystonia underwent comprehensive multidisciplinary assessment prior to implantation of DBS systems. Dystonic symptoms severity was quantified using the Burke-Fahn-Marsden Dystonia Rating Scale Movement Score (BFMDRS-M). 

 

Results

The mean age at surgery was 52.6 years (48 – 55 years) and disease duration was in the range of 4 – 15 years. The follow-up period was between 9 and 141 months. In each case, significant control of truncal dystonic symptoms was achieved. The mean improvement in the BFMDRS-M scores was 79.3 % (71.2 – 88.9%). All patients also experienced significant improvements in their quality of life and were able to reintegrate into society. Rapid improvement (hours to days) was noted in blepharospasm and cervical dystonia with more delayed improvement (weeks to months) seen with truncal control.  Symptom control deteriorated when the implantable pulse generators were near or completely depleted. Only one patient had stimulation-related side effect which was managed with adjustments of the stimulation parameters.  

 

Conclusion

Bilateral GPi DBS is a viable surgical option the management of medically refractory axial dystonia irrespective of aetiology. Careful patient selection and management within a multidisciplinary team is crucial for ensuring best outcomes.

 


Kantharuby TAMBIRAJOO (London, United Kingdom), Luciano FURLANETTI, Michael SAMUEL, Keyoumars ASHKAN
00:00 - 00:00 #23895 - Imaging insights of isolated idiopathic dystonia: a voxel-based morphometry study and meta-analysis.
Imaging insights of isolated idiopathic dystonia: a voxel-based morphometry study and meta-analysis.

Background

Neuroimaging have demonstrated structural changes of wide-spread brain regions in patients with dystonia. However, the understanding of brain abnormalities across different isolated idiopathic dystonia and how they contribute to the clinical outcomes remains poorly understood.

Objectives

To investigate grey matter volume (GMV) abnormalities and their correlation with clinical outcomes in isolated idiopathic dystonia patients. 

Methods

We retrospect 73 isolated idiopathic dystonia patients using voxel-based morphometry (VBM) to investigate their GMV abnormalities and correlated with their clinical outcomes. In addition, a meta-analysis was conducted on 14 VBM studies.

Results

Our VBM study revealed decreased GMV in bilateral putamen shared in all types of dystonia compared to health controls. While increased GMV was observed in frontal, parahippocampa, middle temporal and inferior parietal gyrus. GMV increases were also observed in other regions, such as supramarginal, fusiform and lingual gyrus in subgroups. Left globus pallidus was the only increased region based on meta-analysis. Finally, there is a significant negative correlation between GMV and onset age. Trends of GMV increased in moderate-outcome group compared to superior-outcome group in several regions.

Conclusions

The shared abnormalities of putamen among all groups and globus pallidus from meta-analysis may indicate their pathophysiological roles. Altered brain regions, e.g. sensorimotor cortex, frontal and temporal cortex, were consistent with previous studies, which may likely be compensatory changes from our prospective. Future imaging predictors need to be further explored in those brain regions with multi-model imaging analysis.


Yunhao WU (Shanghai, China), Jie FENG, Yufei LI, Ming ZHANG, Chencheng ZHANG, Hongxia LI, Tao WANG, Bomin SUN, Yiwen WU, Dianyou LI, Hongjiang WEI
00:00 - 00:00 #26144 - Impact of subthalamic deep brain stimulation on motor and sensorimotor cortical oscillatory activity in free-moving hemiparkinsonian rats.
Impact of subthalamic deep brain stimulation on motor and sensorimotor cortical oscillatory activity in free-moving hemiparkinsonian rats.

Background

Altered oscillatory activity in cortical-basal ganglia thalamic circuitries, especially enhanced activity in the beta band, have been linked to motor symptoms in Parkinson`s disease (PD). The subthalamic nucleus (STN) is targeted for deep brain stimulation (DBS) in PD and chronic stimulation has been shown to reduce beta band activity.

Objective

The effect of STN DBS on spectral power of oscillatory activity in the commonly used frequency bands in the motor cortex (MCtx) and sensorimotor cortex (SMCtx) was investigated by recording oscillatory activity via cortical electrode grids in free-moving 6-hydroxydopamine (6-OHDA) lesioned hemiparkinsonian (HP) rats and sham-lesioned controls.

Methods

Fifteen male Sprague Dawley rats (250-350g) were either rendered HP by unilateral injection of 6-OHDA (n=8), or by injection of saline (sham-lesioned; n=7) in the right medial forebrain bundle. After three weeks of surgical recovery, a DBS electrode was implanted in the STN, and an electrocortigram (ECoG) recording array was placed under the dura above the MCtx and SMCtx areas of the right hemisphere. All surgeries were performed under chloral hydrate (360 mg/kg; i.p.) anesthesia.  Six days after surgery, free-moving rats were individually recorded in three conditions: (1) basal activity, (2) during STN DBS (130Hz, biphasic square pulse width of 80 µs, individual current intensity threshold (100 µA - 400 µA)), and (3) directly 300 seconds after STN DBS. Spectral power of oscillatory activity of theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz) and gamma (30-100 Hz) were analyzed in the MCtx and SMCtx areas and compared between HP and sham-lesioned rats.

Results

In HP rats, the relative power of theta band activity was lower, and beta and gamma activity were higher in MCtx and SMCtx. This was reverted towards control level by STN DBS during stimulation and in the first 300 seconds after stimulation. No differences were found between MCtx and SMCtx.

Conclusion

Our results provide evidence that loss of nigrostriatal dopamine leads to increased beta and gamma, and reduced theta oscillatory activity in motor and sensorimotor cortical areas, which is compensated by STN stimulation both during and directly after stimulation.


Arif ABDULBAKI (Hannover, Germany), Theodor DOLL, Joachim K. KRAUSS, Kerstin SCHWABE, Mesbah ALAM
00:00 - 00:00 #22651 - Improving programming in Deep brain stimulation using the GuideXT Assisted Refinement and Optimisation Workflow (GROW).
Improving programming in Deep brain stimulation using the GuideXT Assisted Refinement and Optimisation Workflow (GROW).

Introduction

The best outcomes in Deep Brain Stimulation (DBS) are achieved when 3 factors align, appropriate patient selection, accurate lead placement, and optimal clinical programming. While advancements have been made in the identification of suitable candidates,  in the technology to plan surgery,   and  in the devices  to deliver stimulation,  only limited advances have been made to  improve the initial programming of DBS settings.  Additionally, with the advent of directional leads, clinical programming has become more complicated and is taking more time in clinical practice. In this study, we implement the use of GuideXT software, which enables us to virtually determine theoretical volumes of tissue activation (VTAs), to help refine and optimise programming in DBS patients.

Method

We used our GuideXT Assisted Refinement and Optimisation Workflow (GROW) on

16 patients with DBS for Sub thalamic nucleus  (STN) stimulation  who required refinement or optimisation. Eight were new implants, four patients had suboptimal outcome following DBS and four had good outcomes but were given the choice of further refinement using the software. The UPDRS and clinical side effects were noted pre and post refinement. All patients had directional DBS leads.

Results

New Implants

Five patients had intial DBS programming done without the use of the GuideXT software, the average time for initial programming was 90mins ±30. The average reduction in UPDRS 3 was 31   from 50 to 18, but there were issues with dyskinesia, inadequate tremor control, dystonia, and speech symptoms. Using the GuideXT software allowed resolution of these problems in 4 out of the 5 patients.

In three patients GuideXT was used before initial programming; this reduced the clinic time for initial programming from 90mins to 45mins ±15. However the patients did require further clinical refinement in all cases.

Suboptimal DBS

In this historical group, the patient had significant improvement following DBS implant but suffered from side effects (e.g. dystonia ). Using GuideXT the side effects were reduced in 3/4 patients.

Refine DBS

These patients were happy with their programming, average UPDRS 3 of 10, however, when offered to try an alternative program refined on GuideXT softeware. 2 out of the 4 patients chose the GuideXT refined program as their endpoint, reporting improvements in balance and speech symptoms.

 

Conclusion

GROW has shown to help salvage and optimise historical patients with significant side effects as well as refine and improve outcomes in patients who already have good outcomes. More importantly, GROW can reduce time taken to get to the optimal program by reducing programming time and number of visits required to get the optimal settings.


Mohammed HUSSAIN (Newcastle, United Kingdom)
00:00 - 00:00 #22508 - Is DBS really successful in Lance-Adams Syndrome?
Is DBS really successful in Lance-Adams Syndrome?

Lance-Adams syndrome(LAS) is the chronic type of posthypoxic myoclonus which occurs after succesful cardiopulmonary resuscitation. The detailed pathophysiology of chronic post-hypoxic myoclonus is still not well known. Here, we present a case of a 40-year-old woman who developed myoclonus after cardiopulmonary arrest (CPA) after her first cesarean delivery at age of 26. The patient underwent imlantation of bilateral GPi-DBS about 12th years into her disease course. Myoclonus in this patient was ameloriated with Gpi stimulation. In the literature, there have been worldwide around 100 patients who diagnosed LAS and only four cases of LAS treated with deep brain stimulation. Bilateral Gpi-DBS may offer a safe and effective treatment for refractory cases of LAS. Here, we present the fifth case of LAS after cardiopulmonary arrest during delivery, who was treated with DBS, and review all the cases in the light of the literature.     


Gulsah OZTURK (Istanbul, Turkey), Selcuk PEKER
00:00 - 00:00 #23785 - Long term recording of human STN local field potentials in Parkinson’s disease after deep brain stimulation.
Long term recording of human STN local field potentials in Parkinson’s disease after deep brain stimulation.

Objective: to describe the continuous recording of subthalamic nucleus (STN) local field potentials (LFPs) and their response to electrical stimulation and sleep in a Parkinsons disease (PD) patient after STN deep brain stimulation (DBS).

 

Background: STN DBS improves motor symptoms and quality of life in PD patients suffering from disabling motor complications under optimized medical therapy. Stimulation parameters are classically set during assessment of clinical benefits and adverse effects derived from the combination of several variables, namely selected contact and energy-related parameters. STN beta-band LFPs correlate with bradykinesia and rigidity in PD patients, suggesting their usefulness as clinical surrogate markers. However, real world data on this matter is currently scarce.

 

Methods: We describe new real world long term (>6 weeks) data concerning LFP recording and response to stimulation and sleep in a PD patient. A 70-year old female with PD motor symptoms for more than 10 years, and disabling motor complications under optimized medical therapy was offered STN DBS. The procedure was performed under local anesthesia. Final electrode location was selected after micro-electrode recording using 3 trajectories per hemisphere and assessment of clinical benefits derived from intra-operative stimulation. A new generation implantable pulse generator (IPG) incorporating the ability to sense and chronically record LFPs was placed in infraclavicular position. LFPs were recorded since the immediate post-operative period.

 

Results: LFPs were successfully recorded. During awake time, while off dopaminergic medication and off stimulation, the beta-band power is much higher. Turning on the stimulation causes an immediate decrement of beta-band power, and a “ceiling effect” is clearly seen as stimulation amplitude reaches a maximally suppressed beta level without further impact of stimulation escalation. Beta-band power is lower during sleep, even without night time dopaminergic drugs and presents an oscillatory pattern. All these findings are noticeable in both brain hemispheres.

 

Conclusions: real world LFP recording after STN DBS in PD is a straightforward process. Beta-band LFP power is clearly influenced by electrical stimulation parameters and sleep, and correlates with clinical benefits. Further research might provide valuable clues to guide the optimization of DBS parameters in these patients.


Manuel PINTO (Porto, Portugal), Ana OLIVEIRA, Clara CHAMADOIRA, Rui VAZ, João MASSANO
00:00 - 00:00 #21902 - Long-term Outcome of Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease.
Long-term Outcome of Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease.

Background

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been accepted as an effective treatment for severe Parkinson’s disease (PD). Randomized and controlled studies have demonstrated that STN DBS is more effective in advanced PD than medical treatment. Although there have been some reports of long-term efficacy and safety after deep brain stimulation (DBS) surgery for Parkinson’s disease (PD), little is known about the fate of all patients. We performed a follow-up of all patients who undergone bilateral subthalamic nucleus (STN) DBS surgery for PD before more than 10 years, and assessed the survival rate and long-term outcome of DBS.

Methods

We included all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to Mar 2008 at single institution. Whether or not the patients were alive or dead was investigated, and pre- and postoperative follow-up assessments including UPDRS score were analyzed. 

Results

The mean age at the time of surgery was 72 years (range, 27-82), and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from the DBS surgery to death was 110.46 ± 40.8 months (range, 0-155). Thirteen patients (37.1%) died because of disease progression, followed by 11 patients (31.4%) died due to pneumonia. The cumulative survival rate was as follows: 98.8 ± 1.2% (1 yr), 97.5 ± 1.7% (3 yr), 95.1 ± 2.4% (5 yr), and 79.0 ± 4.5% (10 yr). Of the 46 surviving patients (57%), 36 continued to receive follow-up assessment including the UPDRS scale, but 10 survivors denied follow-up at hospitals due to economic cause or inability to move. Twelve patients (14.8%) underwent revision surgery to correct the electrode location, and the mean interval period between DBS and revision surgery was 14.5 months.

Conclusions

STN DBS is a safe and effective treatment in selective patients with PD. This study was based on the long-term follow-up of large-scale patients, and would contribute to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD. 


Park HYERAN (SEOUL, Korea)
00:00 - 00:00 #22502 - Management of Cervical Dystonia Patient with Deep Brain Stimulation During Pregnancy and Review of the Literature.
Management of Cervical Dystonia Patient with Deep Brain Stimulation During Pregnancy and Review of the Literature.

Deep brain stimulation(DBS) can provide psychosocial and functional improvement in medically refractory  cervical, segmental or generalised moderate to severe dystonia patients. After the DBS treatment of women with dystonia patients, becoming pregnant can be planned. There is a lack of certain published knowledge on pregnancy and DBS. We report  a 24-year-old female patient with cervical dystonia implanted with bilateral GPi-DBS who became pregnant during five years follow-up period after DBS surgery and delivered a healthy baby by caesarean  section under general anesthesia. We review the management of pregnancy in DBS treated dystonic patients with the other published cases in the literature. Based on this review  DBS with rechargeable battery system is effective and safe treatment method in dystonia  during pregnancy period.


Gulsah OZTURK (Istanbul, Turkey), Selcuk PEKER, Gokalp SILAV
00:00 - 00:00 #26186 - MDS UPDRS Item-Based Rigidity and Postural Stability Score Estimations: A Data-Driven Approach.
MDS UPDRS Item-Based Rigidity and Postural Stability Score Estimations: A Data-Driven Approach.

BACKGROUND AND OBJECTIVE

As the second most common chronic neurodegenerative disorder, Parkinson’s disease (PD) affects around 7-10 million people in the world. Patients with PD need to consult regularly for medical care, of which the access may be limited due to geographical and other socioecomonic issues. The telemedicine refers to the remote exchange of medical information for the purpose of providing medical care by means of telecommunication technology. Increasing evidence has suggested the feasibility of the telemedicine in PD. The ongoing global sanitary crisis of coronavirus disease 2019 also emphasizes the necessity of the popularization of the PD telemedicine. However, Among the disadvantages of telemedicine is the impossibility of the complete evaluation of the motor function for PD, as scored by the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III). Despite a modified version of the UPDRS removing rigidity and retropulsion items has been proposed2, its utilization has not been universally accepted. To overcome the difficulty of the scoring of rigidity and postural stability in the PD telemedicine, we investigated whether scores of rigidity and postural stability could be estimated by a combination of other items of MDS UPDRS-III through a data-driven approach. 

METHODS

The experimental dataset included 15763 MDS UPDRS score cases of 2131 patients obtained from the Parkinson’s Progression Markers Initiative (PPMI) database. We randomly selected 3322 cases of 426 patients as the external independent test set, and the remaining 12441 cases of 1705 patients were used for model training and validation. 27 scores of the other 16 items except rigidity and postural stability in the MDS UPDRS-III were taken as initial input features. Afterwards, we adopted a feature selection scheme based on a scoring system (DX score) to remove redundant irrelevant features. Finally, we used support vector machines (SVM) as classifiers to assess the scores of rigidity and postural stability. For the evaluation of model performance, we defined e as the absolute difference between the rater’s score and the predicted score. Due to the subjectivity of raters and inter-rater variability in clinical practice, the classification error of e ≤ 1 is considered acceptable.

RESULTS

There were no significant differences between the model training/validation dataset and the external independent dataset of PPMI regarding demographic and clinical features. The results of 5-fold cross-validation and independent test are shown in Table 1. In the model training and validation dataset, the predictive accuracy of the rigidity subscores was between 92.23% and 96.48% when e ≤ 1, and between 63.38% and 66.27% when e = 0. Similarly in the independent test set of PPMI, the accuracies of rigidity score predictions were between 90.70% and 96.27% when e ≤ 1, and between 59.87% and 67.82% when e = 0. The average accuracy of the rigidity total score estimation was 94.95% in the five-fold CV dataset and 93.32% in the independent dataset. For the postural stability score estimation, the predictive accuracy was 96.08% and 87.69 when e ≤ 1 and e = 0, respectively. Similar results were obtained in the independent test set of PPMI (95.64% and 87.63 when e ≤ 1 and e = 0, respectively). The best features selected by the optimal parameters of SVM for the corresponding rigidity subscore and retropulsion test score prediction were shown in Table 2. 

DISCUSSION

To the best of our knowledge, our study firstly demonstrated a data-driven algorithm to estimate the rigidity and postural stability scores of MDS UPDRS-III based on other items that could be evaluated visually and remotely. Our model respectively estimated the total score of rigidity and retropulsion test with an acceptable average accuracy.

CONCLUSION

The robustness of our algorithm warrants further refinement and validation in larger independent cohort and this model may be suitable for stiffness and retropulsion test score estimation in PD telemedicine in the future.


Zhengyu LIN (Shanghai/Lyon, China), Rui GUO, Chencheng ZHANG, Dianyou LI, Xiaohua QIAN, Bomin SUN
00:00 - 00:00 #23918 - Monitoring Cognitive and Emotional Functioning of Patients with Parkinson’s Disease after Unilateral Deep Brain Stimulation of the Subthalamic Nucleus – Preliminary Results from the 12-month Follow-up.
Monitoring Cognitive and Emotional Functioning of Patients with Parkinson’s Disease after Unilateral Deep Brain Stimulation of the Subthalamic Nucleus – Preliminary Results from the 12-month Follow-up.

Objective:

The primary goal of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with advanced Parkinson’s disease (PD) is the improvement of health-related quality of life by a significant reduction of motor symptoms. However the relationship between STN DBS and cognitive-emotional functioning of these patients are still not consistent. In some studies, patients’ cognition either improved or did not worsen, in other – progressively deteriorated. Some studies emphasize that unilateral STN DBS may represent a risk factor for decrements in cognition and mood.

The presented study aimed to determine the safety of unilateral STN DBS for emotional and cognitive functioning, using questionnaires and neuropsychological tests for attention, memory, and executive functions.

 

 

Methods:

The study gained approval from the local Bioethics Committee, and all PD patients gave their written informed consent prior to participation. Exclusion criteria included a history of other than PD neurological diseases, psychiatric disorders or significant cognitive decline (assessed with Addenbrooke’s Cognitive Examination III, ACE-III).

Study participants underwent clinical evaluation at baseline in the off and on medication states by applying Unified Parkinson’s Disease Rating Scale (UPDRS) part I to IV, Hoehn and Yahr scale (H/Y), Schwab and England scale (S/E) and Parkinson’s Disease Questionnaire – 39 (PDQ-39). They were also subjected to 3 neuropsychological assessments: one preoperative and 2 postoperative at 6, and 12 months since unilateral STN DBS. All neuropsychological assessments were performed in the on medication state and included: six tests from CANTAB battery (Motor Screening Task, MOT; Reaction Time, RTI; Rapid Visual Information Processing, RVP; Pattern Recognition Memory, PRM; Paired Associates Learning, PAL; Multitasking Test, MTT), Auditory Verbal Learning Test (AVLT), Digit Span from WAIS-R (DS), and Beck Depression Inventory (BDI).

 

Results

Among 38 PD patients with unilateral STN DBS, 26 patients completed the 6 months follow-up assessment, and 15  – the 12-month follow-up. There was one death unrelated to surgery within 6 months, and one patient required partial hardware removal due to an infection after 6 months.

The preliminary analyzes were performed in a group of 15 patients [8 males; mean age: 62.5, (SD - 7.1) years; mean ACE-III score: 91.4 (SD 8) points].

None of the cognitive tests used, revealed any significant deterioration in cognitive performance. Moreover, patients slightly but significantly improved in CANTAB RVP test [chi2(2) = 7.17, p = 0.028, Kendall W = 0.3].

Neither positive nor negative effects of unilateral STN DBS were observed in Beck Depression Inventory (chi2(2) = 1.33, p = 0.513, Kendall W = 0.06).

The analyses of postoperative clinical evaluations with UPDRS revealed significant improvements in the on medication state compared to baseline. The improvements were noted in part II [chi2(2) = 16.75, p = 0.001, Kendall W = 0.56] , and part III [chi2(2) = 23.16, p = 0.001, Kendall W = 0.77].  The UPDRS part IV showed significant decreased of complications of levodopa-induced dyskinesia [chi2(2) = 22.53, p = 0.001, Kendall W = 0.75]. Clinical and functional improvement as measured by H/Y and S/E scales, comparing the baseline and 12-month follow-up assessment was observed in 10 (67%) and 12 (80%) participants, respectively. However, self-evaluated functioning as measured by PDQ-39 seemed stable [chi2(2) = 2.09, p = 0.353, Kendall W = 0.09].

 

Conclusions:

Our preliminary results showed no significant cognitive and emotional decrement in 6 and 12 months follow up after unilateral DBS-STN. Interestingly in one cognitive measure assessing attention, and speed of information processing, a significant improvement was revealed. Like previous studies, our analyzes also confirmed significant motor and quality of life improvement after unilateral STN DBS in PD patients. The continuation of this study is warranted with longer follow-up and incorporation of more participants.


Szczepan IWAŃSKI (Warsaw, Poland), Katarzyna POLANOWSKA, Michał SOBSTYL, Angelika STAPIŃSKA-SYNIEC, Aleksandra ZIELIŃSKA, Marcin LEŚNIAK, Joanna SENIÓW
00:00 - 00:00 #23976 - MR-guided High Intensity Focus Ultrasound for treatment of post traumatic tremor: a case report.
MR-guided High Intensity Focus Ultrasound for treatment of post traumatic tremor: a case report.

Introduction: Posttraumatic tremor (PTT) does not represent a uniform syndrome and it refers to a series of atypical tremors that occur secondary to traumatic brain injury. The majority of tremors loosely defined as post-traumatic tremors (PTT) also fill the criteria for Holmes tremor (HT); HT has been defined as a low frequency tremor (below 4,5Hz), present at rest and exacerbated with posture and intensified with action and typically accompanied with ataxia and/or dysmetria, that appear up to 24 months after brain surgery, tumors, stroke or traumatic brain injury. Pharmacological treatment is usually unsuccessful in PTT, leaving stereotactic surgery as a rescue option. However reports on deep brain stimulation (DBS) for treatment of HT are odd, heterogeneous regarding effectiveness and lacking of information in target details and tremor semiology. MR-guided High Intensity Focus Ultrasound (MRgFUS) has recently gained interest as being a noninvasive alternative to conventional neurosurgery in treating essential and Parkinson tremor.

Material & methods: We present a case of 36 years old female, with past medical history of severe traumatic brain injury after a car accident at the age of four. Recovery was evident after 14 days, when she presented mild dysarthria, postural and kinetic tremor in left upper limb and spasticity according to previous medical notes. Her first neurological examination revealed scanning dysarthria, incoordination of both right upper limb with mild dysdiadochokinesia; postural and intention tremor was present in left upper limb. She had spasticity of both upper & lower limbs mainly on her left hemibody with pyramidal type of weakness. Her tandem walking was possible without ataxic gait. She didn´t have voice, mandible or cephalic tremor. Tremor didn´t influence in her daily basic activities but it made difference in her professional life as nurse assistant. The ventral intermedius nucleus (VIM) of the thalamus was the selected target to make a lesion with MRgFUS on 3 Tesla MRI (Insightec®); density skull score was calculated (0.45) with CT. A brain MRI 3T Siemens with T1 MPRAGE, T2 SPACE, T2 FLAIR and DTI scan sequences were used for location of corticospinal tract and dentatorubrothalamic tract (DRT) with SyngoVia® and Brainlab® softwares.

Sonications were carried out, obtaining an average temperature of 61ºC at target.

Results: There was a tremor reduction of 90% according to Clinical Rating Scale for Tremor (Section A 90%, section B 70% and section C 90%) at 6 months follow up. And a control brain MRI (T2 sequences) at this time, showed a lesion on right VIM of 0.022cm3 and changes on the DRT.

Conclusions; MRgFUS was effective and safe to treat PTT in our patient. This is to our knowledge the first case reported of PTT treated with MRgFUS. More studies should be needed to generalize this result as MRgFUS could be consider a noninvasive neurosurgical treatment for PTT.


Alana ARCADI (Pamplona, Spain), Jorge GURIDI, Iciar AVILES, Lain GONZALEZ-QUARANTE, María Cruz RODRÍGUEZ, María GOROSPE
00:00 - 00:00 #23981 - Pallidal Deep Brain Stimulation for involuntary movement afteranti-N-methyl-D-aspartate (NMDA) receptor encephalitis.
Pallidal Deep Brain Stimulation for involuntary movement afteranti-N-methyl-D-aspartate (NMDA) receptor encephalitis.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is caused by antibodies against NR1/NR2 heteromers and results in a characteristic neuropsychiatric syndrome. Dalmau et al. reported that 90 % of the patients are women, the majority of whom have ovarian teratomas. About 10 % of anti-NMDA receptor encephalitis patients are men. The tumor complication rate is low at 20 %. Most patients temporarily develop involuntary movements during the course of the disease. We report the effect of globus pallidus internus (GPi)-deep brain stimulation in a patient with postural dystonia of the limb with orofacial dystonic movements for more than five years after recurrence of anti-NMDA receptor encephalitis. A 13-year-old boy developed psychiatric symptoms such as polyphrasia and agitation at the age of 5 years. Cerebrospinal fluid examination revealed antibodies against NMDA receptors. No major complications including teratoma were evident. Therefore, the diagnosis of anti-NMDA receptor encephalitis was made and he received immunosuppressive therapy. He had residual epileptic seizures and, gradually developed left-side dominant postural dystonia. At the age of 8 years, he developed dysarthria and exacerbation of the left side symptoms. This was diagnosed as recurrence of encephalitis. Immunosuppressive therapy was administered again. However, his symptoms progressed and he also developed dystonia of the limb and trunk, orofacial dyskinesia including grimacing, masticatory-like movements, forceful jaw open-close, dysphonia, and seizures. Various medications were tried but their effects on his involuntary movements were minimal. Fluid-attenuated inversion recovery magnetic resonance imaging showed mixed high and low signals in the bilateral striatum and pallid spheres. 99 m Tc-ethyl-cysteinate dimer single-photon emission computed tomography examination showed hypoperfusion of the bilateral striatum and the insula gyrus. We diagnosed this as generalized dystonia due to the sequelae of encephalitis. The patient underwent bilateral GPi-DBS under general anesthesia with microelectrode recordings. The recordings during the trajectory revealed a general decrease in neural activity in the basal ganglia. We inserted electrodes from the coronal sutures and identified the optic tracts. Boston Scientific Vercise Cartesia Directional Leads were placed 2 mm apart from the optic tract bilaterally. The patient’s facial involuntary movements improved around 1 month postoperatively and his dystonia symptoms in the limbs also improved thereafter. Six months after surgery, his postural dystonic symptoms were mild and his weight had increased. The mechanism of involuntary movements in anti-NMDA receptor encephalitis is unknown in detail, and reports and effects of brain surgery for involuntary movements in anti-NMDA receptor encephalitis are limited. While these symptoms are temporary in most cases, synaptic disturbances result in a loss of control of motor circuits in some cases.Although the intraoperative microelectrode recording of the present case suggested neuronal shedding in the extensive basal ganglia region, DBS was effective even in such a condition. Seventy-five percent of anti-NMDA receptor encephalitis patients have a good prognosis and the disease goes into remission. Although further studies are needed to determine how this disease progresses, DBS appears to be an effective treatment option in cases of residual refractory involuntary movements.


Takefumi HIGASHIJIMA (Yokohama, Japan), Takashi KAWASAKI, Katsuo KIMURA, Yu TSUYUSAKI, Hitaru KISHIDA, Katsumi SAKATA, Tetsuya YAMAMOTO
00:00 - 00:00 #23821 - Preliminary experience with the use of robot assisted laser interstitial thermotherapy in functional neurosurgery.
Preliminary experience with the use of robot assisted laser interstitial thermotherapy in functional neurosurgery.

laser  interstitial thermotherapy (LITT) has been described in neurosurgery oncology to treat brain metastases, primary tumors and post-radiation necrosis with an excellent safety profile. The ILTT procedure appears as an alternative mini-invasive modality in functional neurosurgery. We report our preliminary results on the use of this procedure under robot-assisted stereotactic

Four patients benefited from this procedure in our center for indications in functional neurosurgery. The average age of the patients was 55.5 years (min: 35, max: 85 years). The indications were: hypothalamic hamartoma (n = 1), essential tremor (n = 1), hippocampal sclerosis (n = 1), chronic pain (n = 1). We do not observe any intraoperative or immediate postoperative complications in particular. No haemorrhagic or neurological deficit complication was noted. Postoperative recovery was rapid allowing a short hospital stay of 4.75 days (min: 2 days, max: 8 days). The ILTT procedure under assisted stereotactic seems to be an effective and safe method for indications in functional neurosurgery. 


Meshal JAREBI (Amiens), Michel LEFRANC, Johann PELTIER
00:00 - 00:00 #26080 - Quantifying stridor associated with parkinsonism and deep brain stimulation a case report.
Quantifying stridor associated with parkinsonism and deep brain stimulation a case report.

Stridor is a recognisable harsh and high pitched inspiratory sound associated with impaired vocal fold abduction. In patients with Parkinsonism, it raises the suspicion of Multiple System Atrophy (MSA). Stridor is uncommon in Parkinson’s disease (PD) although cases have been reported. We present the case of a 54 year old male diagnosed with idiopathic PD who presented with stridor. The stridor was variable throughout the day but worst during off periods. The patient was put forward for DBS due to medical refractory dyskinesias.  At time of initial assessment he reported a 4yr history of mild stridor. Following DBS the stridor progressed and become distressful for him on exertion and intrusive in speech. Vocal fold examination 6 months post DBS identified a maximum vocal fold abduction of 4-5mm, at 9 months this was limited to 2.5mm and the possibility of a tracheostomy was discussed.

As the stridor was known to be responsive to medication it was considered feasible that careful adjustment of stimulation might improve it there by delaying or preventing the need for a tracheostomy.  The patient was systematically assessed with and without medication.  A monopolar review aiming to reduce stridor while maintaining motor function was carried out, using both conventional (60 us & 130Hz) and novel approaches, including frequency modulation, the use of shorter pulse width (30us), and directional screening at the vertical level of the chronically used contacts. To quantify the severity of stridor, the patient read a short standard passage following a period of exertion. The laryngograph technique, commonly used in voice clinics was used to provide information on vocal fold behaviour throughout the opening closing cycle in each condition. An audio recording was rated using a perceptual speech assessment (DAB).

Inclusion of medication was found to mildly reduce vocal fold frequency irregularity (IFx 49.91% to 37.89%) caused by high frequency stridor and improved speech on the perceptual scale (14/42-25/42). Use of optimised stimulation settings were successful in markedly improving his speech further (24/44/ 30/42), reducing the stridor and eradicating it in high frequency regions (IFx % 49.91% to 21.91%). UPDRS-III scores on stimulation pre- and post-optimisation (off/on medication) were 28/18 and 25/17 respectively. The stridor in isolation was noted to become increasingly periodic across conditions. At 6 week review the patient reported an experienced reduction in stridor and improvement in speech but an elevated vocal pitch reflective increased vocal fold tone.  Examination of the vocal folds post optimisation of stimulation found the glottic gap to be 7-8mm. The improved glottic gap did not sustain however and at 10 months the patient required a tracheostomy. 

In the absence of any other features to meet diagnostic criteria for MSA, we are treating this gentleman as a patient who has PD with stridor but will continue to observe if he develops autonomic features or other signs more suggestive of MSA. While there have been previous reports of stridor being induced or exacerbated by STN-DBS in PD, to our knowledge this is the first reported case illustrating the utility of neuromodulation in alleviating this problematic symptom and delaying the need for a tracheostomy. Furthermore it illustrated the usefulness of the laryngograph in objectively quantifying stridor severity in a non-invasive manner.


Timothy GROVER (London, United Kingdom), Viswas DAYAL, Alexis DE ROQUMAUREL, Adrian FOUCIN, Patricia LIMOUSIN, Tom FOLTYNIE
00:00 - 00:00 #24081 - Reduced cerebellar lobule volumes in essential tremor.
Reduced cerebellar lobule volumes in essential tremor.

Background

Essential tremor (ET) has been linked to cerebellar neurodegeneration based on symptoms and autopsies. Previous voxel-based morphometric investigations have indicated signs of cerebellar atrophy. However, the involvement of specific cerebellar lobules remains unclarified. Novel automated pipelines allow for segmentation of cerebellar lobules based on magnetic resonance imaging (MRI).

Objective

To volumetrically compare cerebellar lobules and gray matter volumes of ET patients with healthy controls (HC) using the Cerebellar Segmentation (CERES) pipeline.

Methods

Cerebellar segmentations of structural MRI scans of age- and gender-matched HC (n=70; from database) and ET patients (n=70) were performed using the CERES pipeline. Lobule-specific volume and gray matter differences between ET and HC were determined using t-tests corrected for multiple testing.

Results

ET patients demonstrated reduced volumes of the cerebellar lobules I-II, Crus II and VIIB as compared to HC. Moreover, decreased gray matter volumes of the cerebellum and lobules VI, Crus I, Crus II and VIIB were observed in ET as compared to HC.

Conclusions

Patients with ET demonstrated decreased cerebellar volumes and gray matter volumes of regions related to the first motor representation and cognitive areas. The results support the view of a neurodegenerative etiology underlying ET.


Richard ÅGREN, Amar AWAD, Patric BLOMSTEDT, Anders FYTAGORIDIS (Stockholm, Sweden)
00:00 - 00:00 #23946 - Single-centre analysis of precision and precision-influencing factors in deep brain stimulation.
Single-centre analysis of precision and precision-influencing factors in deep brain stimulation.

Introduction: Deep brain stimulation (DBS) is a surgical method used in neurological
motor disease, especially Parkinson's disease (PD), essential tremor (ET) and dystonia. Precision
and accuracy are essential for clinical efficacy, and due to the multi-staged nature of the procedure,
errors accumulate at multiple points. The aim of the present study was to measure the precision of
DBS at one Swedish center (implementing image-guided frame-based DBS-surgery without micro-electrode recording) and
to confi rm and find factors influencing targeting error. Finally, this was put into a clinical context to
asses the eff ect of targeting error on clinical outcome in a subset of PD patients.

Method: We retrospectively examined all DBS operations at Sahlgrenska University Hospital between
2010 and 2020 which amounted to 188 electrodes in 139 patients. 87 patients with 133 electrodes were
included in the final analysis. Pre-operative MRI images were co-registered to post-operative MRI or CT
images using proprietary software (Suretune 3, Medtronic). Both radial and euclidean errors were
calculated and related to age, hemisphere, type of post-op image (as a quality indicator),
intra-operative patient inclination, use of dural sealant, order of sides and target structure. For a subset of 21
PD patients, clinical improvement, measured as Levodopa-equivalent dose (LED) reduction, was also
related to precision.

Results: Median radial error was 1.1 mm (IQR 0.9; 95% CI 1.0-1.2) and median euclidean error was
1.7 mm (IQR 1.0; 95% CI 1.6-1.9). There was a signifi cant diff erence in radial and euclidean error
between hemispheres in favor of right-sided leads (p < 0.01 and p < 0.05 respectively). There was no
signif icant correlation between age and error of any type. Modality of post-operative imaging, the use of
tissue glue and patient position did not signif cantly aff ect targeting error. There was no statistical
association between error magnitude and clinical outcome, although the LED reduction 3- and 6-
month as well as 1-year post-op was highly signifi cant (p < 0.001) compared to the pre-operative dosage.
On average, euclidean error tended to point in a medial (median 0.75 mm), posterior (median 0.52
mm) and inferior (median 0.49 mm) direction compared to the target, suggesting a slight systematic
error.

Conclusion: Targeting error at our center has a magnitude comparable to that of other centers. The
present study was able to confi rm some of the factors thought to aff ect precision in DBS, although
the stability of both positive and negative findings may be limited by sample size, especially for the
clinical subgroup.


Linus KOESTER (Gothenburg, Sweden), Thomas SKOGLUND, Johan LJUNQVIST
00:00 - 00:00 #24001 - Spinal cord stimulation in Parkinson’s disease and Parkinsonism: 10 years later, review of the litterature and future prospects.
Spinal cord stimulation in Parkinson’s disease and Parkinsonism: 10 years later, review of the litterature and future prospects.

Background and purpose: More than 10 years ago, a preclinical study (Fuentès 2009) reported the “restoration of locomotive function in Parkinson’s disease by spinal cord stimulation“. Since that, various case reports and pilot studies suggested that SCS may be used as a therapy for motor and gait dysfunction in parkinsonian states. Is there anything new today on this subject, it’s the goal of this presentation.

Material and method. Data sources for this relevant literature search included usual publishers. We selected the latest and most inovative publications.

Results. Various pilot studies were presented. First line analysed symptom was the “Freezing of gait“, but dystonias as camptocormy or Pisa syndrome could be relevant indications. A preclinical study (Zhang 2019) suggested interesting hypothesis on SCS mechanism in extrapyramidal gait disorders.

Discussion. No RCT were published on the subject. Some problems were not resolved: speed was probably not a good primary outcome. Idem for patient selection and stimulation settings. New technologies in gait studies (fi. muscle synergies study) and spinal cord stimulation (fi. burst stimulation) could be an opportunity to taylor a high level RCT. About the mechanism, SCS probably restored a proper functoning of the spinal CPG (central pattern generator). But is it enough to restore gait and balance.


Jean-Baptiste THIÉBAUT (PARIS), Vincent D'HARDEMARE, Jean-Philippe BRANDEL, Cécile HUBSCH, Didier PRADON, Laurent GOETZ, Nathalie PATTE-KARSENTI, Marc ZIEGLER
00:00 - 00:00 #23659 - Subcutaneous Pneumothorax in a Patient with Cervical Dystonia as a Rare Complication of Deep Brain Stimulation Procedure.
Subcutaneous Pneumothorax in a Patient with Cervical Dystonia as a Rare Complication of Deep Brain Stimulation Procedure.

Objectives:

Deep brain stimulation (DBS) procedure-related adverse events correspond usually to intracerebral haemorrhagic complications. These complications may cause transient or permanent neurological deficits or even death. The intracerebral haemorrhagic complications are related to introduction of microelectrodes or macroelectrodes to a stereotactic target. The another possible source of complication may be related to the internalization of DBS hardware during tunnelling of the connection cable in the neck region. 

Methods:

Here, we describe to our knowledge the first case of a patient who developed a subcutaneous pneumothorax due to passage of a tunneling tool for placement of a connection cable. The patient within 30 minutes after surgery developed a marked subcutaneous pneumothorax. The pneumothorax was related due to the right lung apex injury confirmed by chest radiological examinations. The formal preoperative objective assessment included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The postoperative TWSTRS assessments were done at 3, 6 months and 12 months postoperatively.

Results:

The subcutanoues pneumothorax spontaneously resolved within 5 days. During this time period the patient was carefully monitored in the neurointensive unit. The patient made a full recovery and did not required an urgent thoracic surgery. The resolution of pneumothorax was confirmed by thorax and neck computed tomography examinations. The patient made the full recovery. Bilateral GPi stimulation in this patient resulted in marked reduction of cervical dystonia. At 12 months follow-up visit, the severity, disability and pain scores of TWSTRS were improved by 55 %, 52 % and 45 % respectively.

Conclusions:

This case demonstrates that tunneling for permanent placement of a connection cable may injure some structures in the upper neck region like lung apex. Although an blunt tip for tunneling tool was used in this case we observed this rare complication. Routinely, we utilize only the blunt tips for tunneling a connection cable in the neck region. We do not advocate to utilize an sharp tip of a tunneling tool which is more prone to cause a vascular or another tissue injury.


Michał SOBSTYL (Warsaw, Poland), Angelika STAPIŃSKA-SYNIEC, Anna KUPRYJANIUK
00:00 - 00:00 #23957 - Subthalamic nucleus deep brain stimulation in post-infarct dystonia.
Subthalamic nucleus deep brain stimulation in post-infarct dystonia.

Background


Dystonia secondary to cerebral infarcts present months to years after the initial insult, is usually unilateral, causes significant morbidity and is considered to be the result of aberrant reorganisation of the motor network after brain injury. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is established as the most frequent target in the management of dystonic symptoms. We report our experience with subthalamic nucleus (STN) DBS in three patients with clinically significant refractory post-infarct dystonia, in whom the GPi DBS was not possible.


Methods

Preoperative and postoperative functional assessment data prospectively collected by a multidisciplinary movement disorders team, including imaging, medication and neuropsychology evaluations were analysed with regards to symptom improvement. Quantification of dystonic signs and symptoms was done at baseline and at last follow-up using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score and disability score. 

 

Results

Three patients (2 males) with a mean age of 19 years (range 18 – 21 years) underwent DBS implantation. Internal carotid artery dissection and post-viral encephalitis (in 2 patients) were the causes of the initial infarct. Mean proportion of life lived with dystonia (defined as dystonia duration/age at surgery) was 0.67 (range of 0.61 - 0.78). Two patients had unilateral STN DBS implantation whereas the third patient had bilateral STN DBS implantation for asymmetrical bilateral symptoms. Median follow up was 38.3 months (range of 36 – 43 months). Clinically valuable improvements in dystonic symptoms and pain control were seen in all patients despite variable improvements in the Burke-Fahn-Marsden dystonia rating scores (movement score improvements of 14-64%, disability score improvements of 11-33%), highlighting the inadequate sensitivity of the scale in measuring subtle but clinically meaningful changes. 

 

Conclusion

In the absence of large prospective studies and given the rare nature of stroke-related dystonia and the heterogeneous nature of the condition, the use of subthalamic nucleus deep brain stimulation could be an alternative in the management of patients with post-infarct dystonia with abnormal striatal anatomy which precludes GPi DBS.  


Kantharuby TAMBIRAJOO (London, United Kingdom), Luciano FURLANETTI, Michael SAMUEL, Keyoumars ASHKAN
00:00 - 00:00 #23941 - The Effect of Subthalamic Nucleus - Deep Brain Stimulation and Different Stimulation Frequencies on Cerebral Hemodynamics in Parkinson's Disease.
The Effect of Subthalamic Nucleus - Deep Brain Stimulation and Different Stimulation Frequencies on Cerebral Hemodynamics in Parkinson's Disease.

Objectives:

The effect of the deep brain stimulation of the subthalamic nucleus (STN-DBS) on cerebral hemodynamic parameters is still not clear. Our objectives are to investigate the effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) and to compare low-frequency versus high-frequency STN-DBS on hemodynamic parameters of the middle cerebral artery between patients with advanced Parkinson's disease and age-sex matched healthy controls.

Patients and Methods:

Eighteen patients with advanced Parkinson's disease (PD) who have bilateral STN-DBS and 18 control subjects underwent Transcranial Doppler Ultrasound (TCDU) were included in the study. The hemodynamic parameters including blood flow velocity (FV), pulsatility index (PI) and, resistance index (RI) of the right middle cerebral artery (MCA) were measured and compared during the phases using TCDU. The first DBSoff, the second low-frequency DBS of 60 Hz, and the third high-frequency DBS of 130 Hz were compared.

Results:

PD patients had significantly higher MCA-PI values compared with controls (0.99 ± 0.27 vs. 0.82 ± 0.14) (p = 0.031). Also, the MCA-PI values were higher in the low-frequency DBS (0.94 ± 0.14) and high-frequency DBS (0.93 ± 0.16) than in the controls (0.82 ± 0.14) (p = 0.022 and p = 0.041, respectively). There were no significant differences of FV and RI values among the DBS-on, DBS-off and, controls. The RI values were higher in the PD patients than in the controls, although these were not statistically significant. Also, PI values of the MCA decrease in different frequencies (60 Hz or 130 Hz).

Conclusion:

The results of this study showed that MCA-PI values are higher in advanced PD compared with controls. These indices indicate that MCA resistances and impedances are increased in advanced PD. Low- or high-frequency DBS treatment have beneficial effect to reduce high PI in advanced PD patients.


Atilla YILMAZ (Istanbul, Turkey), Orkun KOBAN, Mustafa Turgut YILDIZGOREN
00:00 - 00:00 #23979 - The role of sedation in patient’s ability to cooperate during DBS surgery. A pilot study.
The role of sedation in patient’s ability to cooperate during DBS surgery. A pilot study.

Purpose: Deep brain stimulation (DBS) is an effective treatment for several conditions including movement disorders. Several techniques have been utilized for acceptable operational conditions during awake state. Management of hemodynamic perturbations is crucial in preventing  complications such as intracranial bleeding. The present pilot study investigated the role of  monitored anaesthetic care during DBS electrode placement and  microelectrode recordings in relation to patients’ ability to cooperate.

Material  and Methods: Three patients with Parkinson’s Disease  who underwent surgery for DBS placement were included in the study. During DBS surgery, all patients received monitored anesthesia care (propofol 25–50 mcg/kg/min and/or remifentanil 0.02–0.05 mcg/kg/min). When the one burr hole was made only local anaesthetics were utilized, whereas in the second mild sedation was additionally used and vice versa. Comparisons between the two methods were made on level of alertness using the Modified Observer`s Assessment of Alertness/Sedation Score (MOAA/S) and hemodynamic parameters.

Results: Three patients (2 males, 1 female, mean age 64.6 years) were included in the study. No significant differences were found in MOAA/S score, mean arterial blood pressure, heart and respiratory rate and blood oxygen saturation levels between the two techniques used. Patient’s cooperation was satisfactory in all cases.

Conclusion: The present pilot study did not reveal any differences in alertness, when different anaesthetic management was utilized, for patients with PD that underwent DBS surgery.


Arian LENAS, George ALEXIOU (IOANNINA, Greece), Zigouris ANDREAS, Spyridon VOULGARIS
00:00 - 00:00 #23664 - Tremulous Cervical Dystonia Treated by Bilateral Pallidal Stimulation. Case Series Report.
Tremulous Cervical Dystonia Treated by Bilateral Pallidal Stimulation. Case Series Report.

Objectives:

The aim of the present study was to present a case series of 4 patients with longstanding debilitating tremulous cervical dystonia (CD). Pharmacological treatment including benzodiazepines as well botulinum toxin injections failed to adequately control dystonic jerking movements of the head and neck. The patients were referred for pallidal deep brain stimulation (DBS) surgery.

Methods:

Four patients underwent bilateral implantation of DBS leads into the posteroventrolateral segment of the globus pallidus internus (GPi). One patient received additional implantation of left lead in the nucleus ventralis intermedius of the thalamus (Vim). All surgeries were uneventful. The formal preoperative objective assessment included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the motor score of Tremor Rating Scale (TRS). The postoperative TWSTRS and TRS assessments were done at 3, 6 months and 12 months postoperatively up to 48 months after surgery.

Results:

At 3 months follow-up visit, the severity, disability and pain scores of TWSTRS were improved by 35 %, 48 % and 44 % respectively. The TRS improved by 68 % when compared to baseline TRS score. At the last follow-up visit, the severity, disability and pain scores of TWSTRS were improved by 51 %, 52 % and 56 % respectively. The TRS improved by 78 % when compared to baseline TRS score. There were no hardware-related complications over follow-up period.

Conclusions:

Our preliminary experience gathered in 4 patients indicates that bilateral pallidal DBS can be an effective treatment for disabling tremulous CD.


Michał SOBSTYL (Warsaw, Poland), Angelika STAPIŃSKA-SYNIEC, Anna KUPRYJANIUK
00:00 - 00:00 #24084 - Unilateral Vim and cZi DBS for treatment of spasmodic dysphonia and arm tremor.
Unilateral Vim and cZi DBS for treatment of spasmodic dysphonia and arm tremor.

Background

The key finding in patients with Spasmodic Dysphonia (SD) is repeated involuntary contractions of the laryngeal muscles during speech. This may severely impair the ability to communicate verbally, having phone conversations and in the long run decrease quality of life substantially. Patients are if necessary treated with repeated botulinum toxin injections (bo-tox) of the laryngeal muscles, but some patients may become refractory to this treatment. Promising result have been reported with unilateral thalamic DBS of the speech dominant hemisphere for a few patients with bo-tox refractory SD [1].

Objective

To analyze the effect of unilateral thalamic (Vim) and subthalamic (cZi) DBS for SD.

Methods

A 75 year old female patient with severely disabling and bo-tox refractory SD as well as concomitant kinetic tremor of both arms was treated with unilateral DBS of the Vim and cZi in order to address tremor of the dominant (right) arm and symptoms of SD.

Results

The patient has thus far only been interviewed by telephone due to the current Covid-19 pandemic. She experiences complete cessation of tremor in her right arm and is now able to have phone conversations with friends and relatives for the first time in many years. More detailed result will be presented at the congress.

Conclusions

Unilateral Vim and cZi DBS might be a beneficial treatment in severe and bo-tox refractory SD.

 

1 Poologaindran A, Ivanishvili Z, Morrison MD, Rammage LA, Sandhu MK, Polyhronopoulos NE, Honey CR: The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: Interrogating cerebellar and pallidal neural circuits. J Neurosurg 2018;128:575-582.


Bjartur SÆMUNDSSON, Catarina WERSCH, Ellika SCHALLING, Mathias SUNDGREN, Göran LIND, Anders FYTAGORIDIS (Stockholm, Sweden)
00:00 - 00:00 #23924 - Vim anatomical variability: an MRI structural connectivity study.
Vim anatomical variability: an MRI structural connectivity study.

Visualising brain structures using MRI to guide and verify targeting is of utmost importance in the success of functional neurosurgical procedures. This is possible for most established targets (e.g. the subthalamic nucleus, the internal pallidum) but not the thalamic Ventralis intermedius nucleus (Vim) target. This has led some to explore the use of structural connectivity to help better define this structure instead of solely relying on atlas-based coordinates adapted to the patient’s anatomy. The aim of this work is three-fold: 1) quantify Vim anatomical variability using the coordinates estimated by tractography 2) quantify the discrepancy between atlas-based and tractography-based coordinates 3) exclude methodological confounds to ensure found variability is truly anatomical. 

One hundred, state of-the-art diffusion MRI datasets of healthy individuals from the Human Connectome Project were processed. We reconstructed the dentato-rubro-thalamo-cortical tract (DRTCT) with probabilistic tractography, using a previously published method (Akram et al 2018)1. Intersections between the thalamus and the DRTCT were used as surrogate for the Vim. Confounding factors such as participant motion and regional brain volumes were explored to ensure the observed variability corresponded to true anatomical variability. We also examined the effect the volume of the superior cerebellar peduncle (SCP), being the narrowest structure the DRTCT crosses, has on the tractography results.

The tractography-based mean coordinate obtained for left Vim was x = -18.75 (anterior-posterior), y = -13.68 (medio-lateral), z = 2.67 (superior-inferior) mm, with standard deviations of 1.19, 1.25 and 1.33 mm, respectively. For right Vim, it was x = -17.59, y = 13.08, z = 4.00 mm, with standard deviations of 1.46, 1.14 and 1.60 mm, respectively. This contrasts significantly with Talairach atlas determined coordinates which are, for left Vim, x = -14.37 (anterior-posterior), y= -12 (medio-lateral), z= 0 (superior-inferior) and for right Vim x = -14.37, y = 12, z = 0. In our work, Vim locations were more variable on the right, and variation was overall more marked in an anterior-posterior direction. There was asymmetry in the connectivity profiles between the left and right sides. Motion and brain volumes had no significant impact on the results, however; left SCP volumes did indeed influence the tractography results, and the SCP was confirmed as a potential source of artificial variance.

This work confirms the disparity between connectivity based and atlas-based approaches in capturing individual Vim location. The significance of this will have to be assessed against patient outcomes in subsequent studies. The left-right asymmetry is a new finding that might be explained by lateralisation of specific functions withing the cerebellum, such as the increasingly recognised role that the cerebello-thalamo-cortical network plays in language processing and localisation as one hypothesis.

Tractography-based methods appear to provide a consistent measure of individual anatomy that could capture variability missed in traditional targeting. These methods are shown here to be robust to major confounds but could be further refined nonetheless in order to improve efficacy and reduce side-effects of thalamic surgery for tremor.

 

References

1. Akram H, Dayal V, Mahlknecht P, et al. Connectivity derived thalamic segmentation in deep brain stimulation for tremor. NeuroImage Clin. 2018. doi:10.1016/j.nicl.2018.01.008


Francisca FERREIRA (London, United Kingdom), Harith AKRAM, John ASHBURNER, Hui ZHANG, Ludvic ZRINZO, Christian LAMBERT
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EP06
00:00 - 00:00

Eposters
NEUROPHYSIOLOGY

00:00 - 00:00 #26130 - Cortical activity in an acute rodent model of Parkinson: possible use for adaptive deep brain stimulation.
Cortical activity in an acute rodent model of Parkinson: possible use for adaptive deep brain stimulation.

Background: Oscillatory activity of local field potentials (LFPs) plays a central role in regulating different states of brain function. In neurological and neuropsychiatric disorders neuronal oscillatory activity between subcortical basal ganglia (BG) and cortical circuits are altered, which may be useful as biomarker for adaptive deep brain stimulation (DBS).

 

Objective: Here we investigate the changes in the spectral power of oscillatory activity in the motor cortex (MCtx) and the sensorimotor cortex (SMCtx) of rats after acute injection of the dopamine (DA) receptor antagonist haloperidol (HALO) and subsequent injection of the DA receptor agonist apomorphine (APO). Further, a convolutional neural network (CNN) model was implemented for classification of the different states of brain signals.

 

Methods: In six male Sprague Dawley rats (270-300g) a sixteen channel surface miro-electrocortigram (ECoG) recording array was placed under the dura above the MCtx and SMCtx areas of one hemisphere under general anaesthesia and perioperative pain management. Seven days after surgery, micro ECoG was recorded in individual free moving rats in three conditions: (1) basal activity, (2) after injection of HALO (0.5 mg/kg), and (3) with additional injection of APO (1mg/kg). Spontaneous basal oscillatory activity was analyzed in the MCtx and SMCtx area. Furthermore, a CNN consisting of 23,530 parameters was applied on the raw data. The network is constructed by stacking six convolutional layers followed by one hidden fully connected layer and one output layer.

 

 Results: Injection of HALO decreased oscillatory theta band activity (4-8Hz) and enhanced beta (12-30Hz) and gamma (30-100Hz) in both MCtx and SMCtx, which was compensated after APO injection (p <0.001). Evaluation of classification performance of the CNN model using the k-Fold method provided an accuracy of 92%, sensitivity of 90% and specificity of 93% on one-dimensional signals of 60s, thus minimizing the required information down to a single channel recording as an input.

 

Conclusion: Injection of HALO in free moving rats leads to changes in the spectral power of oscillatory activity in motor cortical areas that show similarities to those recorded in PD patients, including alleviation by DA receptor agonists. Using the CNN algorithm for classification of neuronal activity state-of-the-art performance was accomplished. The proposed model requires a minimum of sensory hardware and may be integrated into future research on therapeutic devices for Parkinson disease, such as adaptive closed loop stimulation, thus, possibly contributing to a more efficient way of treatment.


Mesbah ALAM (Hannover, Germany), Ali Abdul Nabi ALI, Simon KLEIN, Nicolai BEHMANN, Theodor DOLL, Holge BLUME, Joachim K. KRAUSS, Kerstin SCHWABE
00:00 - 00:00 #26297 - Effect of directional deep brain stimulation of the subthalamic nucleus on the behavior in healthy non-human primate.
Effect of directional deep brain stimulation of the subthalamic nucleus on the behavior in healthy non-human primate.

Introduction

Deep brain stimulation (DBS) of the motor Subthalamic nucleus (mSTN) has become the gold standard surgical treatment for Parkinson’s disease whereas DBS of the non motor part of the STN (noM-STN) has been also used to treat severe obsessive-compulsive disorders. However, the knowledge of the respective distribution of non motor versus motor STN is limited and it has been reported that mSTN- DBS can induce non motor symptoms and, at contrario, noM-STN DBS can show motor side effect such as dyskinesia. Thanks to the recent technological development of directional leads, it is now possible to steer the current toward the mSTN or the noM STN, depending on the mode of stimulation. Here, we investigated the effect of directional STN DBS on the motor and non motor behavior in healthy non-human primate (NHP).

 

Methods

One NHP was implanted with a directional DBS lead into the STN, using pre-operative MRI and per operative ventriculography and micro-recordings to select the best trajectory. In parallel, the NHP was trained to perform a switching task enabling the evaluation of different components of the behavior. Indeed, i) the reaction time evaluated the motor domain, ii) measurement of the error rate during the task discriminated the cognitive domain and, iii) the decisional time, to either check to gain information about the delivery of a large bonus reward or to continue with the default switching task, allowed the evaluation of the emotional domain. STN DBS, at 130 Hz, using a directional mode, was applied during the task to check if a single lead could have a differential effect on those 3 domains. 

 

Results

We observed that DBS of the dorsolateral territory of the STN decreased the reaction time (679±13 ms vs. 552±20 ms; p≤ 0.0001) without changing the error rate. Interestingly, the decisional time was lower for the stimulation of the dorsolateral territory and higher for the stimulation of the more ventral territories compared to the OFF-stimulation condition (841±73 ms for the dorsolateral territory, 1555±405 ms for the ventral ones compared to 1165±110 ms for the OFF-stimulation condition; p≤0.05).

 

Conclusion 

These results highlight that 1) STN DBS of the dorsolateral territory can significantly modify the motor performances, whereas DBS of the ventral territories can significantly impact the cognitive and emotive performances; 2) using the directional mode of stimulation, one can steer the current toward different sub-territories of the STN with motor or non motor effect depending on the subdomain of STN stimulated. A better knowledge of the sub-territories of the STN could help to understand the side effects of STN-DBS, and directional stimulation could help to optimize the effect of STN-DBS in relation to the main motor or non motor symptoms that require a treatment.


Mathilde BERTRAND (FRANCE), Stephan CHABARDES, Julien BASTIN, Brigitte PIALLAT
00:00 - 00:00 #23424 - Intraoperative electrophysiology during deep brain surgeries in disorders of consciousness.
Intraoperative electrophysiology during deep brain surgeries in disorders of consciousness.

The efficacy on deep brain stimulation in disorders of consciousness (DC) is inconclusive. We investigated bilateral 30-Hz low-frequency stimulation designed to overdrive neuronal activity by dual pallido-thalamic targeting to promote conscious behavior in five patients. Five adult patients (mean age 38 years old) were included: one unresponsive-wakefulness-syndrome male (traumatic brain injury); and four patients in a minimally conscious state, one male (traumatic brain injury) and three females (two hemorrhagic strokes and one traumatic brain injury). Pallido-thalamic electrode targeting were performed under sevoflurane general anesthesia with recording of extracellular muti-unit neuronal activity and local field potential (LFP). These data were compared with five GPi DBS implantations (three males) for Parkinson’s disease (n=4) or dystonia (59 years old) and three VIM DBS surgeries (two males) for Parkinson’s disease (n=1) or essential tremor (40 years old).

The electrode implantation was realized after electrophysiological mapping using an intraoperative electrophysiological system for functional neurosurgery (MicroGuide Pro, Alpha Omega Eng., Israel). For each brain hemisphere, the mapping was performed using two exploration electrodes (Alpha Omega Eng.) steered by rigid guide tubes: one on the planned track and a second one on the parallel track located posteriorly at 2mm. The characteristics of our electrophysiological approach were as follow: systematic recordings of the spontaneous neuronal activity every 1 mm during 30 seconds along the distal 8.2 mm (min: 5; max: 13 mm) in the pallidum and the thalamus previously labelled and manually outlined on stereotactic MRI.

Spikes were encountered for 50 out of 130 recordings in the pallidum (38.46%) and for 43 out of 185 (23.24%) in the thalamus of patients with disorders of consciousness. Concerning motor disease (MD) patients implanted under general anesthesia, spikes were found in 52 out of 150 recordings in the pallidum (34.66%) and for 54 out of 82 (65.85%) in the thalamus. Mean firing rate of neurons in the pallidum was 9.84 +/-8.71 Hz and 11.95 +/-10.31 Hz during surgery for patients with DC and MD respectively. Concerning Thalamus, mean firing rate was 3.78 +/-4.87 Hz versus 2.25 +/-2.15 Hz (DC vs MD).

Percentage of raw power spectral density of LFP was similar in GPi for patients with DC and MD. Delta (47.8%), Theta (19.5%) and Alpha (17.0%) bands were preponderant for DC, while Delta (37.2%), Alpha (29.1%) and Beta (17.0%) range were powerful for MD patients.

Pallidal neuronal activity is similar for patients under general anesthesia suffering from DC or MD. Differences were encountered for Thalamus: higher 7-30Hz frequency power was encountered for patients with MD and higher low (<7Hz) and high (>30Hz) band power was observed for DC.

Thalamic neuronal activity differs between MD and DC patients. Few records have been obtained and published for patients with impaired consciousness. These results should be considered with caution given the small number of patients in the study.

This clinical trial (NCT01718249) was funded by the Fondation de l’Avenir (ET1-615 2011; “Deroche Legacy” Grant BO4-001), the University Hospital of Clermont-Ferrand, the Centre Jean Perrin and Medtronic France.

DBS-Post-coma study group and clinical research protocol are detailed here: https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Facn3.648&file=acn3648-sup-0001-Suppinfo.docx


Jérôme COSTE (Clermont-Ferrand), Anna SONTHEIMER, Bénédicte PONTIER, Jean-Jacques LEMAIRE, Dbs-Post-Coma STUDY GROUP
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EP07
00:00 - 00:00

Eposters
ONCOLOGY

00:00 - 00:00 #23925 - Initial experience of an O-Arm-based neuronavigated laser interstitial thermal therapy for malignant brain tumors.
Initial experience of an O-Arm-based neuronavigated laser interstitial thermal therapy for malignant brain tumors.

Background

Evidence on laser interstitial thermal therapy (LITT) utility for malignant brain lesions is increasing. Neuronavigation and intra-operative imaging are valuable for optimizing LITT.

 

Methods

We report our center’s initial experience with O-Arm-based neuronavigated LITT (OA-LITT), namely three cases of malignant brain tumors.

 

Results

Our first case consists of a 75-years-old woman with a right temporal glioblastoma, previously submitted to subtotal resection and Stupp protocol chemoradiotherapy. At 36-months follow-up, a right frontal lesion compatible with high-grade glioma was diagnosed. Due to comorbidities, the patient underwent OA-LITT. One-catheter lesion targeting was successful with a trajectory error <3mm compared to initial planning. Lesioning included total tumor volume. At 11-weeks post-LITT follow-up, no progression was detected.

 

Second case consists of a 42-years-old man with a left parietal anaplastic oligodendroglioma, previously submitted to subtotal resection and PCV chemoradiotherapy. At 55-months follow-up, progression was diagnosed. The patient underwent subtotal resection and temozolomide therapy. At 74-months follow-up progression was diagnosed; due to comorbidities, the patient underwent radiotherapy. At 81-months follow-up, progression was diagnosed and the patient underwent OA-LITT. Two-catheters lesion targeting presented a trajectory error <3mm in the medial catheter and an 8mm error on the lateral. Lesioning was subtotal, including >90% of tumor volume. At 10-weeks post-LITT follow-up, no progression was detected.

 

Third case consists of a 67-years-old woman with a pulmonary adenocarcinoma left middle cerebellar peduncle metastasis, previously submitted to radiosurgery and cisplatin/pemetrexed chemotherapy. At 22-months follow-up, progression was diagnosed, and the cerebellar lesion was re-irradiated. At 30-months follow-up, progression was again diagnosed and the patient underwent OA-LITT. One-catheter lesion targeting was successful with a trajectory error <3mm. Lesioning included total tumor volume. At 7-weeks post-LITT follow-up, no progression was detected.

 

Conclusion

LITT is a valid tool for patients with malignant brain tumors who are not craniotomy candidates. O-Arm-based neuronavigation is effective and precise for LITT-catheter placement.


Vasco PINTO, Sérgio SOUSA, Eduardo CUNHA (Porto, Portugal), Carla SILVA, Alfredo CALHEIROS
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EP08
00:00 - 00:00

Eposters
OTHER

00:00 - 00:00 #26215 - Feasibility and safety of functional magnetic resonance imaging in patients treated with deep brain stimulation: a systematic review.
Feasibility and safety of functional magnetic resonance imaging in patients treated with deep brain stimulation: a systematic review.

Introduction: Deep brain stimulation (DBS) is an effective treatment option for refractory neurological and psychiatric disorders such as Parkinson’s Disease (PD), Obsessive Compulsive Disorder (OCD), and Essential Tremor (ET). The working mechanism of DBS and its effects on the underlying neuronal networks are still largely unknown. One method to investigate these networks is blood oxygen level dependent (BOLD) functional MRI (fMRI), which indirectly measures neuronal activity. Studies have combined fMRI and DBS as changes in parameters, like turning the DBS ON or OFF, frequency changes, or varying voltages may change the BOLD signal within seconds.

The combined use of fMRI and DBS subsided after two studies reported transient or permanent brain tissue damage due to leads’ temperature increase. These cases deviated from the manufacturer’s protocol. After Medtronic received FDA approval for MRI during DBS under specific conditions in 2015, more studies using the combined technology have been published. There is no consensus concerning feasibility and safety of fMRI in patients treated with DBS. Therefore the main goal of this systematic review is to provide insight in the feasibility and clinical safety for fMRI in DBS patients.

Methods: This systematic review has been performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search was based on ‘functional MRI’ and ‘Deep Brain Stimulation’. Only clinical studies were considered and articles were excluded if they did not include one of the following: fMRI, DBS, fMRI after DBS placement, DBS ON/OFF protocol.

To estimate the risk of bias, we adjusted the Risk Of Bias In Non-randomized Study (ROBINS-I) tool to fit DBS-fMRI studies. Data was manually gathered. High heterogeneity was expected, thus no meta-analysis was performed.

Results: From 1888 articles 27 were selected. All studies were cross-over design, of which three case studies. A total 258 patients were included with an average age of 57 year (range 29-80). Disorders were PD (N=207), ET (N=29), OCD (N=26), pain (N=20), Tourette Syndrome (N=5), dystonia (N=4), and epilepsy (N=2). DBS targets were subthalamic nucleus (N=19), thalamus (N=3), ventral intermediate nucleus (N=3), capsula interna (N=3), zona incerta (N=2), internal pallidal globe (N=1), ventral striatum (N=1), periventricular grey (N=1), the anterior nucleus of the thalamus (N=1), the anterior cingulate cortex (N=1).

Fourteen studies used whole brain approach, 9 studies pre-specified regions of interest (ROIs) and 4 studies created ROIs out of the whole brain analysis. Sixteen studies applied resting state fMRI (rs-fMRI) and 11 included a task during fMRI: Finger motor tasks (N=4), joystick movement (N=3), pain stimuli (N=2), pointing tasks (N=1) and disgust provocation (N=1).

All 27 studies were able to reveal significant (p<0.05) increases or decreases in BOLD signal.

Concerning safety, 14 studies created a phantom model and 5 studies used literature and calculations prior to clinical application. Heating was monitored using B1+RMS (N=2) or by specific absorption rate (N=11). Field strength was 1.5T (N=22) or 3.0T (N=8). The average scan time was 21 minutes (range 4.5-90), with 11 studies applying breaks between session. Eventually 8 studies reported no harms, 2 studies reported a patient with discomfort, “uncomfortable” and “general discomfort”, not specifically related to DBS and fMRI. Eventually 17 studies did not report either some or no adverse effects in their population.

By means of the adjusted ROBINS-I tool 12 studies had low, 11 studies moderate, and 4 studies serious risk of bias.

Discussion: This is the first review focused at the feasibility and safety of fMRI in DBS treated patients. Several studies have used fMRI in DBS patients. If manufacturers' guidelines are followed and safety is demonstrated using a phantom model, no serious adverse events are likely to be encountered, both with 1.5T and 3.0T field strength. fMRI was able to reveal network effects of DBS on cortical and subcortical structures. BOLD was sensitive enough to record changes in signal if DBS frequency was modulated or settings were changed from mono- or bipolar. As DBS-fMRI has not yet been FDA approved, it is advisable to combine efforts with manufacturers to improve safety.
Overall, regarding the literature fMRI is a safe and feasible method to study brain networks in DBS patients.


Kay VAN HEESWIJK, Tim A.m. BOUWENS VAN DER VLIS, Albert F.g. LEENTJENS, Sarah HESCHAM, Christopher WIGGINS, Linda ACKERMANS (Maastricht, The Netherlands)
00:00 - 00:00 #23974 - Repetitive transcranial magnetic stimulation in patient with lesions in functional areas.
Repetitive transcranial magnetic stimulation in patient with lesions in functional areas.

Non painful trans cranial magnetic stimulation proved a useful tool for investigation of speech functional areas mainly in presurgical patients evaluation. A  3 D spatial representation of functional brain areas is available in most cases.

Method

A total of 42 patients with perisyslvian   lesions (epilepsy, glioma, cavernoma), were tested. Left or right hemispheric dominance is obtained by Edinburgh handedness test . Counting,  picture object identification and verbal tasks were used for identification of speech related  areas. We used repeated transcranial magnetic stimulation, 5 Hz, rising power progressively above motor threshold till effects were obtained. Both video and audio data were available and  were carefully analyzed. The errors were classified as no response,  hesitation and paraphasia.

 

Results

The deficit is ranked on four levels: none, mild, medium and severe. A number of three patients demonstrated equivocal responses at stimulation. Dysphasia was present in 11 patients  from admittance at a medium level. All patients excepting one presented a none or mild speech problem 2 month after surgery. 

Discussion

Our experience demonstrate the possibility of removing near and even regions traditionally considered inoperable without inducing permanent deficits and the potential use of these areas as a safe passage to deeper territories

Conclusion

Non-invasive language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) has  shown a high correlation in brain mapping

 

 


Felix BREHAR, Tatiana CIUREA, Jean CIUREA (Bucharest, Romania)
00:00 - 00:00 #23928 - Robot-assisted laser interstitial thermal therapy in functional neurosurgical applications: An initial experience.
Robot-assisted laser interstitial thermal therapy in functional neurosurgical applications: An initial experience.

Laser interstitial thermal therapy was reported in the management of varieties of intracranial lesions. The technique is a minimally invasive procedure that is using in alternatives for patients with high comorbidities. The purpose of this study is to report our initial experience of using robot-assisted LITT in functional neurosurgical applications. Nine procedures were performed in 9 patients (age range from 35 to 85 years old). The indications were hypothalamic hamartoma (n=3), essential tremor (n=4), hippocampal sclerosis (n=1), pharmacoresistant  cancer pain (n=1). The mean operative time was 184 minutes.  The length of hospital stay varied between 2 days and 8 days with a good recovery after surgery. The rate of complications in relation to procedures was low. Robot-assisted LITT appears to be safe, accurate, and can be considered as a very valuable additional tool in the momentum of functional neurosurgical procedures.


Michel LEFRANC, Albéric BOCCO (CASABLANCA, Morocco), Jean Marcel OKAMON, Pierre-Henri LAUNOIS, Johann PELTIER
00:00 - 00:00 #23503 - Stereotactic ventriculocisternostomy reduces delayed infarction and improves outcome in patients with aneurysmal subarachnoid hemorrhage.
Stereotactic ventriculocisternostomy reduces delayed infarction and improves outcome in patients with aneurysmal subarachnoid hemorrhage.

Objective:

Delayed cerebral infarction (DCI) due to cerebral vasospasm (CVS) confers considerable morbidity in patients with aneurysmal subarachnoid hemorrhage (aSAH). Stereotactic catheter ventriculocisternostomy (STX-VCS) and fibrinolytic/spasmolytic lavage therapy is a new method for DCI prevention. We report neurological outcome at 6 months, CVS, DCI-rates and the use of rescue therapy in a consecutive and unselected aSAH population 3.5 years BEFORE vs. 3.5 years AFTER STX-VCS became available. 

 

Methods:

436 consecutive aSAH patients admitted to our center in a 7-year period (04/2012 – 04/2019) were included in this study. STX-VCS was available in the second half and 57 of 214 patients (27%) were selected for STX-VCS. DCI was assessed by blinded rating board (neuroradiologist / neurologist / neurosurgeon). 6-months modified Rankin Score (mRS) was assessed by an external and blinded neurologist. Use of induced hypertension (iHTN) and endovascular rescue therapy was assessed. 

 

Results:

118 (53%) patients BEFORE and 139 (65%) patients AFTER (RR 0.79, 95% CI: 0.66–0.95) reached functional independence (mRS 0-3) at 6 months. 40 (18.0%) patients BEFORE and 17 (7.9%) patients AFTER (RR 0.68, 95% CI: 0.57 – 0.86) incurred DCI. Total DCI load was 8933 ml (100%) and 3329 ml (36%), respectively. Induced hypertension was applied in 97 (44%) and 30 (15%) patients, respectively (RR 0.55, 95% CI: 0.46 – 0.65). Endovascular rescue therapy was used in thirty (13.5%) patients BEFORE vs. five (2.3%) patients AFTER (RR 0.17, 95% CI: 0.07 – 0.42). Stereotactic procedures resulted in one (2%) subdural hematoma.

Conclusion: 

Implementation of STX-VCS reduced the DCI incidence and DCI burden by ca. 60% in a consecutive aSAH patient population. This was associated with an improvement in neurological outcome. 

 


Peter C. REINACHER (Freiburg, Germany), Jan Hendrik SCHAEFER, Christian SCHEIWE, Karl EGGER, Wolf-Dirk NIESEN, Jürgen BECK, Volker Arnd COENEN, Roland ROELZ
00:00 - 00:00 #24086 - What do physicians and medical students know about deep brain stimulation? Results from the Swiss DBSurvey.
What do physicians and medical students know about deep brain stimulation? Results from the Swiss DBSurvey.

Aims 

Deep brain stimulation (DBS) has become a worldwide accepted neurosurgical therapeutic option for a multitude of neurological and psychiatric disorders. Nevertheless, many more patients could be potentially considered as candidates for DBS. This raises the important question, if clinicians are too uninformed or reserved regarding DBS and if so, what are the underlying reasons. Therefore, the Swiss physicians and medical students current state of knowledge of, experience with and expectations from DBS was evaluated.

 

Methods 

Based on a Swiss tertiary hospital referral registry, a comprehensive and systematic nationwide online survey among referring physicians including general practitioners (GP), neurologists and psychiatrists as well as among students of all medical schools in Switzerland was conducted. All survey web forms consisted of both multiple choice and open questions and were available in German, French and Italian language. 

 

Results 

Data from 401 survey responses were analyzed (GP n = 201, neurologists n = 56, psychiatrists n = 79, others n = 65). General knowledge regarding DBS principles was high (“good knowledge” n = 140, “heard of it” n = 228, “never heard of it” n = 32) with mainly positive (34%) and only few negative (4%) experiences reported. The risk of permanent neurological deficit (6% ± 9%), surgical site infection (6% ± 8%) or hemorrhage (6% ± 7%) associated with DBS was estimated as significantly increased. Motor symptoms relief caused by stimulation was expected to be 20-80%, whereas non-motor symptoms were presumed as responding not sufficiently by the majority of survey participants (90% and 49%, respectively). Parkinson’s disease and tremor were considered as validated indications by most respondents (79% and 55%, respectively) with up to 40% of patients being estimated as possible candidates for surgery. For epilepsy patients, most physicians preferred DBS when compared to classic lesionectomy (n = 209 vs. n = 71, “don’t know” n = 109). 

 

Conclusions 

For the vast majority of physicians and doctors-to-be in Switzerland, the present survey revealed a gratifying good basic knowledge of DBS and its potential, mainly positive acceptance of this neurosurgical treatment option and relatively realistic expectancies regarding results, response rates and associated risks of DBS therapy. 


Philipp KRAUSS (Munich, Germany), Pierre SCHEFFLER, Lennart H. STIEGLITZ, Christian R. BAUMANN, Luca REGLI, Markus F. OERTEL
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00:00 - 00:00 #26125 - An unusual case of lead migration in occipital nerve stimulation: A case report and literature review.
An unusual case of lead migration in occipital nerve stimulation: A case report and literature review.

Background: Occipital neuralgia is described as a paroxysmal shooting or stabbing unilateral pain in the greater, lesser, or third occipital nerve dermatome. Initial treatment includes occipital nerve block and pharmacological therapy. In the management of refractory occipital neuralgia, radiofrequency rhizotomy and occipital nerve stimulation (ONS) are therapeutic options, being ONS a more invasive procedure. An ONS system includes a lead, an internal pulse generator (IPG), and the lead extension. The lead extension connects the lead, in the occipital region, to the IPG, in the infraclavicular region. Since this is a pathway with high mobility, we produce a stress relief loop with the lead extension so that the lead does not migrate due to higher tension during flexion or extension of the head. Lead migration is a complication often associated with ONS. We present a rare case in which fibrosis in the stress relief loop caused lead migration in the treatment of occipital neuralgia.

Case Description: A 30-year-old woman with a 5-year history of refractory occipital neuralgia, who had been under ONS therapy for 2 months, presented with a sudden onset of typical occipital neuralgia pain associated with cervical muscles spasms and myoclonus. A skull radiography showed lead migration. The patient underwent surgery for lead repositioning. During surgery, we identified extensive fibrosis throughout the stress relief loop that produced several constriction points. The fibrosis in the stress relief loop increased tension on the lead during head-and-neck movement, causing progressive migration of the lead.

Discussion: In this case report, extensive fibrosis constricted the stress relief loop. Therefore, the loop was not able to relief tension during movement of the head and neck, which resulted in lead tension, traction, and migration. The most common complications associated with ONS are lead migration, skin erosion, infection, lead fracture, and lead disconnection. Lead migration is a complication often reported in ONS, but most authors have not identified or informed a clear cause for migration. When a presumptive cause was identified, it included a defect in the lead anchor, iatrogenic lead migration during IPG implantation, and repeated extension traction due to high mobility in the implanted area. The association of fibrosis and lead migration has not, to the best of our knowledge, been reported before in literature.

Conclusion: Although lead migration is a common complication of ONS, its association with fibrosis in the stress relief loop has not, to the best of our knowledge, been reported before. Lead migration can directly affect treatment outcome and it is, therefore, important to fully understand the possible mechanisms that can cause it and how to promptly manage them.


Rafael CAIADO VENCIO (Goiânia, Brazil), Paulo Eduardo ALBUQUERQUE ZITO RAFFA, André COSTA CORRAL PONCE, Bruno PRICOLI MALAMUD, César COZAR PACHECO, Paulo Roberto FRANCESCHINI, Roger THOMAZ ROTTA MEDEIROS, Paulo Henrique PIRES DE AGUIAR
00:00 - 00:00 #23892 - Analgesic effect of paddle type SCS was the most prominent in ongoing pain and pain duration.
Analgesic effect of paddle type SCS was the most prominent in ongoing pain and pain duration.

Introduction:

SCS is considered as one of the best option to treat medically intractable neuropathic pain. Detailed components of neuropathic pain were not recognized as a principal value to measure outcomes of SCS. Purpose of our study was to evaluate effect of paddle-type SCS on each components of neuropathic pain.

Methods:

Between April 2014 and July 2019, medical records of consecutive 18 patients who underwent operation of spinal cord stimulation (SCS) were retrospectively investigated. Neuropathic pain can be segregated into five components of neuropathic pain, which are “superficial pain”, “deep pain”, “paroxysmal pain”, “evoked pain” and “dysaesthesia”. To quantify degrees of pain suffered by patients, the neuropathic pain symptom inventory (NPI) developed by Bouhassira et al. was used. 

Results:

At the last follow-up, the NPI total score was improved significantly (42% ± 35%) compared to the baseline, which were scored 63, and 34 at the baseline, and the last follow-up, respectively (P = 0.0002, pared t-test). For each components of the NPI, statistically significant improvement was observed in the pain time (45% improvement, P = 0.0002) and deep pain scores (58% improvement, P = 0.001). Even though the P-value was not enough for statistical significance, improvement rates of the other pain scores showed clear improvement tendency after implantation of SCS. The improvement of the NPI score after implantation of SCS was accompanied by marked reduction of demand of opioid intake. While the preoperative dosage of MME was 104mg ± 85mg per a day in average, it was down to 54mg ± 64mg per a day at the last follow-up evaluation after SCS.

Conclusion:

SCS is effective treatment modality that improves the duration of pain and the degree of ongoing pain, accompanied by a reduction in opioid use. That reflects that SCS impacts on the entire central nervous system encompassing the spinal cord and the brain. The only difference between patients with favorable and unfavorable results was the absence or presence of delayed loss of analgesic effects of SCS, respectively. 

 


Moonyoung CHUNG (Bucheon, Korea), Ryoong HUH
00:00 - 00:00 #24024 - Bilateral stereotactic anterior cingulotomy for intractable pain caused thalamic glioma.
Bilateral stereotactic anterior cingulotomy for intractable pain caused thalamic glioma.

Introduction

Anterior cingulotomy is effective in the treatment of chronic medically refractory pain. In spite of the superiority of neuromodulation technology, ablative interventions play a significant role in functional neurosurgery. Application of stereotactic lesioning remains important in the treatment of refractory pain in view of economical, geographical and some other reasons. The purpose of case report is to demonstrate the effectiveness of management of thalamic glioma which clinically presents unilateral incredible pain syndrome.

Material and methods

We present the case of 38 year old male who had a lesion in right thalamic and had been suffering for five months of incredible pain and paresthesia in contralateral limbs and trunk. For that period patient used different medications, which include nonsteroidal anti-inflammatory drugs, corticosteroids, antidepressants, antiepileptic drugs and opioids which induced severe allergic dermatitis.

Bilateral anterior stereotactic cingulotomy and stereotactic biopsy of thalamic lesion were performed simultaneously at one surgery. Stereotactic biopsy revealed diffuse astrocytoma (WHO grade II, ICD-O 9400/3), IDH1-wildtype. Three weeks later stereotactic radiosurgery for glioma was performed.

Results

Pain syndrome regressed immediately after anterior cingulotomy and completely abolished on third day after surgery. One and half year follow-up conformed mild volume reduction of glioma, any signs of pain syndrome, mild regression of paresthesia and  abolishing of drug-induced dermatitis. 

Discussion

Anterior cingulotomy is well established as a target for the treatment of patients suffering from  refractory pain. Pain results from lesion of thalamic is well known, such pain can be refractory both to drugs and to non-medical therapies. Surgical stereotactic  ablative treatment of incredible pain with simultaneous histologic verification of lesion and subsequent treatment allow effectively control the pain. Additional radiosurgical treatment of low-grade thalamic glioma may alleviate the pain. Stereotactic lesioning is effective and safe intervention, which allows to reach long-term positive effect and can be renovated in different fields of functional neurosurgery. 


Kostiantyn KOSTIUK (KYIV, Ukraine), Yuri MEDVEDEV, Andriy POPOV, Valerii CHEBURAKHIN, Maxim SHEVELOV, Sergii DICHKO
00:00 - 00:00 #26108 - Connectivity based thalamus parcellation and surgical targeting of somatosensory subnuclei.
Connectivity based thalamus parcellation and surgical targeting of somatosensory subnuclei.

Objective

Anatomy of the posterolateral thalamus varies substantially between individuals, presenting a challenge for surgical targeting. Patient specific, connectivity-based parcellation of the thalamus may effectively approximate the ventrocaudal nucleus (Vc). This remains to be robustly validated or assessed as a method to guide surgical targeting. We assess the validity of connectivity-based parcellation for targeting Vc, and its potential for improving clinical outcomes in pain surgery.

Methods

A cohort of nineteen patients with regional, chronic neuropathic pain underwent pre-operative structural and diffusion MRI, then progressed to deep brain stimulation (DBS) targeting the Vc based on traditional atlas coordinates. Retrospectively, surgical thalami were segmented then parcellated based on tractography estimates of thalamo-cortical connectivity. The location of each patient’s electrode array was analysed with respect to their somatosensory (S1) parcel, and compared across patients with reference to the thalamic homunculus. 

Results

Ten patients achieved long-term pain relief. An average-array was 61% located in the S1 parcel (Q1-Q3: 42-74%). In patients who achieved long-term benefit from surgery, array location in the individually generated S1 parcels was medial for face pain, centro-medial for arm pain, and centro-lateral for leg pain. Patients who did not benefit from surgery did not follow this pattern. Standard stereotactic coordinates of electrode locations diverged from this pattern.

Conclusions

Connectivity-based parcellation of the thalamus appears to be a reliable method for segmenting Vc. Identifying the Vc in this way, and targeting medio-laterally as appropriate for the region of pain, merits exploration in an effort to increase the yield of successful surgeries.


Ashley RAGHU (Atlanta, USA), Sean MARTIN, Tariq PARKER, Tipu AZIZ, Alex GREEN
00:00 - 00:00 #26073 - Convenience, usability and complications of rechargeable extracorporeal pulse generators for wireless spinal cord stimulation: A questionnaire-based, patient-centric study.
Convenience, usability and complications of rechargeable extracorporeal pulse generators for wireless spinal cord stimulation: A questionnaire-based, patient-centric study.

Introduction: Spinal cord stimulation (SCS) has been utilized for more than 50 years to treat refractory neuropathic pain. Currently, SCS systems with fully implantable pulse generators (IPGs) represent the standard. New wireless extracorporeal SCS (wSCS) devices without IPGs promise higher levels of comfort and convenience for patients. However, to date there are no studies on how charging and using this wSCS system affects patients and their therapy. This study is the first questionnaire-based survey on this topic focusing on patient experience.

Material& Methods: Standardized questionnaires were sent to all patients with a wSCS device in use at the time of trial. The primary endpoint was the convenience of the charging and wearing process scored on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints included time needed for charging, the duration of stimulation per day and complication rates.

Results:  Questionnaires of 6 patients were returned and eligible for data analysis. The mean age of patients was 61.3 ± 6.7 (± SD) years. The length of therapy was 20.3 ± 15.9 months (mean ± SD). The duration of stimulation was 17 ± 5.9 hours (mean ± SD) per day. N=5 patients rated the overall convenience as "easy" (4) and evaluated the effort of the charging process and wearing of the wSCS device as "low" (4). N=5 patients considered the wearing and charging process as an active participation in therapy. None of the patients were concerned about forgetting to charge the device. N=5patients would again opt for an extracorporeal device instead of the conventional SCS system. Early or late surgical complications did not occur.

Conclusion: Overall, patients felt confident using extracorporeal wireless SCS devices without any complications. Effort to maintain therapy with this system was rated as low. The results of this pilot study need to be verified with a larger cohort in a prospective trial.


Mohammad Mehdi HAJIABADI (Heidelberg, Germany), Martin JAKOBS, Andreas UNTERBERG, Rezvan AHMADI
00:00 - 00:00 #23787 - Dorsal column and dorsal horn high-frequency stimulation as a rescue therapy in patients with chronic non-cancer pain refractory to chronic conventional SCS.
Dorsal column and dorsal horn high-frequency stimulation as a rescue therapy in patients with chronic non-cancer pain refractory to chronic conventional SCS.

Introduction

Spinal cord stimulation (SCS) has shown to be an efficacious therapy in various pain conditions, improving the quality of life and reducing medication on the long term. However, a loss of efficacy exists after months or years in a certain part of the patient population. Ultimately, SCS-systems may be explanted in refractory cases where multiple new programming sessions show unsatisfactory results. We aimed to investigate the efficacy of new stimulation paradigms in patients who initially benefited from conventional SCS and lost the effect after months/years of stimulation.

 

Methods

Patients presenting with refractory low back and/or leg pain after chronic failure of SCS therapy were included in this study. In the context of a rescue-therapy, patients underwent an externalization of the implanted SCS leads in order to be stationary tested with multiple combination stimulation paradigms, and eventually implanted with new generators. Pain intensity was analyzed using the numeric rating scale (NRS) (from 0-10 points; 0= no pain, 10= worst pain). Data were collected prior to externalization and at variable follow-ups after reimplantation.

 

Results

Thirty-seven patients (18 females and 19 males) with refractory pain after receiving chronic conventional SCS stimulation for months/years underwent externalization of the already implanted intraspinal leads. Surgical indications for SCS included failed-back surgery syndrome, degenerative spine changes, posttraumatic, CRPS II, tethered cord syndrome, pelvic pain syndrome and diabetic polyneuropathy. Mean preoperative NRS score was 8.1/10 points (SD±0.9) for the ON stimulation period. Patients received a combination of either tonic, burst and 1.2kHz high frequency (HF) stimulation (n=22), or burst and 1.2kHz HF stimulation (n=9), dorsal horn HF stimulation (n=3), or 1.2kHz HF stimulation and dorsal horn HF stimulation (n=2), or 1.2kHz HF stimulation alone (n=1) after the procedure. The mean postoperative NRS score after the testing phase with the new stimulation paradigms was 3.8/10 points (SD±2.5), showing a mean significant reduction of 48.0% (p<0.001). In total, 29 patients reported a significant reduction above 50% on the NRS scores and therefore were reimplanted with new generators that had the capacity to deliver the new paradigms (1.2kHz HF stimulation and dorsal horn HF stimulation). The remaining 8 patients underwent full explantation of the SCS-systems after failing the test phase, despite being tested with all possible combinations of waveforms. The indication diagnoses for SCS among responders and non-responders showed no specific differences between both groups. The patients who continued with the new SCS paradigms (n=29) reported mean NRS scores of 3.5/10 points (SD±1.7) 12 months after the surgery, still showing a significant reduction of 43.3% when compared to preoperative scores (p<0.001). Preoperatively, patients were programmed in 91% of the cases with only one waveform, while after the surgical procedure patients reported a better clinical outcome in 89% of the cases with a combination of multiple waveforms. No significant differences in the NRS scores were found between 1.2kHz HF stimulation and dorsal horn HF stimulation in any set of combinations (p>0.05). However, in 86.2% of the cases, the patients preferred a program that included a combination of waveforms that incorporated 1.2kHz HF stimulation. No major complications were documented during the follow-up.

 

Conclusion

Rescue therapy with combination of multiple waveforms including dorsal column tonic, burst, 1.2kHz HF stimulation and dorsal horn HF stimulation was associated with a significant successful rate in patients with failed conventional chronic SCS. This approach can be viewed as a safe and alternative method before considering explantation of the SCS system.


Pablo ANDRADE (Cologne, Germany), Petra HEIDEN, Veerle VISSER-VANDEWALLE, Georgios MATIS
00:00 - 00:00 #26118 - Dorsal root entry zone lesioning for medically refractory pain.
Dorsal root entry zone lesioning for medically refractory pain.

Backgorund: Dorsal root entry zone (DREZ) lesioning (DREZ-otomy) can be considered an effective treatment for medically refractory chronic pain due to spinal cord injuries, brachial and lumbosacral plexus injuries, postherpetic neuralgia, spasticity, and other conditions. The selective destruction of the afferent pain fibers located in the dorsal region of the spinal cord is the basis of this technique. 

Objective: To evaluate the effectiveness of DREZ-otomy for multiple chronic pain etiologies.

Methods: PubMed, MEDLINE and LILACS databases were used as bases for this systematic review. Twenty-three publications were selected, totalizing 1,099 patients. The results were organized in a table for a systematic analysis.

Results: Satisfactory pain control was observed in 70.1% of cases, with variations depending on the technique and pain etiology. Brachial/lumbosacral plexus injuries was the group related to the best results in the post-operative period (effective pain control in 70.8% of patients), while trigeminal pain had the worst results (effectiveness varied between 40 to 67%). For cervical DREZ-lesions, the highest percentage of good or excellent pain relief was found in cancer pain, hyperspastic states and cervical root avulsion. As for conus medullaris DREZ-lesion, plexus injuries, spinal cord injury, peripheral nerve injury and hyperspastic states had the best results. Nucleus caudalis DREZ-lesion was the technique with a fewer number of patients (n= 41) and all of them underwent surgery due to facial pain. The median percentage of good or excellent pain relief was 60% (range: 40-73%).

Conclusion: DREZ-otomy can be considered a great alternative for the treatment of chronic pain, especially in patients who do not tolerate the side effects of the medications used in the clinical management or have refractory pain.


Giovanna GALAFASSI, Paulo Henrique PIRES DE AGUIAR (São Paulo, Brazil), André AKIRA TAKAHASHI, Jorge Roberto PAGURA
00:00 - 00:00 #23923 - Examining the need for routine intensive care unit admission after microvascular decompression.
Examining the need for routine intensive care unit admission after microvascular decompression.

Background: Routine postoperative admission to a neurocritical intensive care unit (NICU) after craniotomy for close monitoring is a common practice in neurosurgery. In this study we retrospectively analyzed our data to determine if there is a real need of NICU admission after microvascular decompression (MVD) or whether it may be abandoned.

Methods: A series of 221 MVD surgeries for trigeminal neuralgia (198), hemifacial spasm (17), vagoglossopharyngeal neuralgia (2), paroxysmal vertigo (2), and pulsatile tinnitus (2) operated by the senior surgeon (JKK) between 2005 and March 2020 were included in this study. The pre- and postoperative medical records were retrospectively analyzed. 

Results: 101 patients (46%) were admitted to NICU postoperatively (patient group 1) whereas 120 patients (54%) returned to ward after the stay in post anesthesia care unit (PACU) (patient group 2). Mean stay in NICU was 23,03 hours (range 2- 111 hours). There was no statistically significant difference in ASA scores, cardiac and pulmonary comorbidities (congestive heart failure, previous MI, COPD, pulmonary embolism), arterial hypertension, diabetes mellitus in both groups. 134 patients (61%) had central venous catheter for the surgery and 4 of them (3%) had pneumothorax secondary to central venous catheter insertion. All 4 patients were admitted to NICU and there was no morbidity related to pneumothorax. One patient with vagoglossopharyngeal neuralgia had postoperative dysphagia, dysphonia and vagus nerve palsy. 

Conclusion: Considering our data, we conclude that routine admission to NICU after uneventful MVD may not be useful. Preoperative careful patient selection would be helpful to decide which patients would benefit from ICU stay and close clinical observation could be sufficient to predict early postoperative complications.


Gökce HATIPOGLU MAJERNIK (Hannover, Germany), Shadi AL-AFIF, Hans E. HEISSLER, Oday ATALLAH, Joachim K. KRAUSS
00:00 - 00:00 #23959 - High frequency sulcomyelotomy (DREZ) in patients with pre - and postganglionic lesion of the spinal cord.
High frequency sulcomyelotomy (DREZ) in patients with pre - and postganglionic lesion of the spinal cord.

High frequency sulcomyelotomy (DREZ) was performed for 42 patients with severe neurogenic pain syndrome, including 24 patients with preganglionic lesions of the spinal cord after brachial plexus injury (avulse roots) and 18 patients with a postganglionic lesion of the spinal cord (postmastectomy pain syndrome). Diagnostic algorithm of examination of patients with severe neurogenic pain syndrome consists of pain assessment at the pain card, short McGill pain questionnaire (MPQ) and visual analogue scale (VAS); depression and anxiety patients were evaluated by Hamilton Rating Scale for Depression  (HRSD), Hamilton Anxiety Rating Scale (HAMA), Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). Additional diagnostic methods  which were also carried out for all patients included x-rays of the cervical spine, MRI cervical spine, ultrasound, ENMG of the brachial plexus.

Observed higher efficacy of surgery in patients with preganglionic lesions of the spinal cord. In our study on a percentage scale, good results immediately after microsurgical operations DREZ coagulation was 100%, in the long term a good result operations were preserved in 91.66% of patients with preganglionic lesions and in 77.77% of patients with postganglionic lesions. In order to evaluate the efficiency of surgery and reduce postoperative complications the need to use intraoperative monitoring of spinal motor and sensory functions noted. The main postoperative complications were temporary in nature, were expressed in violation of proprioceptive sensibility and slight paresis in the ipsilateral limbs.


Oleg DREVAL, Alexey KUZNETSOV, Kristina LYUBIMAYA (Moscow, Russia)
00:00 - 00:00 #25757 - High-cervical spinal cord stimulation and idiopathic trigeminal neuralgia/neuropathy.
High-cervical spinal cord stimulation and idiopathic trigeminal neuralgia/neuropathy.

Introduction

Trigeminal neuralgia (TN) is characterized by brief touch-evoked or spontaneous shock-like paroxysmal pain attacks in one or more divisions of the trigeminal nerve unilaterally. TN is mostly of idiopathic origin, with several theories to explain it presumed mechanism, but also several other causes (such as multiple sclerosis, nerve-vessel-contact) are known.

 There is a large variability in the medical and surgical treatment of idiopathic TN. The role of spinal cord stimulation (SCS) in the management of facial pain involving the cervicomedullary junction (CMJ) remains not fully evaluated. The treatment of facial pain syndromes, especially the TN, is still challenging.

 

Case report

We report a 78-year-old male patient with combined idiopathic trigeminal attacks and neuropathic pain on the right side of his face in the first and second branch of the TN for more than thirty years, treated with different modalities, medical as well as surgical. Ten years ago, he underwent a surgical procedure for peripheral nerve-field-stimulation (PNFS) with two leads (upper and lower orbital margins) in our department, which clearly reduction of the neuropathic pain components. Despite this therapy, he still complained of neuralgic attacks up to ten times per day, persisting for ten to thirty seconds. Medical therapy and interventional treatments (e.g. radiofrequency therapy of the gasseric ganglion, glycerine rhizolysis) did not help on a long-term basis. A high-cervical spinal cord lead at C1 level was implanted followed by a subperceptional stimulation with 1,000 Hz. The patient reported a significant reduction of the attacks to two times per day maximum, at three months follow-up.

Discussion and Conclusion

With placement of the SCS-lead in the high-cervical area or at the CMJ, various pain conditions such as post herpetic neuralgia, trigeminal pain and chronic regional pain syndrome can be treated. There are just a few case-reports on persisting trigeminal neuralgic attacks and neuropathic facial pain treated with SCS. This case-report shows that a positive effect of high cervical stimulation on the neuralgic attacks can be obtained. We need more data and studies to confirm our results.


Enes GÜNDÜZ (Cologne, Germany), Veerle VISSER-VANDEWALLE, Georgios MATIS
00:00 - 00:00 #23970 - Invasive neuromodulation in facial pain syndromes.
Invasive neuromodulation in facial pain syndromes.

Refractory facial pain is one of the difficult pain syndromes, even this pain is caused by organic reasons, including neuropathic pain. Surgical neuromodulation can be used in patient with neuropathic facial pain but level of evidence is very low. One of the most important problem among facial pain syndromes is central neurogenic pain, i. e. anesthesia dolorosa occurring after trigeminal neuralgia surgical treatment. In the literature, authors offer to use different methods: central analgesic drugs,  botulinotherapy, non-invasive  and invasive neuromodulation methods. But in real time, there are no guidelines to choose method of treatment in different clinical cases. 

In our retrospective series we analyze treatment result in 29 patients with trigeminal neuropathy of various etiologies. Among 29 patients, in 7 cases pain syndrome were caused by invasive procedures for trigeminal neuralgia treatment, in 20 case pain syndrome were caused by dental treatment and in 2 case pain syndrome were caused by postherpetic neuralgia.

In 23 cases we implanted the electrodes in trigeminal nerve branches only, in two cases we implanted additional electrode in  trigeminal innervation area (PFNS, Peripheral Nerve Field Stimulation), in patient with trigeminal neuropathy and occipital neuropathy additional electrode were implanted in occipital nerve. Motor cortex stimulation were provided in 3 cases and in one of them this procedure were provided after ineffective PNS trial. The average baseline VAS score was 8,3 ± 0,8 points and decreased to – 2,3  ± 0,8 points in follow-up (p< 0,05). Median analgesic dosage were reduced in all patients. Median dose reduction was 1,8. In three patients system was removed after some years  due to achieve a maximal analgesic result.

Invasive neuromodulation may be an effective method in the management of neuropathic facial pain syndromes but it requires careful patient selection

 


Emil ISAGULYAN (Moscow, Russia), Eugeny DOROCHOV, Alexey TOMSKY, Elisaveta MACKASCHOVA, Valentina MIKHAILOVA
00:00 - 00:00 #26074 - Manageability, compatibility and complications of rechargeable internal pulse generators for spinal cord stimulation: A single-center Pain Recharge Trial.
Manageability, compatibility and complications of rechargeable internal pulse generators for spinal cord stimulation: A single-center Pain Recharge Trial.

Introduction: The non-rechargeable pulse generators for spinal cord stimulation (SCS) therapy provide a battery durability between 2 and 5 years. Since 2004, the rechargeable internal generators (r-IPGs) are implanted and offer a longer service life of up to 25 years. Long-term data on the effects of recharging in chronic pain patients are limited. The aim of the study was to project the convenience and acceptance of r- IPGs and their effect on patients. This is the first patient-focused industry-independent study on rechargeable neurostimulators for pain therapy.

Material & Methods: Standardized questionnaires were sent to all chronic pain patients using a r-IPG device at the time of trial. The primary endpoint was the overall handling and effort of charging process scored on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints were charge burden (time spent per week on recharging), user confidence and complication rates. Endpoints were analyzed for several subgroups.

Results: Data sets of 40 chronic pain patients (42% of sent questionnaires) were returned and eligible for data analysis. The average age of patients was 57.2 ± 12.6 (± SD) years. The length of therapy with r-IPG was 52.1± 32.6 months (mean ± SD). The mean duration of stimulation was 21.1 hours each day. The overall handling of recharging was evaluated as "easy" (4) and the overall effort as "low" (4). The mean charge burden was 112.7 ± 139 min/wk (mean ± SD); 92% of the patients felt confident recharging the neurostimulator. Failed recharges were reported in 37.5% of patients, and 28.9% of patients experienced a disruption of stimulation. All patients (100%) checked and recharged the stimulator themselves. Subgroup analysis did only show a significant impact on overall handling and effort for different type of stimulators (p<0.05). 

Conclusion: Overall, patients felt confident using r-IPG device. Effort to maintain therapy with this system was rated as low. However, the high rate of problems with recharging or interruption of stimulation shows the need for improvement.


Martin JAKOBS (Heidelberg, Germany), Mohammad Mehdi HAJIABADI, Andreas UNTERBERG, Rezvan AHMADI
00:00 - 00:00 #23991 - Microsurgical DREZotomy for Brachial Plexus Injury (video Presentation).
Microsurgical DREZotomy for Brachial Plexus Injury (video Presentation).

A vast majority of patients of brachial plexus injury suffer from refractory neuropathic pain1-6 often described as paroxysmal electric like attaks of pain.

In these patients, spinal cord neurons are disconnected from primary neurons in the dorsal ganglions,. Further, avulsion leads to scarring and gliosis at the surface of the spinal cord and in the superficial layers of the dorsal horn. Generally neurons of the deeper layers of the dorsal horn remain intact and therefore presumably, axons of the second-order neurons of the pain pathways remain functional. These neurons, however, are disconnected both from their primary afferents and from inhibitory inputs of the dorsal columns and they are engulfed by gliosis and scarring at the microscopic level. In this context, local changes in the neuromedaitors of the intercellular space occur and these neurons may become irritable and exhibit hyperactive behavior. Indeed it has been shown microelectrode recordings (in both animal and human models) have demonstrated spontaneous paroxysmal firings of these deafferented second-order neurons.5 It is thought that these discharges relate to the shooting pain attacks often expirieced by BPA patients.

In cases of brachial plexus avulsion, DREZotomy aims to destroy, by a microsurgical technique, these second-order hyperactive neurons (of the spinothalamic tract), thus destroying the pain generators.

Surgical lesion of the dorsal root entry zone (DREZ) was firstly performed in 1972 for the treatment of pain related to brachial plexus lesions. Today, deafferentation pain related to brachial plexus avulsion is its main indicationwhetehr at the cervical level in cases of BPA or more rarely at the lumbosacral levels. Microsurgical approach to the DREZ and lesioning under direct visual control is one of the techniques to perform this surgery, allowing, in our opinion, optimal control and best results.

This presentation illustrates the technique for microsurgical DREZotomy11, 12 and reviews the corresponding literature for an evidence based approach to the design of surgical technique. Point by point all technical elements of the surgery are discussed and compared to the alternatives and the evidence base is evaluated to sustain this type of approach. PRISMA review guidelines were applied to ascertain the relevant literature on all essential elements of open microsurgical DREZ lesioning for BPA related pain. The elements discussed are: design of the surgery, approach, electrophysiological monitoring, dissection of the dorsolateral sulcus, how to perform the lesioning itself and closure. Results and complications are also discussed from a PRISMA review point of view for this specific indication in order to give a full picture of the evidence base for this type of surgery.

 



Andrei BRINZEU (Lyon), Corentin DAULEAC, Patrick MERTENS, Marc SINDOU
00:00 - 00:00 #23988 - Microsurgical DREZotomy for cancer pain (video presentation).
Microsurgical DREZotomy for cancer pain (video presentation).

Cancer is one of the principal causes of death in western society. However, advances in diagnosis and therapy have greatly prolonged the survival of cancer patients in the past decades. Complete cure form most cancers is however still unavailable and for the most part the consequences of the tumours in the body as well as the therapies aimed at eliminating them are a fact in the day to day life of oncology patients. More than 50% of cancer victims will suffer therefore from chronic pain in 20% of them this pain being intractable. Reliance on classical therapies including oral and intravenous opioids greatly impacts the quality of life of patients with cancer in some instances even contributing to early death.

Dorsal Root Entry Zone (DREZ) is an entity including the central portion of the dorsal rootlet, the medial part of the tract of Lissauer and layers I to V of dorsal horn. The first surgical DREZ lesion was performed in Lyon in 1972 to treat pain due to thoracic apex tumor; then it was applied to treat neuropathic pain related to spinal cord injury, amputation, brachial plexus avulsion.

Presently, lesional neurosurgical treatments of cancer pain are worth gaining greater interest due to elements described above: cancer patients have a longer life expectancy and pain is often present for a longer time; medical treatment is sometimes insufficient and associated with deleterious side effects. Intrathecal delivery of antalgic drugs may be even more expensive, more complex (in certain socio-economical contexts) and less efficient than lesional surgery.

Indications for DREZotomy in cancer pain are limited: refractory invalidating topographically-limited pain caused by a well localized lesion, in a patient able to undergo a surgical procedure and with a relatively long life expectancy (>6 months).

DREZ lesioning for the control of pain related to cancer has peculiarities related both to technical aspects but also to patient selection and surgical strategy. Results depend on both the neurological status of the patient as well as the type and extent of cancer.

In this presentation we discuss the full technical aspects of DREZ lesioning both at the cervical and lumbo-sacral levels with an extensive review of the literature to provide evidence based recommendations for the entire gesture. Results and complications of the published series of DREZ lesions for the control of cancer pain are also reviewed extensively.

 


Andrei BRINZEU (Lyon), Patrick MERTENS, Marc SINDOU, Manon DURAFFOURG
00:00 - 00:00 #23921 - Microsurgical re-decompression for recurrent trigeminal neuralgia after previous microvascular decompression.
Microsurgical re-decompression for recurrent trigeminal neuralgia after previous microvascular decompression.

Objective: Microvascular decompression (MVD) is a well-accepted treatment modality for trigeminal neuralgia (TN). The initial success rate is high, however, in a subset of patients TN might recur in the long-term. Recurrent TN after MVD might be due to several causes and treatment algorithms remain unclear. Here, we present the surgical findings and clinical outcome of patients with recurrent TN after MVD who underwent microsurgical re-decompression.

 

Methods: Twenty-seven patients with recurrent TN who underwent microsurgical re-decompression over a period of 10 years were analysed. There were 14 women (54%) and 13 men (46%) with a mean age of 60 years (range, 35-82 years). Patients with multiple sclerosis were excluded. All patients had magnetic resonance imaging before surgery. Microsurgical re-decompression included dissection of the previously inserted Teflon and of scar tissue avoiding any damage to the trigeminal nerve. In no case the trigeminal nerve was lesioned, “combed” or dissected. New Teflon felt was placed in case an offending artery was found. There was no operative morbidity or mortality. All patients were available for postoperative follow-up. The outcome of the repeat intervention was graded according to the Barrow Neurological Institute (BNI) Pain intensity score. Follow-up was analysed postoperatively at 3, 12 and 24 months and at long-term (mean 48.1 months). 

 

Results: Recurrent TN was associated with the following findings as identified intraoperatively: arachnoid adhesions/scar tissue at the trigeminal entry zone (23/27), deformation of the trigeminal nerve/Tefloma (14/27), new nerve/ vein contact (15/27), new nerve/artery contact with marked pulsations (1/27) and compression of the trigeminal nerve by the electrode in cavum Meckeli used for treatment of neuropathic pain (1/27). Most of the patients (23/27 patients) had a combination of findings. Early postoperative pain relief was achieved in all patients. 23 patients were available for 24- month follow-up or longer. Of these, 16/23 patients (69%) had complete pain relief (BNI I), 5/23 patients (22%) had pain relief but continued taking medication (BNI IIIa), and 2 patients (9%) had a BNI pain score of IV or V at 24- month follow-up or longer. Hypaesthesia secondary to microsurgical re-decompression occurred in 1/27 (3%) patients.

 

Conclusion:  Microsurgical re-decompression was highly successful for recurrent TN. There were no serious side effects and the frequency of postoperative hypaesthesia was low. We conclude that microsurgical re-decompression completely preserving the trigeminal nerve is a feasible and beneficial treatment option in this context. Manoeuvres such as dissecting or combing the trigeminal nerve may be avoided.


Gökce HATIPOGLU MAJERNIK (Hannover, Germany), Shadi AL-AFIF, Hans E. HEISSLER, Joachim K. KRAUSS
00:00 - 00:00 #26197 - Neurosurgical interventions for intractable oncological pain: a national survey.
Neurosurgical interventions for intractable oncological pain: a national survey.

INTRODUCTION: The incidence of cancer in France is estimated at 350,000 cases/year. Despite increased attention, pain prevalence in patients with cancer has not decreased over the last decades, and 10% to 40% of cancer patients still suffer from moderate to severe pain due to disease progression or secondary to various etiologic treatments. Neurosurgical ablative procedures have emerged in the 1940s to 1970s with great efficacy. Due to the development of promising analgesics drugs in the 1980s and 1990s, then neuromodulation techniques, the demand for ablative procedures has diminished, progressively leading to a lack of awareness by the pain specialists and oncologists. Concurrently, the implication of the French neurosurgical teams in this field has reduced over the years, eventually preventing knowledge transfer to the next generations of surgeons. As a consequence, despite optimal medical care, some patients still experience intractable pain, sometimes leading to deep sedation.

OBJECTIVE: We aimed at evaluating the current practice of the French neurosurgical teams in the management of cancer pain and more specifically concerning the neuroablative procedures.

METHODS: On behalf of the Cancer Commission of the French Society of Evaluation and Treatment of Pain, and with the collaboration of the French Society of Neurosurgery, we conducted a national survey. An online questionnaire was sent to all public and private French neurosurgical teams.

RESULTS: The survey was completed by 36 French neurosurgical teams across the country, mostly public university hospitals. Neuromodulation techniques with intrathecal pump and intracerebroventricular therapy were performed by 74.3% and 51.4%, respectively. Neurosurgical ablative techniques were performed by 25.7% of the teams for DREZotomy, 14.3% for cordotomy, 11.4% for mesencephalic tractotomy, and 5.7% for commissural myelotomy. Eight neurosurgical teams (22.9%) were not involved in the treatment of cancer pain either due to a lack of demand for these techniques and/or a lack of expertise. Patients were addressed either by the oncologists or pain specialists mostly during multidisciplinary coordination meetings (58.9%). Moreover, 60.6% of the neurosurgical teams reported a reduction of demand in the recent years and all the teams considered that these techniques were underused.

CONCLUSIONS: Management of cancer pain remains a public health priority. The prevalence of pain in patients with cancer has remained unchanged over the last decade despite increased understanding of cancer pain mechanisms and the development of new drugs. The implication of the neurosurgeons in the management of cancer pain has decreased in our country in the last decades and the demand for these highly effective and more specific techniques has shrunk. The place of neurosurgical ablative procedures has to be redefined and the transmission of these techniques to the next generations of surgeons defended.


Anne BALOSSIER (Marseille), Florence TIBERGHIEN, Claire SMALL-BERGEONNEAU, Bich DANG-VU, Karima MEZAIB, Sylvie ROSTAING, Naoufel OUERCHEFANI, Hayat BELAID
00:00 - 00:00 #23789 - Peripheral nerve field stimulation in the craniofacial region: a single center study.
Peripheral nerve field stimulation in the craniofacial region: a single center study.

Introduction

Peripheral nerve field stimulation (PNFS) emerged during the last decades as an effective treatment option for chronic pain refractory to conservative treatment. In contrast to other neuromodulation methods which stimulate the main nerve trunk, PNFS electrodes are placed subcutaneously to stimulate the small nervous endings in the region of the affected nerves. This method is particularly useful for targeting smaller and well-defined pain areas like the facial region. We aimed to report on the outcome of chronic PNFS in the craniofacial region for migraine, occipital neuralgia, atypical facial pain, atypical trigeminal neuralgia or trigeminal neuropathy.

 

Methods

We retrospectively analysed the records of patients who underwent subcutaneous implantation of electrodes during the last two years (January 2018 until December 2019) in the craniofacial area at our clinic. The reduction of pain through stimulation was measured with the numeric rating scale (NRS) (from 0-10 points; 0= no pain, 10= worst pain) preoperatively and postoperatively at different time-points.

 

Results

Eleven patients were included in this study. Patients had a mean age of 63.6 years (range 44-75) at the time of the implantation. One patient was diagnosed with chronic migraine, one patient with occipital neuralgia, three patients with atypical facial pain, four patients with atypical trigeminal neuralgia and two with trigeminal neuropathy. The preoperative mean pain intensity using the NRS was 8.0/10 points (SD±0.77), one week after the procedure was 2.8/10 points (SD±3.03) and at maximum follow-up (mean 9.33 months SD±4.88) was 5.0/10 points (SD±2.98). A significant pain reduction was documented in both time periods, one week after the procedure (p<0.001) and at maximum follow-up (p<0.01), compared to preoperative scores. Electrodes were explanted within the first month after surgery in two patients who did not significantly benefit from PNFS. One electrode in one patient was explanted after 7 months of stimulation due to a local infection. No further complications were documented.

 

Conclusion

PNFS is an effective and safe alternative for patients with chronic pain in the craniofacial area refractory to conservative therapy methods.


Petra HEIDEN, Petros IOANNU, Veatriki VENETI, Veerle VISSER-VANDEWALLE, Georgios MATIS, Pablo ANDRADE (Cologne, Germany)
00:00 - 00:00 #26294 - Progressive and late onset lifethreatning adverse effect of spinal cord stimulation for chronic pain treatment.
Progressive and late onset lifethreatning adverse effect of spinal cord stimulation for chronic pain treatment.

Introduction:

Spinal cord stimulation(SCS) is a recognized effective therapy in refractary chronic pain management. The reported incidence of complications varies from 30-40%. Reports about side-effects caused by SCS are rare and mostly encompass early functional and reversible block of parasympathetic outflow. The authors describe a not yet reported progressive, late onset, reversible and potentially lifethreatning side-effect of SCS.

Case Report:

48-year-old woman, with failed-back surgery syndrome was submitted to dorsal epidural placement of a surgical 16-contact plate electrode in D8-D9 level and a recharchable IPG(Intellis,Medtronic(R)). The best effect on pain (NRS-0) was attained with ciclic programming(+1,-5 active contacts, pulse width-300μs, frequency-60Hz, amplitude-3,5mA). At 8-9 weeks post-op, a reversible and dependent on stimulation(RDS) high frequency right lower limb tremor developed and progressively increased in intensity. RDS urinary incontinence developed 8 months post-op. At 9 monts post-op tremor became generalized and impossible to tolerate, and RDS severe hypertension(over 200mmHg systolic pressure) and tachycardia(over 150bpm) developed and lead to syncope. The patient was admitted at 11 months post-op and monitored with electromiography and intra-arterial invasive pressure monitoring. There was a direct correlation between SCS active periods and development of generalized motor activity compatible with cramp/spasm, urinary incontinence, tachycardia and severe hypertension. Electrode positioning was confirmed on CT. The patient was restarted on morphine and the stimulator was put in off mode permanently.

Conclusion:

SCS may involve not only dorsal horn structures but also somatic and visceral sensory afferents/efferents in an energy dose independent unprecdictable way, with late onset, and progressive increase in severity.


Carla REIZINHO, Alexandra SANTOS, Antonio BARATA, Ana LUIS, Andre CAETANO, Marcelo MENDONÇA, Lidia CUNHA, Catarina JESUS, Naide FERREIRA, Cuco ANTONIO (Lisbon, Portugal)
00:00 - 00:00 #23980 - Punction of foramen ovale under direct visualization: how to avoid complications in trigeminal neuralgia. Laboratory anatomy study.
Punction of foramen ovale under direct visualization: how to avoid complications in trigeminal neuralgia. Laboratory anatomy study.

Background: percutaneous approach to forame ovale is an option for surgical treatment of trigeminal neuralgia. Three percutaneous techniques is available:  balloon microcompression, radiofrequency ablation and glycerol rhizotomy. In the proceed, the foramen ovale is punction under anatomy and radioscopy parameters. This study provide anatomy visualization of the correct punction and also how to avoid catastrophic injury of internal carotid artery and jugular vein.

Methods: on a cadaver specimen a pre auricular transmandibular approach to infratemporal fossa was made to expose forame ovale, follow by microdissection of mandibular trigeminal nerve, internal carotid artery, jugular vein and foramen lacerum to visually illustrate the correct angle of punction and the angles that should be avoided.

Results: petrous internal carotid artery punction in foramen lacerum is not probably because the thick consistency of the ligament. Internal carotid artery punction in carotid canal is seen when needle is direct more posterior and lateral than forame ovale. Jugular vein punction in jugular foramen punction is seen when the needle is direct more posterior and medial.

Conclusions: a correct trajectory visualization of the needle in forame ovale punction is essential to avoid major complications. Knowing all angles needles is an efficient way to succeed in percutaneous approach to foramen ovale.


Cassiano MARCHI, Paulo Henrique PIRES DE AGUIAR (São Paulo, Brazil)
00:00 - 00:00 #26117 - Systematic review: mesencephalotomy for chronic pain.
Systematic review: mesencephalotomy for chronic pain.

Background: Stereotactic mesencephalotomy is a neurosurgical procedure that involves the ablation of the midbrain sensory pathways, effectively decreasing pain. Nowadays, this technique has lost some space to new minimally invasive neurosurgical procedures and also to the explosive use of opioids, related to multiple adverse effects. Mesencephalotomy can still be considered an option especially for patients who do not tolerate the effects of medication.   

Objectives: The goal of this systematic review is to evaluate the results of mesencephalotomy for the management of pain, focusing on the effectiveness and also complications commonly found in this procedure. 

Methods: PUBMED, LILACS and MEDLINE databases were used for this systematic review. Sixteen articles written between 1953 and 2020 met our criteria, totalizing 599 patients. 

Results: 82.3% of patients noticed significant pain relief after the procedure and 17.4% reported unsatisfactory results. Most common complications were gaze palsies (6.92% of patients), especially Parinaud's syndrome (2.98%), and ysesthesia (3.46%). Lung cancer, head and neck cancer and thalamic pain were the most frequent etiologies. The main pain localizations were cervical plexus (39.2%), brachial plexus (19.4%) and lower limbs (13.6%).   

Conclusions: Our results showed that mesencephalotomy is an effective procedure for most chronic pain conditions. Furthermore, the development of evoked potentials decreased the complications of this technique, allowing safer surgeries. We concluded that mesencephalotomy should still be considered an option for the management of refractory pain.  


Paulo Henrique PIRES DE AGUIAR (São Paulo, Brazil), Giovanna GALAFASSI, André AKIRA TAKAHASHI, Manuela CORRÊA PERES, Paulo Eduardo ZITO RAFFA, Pedro Henrique SIMM PIRES DE AGUIAR, Carolina ANGELI KALAF MUSSI, Raphael Vinícius GONZAGA VIEIRA, Paulo Roberto FRANCESCHINI
00:00 - 00:00 #23940 - TRACTOTOMY OF SPINO THALAMIC BEAM MESENCEPHALIQUE.
TRACTOTOMY OF SPINO THALAMIC BEAM MESENCEPHALIQUE.

INTRODUCTION :

Chronic cancer pain can not be managed always by pharmacological modalities. When patients have to be treated with high doses of major analgesics (morphine or morphine derivatives), the need of reliving the pain via surgery becomes necessary.

Stereotactic mesencephalic tractotomy (SMT) is considered a valid surgical intervention for patients with upper body pain, intractable to conservative treatment. The convergence of the central trigeminal and spinothalamic tracts in the pons and mesencephalon offers an opportunity for division of the pain pathways from the opposite half of the body. Dogliotti 1 (1938) first carried out this procedure in the upper pons. Walker 6 in 194s showed that the same result could be obtained in a less hazardous manner by tractotomy at the level of the mesencephalon.

 CASE REPORT

A 47 YEARS OLD MALE PATIENT UNDER PALATIVE CARE WITH A HISTORY OF MELANOMA STAGE III DISCOVERED ON UPPER RIGHT SIDE LYMPHADENOPATHY WITH COMORBIDITIES OF SUPRAVENTRICULAR RHYTHM DISORDER, AND HYPERTENSTION. REFEERED TO NEUROSURGERY FOR PERSISTANT PAIN OF SEVER RIGHT UPPER ARM DESPITE ADAPTABLE ANALGESICS.

ON EXAMINATION, PATIENT IN SEVER PAIN. HYPERTROPHY OF THE RIGHT ARM (right axillary post-surgical pain). Neurologically intact.

INVISTGATION

LABORATORY ANALYSES FOR COMPLETE BLOOD COUNT

ELECTROLYTES

MRI 

 OPRATIVE MANAGMENT

PATIENT WENT UNDER ROBOTIC ASSESSMENT Stereotactic MESENCEPHALIC TRACTOTOMY under local anesthesia.

OF SPINO THALAMIC BEAM MESENCEPHALIC.  

POST OPRATIVE COURSE AND OUTCOME

REHABILITATION STARTED AFTER THE SURGERY. HE HAD AN UNREMARKABLE POSTOPRATIVE COURSE. NO EARLY PROPRIOCEPTIVE OR GAZ DEFICITS WERE NOTED. NO CENTRAL NERVOUS SYSTEM INFECTION OR CEREBROSPINAL FLUID LEAKAGE OCCURED. IN FACT, THE IMMEDATE POST OPRATIVE RESULT WAS POSITIVE OUTCOME AND A REMARKABLE OF COMPLETE PAIN RELIEF WITHOUT ANY IMPAIRMENT OF NEUROLOGICAL FUNCTIONS.  

 

DISCUSSION

Cancer-related pain may be presented as a major issue of healthcare systems worldwide. The pain has different causes and there are different types. The amount of cancer pain depends on different factors, including the type of cancer, its stage, other health problems associated, and pain threshold (tolerance for pain).

The intensity of pain and the treatment outcomes should be assessed regularly and consistently using the VAS or NRS. It is important to prescribe a therapy that can be managed simply by patients and families themselves via administing an appropriate analgesic regimen and their efficacy and tolerability. Analgesics for chronic pain should be prescribed on a regular basis and not on an ‘as required’ schedule. The oral route of administration of analgesic drugs should be advocated as the first choice. Continuous pain that never resolves even with a high dose of Morphine is a considering indication to do a mesencephalic tractotomy.

 The development of numerous robotic systems in surgery generally has been rapidly growing and adapted accurately. In fact, neurosurgery has been at the first line of advancing technologies, adapting new techniques and devices successfully in an effort to increase the safety and efficacy of neurosurgery, particularly of surgical robotics and likely to overcome many major milestones in robotic technology in the coming years.

 

The most important factors to consider when classifying a surgical robot are in its surgical applications, its level of interaction with the surgeon and the role of the robot in the surgery. Several robotic solutions have been developed to address the specific challenges associated with interventions on the brain like minimizing damages to normal tissue. As an example Rosa which followed a system that involves a passive robotic arm which moves in a pre-programmed direction to a specific site defined by integrated neuronavigation systems for stereotactic biopsy or functional neurosurgical applications.

 CONCLUSTION

Surgical robots in the practice of neurosurgery and MRI-based stereotactic mesencephalic tractotomy as an integrations of new focused technologies has shown a valid and successful method for the surgical treatment of chronic cancer pain syndrome.


Faisal ALKATHERY, Michel LEFRANC (AMIENS), Johann PELTIER
00:00 - 00:00 #26221 - Trigeminal pain classification revised : the key to neurosurgical management.
Trigeminal pain classification revised : the key to neurosurgical management.

It is indisputable that the global advances in neurosurgical management of facial pain have benefited enormously from the operational diagnostic criteria in the milestone publication by Burchiel (2003).  Today, this classification system is indispensable. The main significance Burchiel proposed facial pain classification scheme was more accurate, rigorous, and precise communication among different specialists treating patients with facial pain syndromes. However, it did not provide adequate advice regarding treatment modalities. Although patient’s history is the key to Burchiel classification, but neuroimaging findings can aid classification when such information is available. Recently tremendous work and significant progress has been achieved – the Classification Committee of The International Headache Society published the third edition of the International Classification of Headache Disorders. Based on this developments and review of literature we revised Facial Pain Classification with first-choice neurosurgical management modalities. The net result of the revised classification should be greater clarity of understanding treatment choices by the neurosurgical community.

Figure 1 illustrates the revised Facial Pain classification. This classification is based upon an extension of the Burchiel scheme 2003


Serge RASSKAZOFF (Victoria Island, Nigeria)
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PSYCHIATRIC DISORDERS

00:00 - 00:00 #23949 - Biological mechanisms of neurostimulation: An in situ based study comparing deep brain stimulation and optogenetic stimulation of the medial forebrain bundle.
Biological mechanisms of neurostimulation: An in situ based study comparing deep brain stimulation and optogenetic stimulation of the medial forebrain bundle.

Deep Brain Stimulation (DBS) of the medial forebrain bundle represents a promising treatment for refractory depression, albeit the mechanisms of action are not well understood. The study addressed the impact of different stimulation times and parameters on the expression of key biological markers following the unilateral selective optical stimulation of midbrain dopaminergic pathways or non-selective electrical Deep Brain Stimulation (DBS) of the medial forebrain bundle (MFB).

TH-cre rats either received i.) Unilateral AAV Virus injection in the ventral tegmental area (VTA) and optical fibers implanted in MFB (Opto-group); or ii.) Unilateral electrode implantation in the MFB (DBS-group). The stimulation parameters and relative group design are shown in Table1. Brain tissues from selected areas of interest were recovered and in situ hybridization was carried out for key biological markers.  

Despite the unilateral stimulation, most of the changes in the expression levels occurred bilaterally, and the stimulation affected the biomarkers differently in different regions. Stimulation with both modalities increased gene expression, although more so with DBS compared to optogenetic stimulation. Increased stimulation sessions, i.e. 7 daily stimulations versus a single stimulation, didn’t translate into increased expression in most cases, and neither did the frequency (30 vs 130Hz) have a clear cut effect, if anything, 30Hz increased gene expression more. Specific results broken down into biomarkers and regions are shown in Table 2.

Unilateral stimulation can impact gene expression in both hemispheres, but differences were observed across stimulation durations and frequencies. The stimulation induced differences in patterns of gene expression changes are interpreted in the context of stimulation modality, parameters and MFB connectivity.


Wen ZHAO (Freiburg, Germany), Jasmin WEIS, Volker Arnd COENEN, Máté DÖBRÖSSY
00:00 - 00:00 #26032 - Cognitive Outcome after Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: a systematic review and case series.
Cognitive Outcome after Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: a systematic review and case series.

Introduction

Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Neuropsychological assessment contributes to DBS treatment in several ways: it monitors the cognitive safety of the treatment, identifies beneficial or detrimental cognitive side-effects and it could aid to explain variability in treatment outcome, and possibly the treatment’s working mechanism(s). BackgroundThis systematic review and case-series assessed the cognitive safety of DBS for OCD and explored whether changes in cognitive function may help explain its working mechanism(s).

Methods

EMBASE, PubMed/Medline, Psycinfo and the Cochrane Library were systematically searched for studies reporting cognitive outcomes following DBS for OCD. Searches were completed to November 2020. Included studies were appraised for study design and quality according to NIH quality assessment tools. For the case series, the cognitive outcome of seven patients was retrospectively assessed.

Results

Five randomized controlled trials and nine observational studies comprising a total of 171 patients were analyzed collectively. Variable outcomes of DBS were observed in the domains of attention, memory and executive functioning and in particular cognitive flexibility. In the case series, the Trail Making Test ratio, which is indicative for cognitive flexibility, showed a significant decrease, with a medium effect size of 0.63.

Conclusion

Although individual studies generally do not report cognitive deterioration after DBS for OCD, the variability of study designs and the multitude of cognitive measures used, precluded a meta-analysis to confirm its safety and recognition of a cognitive pattern through which the efficacy of DBS for OCD might be explained. Future, prospective studies should preferably include a standardized neuropsychological assessment battery specifically addressing executive functioning and have a longer-term follow-up in order to demonstrate the cognitive safety of the procedure. Such prospective and more uniform data collection may also contribute to our understanding of the working mechanisms of DBS in OCD.


Tim BOUWENS VAN DER VLIS (Maastricht, The Netherlands), Annelien DUITS, Megan VAN DE VEERDONK, Anne MULDERS, Koen SCHRUERS, Yasin TEMEL, Linda ACKERMANS, Leentjens ALBERT
00:00 - 00:00 #23929 - Deep brain stimulation of the posteromedial hypothalamus including post-hypothalamotomy surgical rescue for severe and intractable aggressive behavior in mentally retarded patients.
Deep brain stimulation of the posteromedial hypothalamus including post-hypothalamotomy surgical rescue for severe and intractable aggressive behavior in mentally retarded patients.

TITLE

Deep brain stimulation of the posteromedial hypothalamus including post-hypothalamotomy surgical rescue for severe and intractable aggressive behavior in mentally retarded patients.

 

 

AUTHORS

Oscar Andrés Escobar Vidarte. MD. FACS.

Associate Professor, Neurosurgery Section, Universidad del Valle, Cali, Colombia.

Professor, Department of Medical Clinics, Pontificia Universidad Javeriana, Cali, Colombia.   

Coordinator Neorosurgery Service, Comfandi Amiga Clinic, Cali, Colombia.

Functional Neurosurgeon, Castellana Clinic, Cali, Colombia.

Functional Neurosurgeon, Latin American Institute of Neurology and the Nervous System (ILANS), Bogotá, Colombia.

First author and speaker.

 

Javier Orozco Mera. MD. FACS.

Professor, Neurosurgery Section, Universidad del Valle, Cali, Colombia. 

Neurosurgeon of Tumors and Skull Base Surgery, Neurosurgery Service, Comfandi Amiga Clinic, Cali. 

 

Gabriel José Arango Uribe. MD.

Movement Disorders Neurologist.

Latin American Institute of Neurology and the Nervous System (ILANS), Bogotá, Colombia. 

Marly Clinic, Bogotá, Colombia. 

 

Juan Camilo Salcedo. MD.  

Neurosurgery Program Specialization Resident.  

Neurosurgery Section, Universidad del Valle, Cali, Colombia.

 

 

TOPIC

Psychiatric disorders

 

 

KIND OF COMMUNICATION

Poster presentation

 

 

KEY WORDS

Aggressive behavior, surgical rescue, deep brain stimulation

 

 

INTRODUCTION

Aggressive behavior in mentally retarded patients can be resistant to pharmacological treatment and compromise the integrity of the patient, of the patient's family or the caregivers. Hypothalamic deep brain stimulation (DBS) has been used to improve this type of behavior in severe and refractory cases.

 

 

OBJECTIVE

To describe and analyze the posteromedial hypothalamus DBS long-term impact as a treatment to improve severe and refractory aggressive behaviors, even hypothalamotomy in mentally retarded patients.

 

METHODS

Twelve patients were driven to a bilateral DBS of the posteromedial hypothalamus, medical records were reviewed and the impact on behaviour was measured by means of a preoperative and postoperative Modified Overt Agression Scale (MOAS) during the last follow-up medical visit.

 

RESULTS

Nine of 12 patients presented a signifcant decrease in the severity of aggressive behavior, with a 50.5 preoperative and 20.6 postoperative MOAS value average, with an overall improvement of 59.3% and a mean follow-up value during 5.1 years, including, in this group, the case of a patient previously intervened with a bilateral radiofrequency hypothalamotomy. The most common adverse effect of the use of stimulation was the alteration of extraocular movements, which was solved by modulation of electrical parameters. There were no major neurological complications or deaths associated with the procedure.

 

 

CONCLUSION

Posteromedial hypothalamus DBS could be effective in improving severe and refractory aggressive behavior in patients with long-term mental retardation, being a safe and reproducible procedure.


Oscar ESCOBAR (Cali, Colombia), Javier OROZCO, Gabriel ARANGO, Juan SALCEDO
00:00 - 00:00 #24085 - Functional Neurosurgery for Psychiatric Illness in Africa: Challenges and Opportunities.
Functional Neurosurgery for Psychiatric Illness in Africa: Challenges and Opportunities.

Functional Neurosurgery for Psychiatric Illness in Africa: Challenges and Opportunities

 

Authors

R.V. Passchier1,2

 

Affiliations

1Department of Neurosurgery, Groote Schuur Hospital, Cape Town, South Africa

2Neuroscience Institute, University of Cape Town, South Africa

 

Keywords

Functional Neurosurgery, Psychiatry, Africa, World Health Organization (WHO) Health System Framework

 

Objectives

Mental, neurological and substance use disorders are a leading cause of disability worldwide, and more so in Africa where treatment and resources are scarce. This review explores the opportunities and challenges of implementing functional neurosurgery for psychiatric illness in Africa, based on the six building blocks of the World Health Organization (WHO) Health System Framework. In the context of the current South African health system, leadership, finance, workforce, technologies, information and service delivery are explored from the neurosurgical perspective.

 

Design

Scoping review  

 

Methods: 

Literature, current policy and population health statistics were used to identify and map the evidence on the availability and potential of neurosurgery for psychiatric illness in South Africa. Current burden of disease, services and resources, as well as opportunities for growth were explored.

 

Results: This study is in progress

Results will be organised according to the WHO Health systems framework. Neurosurgery leadership, finance, workforce, technologies, information and service delivery in the South African public health system will be summariesed. This will be used to discuss barriers as well as potential solution towards implementation and provision of neurosurgery for mental illness in Africa.

 

Conclusions This study is in progress

Through considerations such as these, we hope to promote the need for training and resources for psychiatric neurosurgery in Africa.


Ruth Verity PASSCHIER (Cape Town, South Africa)
00:00 - 00:00 #23898 - Incisionless MR-guided focused ultrasound: technical considerations and current aaproaches in psychiatric disorders.
Incisionless MR-guided focused ultrasound: technical considerations and current aaproaches in psychiatric disorders.

Introduction: Pharmacological and psychotherapeutic interventions represent the first-line treatment for

   psychiatric disorders.

However, one-third of psychiatric patients achieve a limited response or suffer from drug-associated side effects. Under such circumstances, noninvasive [transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), electroconvulsive therapy (ECT), ablative Gamma Knife radiosurgery (GKRS), MR-guided focused ultrasound (MRgFUS)] and invasive brain modulation procedures [deep brain stimulation (DBS), surface/epidural brain stimulation (EpS), ablative radiofrequency (RFA), extracranial cervical vagus nerve stimulation (VNS)] have resulted in encouraging responsiveness (depending on the applied technique) and are currently under clinical investigation [1-16]. Noninvasive [transcranial magnetic stimulation, transcranial current stimulation, electroconvulsive therapy, gamma knife radiosurgery, MR-guided high intensity focused ultrasound] and invasive (deep brain stimulation, radiofrequency, surface/epidural brain stimulation, cervical vagus nerve stimulation] brain modulation procedures have exhibited a meaningful responsiveness in psychiatric disorders and are currently under clinical investigation.

Most recently, a non-invasive approach, namely, stereotactic MRgFUS using high-intensity focused ultrasound lesioning (HIFU; 650-720 kHz) was clinically introduced targeting deeper brain areas, such as the basal ganglia and the thalamic nuclei.

Stereotactic MR-guided high-intensity focused ultrasound (thermal lesioning) has been reported to be safe and effective for movement disorders, neuropathic pain and most recently neuropsychiatric disorders, while low-intensity focused ultrasound (non-lesioning thermal/mechanical) represents a non-lesioning approach to modulate deeper brain structures. This narrative review introduces and discusses the therapeutic potential of incisionless stereotactic MR-guided high-intensity focused ultrasound of deep brain structures for the treatment of psychiatric disorders.

Methods/Materials: A literature review (PubMed, MEDLINE/OVID, SCOPUS and manual searches of the bibliographies of known primary and review articles) was performed using the following search terms: MR-guided stereotactic ultrasound (high-intensity/low-intensity), psychiatric disorders, brain stimulation, randomized controlled trials, safety/efficacy, and complications.

Results: Currently, stereotactic MR-guided high-intensity focused ultrasound ablation is under clinical investigation for obsessive-compulsive disorders (OCDs) [NCT 01986296/ NCT 03156335; anterior cingular cortex] and depression/anxiety disorders [NCT 02348411/ NCT 02685488; anterior cingulate cortex] and has demonstrated a clinical improvement in OCD and depression in preliminary reports. Low-intensity ultrasound applications have been explored in Alzheimer´s disease (phase 1 study) and healthy subjects.

Discussion: Therapeutic use of intracranial ultrasound has been under investigation for some decades, but its accessibility has been limited by the necessity of craniotomy and the lack of neuroimaging monitoring (thermal mapping) modalities to control the ablated tissue volume (basal ganglia/thalamic nuclei) through the intact skull (incisionless) by using a frame-based (stereotactic) MR-thermal mapping approach.  

  Brain lesioning utilizing stereotactic MR-guided high-intensity ultrasound represents an emerging minimally invasive treatment strategy in neuropsychiatric disorders that may become complementary to established invasive and non-invasive brain stimulation procedures with comparable effectiveness.

Conclusions: However, based upon its non-invasive and standardized procedural characteristics and the potential therapeutic impact, MRgFUS may be more appropriate than other brain stimulation methods for comparable clinical conditions. While these nascent developments are exciting and MRgFUS constitutes a potential renaissance for ablative and non-ablative brain modulation, the question whether MRgFUS serves as a complementary or competitive procedure compared to NIBS, DBS, RFA and GKRS remains premature to appraise at this stage. In addition, significant safeguards are highly waranted prior to performing this kind of procedure, as severely ill psychiatric patients deserves ressources that may not be considered ahead of time.

 

 


Thomas KINFE (Erlangen, Germany), Michael BUCHFELDER
00:00 - 00:00 #23947 - Optogenetic stimulation of VTA dopaminergic neurons in a rodent model of depression.
Optogenetic stimulation of VTA dopaminergic neurons in a rodent model of depression.

Major depressive disorder (MDD) is one of the most common mental disorders, and more than 300 million of people suffer from depression worldwide. Recent clinical trials found that Deep Brain Stimulation (DBS) of the Medial Forebrain Bundle (MFB) can have rapid onset and long-term antidepressant effects with Treatment Resistant Depressive patients. However, the mechanisms of action are elusive. In this study, we focus on i.) the potential anti-depressant effects of selective optogenetic stimulation of the Ventral Tegmental Area’s (VTA) dopaminergic (DA) neurons passing through the MFB and ii.) compare the therapeutic effects of different stimulation patterns.

22 female TH:Cre rats (10-12 wks old) were matched into two groups according to their baseline behavioral performance. Animals in each group received ChR2 or control virus into the VTA bilaterally, followed by the implantation of the optic fibers in the MFB. After recovery, the animals were exposed to the Chronic Mild Unpredictable Stress (CMUS) paradigm once or twice daily for 6 weeks to induce the depressive-like phenotype. During the CMUS induction period, half the animals received optic stimulation during 6 weeks (n=10; “Preventive Stim” group), or they received optic stimulation only after the 6 weeks CMUS induction period (n=12; “Post Stim” group). Behavior tests classically sensitive to depressive-like phenotype such as the Open Space Swimming Test (OSST), the Elevated Plus Maze (EPM) were monitored.

Following 6 weeks of CMUS, animals demonstrated depressive-like phenotype including lower mobility in OSST and higher anxiety index in EPM. Preventive Stim, but not Post Stim, showed significant higher mobility in OSST compared to the Controls’, which suggests a stimulation mediated rescue from the depressive-like phenotype. Meanwhile, Preventive Stim reduced adrenal weight significantly.  On the other hand, CMUS caused a delayed effect on anxiety-like phenotype and Post stim pattern decreased anxiety index in the EPM.

In summary, CMUS induced depressive-like and anxiety-like phenotypes as assessed by behavioral testing. However, Preventive optogenetic stimulation of the VTA dopaminergic projections could “rescue” some to the behaviors. The Post stimulation condition had better anti-anxiety effect, while the Preventive stimulation pattern had more impact on motivation.


Yixin TONG (Freiburg, Germany), Volker Arnd COENEN, Máté DÖBRÖSSY
00:00 - 00:00 #23985 - Preoperative anxiety in patients admitted for brain surgery: a systematic review.
Preoperative anxiety in patients admitted for brain surgery: a systematic review.

Introduction

Up to 80% of patients scheduled for surgery experience preoperative anxiety, which is associated with psychological and physical changes that may increase the use of medications, affect surgical outcome and decrease postoperative satisfaction of patients.

During the last decade, a relevant number of studies were focused on preoperative anxiety in patients undergoing neurosurgical procedures, but controversial evidence exists, and it lacks a systematic analysis.

 

Objective

Our aim is to systematically review the phenomenon of preoperative anxiety in brain surgery patients considering: its prevalence and factors that lead to a higher level of anxiety, its influence on the perioperative period and on surgical outcomes, and the strategies to lower preoperative anxiety.

 

Methods

We performed a systematic review of literature by searching PubMed, Embase, and Cochrane Library databases. Our inclusion criteria were studies of any level of evidence published in peer-reviewed journals. Data were extracted using the PICO framework. PRISMA guidelines were applied, and the risk of bias was assessed using the RoB 2 and ROBINS tools, as was the methodological quality of the included studies, following GRADE criteria. We excluded articles with serious risk of bias and/or very low quality after the assessment.

 

Results

We included twenty-seven articles, accounting for 2558 patients (45% M and 55% F, mean age 49 years) involved in various brain surgery procedures; these studies were conducted in the wards of anesthesiology, neurology and neurosurgery of twelve different countries. On average, the prevalence of preoperative anxiety was between 30% and 60 % of patients admitted for brain surgery, reaching higher levels in female gender and younger patients. Some correlations were found between level of anxiety and laterality of tumor, whereas none were found with histological type of tumor. Two studies confirmed the validity and reliability of STOA, APAIS and VAS scales to detect preoperative anxiety in neurosurgical patients, providing also the optimal cut-off scores for this specific group of patients.

It was shown that preoperative anxiety could influence the pre-operative period: anxious patients needed more information about surgical outcome and performed worse in cognitive tasks or had worse subjective evaluation of their cognitive abilities. In the awake surgery setting, levels of preoperative anxiety were not higher than before traditional surgery; in addition anxiety could be associated with depression, less ability to relax after surgery and higher pain before and three days after surgery. During the post-operative period, preoperative anxiety was associated with longer hospitalization, increase of physical disability in brain tumor patients, poorer memories and complication in epilepsy surgery; no correlation with survival rate was found. Various strategies were proven effective in reducing anxiety levels: seven studies attested the efficacy of acupuncture, music therapy, exposure to virtual reality or pharmacological support including the use of Oxazepam, Pregabalin and Flupirtine.

 

Conclusion

Preoperative anxiety in brain surgery patients is a common experience that should not be underestimated in a medical approach to achieve a better perioperative care considering also quality of life of patients. It would be desirable to prevent and manage preoperative anxiety by detecting patients’ groups at higher risk, with the most suitable scales of assessment, and ensure them the best pharmacological or non-pharmacological support.

Further studies are encouraged in order to corroborate these conclusions.


Vittorio OTERI, Anna MARTINELLI (Padova, Italy), Elisa CRIVELLARO, Francesca GIGLI
00:00 - 00:00 #25944 - RechargePSYCH: Rechargeable implantable pulse generators in patients with deep brain stimulation for psychiatric disorders.
RechargePSYCH: Rechargeable implantable pulse generators in patients with deep brain stimulation for psychiatric disorders.

Objective:

Implantable pulse generator (IPGs) replacements represent the most common type of scheduled follow-up surgeries as stimulation parameters are usually higher compared to movement disorder patients. Rechargeable IPGs offer longer battery life causing fewer surgical replacements combined with a smaller implant size. The impact of this technology on psychiatric patients as well as the amount of time necessary to maintain therapy are still unknown.

 

Methods:

A single center database analysis was performed to identify all DBS patients who were implanted with a rechargeable IPG for a psychiatric indication from 2003 to 2019. Patients that were still implanted with a rechargeable device at the time of the trial were asked to complete a standardized online questionnaire. Primary endpoint was the rating of the convenience of recharging of the entire process and each individual step on an ordinal scale (0-10). Secondary endpoints were the rate of user confidence, user satisfaction, complications and the charge burden (minutes per week necessary to recharge the IPG).

These endpoints were tested for differences in several subgroups (age, gender, indication, IPG model, confidence).

 

Results:

N=21 patients completed the questionnaire (return rate 65.6%) including n=13 patients with major depression, n=6 patients with anorexia and n=2 patients with OCD. More than 80% of patients were female. Mean age was 50.7 years with an average time of therapy with the rechargeable IPG of 31.8 months. Patients had undergone a median of 3 IPG replacements before receiving the rechargeable IPG.

Convenience of recharging was rated high (8.0 out of 10.0 points). Keeping the connection during the charging process (p=0.004) as well as putting on the charging belt (p=0.011) was rated worse compared to the convenience of charging the charger.

The mean charge burden was 286 minutes, which was regarded as acceptable by only 43% of patients.  The mean acceptable charge burden was 121 minutes.

81% of patients felt confident using the device. 66.7% would recommend and 62% would choose a rechargeable IPG again. 33% of patients experienced a failed recharge and 38% had an unintentional interruption of therapy.

Age, sex and the IPG model and none of the associating factors had any influence on any endpoint. Depression patients rated the convenience of recharging significantly worse compared to OCD patients (p=0.027). Patients that did not feel confident were less likely to recommend (p=0.006) or choose a rechargeable IPG again (p=0.012).

 

Conclusion:

Rechargeable IPGs can be safely implanted in DBS patients with psychiatric indications. Charge burden and complication rates are higher compared to movement disorder patients.


Martin JAKOBS (Heidelberg, Germany), David Hernán AGUIRRE-PADILLA, Peter GIACOBBE, Andreas UNTERBERG, Andres LOZANO
00:00 - 00:00 #23961 - Reserpine-induced chronic rat model of depression: behavioral and physiological based validation.
Reserpine-induced chronic rat model of depression: behavioral and physiological based validation.

The monoamine hypothesis of depression, albeit not applicable to all cases, has been a leading hypothesis for decades. Using a longitudinal design, the current study aims to validate a pharmacological induced model by assessing the behavior, and the associated depletion of central monoamine levels on reserpine administration.  The validation of this model will permit at a later date the investigation of novel treatment strategies such as DBS and optogenetics. 

Following baseline behavior testing using tasks sensitive to depressive-like phenotype and locomotion (Phase 1), Sprague-Dawley rats were administered saline, low (0.2 mg/kg) or high (0.8 mg/kg) dose reserpine for three weeks using a pre-determined intermittent schedule with continuous reassessment of emerging behavioral phenotypes  (Phase 2). After 10 days wash-out period, a final behavioral assessment was carried out (Phase 3). At the end of each phase, brains from subgroups of animals were removed for UV-HPLC analysis for different neurotransmitters and metabolites (dopamine, serotonin, norepinephrine and its respective metabolites: HVA, DOPAC and 5-HIAA) from the potential and expected dysregulated regions mainly from the mesolimbic pathway involved in mood and motivation related processes (PFC, nucleus accumbens, striatum, lateral habenula, amygdala, VTA and hippocampus).

Early data suggests dose dependent behavioral deficits including both motor and non-motor behavior, with a measured dependent body weight loss that appears to recover during Phase 3. The experiment is ongoing and the full behavioral, and chemo-analytical (HPLC) analysis will be presented at the meeting.

Reserpine inhibits VMAT2 in central presynaptic terminals, resulting in the reduction of available monoamines for release into the synaptic cleft. We predict that the data will mirror this monoamine depleting action in a dose dependent manner in the strength of behavioral phenotype, in the reduction of central dopamine as shown by reduced monoamines and metabolite measured by HPLC. Furthermore, we predict a partial normalization of behavior and of the assessed biological/ physiological parameters following the wash-out period.


Lidia MIGUEL TELEGA (Freiburg im Breisgau, Germany), Ann-Christin EDER, Philipp Tobias MEYER, Volker Arnd COENEN, Máté DÖBRÖSSY
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EP11
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Eposters
RADIOSURGERY

00:00 - 00:00 #23893 - Frame-based and mask-based stereotactic radiosurgery: the patient experience, compared.
Frame-based and mask-based stereotactic radiosurgery: the patient experience, compared.

Introduction: We sought to compare patient perceptions of frame-based (FB) and mask-based (MB) SRS with respect to comfort and pain, and to examine possible effects of lesion type on the patient experience of SRS.

Methods: Over a one-year period, patients who underwent FB or MB SRS at our institution were given an eight-question survey about their experience with the procedure immediately after treatment was completed. Descriptive statistics were applied.

Results: A total of 117 patients completed the survey with 65 FB and 52 MB SRS treatments, all on the same treatment platform. Patients having FB SRS (M = 5.64, SD = 2.55) found the procedure to be more painful than those treated with MB SRS (M = 0.92, SD = 2.24); t(114), p < 0.001. Patient comfort during the procedure was also higher for those having MB SRS (p < 0.001). Mixed results were obtained when investigating if benign vs. malignant diagnosis affected patient experience of SRS. Diagnosis played no role on pain levels when all patients were analyzed together. The treatment technique had no effect on patient comfort in patients with benign diagnoses. When malignant pathologies were analyzed, patients treated with the mask were more likely to be comfortable (p < 0.001). Between only FB treatments, diagnosis played no role on patient comfort. When only MB treatments were analyzed, patients were more likely to be comfortable if they had a malignant lesion (p < 0.01).

Conclusions: Patients treated with MB SRS experience the procedure as more comfortable and less painful compared to those treated using a frame. Overall, this difference was not affected by a benign vs. a malignant diagnosis. However, within diagnosis groups, patients with benign pathologies had equal comfort with both treatments, while those with malignancies preferred MB SRS.


Matthew PAVLICA, Michael SCHULDER (Lake Success, NY, USA), Anuj GOENKA, Troy DAWLEY
00:00 - 00:00 #26223 - Gamma Knife radiosurgery for unusual sellar lesions treatment.
Gamma Knife radiosurgery for unusual sellar lesions treatment.

The group of so-called :"Sellar region masses" consists of heterogeneous neoplasms and tumor-mimicking lesions, whose differential diagnosis may be challenging due to the overlapping of clinical and radiological features, that can be found both in “common” and “uncommon” lesions.  The choice of a correct treatment strategy is still challening and requires, when possible, an histological analysis. Gamma Knife Radiosurgery (GKRS) has already been reported as a safe and effective treatment in pituitary adenomas and craniopharingiomas, while its role has rarely been described in case of a less common hystopathology. Aim of this study is to assest local tumor control and neurological sequeale in patients treated with GKRS for these tumors, in a long period follow-up. 

MATERIALS AND METHODS. Between February 1993 and February 2021, 921 patients with pituitary lesions were subjected to GKRS at the Verona Hospital: nine of these could  be defined as "rare" and it was possible to obtain at least a 5 years follow-up. Three cases of hypothalamic hamartoma (HH), 2 cases of Rahtke's Pocket Cyst (RCC), 1 case of Langerhans Cell Histiocytosis (LCH), 1 case of spindle cell oncocytoma (SCO), 1 case of Chorioid Plexus Papilloma (CPP) and one case of Ossifying Fibroma were reported. M: F ratio was 2: 7, mean age 49 (range 24-78). The main clinical onset consisted of headache (n = 4), visual acuity deterioration (n = 4), followed by fatigue, hormonal disturbances, paralysis of the cranial nerves, epilepsy and diabetes insipidus. All patients underwent radiosurgery Stereotaxic with Gamma Kife (Models B, C and Perfexion. Elekta Sweden) through a localization with Magnetic Resonance Imaging (MRI) with a dedicated neuro-radiological protocol. The mean prescription dose was 10.3 Gy (range 9-12) with a prescription isodose of 50%. The first follow-up at 7 months included a contrast-enahnced MRI, a complete hormonal assay and opthalmological examination with visual field.  Subsequent follow-ups were scheduled at six months, annually or biennally.

RESULTS. Over a follow-up period of at least 60 months, local tumor control was radiologically obtained in all 9 cases. Only one patient died (CPP) due to liquoral seeding. A second patient died from causes unrelated to the cerebral pathology. There were no cases of visual worsening after radiosurgery. One patient showed transient worsening of diplopia, another a worsening of a pre-existing hormonal deficit  that required replacement therapy. In 3 cases (HH) seizures improved after radio-surgical treatment. There were no cases of GKRS-related neurological worsening. 

CONCLUSIONS. The clinical / radiological findings of this series, with a long period follow-up, suggest that GKRS may also be a well tolerated treatment for "uncommon" sellar lesions, with low risk of radio-toxic effect especially for the optic pathways.  Radiosurgery could therefore represent an effective non-invasive adjuvant treatment option even in this rare type of pathology.


Giorgia BULGARELLI (Verona, Italy), Antonio NICOLATO, Valeria BARRESI, Riccardo LAVEZZO, Emanuele ZIVELONGHI, Paolo Maria POLLONIATO, D'amico ANNA, Carlo CAVEDON, Giuseppe Kenneth RICCIARDI, Giampietro PINNA, Francesco SALA, Michele LONGHI
00:00 - 00:00 #22800 - Hypofractionated Gamma Knife Radiosurgery for Cerebral Arteriovenous Malformations: Preliminary Results.
Hypofractionated Gamma Knife Radiosurgery for Cerebral Arteriovenous Malformations: Preliminary Results.

Background: Cerebral arteriovenous malformations (AVMs) are congenital lesions associated with high morbidity and mortality. This study aimed to evaluate the short-term treatment results in patients with AVMs treated with hypofractionated Gamma Knife Radiosurgery (fGKRS).

Methods: Forty-four consecutive patients who applied to our clinic between August 2017 and March 2020 with AVMs, and who were treated by fGKRS were retrospectively reviewed. Thirty-seven of these patients had a follow-up period ≥ 6 months, and treatment results from these patients were evaluated.

Results: Thirty-seven patients (21 men, 16 women) with a mean AVM volume of 14.9 cmand a median volume of 13.8 cm3 (range: 1.0-41.2) were treated with fGKRS. Sixteen AVM (43.2%) underwent embolization before fGKRS. Seventeen patients (46.0%) presented with headaches, whereas the remaining patients presented with hemiparesis, seizures, or focal neurological symptoms. The mean age at the time of treatment was 31.5 ± 13.2 years (range: 12–67). fGKRS was performed in three (7 patients), five fractions (27 patients), seven fractions (1 patient), or ten fractions (2 patients). The median total dose, dose per fraction, and isodose line were 30 Gy (range, 20-40), 6 Gy (range, 4-8), and 45% (range, 40-55%), respectively. Median follow-up was 16 months (range, 6-30). Overall, 13 patients (35.1%) showed regression in the 6th month, and 23 patients remained stable. One patient experienced ICH in the 6th month, and one patient experienced ICH in the 18th month; however, both patients only required medical treatment. There was no treatment-related morbidity and mortality.

Conclusion: fGKRS could be used as an alternative in treating AVMs not suitable for single fraction radiosurgery; however, long-term results should be evaluated. 


Yavuz SAMANCI (Istanbul, Turkey), Ali Ihsan ATASOY, Fatih KARAKÖSE, Nülifer KILIC DURANKUS, Selçuk PEKER
00:00 - 00:00 #23931 - Stereotactic radiosurgery for Solid vs. Cystic Vestibular Schwannoma: Systematic Review and Meta-analysis.
Stereotactic radiosurgery for Solid vs. Cystic Vestibular Schwannoma: Systematic Review and Meta-analysis.

Background:

Cystic vestibular schwannomas (VS) have variable growth behavior and may respond differently to

radiosurgery than solid VS. This meta-analysis sought to compare radiosurgical outcomes.

Methods:

Following the PRISMA guidelines, MEDLINE, EMBASE, Cochrane, and web of science were searched for terms

relevant to VS and radiosurgery from inception to September 2019. Data pertaining to outcome following

radiosurgery was extracted from studies explicitly noting a minimum of10 cystic VS cases along with solid VS. Random effects models calculated as

relative risks (RR) with 95% CIs were utilized to estimate the overall effect.

Results:

Six studies, all using gamma knife, were meta-analyzed (n=1070 solid and n=347 cystic VS). There was no

difference in size (mm) between cystic (19.1±2.2) or solid VS (14.0±0.6) (p=0.08). Pooled analysis did not

show a difference in tumor control (RR: 1.02, 95%CI 0.91-1.16, p=0.70). Three studies reported

complications: (Table-1)

Conclusions:

This meta-analysis of predominantly low-quality retrospective studies shows that radiosurgery can achieve

similar control rates for cystic and solid VS.


Nima HAMIDI (Glendale, USA), Elie MASSAAD, Jacalynn GOETZ, Alireza MANSOURI
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EP12
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Eposters
SPASTICITY

00:00 - 00:00 #24070 - High frequency spinal cord electrostimulation in cerebral palsy.
High frequency spinal cord electrostimulation in cerebral palsy.

The high prevalence, social significance and lack of effectiveness of the traditional rehabilitation of patients with cerebral palsy necessitate the search for new methods of correcting motor disorders in this disease. Existing pharmacological methods of reducing spasticity, including through local administration of drugs, do not always meet the expectations of both doctors and patients or their relatives. Given the side and non-selective effects of drugs used in neurology, it is of interest to use methods of electrical stimulation of the spinal cord. However, traditional methods of low-frequency electrical stimulation are not always effective enough.

Purpose of the study. To evaluate the effectiveness of high-frequency electrical stimulation of the spinal cord in order to correct motor disorders in cerebral palsy.

Materials and methods. The study was conducted on 6 patients aged 18 to 22 years with cerebral palsy. The selection criteria were: a predominant increase in tone in the lower extremities, preserved cognitive functions, the absence of surgical interventions on the spine and spinal cord, contractures in the lower extremities, the effectiveness of test epidural electrical stimulation of the spinal cord. A StimWave Freedom 8A stimulation system was implanted in all patients. Spinal cord stimulation was performed intermittently (5 s ON and 10 s OFF) with a frequency of 1000 Hz, pulse duration 100 μs. Patients were recommended to conduct electrical stimulation of the spinal cord 2 times a day for at least 2 hours. The severity of spasticity was assessed using the Ashworth scale, the degree of locomotor dysfunction was evaluated using the Arens scale.

Results. In the preoperative period, the average level of neurological disorders, according to the Ashworth spasticity scale, corresponded to 2.8 ± 0.3 points, the degree of locomotor function impairment was 2.4 ± 0.4 points. In the first minutes after the inclusion of stimulation in patients, a significant decrease in pathological muscle tone was observed. The average level of spasticity on the Ashworth scale at 3 days after surgery was 1.2 ± 0.15 points (P <0.01). In the long-term postoperative period (3-4 months), these indicators did not significantly change (1.1 ± 0.2 points on the Ashworth scale), a moderate improvement in the function of the pelvic organs, statics, and locomotor functions to 3.7 ± 0.3 points was noted (P <0.05). In all cases, a prolonged persistence of the stimulation effect was observed from several hours to several days.

Conclusion. High-frequency electrical stimulation of the spinal cord is a promising and more effective, in comparison with low-frequency stimulation, method of correction of motor disorders in cerebral palsy. The use of implantable radiofrequency neurostimulators, in particular StimWave, has several advantages: minimal invasiveness of surgical intervention, lack of baclofen dependence and restrictions on rehabilitation.


Andrei SHAPKIN (Tyumen, Russia), Albert SUFIANOV