Wednesday 27 September
Time ROOM A1 ROOM C1-C2 ROOM C3 ROOM C4
14:00
14:00-16:00
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C12
Workshop
Technical tools for DBS simulation and optical guidance

Workshop
Technical tools for DBS simulation and optical guidance

Arranged by:
Department of Biomedical Engineering, Linköping University, Sweden
Department of Neurosurgery, Linköping University Hospital, Sweden
Institute for Medical Engineering and Medical Informatics, University of Applied Sciences and Arts Northwestern Switzerland

Financially supported by:
The Swedish Strategic Research Foundation (SSF)
VR, SNSF, FHNW, LiU-LiTH
14:00 - 16:00 An introduction to tools for optical guidance in neurosurgery and DBS electric field simulations. Karin WARDELL (Professor) (Linköping, Sweden)
14:00 - 16:00 Clinical use of optical guidance in DBS implantation and tumor biopsy. Johan RICHTER (Senior Consultant) (Linköping, Sweden)
14:00 - 16:00 DBS - data analysis for clinical support. Simone HEMM (Docent/ Researcher) (Muttenz, Switzerland)
14:00 - 16:00 DBS Apps for patient-specific electric field simulation and visualization. Teresa NORDIN (Assistant University Lecturer) (Linköping, Sweden)
14:00 - 16:00 Demonstrations and hands-on.
14:00 - 16:00 DBS APPs for electric field simulation and visualization.
14:00 - 16:00 FluoRa – a system for optical guidance in neurosurgery.

14:00-17:15
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D10
EANS ESSFN EUROPEAN DIPLOMA OF RADIOSURGERY

EANS ESSFN EUROPEAN DIPLOMA OF RADIOSURGERY

14:00 - 17:15 Introduction. Piero PICOZZI (Consultant) (Milano, Italy), Jean REGIS (PROFESSEUR) (MARSEILLE, France)
14:00 - 17:15 Historical perspective. Christer LINDQUIST (Medical co-director) (LONDON, Sweden)
14:00 - 17:15 Volumetric response definition of cure/failure. Anne BALOSSIER (Dr) (Marseille, France)
14:00 - 17:15 Hearing preservation. Jean REGIS (PROFESSEUR) (MARSEILLE, France)
14:00 - 17:15 Oncogenetic risk. Giorgio SPATOLA (Neurosurgeon) (Brescia, Italy)
14:00 - 17:15 Combined approaches. Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Lausanne, Switzerland)
14:00 - 17:15 Quality of life after SRS or MS (Gait balance, Tinnitus, lacrymal deficit,...). Morten LUND-JOHANSEN (Professor, Consultant) (Bergen, Norway)
14:00 - 17:15 Other Schwannomas. Piero PICOZZI (Consultant) (Milano, Italy)
14:00 - 17:15 Surgery after Radiosurgery. Lucas TROUDE (MCU-PH) (Marseille, France)
Video presentation
14:00 - 17:15 SRS for NFII patients. Giorgio SPATOLA (Neurosurgeon) (Brescia, Italy)
14:00 - 17:15 Linac based VS SRS and role of fractionation. Marcello MARCHETTI (physician) (Milano, Italy)
14:00 - 17:15 Conclusions. Jean REGIS (PROFESSEUR) (MARSEILLE, France), Piero PICOZZI (Consultant) (Milano, Italy)

15:30
15:30 - 16:00 COFFEE BREAK
16:00
16:00-17:50
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C13
Young Functional Neurosurgeon Workshop
Opportunities and challenges for education and training in stereotactic and functional neurosurgery

Young Functional Neurosurgeon Workshop
Opportunities and challenges for education and training in stereotactic and functional neurosurgery

Moderators: Patric BLOMSTEDT (Neurosurgeon) (Umeå, Sweden), Martin JAKOBS (Consultant) (Heidelberg, Germany)
Coordinator: Martin JAKOBS (Heidelberg, Germany)
16:00 - 16:15 How to become a functional neurosurgeon - Personal reflections. Joachim K. KRAUSS (Chairman and Director) (Hannover, Germany)
16:15 - 16:25 Educational resources. Oystein TVEITEN (Neurosurgeon) (Bergen, Norway)
16:25 - 16:35 ESSFN Hands on courses - a. Presentation of the course cycle. Jean REGIS (PROFESSEUR) (MARSEILLE, France)
16:35 - 16:45 Stereotactic Neurosurgery Hands-on Workshop - Presentation of the course concept. Peter REINACHER (Stereotactic Neurosurgeon) (Freiburg, Germany)
16:45 - 16:55 DBS and Pain interventions Cadaver Course - Presentation of the cadaver course. Atilla YILMAZ (Nerosurgeon) (Istanbul, Turkey)
16:55 - 17:05 Stereotactic Academy - a. What have I learned from the stereotactic academy. Amar AWAD (MD. PhD.) (Umeå, Sweden, Sweden)
17:05 - 17:15 Stereotactic Academy - b. Discussion. Patric BLOMSTEDT (Neurosurgeon) (Umeå, Sweden)
17:15 - 17:25 EANS courses - a. Educational functional neurosurgery programs of the EANS. Marie KRUEGER (Consultant Neurosurgeon) (London, United Kingdom)
17:25 - 17:40 Panel Discussion - a. Opportunities and challenges with all panel speakers. Martin JAKOBS (Consultant) (Heidelberg, Germany)
17:40 - 17:50 Networking - Places and times to meet. Erik ÖSTLUND (Sweden), Rasmus STENMARK P. (PhD student, Resident) (Umeå, Sweden)

14:00-17:15
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D10
EANS ESSFN EUROPEAN DIPLOMA OF RADIOSURGERY

EANS ESSFN EUROPEAN DIPLOMA OF RADIOSURGERY

14:00 - 17:15 Introduction. Piero PICOZZI (Consultant) (Milano, Italy), Jean REGIS (PROFESSEUR) (MARSEILLE, France)
14:00 - 17:15 Historical perspective. Christer LINDQUIST (Medical co-director) (LONDON, Sweden)
14:00 - 17:15 Volumetric response definition of cure/failure. Anne BALOSSIER (Dr) (Marseille, France)
14:00 - 17:15 Hearing preservation. Jean REGIS (PROFESSEUR) (MARSEILLE, France)
14:00 - 17:15 Oncogenetic risk. Giorgio SPATOLA (Neurosurgeon) (Brescia, Italy)
14:00 - 17:15 Combined approaches. Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Lausanne, Switzerland)
14:00 - 17:15 Quality of life after SRS or MS (Gait balance, Tinnitus, lacrymal deficit,...). Morten LUND-JOHANSEN (Professor, Consultant) (Bergen, Norway)
14:00 - 17:15 Other Schwannomas. Piero PICOZZI (Consultant) (Milano, Italy)
14:00 - 17:15 Surgery after Radiosurgery. Lucas TROUDE (MCU-PH) (Marseille, France)
Video presentation
14:00 - 17:15 SRS for NFII patients. Giorgio SPATOLA (Neurosurgeon) (Brescia, Italy)
14:00 - 17:15 Linac based VS SRS and role of fractionation. Marcello MARCHETTI (physician) (Milano, Italy)
14:00 - 17:15 Conclusions. Jean REGIS (PROFESSEUR) (MARSEILLE, France), Piero PICOZZI (Consultant) (Milano, Italy)

17:15
18:30 - 19:00 WELCOME ADDRESS - CITY HALL
19:00 - 20:00 WELCOME RECEPTION - CITY HALL
Thursday 28 September
Time ROOM A1 ROOM C1-C2 ROOM C3 ROOM C4
08:30
08:30-10:00
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A21
PLENARY SESSION 1 - OPENING CEREMONY & SPECIAL LECTURES

PLENARY SESSION 1 - OPENING CEREMONY & SPECIAL LECTURES

Moderators: Patric BLOMSTEDT (Neurosurgeon) (Umeå, Sweden), Lorand EROSS (Director of the institute) (Budapest, Hungary), Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (LISBON, Portugal)
08:30 - 08:50 A brief history of the ESSFN. Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (LISBON, Portugal)
08:50 - 09:10 Computational Physiology of the basal Ganglia. Hagai BERGMAN (Prof) (Jerusalem, Israel)
09:10 - 09:25 BEST OF 2021-2023: Movement disorders & psychiatry. Marwan HARIZ (neurosurgeon) (Umeå, Sweden)
09:25 - 09:40 BEST OF 2021-2023: Pain Surgery. Patrick MERTENS (Head of the department) (LYON, France)
09:40 - 09:55 BEST OF 2021-2023: Epilepsy surgery. Lorand EROSS (Director of the institute) (Budapest, Hungary)

10:00 - 10:30 COFFEE BREAK - FLASH POSTERS SESSION 1 - EXHIBITION
10:30
10:30-12:00
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A23
PLENARY SESSION 2

PLENARY SESSION 2

Moderators: Volker COENEN (Head of Department) (Freiburg, Germany), Maxime GUYE (Professor) (Marseille, France)
10:30 - 10:50 Connectivity imaging in Functional Neurosurgery. Harith AKRAM (Associate Professor) (London, United Kingdom)
10:50 - 11:10 fMR DBS setting. Andres LOZANO (Alan & Susan Hudson Cornerstone Chair in Neurosurgery, University Health Network) (Toronto, Canada)
11:10 - 11:30 7T MRI in Functional Neurosurgery: What Now, What Next? Maxime GUYE (Professor) (Marseille, France)
11:30 - 11:50 VOMIT. Marwan HARIZ (neurosurgeon) (Umeå, Sweden)
11:50 - 12:00 #35639 - PL01 Deep Brain Stimulation in Disorders of Consciousness: 10 years of a single center experience.
PL01 Deep Brain Stimulation in Disorders of Consciousness: 10 years of a single center experience.

Background: Disorders of consciousness (DoC), namely unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), represent severe conditions with significant consequences for patients and their families. Several studies have reported the regaining of consciousness in such patients using deep brain stimulation (DBS) of subcortical structures or brainstem nuclei. Our study aims to present the 10 years’ experience of a single center using DBS as a therapy on a cohort of patients with DoC.

Methods: Eighty Three consecutive patients were evaluated between 2011 and 2022; entry criteria consisted of neurophysiological and neurological evaluations and neuroimaging examinations. Out of 83, 36 patients were considered candidates for DBS implantation, and 32 patients were implanted: 27 patients had UWS, and five had MCS. The stimulation target was the centromedian-parafascicular complex in the left hemisphere in hypoxic brain lesion or the one better preserved in patients with traumatic brain injury.

Results: The level of consciousness was improved in seven patients. Three out of five MCS patients emerged to full awareness, with the ability to interact and communicate. Two of them can live largely independently. Four out of 27 UWS patients showed consciousness improvement with two patients emerging to full awareness, and the other two reaching MCS.

Conclusion: In patients with DoC, spontaneous recovery to the level of consciousness is rare. Thus, DBS of certain thalamic nuclei could be recommended as a treatment option for patients who meet neurological, neurophysiological and neuroimaging criteria, especially in earlier phases, before occurrence of irreversible musculoskeletal changes. Furthermore, we emphasize the importance of cooperation between centers worldwide in studies on the potentials of DBS in treating patients with DoC.


Darko CHUDY (Zagreb, Croatia), Vedran DELETIS, Darko ORESKOVIC, Andelo KASTELANCIC, Petar MARCINKOVIC, Marin LAKIC, Fadi ALMAHARIQ, Domagoj DLAKA, Dominik ROMIC, Veronika PARADŽIK, Marina RAGUŽ

12:00 - 13:30 INDUSTRIAL LUNCH WORKSHOPS
12:30
12:30-13:30
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A24bis
INDUSTRIAL LUNCH WORKSHOPS - INSIGHTEC
MRgFUS: From state of the art in ET to new frontiers

INDUSTRIAL LUNCH WORKSHOPS - INSIGHTEC
MRgFUS: From state of the art in ET to new frontiers

Chairperson: Ludvic ZRINZO (Professor of Neurosurgery) (London, UK, United Kingdom)
12:30 - 13:30 Introduction. Ludvic ZRINZO (Professor of Neurosurgery) (London, UK, United Kingdom)
12:30 - 12:45 MRgFUS and the state of the art in Essential Tremor. Lennart STIEGLITZ (Head of functional neurosurgery division) (Zurich, Switzerland)
12:45 - 13:00 The potential of MRgFUS in Parkinson’s disease. Marta DEL ALAMO (Neurosurgeon) (Madrid, Spain)
13:00 - 13:15 MRgFUS: Advanced methods to open new frontiers. Vibhor KRISHNA (Neurosurgeon / Associate Professor, Clinical) (Chapel Hill, USA)
13:15 - 13:30 Discussion.

12:30-13:30
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C24bis
INDUSTRIAL LUNCH WORKSHOPS - ABBOTT
Transforming Care and Improving Patients Quality of Life

INDUSTRIAL LUNCH WORKSHOPS - ABBOTT
Transforming Care and Improving Patients Quality of Life

Moderators: Cristina TORRES (Staff Neurosurgeon) (Madrid, Spain), Veerle VISSER-VANDEWALLE (Head of Dep. of Ster. and Funct. NS) (Cologne, Germany)
12:30 - 12:40 Optimizing DBS therapies with Teleprogramming: Results of a Multicenter RCT. Alireza GHARABAGHI (Medical Director) (Tuebingen, Germany)
12:40 - 12:50 Improving your patients ‘ QoL based on your DBS Platform selection. Alexandra BOOGERS (Fellow) (Toronto, Canada)
12:50 - 13:00 Hybrid systems – Practical tips and patient benefits. Patric BLOMSTEDT (Neurosurgeon) (Umeå, Sweden)
13:00 - 13:10 Adoption of Remote Programming to extend access to patients: A real world experience. Peter SILBURN (ESSFN XXIII Congress) (BRISBANE, Australia)
13:10 - 13:25 Discussion.
13:25 - 13:30 Closing.

12:30-13:30
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D24bis
INDUSTRIAL LUNCH WORKSHOPS - ELEKTA
Extending the horizons of your discipline

INDUSTRIAL LUNCH WORKSHOPS - ELEKTA
Extending the horizons of your discipline

12:30 - 12:40 Elekta 50 years of Functional Neurosurgery – Continuing to extend the horizons of your discipline.
12:40 - 13:00 Embracing the change – moving to Leksell Vantage Stereotactic System. Witold POLANSKI (Germany)
13:00 - 13:20 Improving quality of life after functional neurosurgery with Leksell Gamma Knife. Geert-Jan RUTTEN (neurosurgeon) (Tilburg, The Netherlands)
13:20 - 13:30 Discussion.

13:30
13:30-15:00
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A27
PARALLEL SESSION 1
Movement Disorders 1

PARALLEL SESSION 1
Movement Disorders 1

Moderators: Hidehiro HIRABAYASHI (Director) (NARA,JAPAN, Japan), Kostiantyn KOSTIUK (Neurosurgeon) (KYIV, Ukraine), Ali SAVAS (Prof Dr) (Ankara, Turkey), Rick SCHUURMAN (neurosurgeon) (Amsterdam, The Netherlands)
13:30 - 13:40 #33987 - OP001 Evaluation of Bilateral VIM Radiosurgery in patients with a severe Essential Tremor : a propsective trial.
OP001 Evaluation of Bilateral VIM Radiosurgery in patients with a severe Essential Tremor : a propsective trial.

Background : Safety efficacy of unilateral VIM Gamma Knife Radiosurgery (VIM GK) has been well demonstrated for Essential tremor. The safety-efficacy of bilateral VIMGK has never been assessed strictly. We conducted a prospective and objective assessed of the changes in cognitive functions (primary criteria), speech, balance in addition to the evaluation of the impact activities of daily living.

Material & method : Between 03/06/2014 & 09/11/2021 have been treated contralaterally by GKS 33 patients presenting with a severe drug-resistant essential tremor previously treated by VIM GK on the dominant side at least 12 months before (monocentric, prospective, non comparative N° EUDRACT : 2013-A01289-36). After frame application stereotactic MR and CTscan imaging a single isocenter of 4mm was positioned at the location of the VIM according to Guiot and adjustment of the target based on a preoperative DTi according to our usual standard technic. Quantitative assessment before, at 6 & 12 months was including neuropsychological testing (MMS, apathy Starkstein scale, Stroop, verbal fluences, similitudes), evaluation of the voice, writing, walk gait (Kinematic gait analysis was performed with the SMART TV image processing system, eMOtion), posture (AMTI force platform), tremor severity (Fahn-Tolosa-Marin rating scale) ADL (Bain Scale) and MRI (volume of T1 contrast enhancement and edema score).). The assessment was perform independently from the neurosurgical team. The results were followed and reviewed by an international independent surveillance committee (MH and PK). Patients acted as their own controls

Results : All the 33 patients have completed the study after the one year follow up (19 male 14 female, 32 right VIM and 1 left). Only one adverse event (expected) was observed (hemi-proprioceptive ataxia & dysarthria due to hyper-response 11 months after VIM GK). The mean age was 71 (55-83). The mean delay between the first and the second GK was 28,7 months. The primary outcome criteria of tolerance on the cognitive functions was altered in none of the patients. The evaluation of speech walk gait and posture (secondary outcome criterion) have shown no worsening. In term of efficacy at 1 year the severity score was improved of 58,5%, the disability score of 84,8% and the functional impact score of 68,6%. Only 4 patients failed to respond but for the 29 remaining the mean improvement was of 74,4% improvement of the tremor on the treated upper limb. No side effect related to the bilaterality of the VIM GKS was found in spite of the independent meticulous prospective assessment.

Conclusion : This is the first prospective trial assessing the safety efficacy of bilateral VIM GK. This trial is demonstrating the excellent safety efficacy of VIM GK of the contralateral side in a subgroup of selected candidates previously treated by VIM GK at least 1 year before with a good response of the first side operated.


Jean REGIS, Axel CRETOL (MARSEILLE), Marwan HARIZ, Paul KRACK, Tatiana WITJAS
13:40 - 13:50 #35764 - OP002 Bilateral stereotactic radiofrequency lesioning for Parkinson’s disease: an experience of 41 patients.
OP002 Bilateral stereotactic radiofrequency lesioning for Parkinson’s disease: an experience of 41 patients.

Introduction

Despite the dominance of neurostimulation technology, stereotactic lesioning operations play a significant role in the treatment of movement disorders. Bilateral lesioning surgeries  for Parkinson’s disease (PD) facing criticism, because of the high rate of postoperative complications. However, recent advantages in neuroimaging, wide use high-field MRI, and substantial improving software of planning stations allow to accurately identify the anatomical details of the target and create a safe surgical plan. The aim of the study is to evaluate the effectiveness and safety of staged bilateral radiofrequency stereotactic lesioning for PD. 

Material and methods

41 patients with advanced PD, aged from 40 to 72 years (mean 56.6 years) were enrolled in a retrospective study. Stereotactic RF thalamotomy and consecutive contralateral pallidotomy were performed in 29 (71%) patients (group Vim-GPi), thalamotomy and consecutive contralateral lesion of subthalamic nuclei (STN) were performed in 12 (29%) cases (group Vim-STN). Patients who had severe hypokinesia or progressive hypokinesia after unilateral lesioning, were not candidates for staged bilateral stereotactic lesioning. The mean duration of disease before the first surgery was 9.5 years. Mean interval between the two operations was 3.1 years. Operations were provided without microelectrode recording. Neurological and neuropsychological assessments were performed before surgery and one year after second operation.

Results

One year after treatment total UPDRS score in the OFF state improved in group Vim-GPi by 45% and in group Vim-STN by 42%. Slightly more prominent improvement was evident in the motor UPDRS III score, which improved in the OFF state by 52% in group Vim-GPi, and by 61% in group Vim-STN. Overall, levodopa dose was reduced by 41%.  

Regression of motor symptoms allowed to improve general motor activity, functional independence and quality of life, which was confirmed by improvement of mean Schwab & England daily living score from 55% to 71% in group Vim-GPi (29% improvement) and from 59% to 82% in group Vim-STN (39% improvement). Bilateral stereotactic lesioning had no apparent effect on cognitive function. We didn’t note significant changes in UPDRS mentation, behavior and mood subscores after second operation 

Among 82 interventions in 5 (6.1%) cases we performed repositioning of the electrode after intraoperative macrostimulation. There were no adverse effects after the first operation. After the second intervention, neurological complications were observed in 4 (9.8%) cases, among them 1 (2.4%) patient had permanent events, relating to local ischemia after pallidotomy. 

Discussion

In recent years there has been a renewed interest in lesioning interventions has been observing in stereotactic neurosurgery for movement disorders. This can be explained by the significant achievements of neuroradiological, neurophysiological, and stereotactic software technologies. Nevertheless bilateral lesioning surgeries facing criticism, because of the development of postoperative balance or gate problems, speech disturbances, dysphagia and other adverse effects. To eliminate the risk of adverse events, we proposed to create staged asymmetric lesions for advised PD - thalamotomy and consecutive contralateral pallidotomy or thalamotomy and consecutive contralateral subthalamic nucleotomy. 

In the present study, applying of careful patient selection for staged bilateral lesioning allowed to achieve significant improvement. Suppression of the cardinal motor features of PD together with elimination of levodopa-induced dyskinesias  and motor fluctuations played a crucial role in the improvement of UPDRS score one year after second operation. Careful identification and selection of patients for ablative surgery allow to achieve optimal results in the treatment of PD with bilateral symptoms. 


Kostiantyn KOSTIUK (KYIV, Ukraine), Yuri MEDVEDEV, Andriy POPOV, Valerii CHEBURAKHIN, Vladyslav BUNYAKIN, Sergii DICHKO
13:50 - 13:55 #35843 - OP003 STAGED BILATERAL MAGNETIC RESONANCE IMAGE-GUIDED FOCUS ULTRASOUND THALAMOTOMY FOR ESSENTIAL TREMOR.
OP003 STAGED BILATERAL MAGNETIC RESONANCE IMAGE-GUIDED FOCUS ULTRASOUND THALAMOTOMY FOR ESSENTIAL TREMOR.

1. Introduction

Essential tremor in the most common movement-disorder and bilateral symptoms are typical.However bilateral surgery has been contraindicated because the incidence of speech disorders in bilateral thalamic coagulation is 40% or higher. In conventional surgery, the target is determined based on the atlas that does not consider individual differences, and the position and extension of the coagulation lesion cannot be confirmed during the surgery, but MRgFUS can monitor the position and progress of the coagulation lesion in real time. In ET, language complications were as low as 13.9% even with bilateral thalamotomy, so we performed staged bilateral thalamotomy at intervals of 1 year or more with sufficient informed consent

2. Methods and Materials

We enrolled9 consecutive patients with refractory essential tremor between September 2016 and June 2022. Patients underwent a second operation at least 1 year after the operation.

For treatment, ExAblate Neuro 4000  system (Insightec,Haifa,Israel)was used on 1.5 Tesla MRI. The clinical effects was assessed by the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM).

3. Results

Mean patient age was 57.6, and the mean interval between two operations were27.8 months. The second lesion center was superior to the first lesion in all patients.

The baseline CRST score of 63.6 improved significantly to 49.2 after the first surgery and 21.8 after the second surgery. In particular, in Part C of CRST, the baseline of 18.4 improved significantly to 8.2 after the first operation and 2.6 after the second operation.

Adverse events occurred in 6 of 9 patients, one with very mild but permanent dysarthria, while the other two were transient. The patient with permanent sequelae was satisfied with the results because improvement of the tremor.

4. Discussion

It was said that speech disturbance occurred to be 15% in unilateral and 40% in bilateral thalamotomy.Thalamotomy on the dominant hemisphere is said to be three times more risky than on the non-dominant side. On the other hand, the incidence of dysarthria in essential tremor surgery is one-third that of Parkinson's disease.

Therefore, it is considered that safer treatment can be achieved by performing MRgFUS on the dominant hemisphere first, confirming that no adverse event has occurred, and then performing MRgFUS on the non-dominant side after a while.

5. Conclusions

As a treatment method for ET, MRgFUS is comparable to DBS, which has been the golden standard so far, in terms of treatment results and safety.

the improvement of QOL is superior to DBS because it does not require device placement.

6. References

Fukutome K, Hirabayashi H, Osakada Y 4Yoshihiro Kuga Y Ohnishi H: Bilateral Magnetic Resonance Imaging-Guided Focused Ultrasound Thalamotomy for Essential Tremor Stereotact Funct Neurosurg.;1-9.2021 doi: 10.1159/000518662.

Alomar S Nicolas King N Tam J Bari AA, Hamani C Lozano AM:Speech and language adverse effects after thalamotomy and deep brain stimulation in patients with movement disorders: A meta-analysis Mov Disord. ;32(1):53-63. 2017 doi: 10.1002/mds.26924.

Martínez-Fernández R, Mahendran S, Pineda-Pardo JA, Imbach LL, Máñez-Miró JU, Büchele F, Del Álamo M, Rodriguez-Rojas R, Hernández-Fernández F, Werner B, Matarazzo M, Obeso I, Gonzalez-Quarante LH, Deuschl G, Stieglitz L, Baumann CR, Obeso JA.J:Bilateral staged magnetic resonance-guided focused ultrasound thalamotomy for the treatment of essential tremor: a case series study. Neurol Neurosurg Psychiatry. ;92(9):927-931.2021 doi: 10.1136/jnnp-2020-325278. Epub 2021 Apr 27.PMID: 33906933


Hidehiro HIRABAYASHI (NARA,JAPAN, Japan), Kenji FUKUTOME, Yousuke OSAKADA, Hideyuki OHNISHI
13:55 - 14:05 #36124 - OP004 Bilateral staged VIM thalamotomy for essential tremor.
OP004 Bilateral staged VIM thalamotomy for essential tremor.

Background: Unilateral MRI-guided focused ultrasound (FUS) has established efficacy in tremor relief. Data regarding the safety and efficacy of bilateral, staged treatments is scarce. 

Objective: To report preliminary results of a clinical trial to evaluate the safety and efficacy of staged bilateral FUS thalamotomy in essential tremor (ET) patients that previously underwent unilateral FUS treatment on the opposite side

Methods: Nine patients that underwent unilateral FUS thalamotomy for medication refractory tremor at least six months before (median 1.7 years) and had severe tremor on the untreated side - underwent FUS treatment to relieve tremor. The target within the VIM was chosen based on the contralateral lesion (as a mirror targeting) and modified based on its clinical effect. The primary outcome was the change in tremor score in the treated hemi-body relative to baseline, using the Clinical Rating Scale for Tremor (CRST). The secondary outcome was the change in quality of life (QOL) in ET (QUEST) score relative to baseline. In addition, an adverse event profile was collected.

Results: Tremor significantly improved following treatment from a median score of 14 at baseline to a median score of 2.5 at 1 month, 3 at 3 months (P=0.001). Quest score improved from a median score of 31 before FUS to 11 at 1 month and 10 at 3 months. All nine patients experienced mild transient ataxia that lasted between 2 days and 4 weeks. Two patients reported tongue sensation abnormalities that did not resolve at 1-month visit. One patient had an ipsilateral minor cerebellar stroke secondary to an antiaggregant medication cessation for the procedure. No speech deficits were noted.

Conclusions: Our preliminary results suggest that staged bilateral magnetic resonance-guided focused ultrasound thalamotomy was effective and safe and improves the tremor and quality of life of patients with ET. Second-side lesions may correlate with a higher rate of ataxia, though probably transient. More extensive studies and longer-term follow-ups are needed to validate these findings. 


Schlesinger ILANA, Sinai ALON, Nassar MARIA, Sederova INNA, Shornikov LEV, Shalem NOAM, Katson MARK, Erikh ILANA, Constantininescu MARIUS, Lev-Tov LIOR (Haifa, Israel)
14:05 - 14:10 #33825 - OP005 Combined Unilateral Radiofrequency Lesioning of the Motor Thalamus, Field of Forel, and Zona Incerta: A Series of Cases With Dystonia.
OP005 Combined Unilateral Radiofrequency Lesioning of the Motor Thalamus, Field of Forel, and Zona Incerta: A Series of Cases With Dystonia.

Background: Dystonia is a group of disorders characterized by involuntary slow repetitive twisting movements and/or abnormal posture. Surgical options such as neuromodulation through deep brain stimulation and neuroablative procedures are available for patients who do not respond to conservative treatment.

Objective: To present our series of patients with dystonia who were treated with stereotactic combined unilateral radiofrequency lesioning of the motor thalamus, field of Forel, and zona incerta.

Methods: Medical records of 50 patients with dystonia who were treated with unilateral combined lesions were reviewed. Outcomes of the surgical procedure were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (with movement and disability subscales) and Unified Parkinson's Disease Rating Scale-tremor items.

Results: Based on the symptoms, patients were categorized as having generalized dystonia (34%), hemidystonia (30%), and dystonic tremor (DT) (36%). Primary/idiopathic dystonia, primary genetic/hereditary dystonia, and secondary dystonia accounted for 16%, 4%, and 80% of patients, respectively. The mean follow-up duration was 156.2 ± 88.9 mo. The overall improvement in the Burke-Fahn-Marsden Dystonia Rating Scale scores (movement and disability, respectively) was 57.8% and 36.4% in generalized dystonia, 60.0% and 45.8% in hemidystonia, and 65.6% and 56.8% in DT. Patients with DT showed an 83.3% improvement in mean Unified Parkinson's Disease Rating Scale tremor score. Patients with cerebral palsy showed mean improvements of 66.7% in movement scores and 50.8% in disability scores. No mortality or major morbidity was observed postoperatively.

Conclusion: Stereotactic radiofrequency unilateral combined thalamotomy, campotomy, and zona incerta lesions may be an effective surgical alternative for patients with dystonia, especially those with secondary dystonia resistant to deep brain stimulation.


Ali SAVAS (Ankara, Turkey), Eyup BAYATLI, Umit EROGLU, M. Cenk AKBOSTANCI
14:10 - 14:20 #36129 - OP006 Stimulation of combined Subthalamic Nucleus and Substantia Nigra for Refractory Freezing of Gait in Advanced Parkinson Disease: Experience from our center.
OP006 Stimulation of combined Subthalamic Nucleus and Substantia Nigra for Refractory Freezing of Gait in Advanced Parkinson Disease: Experience from our center.

Introduction:
Deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) is a safe procedure to treat motor symptoms in patients with Parkinson's disease (PD). Most patients develop gait disorders and freezing of gait (FOG) as PD progresses. Alternative DBS targets to successfully treat these symptoms have been explored, including the stimulation of the pars reticulata of substantia nigra (SNr). This anatomical landmark is deep to the STN, allowing for combined stimulation of both targets with a single electrode.

Objectives:
To report our series of patients operated with low frequency SNr-DBS combined with standard high frequency STN, for improving freezing of gait in PD patients.

Material and Methods:
16 patients with advanced PD were operated on using multidirectional electrodes. Surgical planning was performed with the aid of BrainLab Elements planning station (BrainLab, Munich, Germany). Target was selected 2mm into the SNr trough the STN. Surgery was carried out with a Leksell stereotactic frame (Elekta, Stockholm, Sweden). The procedure was done under sedation and local anesthetic, with intraoperative registration and stimulation test. Final electrode position was verified though an intraoperative OARM2-CTscan (Medtronic, Minnesota, USA). Patients follow up was done by a neurologist on a weekly basis for a month, to adjust DBS therapy, and then adjusted according to patient needs.

Results:
All 16 patients (32 electrodes) had an adecuate SNr-STN electrode positioning (Accuracy between 0,16-0,42mm). 1 of 16 patients su
ffered minor complication (bleeding in the electrode trajectory). 3 out of the 32 electrodes produced minor adverse secondary effects at 1,5mAh (2 produced diplopia and 1 internal capsule stimulation). Clinical global impression (CGI) from patient and neurologist was marked improvement in 15 out of 16 patients. 9 of 16 patients presented FOG before DBS implant. 4 of them referred improvement with STN stimulation only, while the other 5 referred significant reduction in FOG with STN-SNr stimulation.

Conclusion:
In our series, implant of STN-SNr electrodes was a safe procedure with few minor complications , not clearly attributable to the selected target. The STN-SNr resulted in a useful alternative target in patients with FOG resistant to levodopa + STN stimulation alone. This information could be useful for target selection in patients with advanced PD an FOG. Further research in this field is required to optimally select patients that can benefit from this additional therapy target.


Juan Pablo VALENCIA SALAZAR (Valencia, Spain), Luis REAL PEÑA, Felix PASTOR ESCARTIN, Jose Maria SALOM JUAN, Marta Maria QUIROS MARTÍ, Xavier PERIS FUERTES, Jose Manuel GONZALEZ DARDER
14:20 - 14:30 #36167 - OP007 The efficacy of bilateral dbs with double targeting vim and psa for treatment of rare tremor syndromes.
OP007 The efficacy of bilateral dbs with double targeting vim and psa for treatment of rare tremor syndromes.

Background: Tremor is an involuntary, rhythmic, and oscillatory movement of a body part. It is a common symptom in movement disorders appearing sometimes in isolation and sometimes in combination with other symptoms. When sufficient relief cannot be achieved with pharmacological treatment, Deep Brain Stimulation (DBS) has proven effective for ET (Essential Tremor) and Parkinson’s Disease tremor. The Vim (Ventromedial Nucleus) has been the main target for tremor DBS surgery. Unfortunately, there is a scarcity of data regarding the effect of Vim DBS on rare tremor syndromes, for some conditions limited to a few case reports and sometimes with conflicting results. The PSA (Posterior Subthalamic Area), is a relatively new target for DBS and  lies in the proximity of Vim, why it is possible to align an electrode to place contacts in both targets (Double target). Double targeting of the VIM and PSA is a rather recent practice, allowing us to stimulate both targets simultaneously or separately. In the current study we decided to apply double targeting to some rare tremor conditions, to decide on the effect and safety of the procedure.

 

Methods: Between 2019 and 2023, 22 patients with rare tremor syndromes were bilaterally implanted using the double targeting: 7 isolated head tremor, 1 hepatic encephalopathic tremor due to Abernethy Syndrome, 2 voice tremor, 4 dystonic tremor, 8 Holmes tremor (2 MS, 2 cerebellar insult, 4 post-traumatic). The patients’ demographic characteristics, clinical aspects, tremor scores and relevant symptoms are shown in Table 1.

Results: All 22 patients who underwent double targeted DBS surgery demonstrated a remarkable improvement of tremor symptoms. The outcome at 12 month is presented in Table 1, with the items selected in accordance with the patients’ specific condition.

 

Conclusions: In the current study, double targeting of the Vim and PSA provided a very satisfying degree of tremor reduction in several rare tremor syndromes. Further studies are needed to decide on the relative effectiveness of the two targets in relation to combined targeting, as well as on the role of DBS in various rare tremor conditions.


Atilla YILMAZ (Istanbul, Turkey), Anil ERAY, Ali SAVAS, Patric BLOMSTEDT
14:30 - 14:35 #35633 - OP008 High-resolution intra-operative data for the generation of probabilistic stimulation maps in DBS of Vim for ET.
OP008 High-resolution intra-operative data for the generation of probabilistic stimulation maps in DBS of Vim for ET.

Group analysis consists of using an anatomical space as reference, transferring data such as contact location and extend of stimulation from each patient and relating them to the symptomatic effect. Analyzing past implantations should support understanding the mechanisms of action of DBS and predicting outcome in new patients. 

Most studies place their focus on the chronic stimulation situation, with the lead at a fixed position in the brain. This results in few data samples per patient, requiring large cohorts. On the other hand, intra-operative tests are an attractive source of data. The aim of this study was to develop a fully automated pipeline for analyzing the results of intra-operative stimulation tests of ventro-intermediate nucleus of the thalamus (Vim) for ET using high-fidelity data and exemplify the pipeline on a group of patients. 

Data from 19 DBS patients (6 ET, 16 PD) from the University Hospital Clermont-Ferrand (France) was used to create an MR template including patient-specific labels, resulting in a probabilistic definition of 57 deep brain structures. 

Data from the 6 ET patients in the group was used to create a probabilistic stimulation map (PSM). Tremor reduction was assessed during intra-operative stimulation tests using a wrist-worn acceleration sensor. These scores were combined with patient-specific electric field (EF) simulations into a 4D volume. The latter was first summarized into a weighted mean map (average of the improvement weighted by the EF norm). Voxels with low occurrence of fields (10% of max) and number of patients (2 of 6) were excluded. Secondly, the significance of the relationship between tremor reduction and electric field was estimated with Linear mixed models using patient as a random effect. Voxels in the weighted mean map with |p|>0.05 were excluded. 

Figure 1 presents the anatomical structures of the group-specific deep brain atlas together with the clusters presenting a positive and negative relationship between EF and tremor reduction (respectively green and red surfaces with black edges). The largest part of the cluster significant for positive correlation covers the inferior half of the Vim and extends in the direction of subthalamic nucleus in the posterior subthalamic area, covering parts of Forel fields. 

A fully automated, reproducible workflow was established to normalize and analyze intra-operative data and allowed to identify regions with significant relationship between electric field and tremor suppression. In the future more patients will be integrated to conduct statistical verification of the identified regions. 


Dorian VOGEL (Basel, Switzerland), Karin WÅRDELL, Coste JÉRÔME, Jean-Jacques LEMAIRE, Simone HEMM
14:35 - 14:40 #36094 - OP009 Shifting from deep brain stimulation to Brain lesioning, one year experience after relocation from developed to developing countries.
OP009 Shifting from deep brain stimulation to Brain lesioning, one year experience after relocation from developed to developing countries.

Shifting from deep brain stimulation to Brain lesioning, one year experience after relocation from developed to developing countries. 

Mahmoud Abdallat  1,2Mahmoud.Abdallat@ju.edu.jo  

Nora AbuAmmouneh 2, Noraabuammouneh@gmail.com 

Rand AlQaseer 2, Randalqaseer.7@gmail.com 

Yazan Dabbah 2, Yazan.dabbah@gmail.com 

Bdour Abdallat 2, bdoor.abdallat@hotmail.com 

Abdallah Barjas Qaswal 3, qaswalabdullah@gmail.com 

Radwan Banimustafa3, r.banimustafa@ju.edu.jo 

1 Department of Neurosurgery, The University of Jordan, Amman, Jordan 

2 School of Medicine, The University of Jordan, Amman, Jordan 

3 Department of Psychiatry, The University of Jordan, Amman, Jordan 

 

Introduction: Brain lesioning though used since the 1950s, had been replaced by DBS in the 1990s. The Author had an experience doing as Assistant and first surgeon more than 300 deep brain stimulation operations in Hannover/ Germany and London Ontario/ Canada from 2009 to 2019. In 2019 the Author relocated to his Homeland Jordan to transfer the functional neurosurgery experience to his country. Due to the financial situation of the public insurance system, the Author shifted from deep brain stimulation operations to the brain lesioning operation using Radiofrequency and Gamma Knife. On 21.07.2022 he performed the first Radiofrequency lesioning. Since then, 31 Radiofrequency Brain lesioning operations have been performed (26 unilateral and 1 bilateral pallidotomy for Parkinson as well as 2 unilateral pallidotomy and 2 bilateral pallidotomy for Dystonia). Brain lesioning using the Gamma Knife Icon have been also performed, 4 unilateral subthalamotomy for Parkinson patient, 1 Thalamotomy for essential tremor, 1 cingulotomy for anxiety disorder and 4 internal capsulotomy for medical intractable obsessive-compulsive disorder (OCD). 

Results: the median Improvement in Radiofrequency and GammaKnife of the Unified Parkinson's Disease Rating Scale (UPDRS) III was 30.1%, significant improvement of the essential tremor patient, 2 patients improved from severe to mild OCD and 2 OCD patients had no improvement. Moderate improvement of dystonia patients, an overall mean improvement of 35% in the BFMDRS-M score was achieved. 

Conclusion: Brain lesioning can be considered as a good treatment option in the developing countries, where deep brain stimulation is not often financially affordable.  


Mahmoud ABDALLAT (Amman/ Jordan, Jordan)
14:40 - 14:45 #35709 - OP010 Imaging-based programming in bilateral subthalamic deep brain stimulation for Parkinson’s disease: a retrospective pilot study.
OP010 Imaging-based programming in bilateral subthalamic deep brain stimulation for Parkinson’s disease: a retrospective pilot study.

Introduction

Bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment of choice in Parkinson’s disease (PD) with motor fluctuations. Conventional programming in the ring mode (CP-RM) is used as standard to choose the best therapeutic contact – an exhausting process for patients and caregivers. We instead used guidance software to estimate the patient-specific volume of tissue activated (VTA), facilitating selection of contacts and programming parameters. We aimed to demonstrate similar efficacy between VTA programming and CP-RM.

Methods

Consecutive STN-DBS PD patients (February 2019 to January 2021) were programmed using VTA guidance (VTA group). Their clinical data were retrospectively compared to a historical cohort of STN-DBS PD patients (March 2011 to February 2014) whose stimulation parameters had been determined using CP-RM. Primary outcome: improvement in the Unified Parkinson’s Disease Rating Scale part III score between the preoperative OFF phase and on-stimulation/off-drug condition 1-year postoperatively.

Results

Twenty-six patients were included (VTA n=12; CP-RM n=14; mean age 62.4±7.55 years). There was no significant difference between groups in the primary endpoint (VTA 43.62 vs. CP-RM 41.29). The immediate postoperative length of stay (6.25 vs. 18.93; p<0.0001) and number of hospitalizations post-discharge (1.17 vs. 2.00; p=0.007) were significantly lower in the VTA vs. CP-RM group, respectively.

Discussion

The ability to direct stimulation towards the optimal, patient-specific target has the potential to improve outcomes in PD. However, the increased complexity in programming options has led to conventional programming becoming unwieldy and even more time consuming, placing considerable burden on the patient. Anatomy-based, image-guided visualization software to facilitate the process is essential – but in these relatively early days, the long-term impact of using such software alone to select the optimal contacts and stimulation parameters is uncertain.

Despite the small number of patients, our initial results suggest that use of VTA software alone to choose the optimal contacts for stimulation and subsequently refine therapy does not impair the improvement in motor symptoms over the long term and will reduce both the number of hospitalizations required and the length of the hospital stay. These reductions should help to streamline the care pathway, without compromising therapeutic efficacy. It is our view that VTA software should be used routinely to program patients and at all follow-ups to facilitate individualized patient management and simplify the care pathway. Results must be validated in a larger, multicentric cohort.


Alexis BERRO, Mickael AUBIGNAT (Amiens), Melissa TIR, Michel LEFRANC
14:45 - 14:55 #36174 - OP011 ROAM-DBS: Teleprogramming Reduces the Time to Optimize DBS Therapy.
OP011 ROAM-DBS: Teleprogramming Reduces the Time to Optimize DBS Therapy.

Background: Deep Brain Stimulation (DBS) management for Parkinson’s Disease (PD)  can be limited by the burden of traveling to the clinic for care. Patients must travel to the clinic to receive updates to the stimulation, which can be challenging and costly, leading to reduced access. Teleprogramming may reduce the burden of DBS management by enabling DBS device interrogation and programming remotely. The ROAM-DBS trial compares the impact of teleprogramming and in-clinic programming on the time-course of symptom improvement after DBS implant.

Methods: The ROAM-DBS study is a multicenter, prospective randomized controlled trial for PD patients comparing in-clinic DBS programming only with teleprogramming using Abbott’s Neurosphere™ Virtual Clinic platform. After each programming visit, participants are asked to evaluate their symptom improvement using the Patient’s Global Impression of Change (PGI-C), and clinicians rate symptoms using the Clinician’s Global Impression of Change (CGI-C). In addition, participants are asked to complete the PDQ-39 quality of life questionnaire monthly.

Results: 82 patients had enrolled in the ROAM study by March 7, 2023, and 51 had completed the 3-month follow-up. Initial PDQ-39 quality of life scores of 26.8+/-11.8 in the teleprogramming arm are similar to those from the in-clinic arm of 25.8+/-13.6 (p=0.84). After 3-months, most subjects report improvement in PGI-C scores (teleprogramming arm: 23/26; in-clinic arm: 18/25, p=0.41). The teleprogramming arm shows a shorter time to improvement of 34.0+/-16.6 days compared to 46.8+/-19.1 days for the in-clinic arm (p<.05), and 2.8+/-2.4 programming visits compared to 1.25+/-1.1 visits in the clinic arm(p<.01). Similar outcomes are observed with the CGI-C, with 35.9+/-20.1 days to improve 1 point in the teleprogramming arm compared to 51.2+/-16.7 days for the in-clinic arm (p<.01). 2 non-serious, and 2 serious Adverse Events (AE) were reported in the teleprogramming arm, while 3 non-serious and 2 serious AE were reported for the in-clinic arm. 3 of the serious AE were either related to the implant procedure or in 1 case related to cardiac disfunction, and were not the result of programming changes. 

Conclusions: Despite similar baseline symptoms, Parkinson’s patients in the teleprogramming arm improved faster than the in-clinic arm. This suggests that easier access to programming sessions enabled by teleprogramming reduces the time necessary to optimize DBS therapy. Both arms reported similar Adverse Event rates, suggesting that use of teleprogramming does not affect safety of DBS therapy. These early results highlight the potential improvements in DBS care using digital healthcare solutions.


Alireza GHARABAGHI (Tuebingen, Germany), Sergiu GROPPA, Marta NAVAS GARCIA, Lydia LOPEZ MANZANARES, Alfons SCHNITZLER, Corneliu LUCA, Vicky MARSHALL, Laura MUNOZ DELGADO, Ramiro ALVAREZ, Lin ZHANG, Mary FELDMAN, Michael SOILEAU, Hong LEI, Benjamin WALTER, Chengjuan WU, Lan LUO, Tucker TOMLINSON, Yagna PATHAK, Daniel WEISS
14:55 - 15:00 #36202 - OP012 Probabilistic and AI-based computed assisted DBS programming.
OP012 Probabilistic and AI-based computed assisted DBS programming.

DBS has shown been shown to drastically improve symptoms of movement disorders such as Parkinson’s Disease, Essential Tremor and Dystonia. . High precision in targeting and electrode implantation has been correlated with good clinical outcomes. In the recent years, DBS with segmented leads have not only pioneered novel directional DBS, but also provided innovative approaches in targeting and patient programming. Improvement of imaging, development of intraoperative monitoring research as well as collaboration between biomedical engineers and clinicians has empowered  the development of computer models of DBS as well as their use for computer based DBS programming, either based on probabilistic sweet spots, or more recently, using artificial intelligence (AI). We describe these different approaches and report  our experience in implementing them with local and multicenter clinical data provided by international teams. These approaches facilitate DBS programming and also promote a better understanding of brain networks dysfunctions underlying neurologic and psychiatric disorders.


Thủy Anh Khoa NGUYEN, Jan WALIGORSKI, Sabry BARLATEY, David ZHANG, Andreas NOWACKI, Claudio POLLO (Bern, Switzerland)

13:30-15:00
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PARALLEL SESSION 2
Psychiatry 1

PARALLEL SESSION 2
Psychiatry 1

Moderators: Juan Antonio BARCIA (Neurosurgeon) (Barcelona, Spain), Ali REZAI (Neurosurgery) (Morgantown, USA), Veerle VISSER-VANDEWALLE (Head of Dep. of Ster. and Funct. NS) (Cologne, Germany)
13:30 - 13:40 #33854 - OP013 Anatomical characterisation of three different psychosurgical targets in the subthalamic area: from the basal ganglia to the limbic system.
OP013 Anatomical characterisation of three different psychosurgical targets in the subthalamic area: from the basal ganglia to the limbic system.

Effective neural stimulation for the treatment of severe psychiatric disorders needs accurate characterisation of surgical targets. This is especially true for the medial subthalamic region (MSR) which contains three targets: the anteromedial STN for obsessive compulsive disorder (OCD), the medial forebrain bundle (MFB) for depression and OCD, and the “Sano triangle” for pathological aggressiveness. Blocks containing the subthalamic area were obtained from two human brains. After obtaining 11.7-Tesla MRI, blocks were cut in regular sections for immunohistochemistry. Fluorescent in situ hybridisation was performed on the macaque MSR. Electron microscopic observation for synaptic specialisation were performed on human and macaque subthalamic fresh samples. Images of human brain sections were reconstructed in a cryoblock which was registered on the MRI and histological slices were then registered. The STN contains glutamatergic and fewer GABAergic neurons and has no strict boundary with the adjacent MSR. The anteromedial STN has abundant dopaminergic and serotoninergic innervation with sparse dopaminergic neurons. The MFB is composed of dense anterior dopaminergic and posterior serotoninergic fibres, and fewer cholinergic and glutamatergic fibres. Medially, the Sano triangle contains orexinergic terminals from the hypothalamus, and neurons with strong nuclear oestrogen receptor-alpha staining with a decreased anteroposterior and mediolateral gradient of staining. These findings provide new insight regarding MSR cells and their fibre specialisation, forming a transition zone between the basal ganglia and the limbic systems. Our 3D reconstruction enabled us to visualise the main histological features of the three targets which should enable better targeting and understanding of neuromodulatory stimulation results in severe psychiatric conditions. 


Marie Des Neiges SANTIN, Nicolas TEMPIER (Paris), Hayat BELAID, Matthieu ZENONI, Sylvie DUMAS, Åsa WALLÉN-MACKENZIE, Eric BARDINET, Christophe DESTRIEUX, Chantal FRANÇOIS, Carine KARACHI
13:40 - 13:50 #35844 - OP014 Deep Brain Stimulation of the anteromedial STN (amSTN) and the superolateral medial forebrain bundle (slMFB) in obsessive-compulsive disorder each address a distinct network.
OP014 Deep Brain Stimulation of the anteromedial STN (amSTN) and the superolateral medial forebrain bundle (slMFB) in obsessive-compulsive disorder each address a distinct network.

Objective: Obsessive-compulsive disorder (OCD) is a prevalent disease (1-3%). Patients suffer from ego-dystonic intrusive thoughts (obsessions) which lead to repetitive stereotypic actions (compulsions) (Figure 1B). There are effective treatments for OCD (SSRI and CBT) and if resistant, DBS appears to be an option. Four networks have been described to be relevant for OCD (1). Numerous DBS target regions have been described and there is a recent tendency to unify these regions and to attribute anti-OCD efficacy to a common pathway (2). We have here researched the antero-medial subthalamic nucleus (amSTN) and the superolateral medial forebrain bundle (slMFB) for the potential to unfold their efficacy through addressing neighboring but distinct networks of the OCD circuitry (1). 

Methods: We applied a microscopic short range fiber atlas (3) and investigated DBS electrodes from an amSTN cohort (Grenoble, n=14, same as used in (2)) and an slMFB cohort (Freiburg, n=11) with respect to midbrain fiber anatomy. Effective contacts (EC) were identified in postoperative imaging (MRI, CT), fused into MNI space and their respective volume of activated tissue (VAT) simulated (Figure 1A, amSTN blue spheres, slMFB green spheres), based on their stimulation settings. The distance to distinct fiber pathways (slMFB mesocortical=mc, mesolimbic=ml, cerebral peduncle: p1, p2, p3) were estimated with increasing VTA sphere diameters (Figure 1, C-D). A maximal distance of 2-3 mm to a fiber pathway was interpreted to explain therapeutic effectiveness. 

Results: Our analysis was not able to differentiate responders from non-responders in both target regions based on differential fiber recruitment. However, principle patterns of fiber architecture recruitment of the two target regions could be analyzed. Effectiveness of slMFB DBS can in principle be explained with both slMFBmc and slMFBml (Figure 1C). Efficacy of amSTN in our analysis can in part be explained through p1/p2 (so associative STN) but in part also through slMFBmc/ml.

Discussion: Typical amSTN effectiveness can be attributed to p1/p2 as part of the motor control network (Figure 1B and (1)). If amSTN utilizes ECs very deep and medial in the nucleus, effectiveness might be attributed to a proximity to slMFBmc/ml as part of the reward network as suspected earlier (3,4). 

Conclusion: Our results suggest a clinical effectiveness obtained by stimulating 2 distinct pathways as parts of different networks (2). Our results shed new light on the previous definition of a common pathway (2) and underpins an alternative anatomical and physiological hypothesis. Future analyses are sought to highlight differential impact of the two network components on various OCD dimensions by this linking clinical improvement to distinct network interactions. 

References:

  1. Coenen et al. 2020. 10.1016/j.nicl.2020.102165

  2. Li et al. 2020. 10.1038/s41467-020-16734-3

  3. Coenen et al. 2022. 10.1007/s00429-021-02373-x

  4. Tyagi et al. 2019. 10.1016/j.biopsych.2019.01.017


Volker Arnd COENEN (Freiburg, Germany), Mircea POLOSAN, Thomas Eduard SCHLAEPFER, Stephan CHABARDES, Manuel CZORNIK, Horst URBACH, Bastian SAJONZ, Marco REISERT
13:50 - 14:00 #34673 - OP015 The prefrontal leucotomy for psychiatric diseases in times past – Study with the combination of Tractography and Scalp EEG Functional Connectivity Analysis –.
OP015 The prefrontal leucotomy for psychiatric diseases in times past – Study with the combination of Tractography 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.

    It is now widely accepted that some brain functions are not supported by isolated areas but rather by a dense network of nodes interacting in various ways.

    This study aimed to identify structural and functional connectivity severed by the prefrontal leucotomy.

 

Methods:

    Diffusion tensor imaging (DTI) scans were acquired from six schizophrenia patients and six prefrontal leucotomized patients with schizophrenia, group-matched for age, on a 1.5T scanner. All leucotomized patients underwent the surgeries approximately more than a half-century ago. Voxelwise statistical analysis of the fractional anisotropy (FA) data in white matter tracts was compared between the leucotomized schizophrenia group and the non-leucotomized schizophrenia patient group.

    We calculated oscillation-based functional connectivity with imaginary coherence for the connectivity analysis. Routine scalp-EEG (19 electrodes) was recorded from 3 prefrontal leucotomized patients and six schizophrenia patients matched for age while they were at rest with eyes closed (resting state). This measured the imaginary part of coherence and the node degrees using the graph theory between all pairs of ROIs for each frequency band and group.

 

Results:

    The statistical analysis with TBSS shows that the Prefrontal leucotomy disrupted the frontolimbic white matter tract, including the genu of the corpus callosum (CC), the anterior cingulate cortex, and the anterior limb of the internal capsule (ALIC). In analyzing EEG functional connectivity for the resting state, a weaker node degree, namely, weaker connectivity, was apparent in the cingulate cortex throughout the delta to beta bands in the leucotomized brain compared to the control. In addition, the prefrontal connection where the surgical maneuvers were made was highly severed in the theta frequency band.

 

Conclusions:

1) The prefrontal leucotomy disrupted the frontolimbic white matter tract, including the genu of the corpus callosum (CC), the anterior cingulate cortex, and the anterior limb of the internal capsule (ALIC). These affected regions by the prefrontal leucotomy are therapeutic targets of contemporary surgeries for psychiatric disorders such as obsessive-compulsive disorder (OCD), depression, and anxiety.

2) The prefrontal leucotomies decreased connectivity of the cingulate cortex and affected the extensive cortical regions beyond the limbic areas, which could contribute to several adverse effects of the surgery.


Katsushige WATANABE (Tokyo, Japan), Sumito SATO, Masashi HORIUCHI, Chiho NAKAGAMI, Hiroyuki FUKUYAMA, Kiyomi AMEMIYA
14:00 - 14:10 #34743 - OP016 Individualized targeting is warranted in subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression: a tractography analysis.
OP016 Individualized targeting is warranted in subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression: a tractography analysis.

Introduction: Subcallosal cingulate gyrus (SCG) is a target of deep brain stimulation (DBS) for treatment-resistant depression. However, previous randomized controlled trials report that approximately 42% of patients are responders to this therapy of last resort, and suboptimal targeting of SCG is a potential underlying factor to this unsatisfactory efficacy. Tractography has been proposed as a supplementary method to enhance targeting strategy.

Methods: We performed a connectivity-based segmentation in the SCG region via probabilistic tractography in 100 healthy volunteers from the Human Connectome Project. The SCG voxels with maximum connectivity to brain regions implicated in depression, including Brodmann Area 10 (BA10), cingulate cortex, thalamus, and nucleus accumbens were identified, and the conjunctions were deemed as tractography-based targets. We then performed deterministic tractography using these targets in additional 100 volunteers to calculate streamline counts compassing to relevant brain regions and fibers. We also evaluated the intra- and inter-subject variance using test-retest dataset.

Results: Two tractography-based targets were identified. Tractography-based target-1 had the highest streamline counts to right BA10 and bilateral cingulate cortex, while tractography-based target-2 had the highest streamline counts to bilateral nucleus accumbens and uncinate fasciculus. The mean linear distance from individual tractography-based target to anatomy-based target was 3.2 ± 1.8 mm and 2.5 ± 1.4 mm in left and right hemispheres. The mean ± standard deviation of targets between intra- and inter-subjects were 2.2 ± 1.2 and 2.9 ± 1.4 in left hemisphere, and 2.3 ± 1.4 and 3.1 ± 1.7 in right hemisphere, respectively.

Conclusion: Individual heterogeneity as well as inherent variability from diffusion imaging should be taken into account during SCG-DBS target planning procedure.


Zhoule ZHU, Zhu JUNMING, Wu HEMMINGS (Hangzhou, China)
14:10 - 14:15 #35744 - OP017 Long-term follow-up of deep brain stimulation in generalized anxiety disorder and treatment-resistant depression – a case report of two patients.
OP017 Long-term follow-up of deep brain stimulation in generalized anxiety disorder and treatment-resistant depression – a case report of two patients.

Background: Generalized anxiety disorder (GAD) and depression are associated with severe functional impairment and great suffering. Deep brain stimulation (DBS) is a neurosurgical procedure in which electrodes are implanted into specific brain regions. DBS has emerged as a treatment alternative in severe treatment-resistant depression, and around 350 patients worldwide have received DBS. Until now, very little is known about DBS for severe anxiety including GAD. There are a few case reports describing effects of DBS in patients with comorbid GAD.

 

Objective: We here describe long-term follow-up of two patients with treatment-resistant GAD and depression, who received DBS with dual implants in the medial forebrain bundle (MFB) and bed nucleus of stria terminalis (BNST).

 

Method: Participants were enrolled in a randomized controlled study on DBS for treatment-resistant depression. DBS electrodes were implanted bilaterally in MFB and BNST. Patient 1 (P1) was randomized to DBS in BNST for three months, followed by DBS in MFB for three months. Conversely, Patient 2 (P2) was randomized to DBS in MFB, followed by DBS in BNST. After the six-month-long randomization phase, P1 continued to receive mainly BNST stimulation for four years but MFB augmentation was tried. P2 received continuous BNST stimulation for five years. Patients were followed with the clinical interview versions of Montgomery–Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A).

 

Results: P1 responded to DBS in BNST after three months with marked reduced anxiety and depression scores in relation to baseline (HAM-A: 65%, MADRS:77% reduction). After switching to DBS in MFB, the improvement was reversed. P2 did not respond to the initial DBS in MFB, but after switching to DBS in BNST, depression scores (MADRS) were reduced by 51%. At follow-up after four (P1) or five years (P2), stable improvements were observed regarding depressive symptoms (MADRS reduction: P1 48%, P2 55%). Interestingly anxiety symptoms were markedly reduced compared to baseline (HAM-A reduction: P1 70%, P2: 65%).

 

Conclusion: In this case report, DBS in BNST had effects on anxiety symptoms in GAD and depression that persisted over the four- to five-year follow-up period, while the effect from MFB stimulation was uncertain. The observed improvements in anxiety from long-term DBS highlight DBS in BNST as a potential treatment option for GAD. However, it is difficult to unravel whether the effects on anxiety symptoms result from a general improvement in depression or a direct DBS effect on brain circuits involved in anxiety regulation.


Viktoria JOHANSSON (Stockholm, Sweden), Blomstedt PATRIC, Naesström MATILDA
14:15 - 14:20 #36065 - OP018 Exploring the mechanism of action of deep brain stimulation in depression: role of noradrenergic fibers in the medial forebrain bundle.
OP018 Exploring the mechanism of action of deep brain stimulation in depression: role of noradrenergic fibers in the medial forebrain bundle.

Introduction: Superolateral medial forebrain bundle deep brain stimulation (slMFB DBS) has demonstrated promising clinical anti-depressant effects in drug-refractory depressive patients. Its mechanisms of action remain elusive. In this study, using control and a rodent model of depression, we investigated i.) in vivo noradrenalin (NA) release (using fiber photometry) in the prefrontal cortex (PFC) and nucleus accumbens (NAC) after mfb stimulation; ii.) the state of myelination of NA projections in the mfb;  and iii.) the activation of NA neurons in brain stem and the feedforward inhibition circuitry in PFC and NAC.

Methods and Material: Male Sprague Dawley (SD, n=20) and Flinders Sensitive Line rats (FSL, n=20) were used, with subgroups undergoing phenotyping using the Forced Swim Test (FST). To look at myelination and distribution of NA fibers, the brains were sliced and double stained for DßH, or DßH/myelin. To study mfb stimulation evoked NA release, unilateral AAV-hsyn-NE2m NA sensor was injected, and optic fiber implanted at PFC or NAC, and DBS electrodes in the ipsilateral mfb. Five seconds mfb-DBS with 30Hz/130Hz frequency and 100µs/250µs/350µs pulse-width (pseudo random, one condition/ day) were repeated 20 times with 50s interval over 6 days. In vivo NA release and ultrasonic vocalization (USV) were recorded. USVs in the positive affective band (40k-60k) were quantified. To look at network activation, animals were stimulated at 130Hz, 100µs 24hrs after the last recording and sacrificed for histology. Parvalbumin/cFOS at PFC, NAC and DßH/cFOS at brain stem were compared with matched sham animals.

Results: FST immobility was significantly higher in the FSL group (p=0.0022). The NA (DßH+) fibers were found unmyelinated, and at the medial part of the mfb. Stimulation evoked a NA release in PFC and NAC in both groups. The FSL group showed significant higher NA release in NAC (p<0.001) but not PFC (p=0.268). The accumulative positive affective ultrasonic calls during the mfb-DBS recording showed a significant greater number of events amongst the FSLs (p=0.0100). NA cell groups A1, A2, and A6 and PV interneurons in the PFC/ NAC, showed bilateral cFOS co-localization.

Discussion: NA dependent mechanism of clinical slMFB DBS have been under investigated although they could contribute to the modulation of the central (e.g. arousal/alertness) and the autonomic nervous systems (e.g. change in heart rate). In our study, unilateral mfb-DBS indirectly activated the unmyelinated NA fibers originating from A1/ A2/ A6 NA neurons and projecting to PFC and NAC. Interestingly, unilateral stimulation resulted in bilateral pathway activation as shown by c-FOS data. FSLs, compared to SD controls, showed a significantly higher NA release at NAC, but not at PFC. In the PFC, the NA release observed where comparable across the experimental groups, however, the release varied by pulse width and frequency. Finally, our data suggests that the NA inputs can potentially modulated the PV interneurons in the PFC and the feed forward inhibition circuitry in striatum. Further research on the role of NA in slMFB DBS is need to gain better understanding of the anti-depressant mechanisms of this promising experimental therapy.


Zhuo DUAN (Freiburg, Germany), Yixin TONG, Lidia MIGUEL TELEGA, Xiongpeng WENG, Volker Arnd COENEN, Máté DÖBRÖSSY
14:20 - 14:30 #36109 - OP019 Deep brain stimulation to the medial forebrain bundle: anti-depressant response and network effects.
OP019 Deep brain stimulation to the medial forebrain bundle: anti-depressant response and network effects.

Objective

Deep brain Stimulation (DBS) to the superolateral branch of the Medial Forebrain Bundle(MFB) has been reported to be effective in rapidly improving treatment resistant depression. This report is an update to our recently published results (Conner 2022).

Methods

To identify a brain network associated with the therapeutic effects of MFB-DBS, we acquired FDG PET scans (n=13) at baseline (preoperative), 6 and 12 months. Therapeutic response were evaluated with the Montgomery-Asberg Depression Rating Scale (MADRS). To identify a brain network associated with therapeutic effects of MFB-DBS, we applied ordinal trend canonical variates analysis (OrT/CVA) to the three timepoint scans and assessed relationships between pattern expression and MADRS clinical ratings.

Results

A significant therapeutic effect after MFB-DBS was seen (mean percent decrease in MADRS from baseline was 56.1% & 65.1% at 6 & 12 respectively) after stimulation, with 10/13 patients deemed responders (> 50% decrease from baseline) with a mean percent decrease of 77.2% at 12 months.

Within the OrT/CVA analysis we identified a significant spatial covariance pattern (p<0.005, permutation test) that consistently increased from baseline with stimulation (Figure 1). This network was characterized by increases in the postcentral gyrus, superior parietal lobule and cerebellar vermis & decreases in the superior and middle frontal gyrus, frontal operculum, bilateral caudate and cingulate cortex (Figure 2). Increases in pattern expression from baseline correlated with improvements in MADRS scores at 6 & 12 (r=0.6820 & r=0.6579,p<0.05) (Figure 3a). Baseline pattern expression correlated with postoperative stimulation mediated therapeutic effects (r=0.6150,p<0.05) (Figure 3b).

Conclusion

Bilateral MFB-DBS is associated with significant anti-depressant effects and this data suggests that it modulates a network that correlates with it’s therapeutic benefit, with the potential to serve as a radiological biomarker of efficacy and potentially a predictor of DBS response.


Prashin UNADKAT (New York, USA), Christopher CONNER, An VO, David EIDELBERG, Albert FENOY
14:30 - 14:40 #35984 - OP020 Connectivity profiles in nucleus basalis Meynert deep brain stimulation for Alzheimer's disease.
OP020 Connectivity profiles in nucleus basalis Meynert deep brain stimulation for Alzheimer's disease.

Objectives:

The nucleus basalis Meynert (nbM) contains a large population of cholinergic neurons that project their axons to the entire cortical mantle, the olfactory tubercle, and the amygdala. Its degeneration has been linked to dementia-related disorders like Alzheimer's disease (AD). Since the nbM neuronal loss is not homogeneous and its projections differ depending on the different anatomical divisions within the nbM, we aimed to analyze the network profiles based on the stimulation site and clinical outcome in AD patients that underwent deep brain stimulation (DBS) surgery.

 

Methods:

We analyzed the data of 11 AD patients operated at the University Hospital Cologne for nbM DBS. Clinical data was obtained before surgery and 6, 12 and 18 months postoperatively, including stimulation parameters and cognitive tests Mini-Mental Status Test (MMST) and Alzheimer's Disease Assessment Scale Cognitive Behavior Section (ADAS-cog). For the connectivity analysis, the nbM was segmented following its histological subdivision into anterior, intermediate and posterior as well as medial and lateral for both hemispheres. After this, we calculated the volume of tissue activated and tractography analysis using a normative connectome.

 

Results:

Follow-up data was obtained to a maximum of seven years in one patient. The majority of fibers were located in the intermediate-lateral (IL) subdivision with 43%, followed by the anterior with 10% and the posterior with 4%. For the anterior region, 39% of the fibers projected to the orbitofrontal cortex (OFC), 27% to the dorsolateral prefrontal cortex (DL-PFC), 20% to the temporal region (TR), and 7% to dorsomedial PFC (DM-PFC). For the posterior region, 10% of the fibers projected to OFC, 7% to the DL-PFC, 15% to the TR, and 5% to DM-PFC. For the IL, 33% of the fibers projected to the DL-PFC, 27% to the OFC, 33% to the TR, and 9% to DM-PFC. In each case where the anterior-intermediate-lateral and posterior-intermediate-lateral regions were stimulated, the majority of fibers projected to the fornix and hippocampus. After 18 months, anterior bilateral regions showed a significant clinical negative correlation, while posterior bilateral regions showed a significant positive correlation meaning a slower cognitive deterioration.

 

Conclusion:

Intermediate-lateral stimulation showed a higher connectivity to DL-PFC, DM-PFC and OFC areas simultaneously when compared to anterior and posterior regions. The fornix that has also been used as a DBS target for AD, could be modulated with nbM DBS. DBS of the nbM posterior regions showed a positive correlation associated with a better cognitive outcome.


Pablo ANDRADE (Cologne, Germany), Rabea SCHMAHL, Ricardo LOUÇAO, Petra HEIDEN, Juan BALDERMANN, Jens KUHN, Veerle VISSER-VANDEWALLE
14:40 - 14:50 #36041 - OP021 Focused ultrasound guided blood brain barrier opening in combination with anti-β-amyloid antibody enhances β-amyloid plaque reduction in patients with Alzheimer’s disease.
OP021 Focused ultrasound guided blood brain barrier opening in combination with anti-β-amyloid antibody enhances β-amyloid plaque reduction in patients with Alzheimer’s disease.

Background

Anti-β-amyloid monoclonal antibodies are the new class of FDA-approved treatments for Alzheimer’s disease (AD) that reduce β-amyloid plaques and disease progression. However, this therapy requires long-term treatment of >12-18 months, frequent and higher dosing, and associated side-effects. The blood-brain barrier (BBB) is a significant challenge limiting antibody delivery to the brain. Focused ultrasound (FUS) has been shown to non-invasively, safely, and reversibly open the BBB. We initiated the first in human study to evaluate the safety, feasibility, and effects of combining aducanumab anti-β-amyloid antibody with FUS-mediated BBB opening (BBBO) in AD. 

 

Methods

Participants with AD underwent anti-β-amyloid plaques antibody (aducanumab) infusion followed by MRI-guided focused ultrasound BBBO in the brain regions with high density of β-amyloid plaques. Participants had serial neurological, cognitive, and imaging assessments as well as β-amyloid PET scans.

 

Results

Two males (ages 77 and 60 years) completed 6-cycles of monthly aducanumab infusion with FUS-BBBO. FUS-BBBO targeted the frontal and parietal lobes with high β-amyloid plaque burden. All FUS procedures were tolerated well with immediate BBBO demonstrated by focal parenchymal gadolinium enhancement followed by BBB closure within 24-48 hours. There were no serious neurological, cognitive, or imaging adverse events. PET scans revealed a progressive and significant decrease in β-amyloid levels in regions of FUS-BBBO as compared to non-FUS treated contralateral homologous regions. There was a reduction of 48% and 49% after 6-months in the first two participants respectively.

 

Conclusion

This first-in-human proof-of-concept study demonstrates that FUS-BBB opening can be safely combined with anti-β-amyloid antibody infusions with an accelerated and greater reduction in β-amyloid. This novel combined targeted therapeutic strategy has the potential to enhance the delivery and impact of therapeutics in AD and other neurological disorders.  Additional studies with a larger number of patients are needed.


Ali REZAI (Morgantown, USA), Pierre-Francois D’HAESE, Manish RANJAN, Jeffrey CARPENTER, Kirk WILHELMSEN, Rashi MEHTA, Tarabishy ABDUL, Teixeira CAMILA, Victor FINOMORE, Sally HODDER, Mark HAUT
14:50 - 15:00 #36056 - OP022 Deep Brain Stimulation does not modulate brain activity in resting-state or during working-memory processing.
OP022 Deep Brain Stimulation does not modulate brain activity in resting-state or during working-memory processing.

Background

While the effectiveness of deep brain stimulation (DBS) in alleviating essential tremor (ET) is well-established, the underlying mechanisms of the treatment are still poorly understood. ET, as characterized by tremor during action, is proposed to be driven by a dysfunction in the cerebello-thalamo-cerebral circuit that is evident not only during motor actions but also during rest. Moreover, dysfunction in this circuit has been linked to cognitive deficits within the domains of executive function and attention in ET patients. 

By combining task-based fMRI with DBS in the caudal zona incerta (cZi) during different motor tasks, we showed that DBS resulted in modulation of the sensorimotor cerebello-thalamo-cerebral circuit BOLD signal in a complex manner as exhibited by task-depended as well as task-independent effects. Whether DBS modulates the functional connectivity and activity within the cerebello-thalamo-cerebral circuit during resting-state and working-memory processing is still unknown and has not been studied before.

 

Methods

We explored the effects of cZi-DBS on resting-state BOLD fluctuations as measured by resting-state fMRI and on cerebello-cerebral activity during working-memory processing in ET patients with fully implanted DBS in the cZi during On and Off therapeutic stimulation.  

For resting state (completed by 16 patients), functional connectivity was calculated between different constellations of sensorimotor as well as non-sensorimotor regions (as derived from seed-based and data-driven approaches), and differences between On and Off conditions are calculated. The working-memory task (completed by 14 patients) included two delayed match-to-sample Maintenance and Manipulation working-memory conditions and a control condition. A region-of-interest (ROI) approach was applied and the ROIs were functionally defined as regions exhibiting higher activation during the Manipulation condition as compared to the Maintenance condition (lateral prefrontal cortex, angular gyrus, and cerebellar Crus II). Differences between On and Off conditions are calculated.

 

Results

We found that DBS did not modulate resting-state functional connectivity, nor did it modulate cerebello-cerebral BOLD activity during working-memory processing.

 

Conclusions

The lack of DBS modulation during resting-state and working-memory processing, in combination with previously demonstrated effects on the cerebello-thalamo-cerebral circuit during motor tasks, suggest that DBS modulation in ET is action-dependent.


Amar AWAD (Umeå, Sweden, Sweden), Johanna PHILIPSON, Grill FILIP, Lena LINDSTROM, Patric BLOMSTEDT, Marjan JAHANSHAHI, Nyberg LARS, Johan ERIKSSON

13:30-15:00
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C27
PARALLEL SESSION 3
Tumor Stereotaxis

PARALLEL SESSION 3
Tumor Stereotaxis

Moderators: Anne BALOSSIER (Dr) (Marseille, France), Chris HONEY (Neurosurgeon) (Vancouver, Canada), Marie KRUEGER (Consultant Neurosurgeon) (London, United Kingdom)
13:30 - 13:35 #33920 - OP023 Less is more - Retrospective analysis of the two-incision implantation technique for hypoglossal nerve stimulation and comparison of respiratory sensing lead curves against the three-incision technique.
OP023 Less is more - Retrospective analysis of the two-incision implantation technique for hypoglossal nerve stimulation and comparison of respiratory sensing lead curves against the three-incision technique.

Objective: Breathing-synchronised hypoglossal nerve stimulation is a treatment option for suitable patients with severe obstructive sleep apnea. The classical implantation technique requires three incisions: anterior submandibular to place the stimulating electrode on the hypoglossal nerve, subclavicular to place the impulse generator and on the lateral chest wall to place the sensor lead. More recently, a two incision technique has been propagated whereby the sensor lead is placed deeper to the IPG pocket. Our department switched to the 2-incision technique in May 2021 and we set out to compare the two methods in respect to the generated breath curves at implantation and clinical follow-up parameters.


Methods: Cases operated between October 2020 and September 2022 were included. Parameters considered included age, gender, BMI, OR time, positioning of the sensor lead, preoperative Apnea-Hypopnea Index (AHI) and Epsworth Sleepiness Scale (ESS). The generated breath curves were categorised by an independent expert blinded to the surgical technique into "good" and "satisfactory" curves regarding conduciveness to optimal stimulation.


Results: 24 patients were included. 5 of these were operated with the 3-incision technique. There were no significant differences in the recorded parameters among the two groups. The expert opinion on the breath curves did not vary between groups. Mean OR time was marginally shorter in the 2-incision group by 4% (138.2 minutes for the 2-incision vs. 144 minutes for the 3-incision group). This might however be attributed to increasing surgeon expertise over time.


Conclusion: The 2-incision technique generates breath curves at par with those generated with 3-incision implants. The limited patient data collected in this analysis suggests the OR-time can be reduced using the 2-incision technique. There were no cases of postoperative infection in our patient group but it can be postulated that a 2-incision implant might have a lower risk of infection due to the reduced wound surface.


Nikhil THAKUR (Frankfurt, Germany), Valentin KRÜGER, Felix CORR, Gerhard MARQUARDT, Marcus CZABANKA, Johanna QUICK-WELLER
13:35 - 13:40 #33928 - OP024 Vagus nerve block – the diagnostic test for neurogenic cough due to neurovascular compression of the Xth nerve.
OP024 Vagus nerve block – the diagnostic test for neurogenic cough due to neurovascular compression of the Xth nerve.

The recent discovery that neurovascular compression of the vagus nerve can generate an intermittent tickling sensation in the lungs that triggers a chronic cough which can be cured with microvascular decompression (MVD) raises an important question.  What is the diagnostic test of choice?  There is a growing recognition of neurogenic cough by otolaryngologists and it is vitally important that neurosurgeons only operate on those with vagus associated neurogenic cough occurring due to unilateral encroachment of its root (VANCOUVER syndrome).  This study proposes two screening tests and the definitive diagnostic test of choice for VANCOUVER syndrome.

The vagus nerve provides sensation (tickle not pain) to the tracheobronchial tree. Similar to trigeminal neuralgia, intermittent sensations can be triggered by a vascular compression of the nerve (and cured with MVD). Continuing the analogy with trigeminal neuralgia, these vagus sensations – tickling that forces an irresistible cough - can be damped with anti-neuralgia medications and temporarily eliminated with local anesthetic. Our first screening test is inhaled nebulized lidocaine (a common procedure in the laryngologist’s office) which eliminates the tickling sensation and therefore coughing for the duration of the anesthetic effect. Our second screening test is MRI of the lower cranial nerves. A prospective analysis of 100 consecutive patients receiving MRI of their lower cranial nerves showed that half of asymptomatic individuals have a vessel compressing one their vagus nerves. Vascular compression of the vagus nerve is therefore required but not sufficient for the diagnosis.

Our proposed definitive diagnostic test is a unilateral percutaneous vagus nerve block. If coughing stops in response to a unilateral block and does not stop following a later contralateral block then the vagus pathology is unilateral. If that side correlates with a vascular compression of the vagus nerve on MRI, then consideration for MVD of that Xth nerve is offered.

The technique for vagus nerve block is presented with case examples. The intraoperative findings in VANCOUVER syndrome are presented.

 

 

 


Christopher HONEY (Vancouver, Canada), Hu AMANDA
13:40 - 13:45 #33929 - OP025 OP02( The diagnostic protocol for hemi-laryngopharyngeal spasm due to neurovascular compression of the Xth nerve.
OP02( The diagnostic protocol for hemi-laryngopharyngeal spasm due to neurovascular compression of the Xth nerve.

Patients with hemi-laryngopharyngeal spasm (HeLPS syndrome) present with intermittent severe throat contractions and coughing due to neurovascular compression of the vagus nerve and can be cured with microvascular decompression (MVD) of the Xth nerve. Without treatment, symptoms can lead to tracheostomy and repeated syncope. Patients are often misdiagnosed as 'psychosomatic' because the condition is not recognized. A definitive diagnostic protocol is required because the symptoms of coughing and choking are common and compression of the vagus nerve can be seen in up to 50% of asymptomatic individuals’ MRI.

We propose a diagnostic protocol for hemi-laryngopharyngeal spasm. Patients are screened by a laryngologist to rule out common causes of throat contractions and cough. Laryngoscopy may demonstrate a pathognomonic unilateral vocal cord movement disorder in approximately one-third of patients (examples will be shown). Patients can lateralize their throat contractions if the affected muscles are in their pharynx (or if they have concomitant glossopharyngeal neuralgia). Patients will not be able to lateralize their symptoms and instead describe a circumferential choking if the affected muscles are in their larynx.  For patients who can not lateralize their symptoms, unilateral botulinum toxin injections into the affected laryngeal muscles will dramatically reduce the contractions for several months (similar to hemifacial spasm).  If contralateral injections, done at a later date (>3 months), do not relieve the muscle spasms then the vagus nerve pathology is unilateral.  If this correlates with the side of compression on an MRI, then consideration can be given to MVD of the Xth cranial nerve.

The intraoperative findings in hemi-laryngopharyngeal spasm are presented. Functional neurosurgeons need to be aware of this recently discovered medical condition and are encouraged to share this knowledge with their otolaryngology colleagues.


Christopher HONEY (Vancouver, Canada), Hu AMANDA
13:45 - 13:50 #34566 - OP026 Interstitial photodynamic therapy of malignant gliomas of supratentorial localization by stereotactic method.
OP026 Interstitial photodynamic therapy of malignant gliomas of supratentorial localization by stereotactic method.

Objective. Interstitial photodynamic therapy (iPDT) is a minimally invasive treatment based on the interaction of light, a photosensitizer and oxygen. In brain gliomas, iPDT consists in the stereotaxic introduction of one or more light guides into the tumor area, without extensive craniotomy, to irradiate photosensitized tumor cells. iPDT causes necrosis and/or apoptosis of tumor cells, can destroy the tumor vasculature and induce an inflammatory reaction that triggers the stimulation of an antitumor immune response.

Purpose. To analyze the possibilities of iPDT in the treatment of deep-seated, small-sized relapses of malignant gliomas.

Materials and methods. The study with iPDT included 3 patients with a Karnofsky score of at least 70 points, who had a recurrence of single-focal limited malignant glioma after standard complex therapy. Local tumor recurrence, or tumor progression, did not exceed a maximum spread of 3 cm as determined by tumor enhancement on gadolinium T1-weighted MRI. Tumor tissue viability was preliminarily confirmed using minimally invasive stereotaxic biopsy procedures, followed by morphological examination to rule out effects associated with treatment or pseudoprogression of the tumor. The size limitation was based on the maximum number of light fibers per laser, since the optimal distance between light diffusers is about 7–9 mm, for accurate tissue irradiation without critical thermal effects. Photoditazine with the active ingredient chlorin e6 diluted in 200 ml of saline at the rate of 1 mg of the drug per 1 kg of the patient's body weight was used as a photosensitizer. Interstitial irradiation was performed using a laser (Latus 2.5 (Atkus, Russia)) with a wavelength of 662 nm and a maximum power of 2.5 W and cylindrical scattering fibers. Target volume was determined after combining multimodal CT images (contrast-enhanced scan, 0.6 mm axial slices) with preoperative MRI. Spatial accurate interstitial irradiation of the tumor volume was planned using software. The duration of irradiation did not exceed 15–20 min. To prevent the possibility of thermal tissue damage during irradiation, the bed was continuously irrigated with saline. The light dose averaged 150 J/cm2.

Results. Postoperative MRI performed within 24 hours after iPDT showed a decrease or absence of contrast enhancement in the PDT area, at a distance of about 10 mm from the irradiation center. No transient increase in edema around the tumor irradiation zone was observed. In 1 patient, a transient worsening of the neurological status was observed. Follow-up was followed in all 3 patients. The median duration of follow-up after iPDT was 13.9 months. The cause of death was tumor progression. Median overall survival from first diagnosis of malignant glioma to death was 25 months. Median time between first diagnosis and iPDT was 11 months.

Conclusions. Interstitial PDT of gliomas remains a challenging procedure due to the limited depth of light penetration into the brain tissue, the complex procedure for planning and implanting the irradiator, and the potential risk of clinical deterioration, especially after treatment in functionally significant areas of the brain. However, iPDT may be a promising treatment option in a high-risk patient population. It does not interfere with, but rather can complement, other treatment options for recurrent disease, such as repeat radiation therapy and chemotherapy. iPDT remains a potential option for deep-seated gliomas in patients with high surgical risk and tumor recurrence. The hospital stay can be 3-4 days, which reduces the cost of hospitalization. Patients treated with iPDT may receive adjuvant treatment faster than patients with standard craniotomy. These data strongly support further studies under controlled prospective conditions.


Artemii RYNDA (Saint-Petersburg, Russia), Victor OLYUSHIN, Dmitriy ROSTOVTSEV, Yulia ZABRODSKAYA
13:50 - 13:55 #34648 - OP027 Endocavitary treatment of cystic craniopharyngiomas with interferon alpha 2b.
OP027 Endocavitary treatment of cystic craniopharyngiomas with interferon alpha 2b.

Introduction:

The craniopharyngioma, histologically benign tumor, is a disease of life.

Many authors agree to use the term remission rather than cure.

Microsurgical excision, radiosurgery and endocavitary treatments being different therapeutic choices which must be complementary.

Endocavitary treatment with interferon alpha 2b currently holds an important place in the therapeutic arsenal for craniopharyngioma cysts.

Methods :

Fourteen patients were treated with this even less invasive and structurally less aggressive technique of adjacent vessels and nerves.

Interferon alpha 2b is currently recognized as the least neurotoxic product among the various molecules to be instilled.

The placement of the subcutaneous reservoirs, Rickham or Omaya, is carried out under stereotactic conditions under MRI, assisted by neuronavigation allowing a better study of the trajectory and the structures with a path going from the entry orifice to our deep target.

Results :

Our series of cystic craniopharyngiomas treated with interferon alpha allowed us a satisfactory tumor control rate, comparable to the series published in the literature which are close to controls by nearly 80% with an interest in recurrent forms.

Conclusion:

This technique, practiced with a view to inhibiting the secretion of tumor fluid by the internal wall of the cyst, without significantly damaging the adjacent vascular and neural structures, is currently recognized and practiced for the treatment of this serious chronic pathology.


Samir Amine BENBOUALI (Alger, Algeria), Amine MAHTOUT, Rachid GHOUL, Nacer TABET, Fateh BOUAOUINA, Linda ZIANI, Leila BOUNAB, Karima SEDDIKI, El Mountassir OURRAD
13:55 - 14:00 #35523 - OP028 Robotic assisted frameless brain biopsy and laser ablation in pediatric patients using a small robotic device (Stealth Autoguide) : A preliminary experience in children.
OP028 Robotic assisted frameless brain biopsy and laser ablation in pediatric patients using a small robotic device (Stealth Autoguide) : A preliminary experience in children.

INTRODUCTION: The use of robot-assisted frameless stereotactic biopsy or laser ablation  is becoming more common. Among available robotic arms, Stealth Autoguide (Medtronic, Minneapolis, MN, USA) is a miniaturized device, that is used together with a standard head fixation device. Experience with the stealth autoguide is recent and limited to adult patients. The aim of this study is to present our preliminary  experience in pediatric patients.

METHODS: Clinical and surgical data of all patients undergoing frameless stereotactic biopsies using theStealth Autoguide from 2020 to May 2023 have been prospectively collected and retrospectively analyzed.

RESULTS: Thirty-four patients were included in the study; they underwent 15 bioptic procedures as stand-alone procedure and 19 laser ablation procedures . Mean age was 8 years old, range 2-18. The most common indication for biopsy was diffuse intrinsic brain stem tumor (to confirm diagnosis and to obtain tissue for molecular studies), followed by diffuse supratentorial tumor. Laser ablation was indicated for epilepsy (4 pts) , cavernoma (2 pts) or brain tumors (9 low grade tumors and 4 high grade tumors).  13 procedures were performed in prone position, 18 in supine position and 3 in lateral position. Facial surface registration was adopted in 5 cases. In all MRgLITT cases positioning of skull fixed fiducials were preferred and also , in the biopsy group, for patient in prone position and/or affected by deep lesion. In younger patients (less than 5 year-old), the head was fixed using a DORO skull clamp with 4 pediatric cranial pins, and it was also supported on the integrated Gel Head Ring, (DORO QR3 multipurpose skull clamp set - Pro Med Instruments). Diagnostic tissue samples were obtained in all cases and all patients received a definitive histological diagnosis. Laser fiber insertion was successuful in all MrgLITT patients. Neither mortality nor morbidity related to the surgical procedure were recorded.

CONCLUSION: The Stealth Autoguide was able to compensate for surgeon movement and , together with neuronavigation, provide real-time feedback during the procedure, leading to improved accuracy and reduced complications.  Our preliminary experience with the use of the Stealth Autoguide as an aid in frameless stereotactic procedures in pediatric neurosurgery suggests that this technology is safe, feasable and accurate also in pediatric patients. Virtually all position can be used, also prone position that is precluded to other kind of robotic arms.


Giuseppe MIRONE, Claudio RUGGIERO (Napoli, Italy), Pietro SPENNATO, Giuseppe CINALLI
14:00 - 14:05 #35755 - OP029 Stereotactic frame-based biopsy of infratentorial lesions via the suboccipital transcerebellar approach with the zamorano-duchovny stereotactic system– a retrospective analysis of 79 consecutive cases.
OP029 Stereotactic frame-based biopsy of infratentorial lesions via the suboccipital transcerebellar approach with the zamorano-duchovny stereotactic system– a retrospective analysis of 79 consecutive cases.

Objective

Lesions of the posterior fossa (brainstem and cerebellum) are challenging regarding diagnosis and treatment since they are often located in eloquent areas and total resection is rarely possible. Therefore, frame-based stereotactic biopsies are commonly used to asservate tissue for neuropathological diagnosis and further treatment determination. The aim of our study was to assess the safety and diagnostic success rate of frame-based stereotactic biopsies for lesions in the posterior fossa via the suboccipital, transcerebellar approach.

Methods

We performed a retrospective database analysis of all frame-based stereotactic biopsy cases at our institution since 2007 to identify all cases of surgeries for infratentorial lesion biopsies via the suboccipital, transcerebellar approach. We collected clinical data regarding outcome, complications, diagnostic success, radiological appearances and stereotactic trajectories.

Results

A total of n=79 cases of stereotactic biopsies for posterior fossa lesions via the suboccipital, transcerebellar approach (41 women and 38 men) utilizing the Zamorano-Duchovny stereotactic system were identified. Mean age at the time of surgery was 42.5 years (+/-23.3, range: 1-87 years). All patients were operated with intraoperative stereotactic imaging (n=62 MRI, n=17 CT). The absolute diagnostic success rate was 87.3%. Most common diagnoses were glioma, lymphoma and inflammatory disease. The overall complication rate was 8.7% (7 cases). All patients with complications showed new neurological deficits which were permanent in 3 cases. Hemorrhage was detected in 5 cases with complications. The 30-day mortality rate was 7.6%, 1 year survival rate was 70.0%.

Conclusion

Our data suggests that frame-based stereotactic biospies with the Zamorano-Duchovny stereotactic system via the suboccipital, transcerebellar approach are safe and reliable for infratentorial lesions bearing a high diagnostic yield and an acceptable complication rate. Further research should focus on the planning of safe trajectories and a careful case selection with the goal to minimize complications and maximize diagnostic success.


Manuel KAES (Heidelberg, Germany), Jan-Oliver NEUMANN, Christopher BEYNON, Andreas UNTERBERG, Karl KIENING, Martin JAKOBS
14:05 - 14:10 #36022 - OP030 The impact of correction of magnetic resonance imaging distortions on Gamma Knife radiosurgical treatment planning.
OP030 The impact of correction of magnetic resonance imaging distortions on Gamma Knife radiosurgical treatment planning.

Magnetic resonance imaging (MRI) is a powerful non-invasive technique that allows excellent contrast in soft tissues and high spatial resolution. Although MRI is the preferred imaging modality for stereotactic radiosurgery treatment planning, anatomic distortion is present in all MRI data due to hardware- and patient-related disturbances of the magnetic field homogeneity, thereby potentially jeopardizing the efficacy of SRS treatments. This study evaluated the potential for uncorrected MRI to lead to inadequate treatment planning in Gamma Knife radiosurgery (GKRS) for metastatic brain tumors (METs). We performed a retrospective analysis of 26 consecutive patients with 70 METs treated in our department from 2020-2021. MRIs were corrected for distortion using commercially available software (Cranial Distortion Correction, Brainlab Elements, Brainlab AG, Munich, Germany). To assess the clinical significance of anatomic distortion, an SRS plan was generated using each uncorrected tumor volume, and these plans were evaluated for coverage of the corrected tumor volume to demonstrate the dose distribution that would be achieved if the distortion had not been corrected. Plans were considered inadequate if ≥2% of the corrected tumor volume received less than 100% of the prescription dose. Displacement of the center of mass of the uncorrected tumor volume, relative to its corrected position, was measured for each lesion in millimeters. The median target volume was 0.381 cm3 (range, 0.01-12.382 cm3), and all radiosurgery plans met the optimization criterion of at least 98% of the uncorrected tumor volume (median 99.55%, range 98.1-100%) receiving at least 100% of the prescription dose. However, the percent of the corrected tumor volume receiving the full prescription dose was a median of 95.45%, with a range of 23.1-99.5%. The median displacement was 0.545 mm (range, 0.1-2.87 mm), and there was a statistically significant, strong negative correlation between corrected tumor volume and displacement (r=-.538, p<0.001). While MRI distortion is often subtle on visual inspection, this distortion has a significant clinical impact on SRS planning. Distortion-corrected MRI should uniformly be used for intracranial radiosurgery planning as distortion is sometimes sufficient to cause a volumetric miss of SRS targets. 


Yavuz SAMANCI (Istanbul, Turkey), Ali Haluk DUZKALIR, Mehmet Orbay ASKEROGLU, Selçuk PEKER
14:10 - 14:15 #36050 - OP031 Radiosurgery for the treatment of trigeminal neuralgia.
OP031 Radiosurgery for the treatment of trigeminal neuralgia.

Objective: Medically refractory trigeminal neuralgia can be treated by microvascular decompression of the trigeminal nerve, by ablative percoutaneous treatments such as thermocoagulation, glycerol/ alcohol injection and ballon compression of the ganglion Gasseri or, far less invasive, by radiosurgery that has been proven to elegantly and highly effictively treat this pain condition. We here report about the results at our institution

Methods: We evaluated our outcomes retrospectively in our patients with medically refractory trigeminal neuralgia treated with radiosurgery. One 4mm shot was placed allong the  the trigeminal nerve (either retrogasserian, midcysternal or at the root entry zone) as the chosen target. Pain scores and side effects were documented regularely.

Results: 232 patients treated between the years 1999-2019 were included into this study. 15 patients received repeated gamma Knife radiosurgery. The average age was 65 years. 58 patients had prior therapies other than medication. Mean follow up was 406 days. Multiple sclerosis as a comorbidity was present in 38 patients. Pain condition last in average 10 years till radiosurgery was performed. The average dose was 89Gy.  The 10Gy volume oft he brain stem in average was 0,12ccm. Radiosurgery was succesfull in 78% as defined by the Barrow neurological institute pain score (BNI) I-III and failed in 22% oft he patients. Hypesthesia was seen in 12%. Pain quality changed to ongoing pain in 4 patients.

Conclusion: Radiosurgery is proven to be an effective and safe treatment option for trigeminal neuralgia and long term results are available. In our patients side effects are rare and less present then generally sited in the literature and its risk profile is lower compared to any other treatment. Given the fact of absent invasivness radiosurgery shoud be considered in the first place in patients with (high risk) comorbidities, elderly patients and patients with prior surgically treatments and refractory/ relapse pain condition. 


Goetz LUETJENS (Hannover, Germany), Bert VAN ECK, Gerhard HORSTMANN
14:15 - 14:20 #36087 - OP032 Dynamics in lesions during and after MR-guided Laser Interstitial Thermal Therapy – TLVMC experience.
OP032 Dynamics in lesions during and after MR-guided Laser Interstitial Thermal Therapy – TLVMC experience.

Introduction

MR-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive technique that can be used for treatment of deep-seated brain lesions. Currently the radiological changes that occur after the ablation are still not completely characterized.

The goal of this current study is to retrospectively examine the outcome and describe the radiological volume changes that occur after MRgLITT ablation of brain tumors.

 

Method

We retrospectively collected clinical and imaging data of all adults’ patients that underwent MRgLITT of brain tumors (primary and metastatic) between 2020-2023 at the Tel-Aviv Medical Center. Lesions’ volume, length and diameter were measured before, during and in follow-ups on T1-weighted images with contrast. The post-operative ablation volume was compared to Medtronic thermal damage estimate (TDE). Local control was assessed at last follow-up.

Results

Twenty patients (average age 57±11 years) were available for follow-up. Most lesions (n=11) were metastatic, and the rest 9 patients had high grade gliomas. Mean follow-up was 8±7.5 months. Average pre-op tumor volume was 2.26±1.96 CC3, and immediate post-op (in the end of the ablation) was 4.65±2.5 CC3. During follow-up the average lesion volume was: one week 7.7±4.85 CC3, 1-2 month 4.8±3.22 CC3, 3 months 4±3 CC3, 6 months 2±1.86 CC3 and 9 months 1.2±1.2 CC3. Forward extension of the enhancing lesion from the tip of the catheter post ablation was on average 3.4±2 mm. All high-grade glioma tumor had a failure (local/distance after 3-6 months).

Discussion

MRgLITT can cause an enlargement in the lesion volume during the first months after the ablation, moreover the forward thermal damage is around 4mm.


Lottem BERGMAN (Tel Aviv-Yafo, Israel), Ariel AGUR, Segev GABAY, Tal SHAHR, Rachel GROSSMAN, Ido STRAUSS
14:20 - 14:25 #36102 - OP033 Laser interstitial thermal therapy using an uncooled laser catheter in a diagnostic MR suite.
OP033 Laser interstitial thermal therapy using an uncooled laser catheter in a diagnostic MR suite.

Title

Laser interstitial thermal therapy using an uncooled laser catheter in a diagnostic MR suite

Hjalmar Bjartmarz, Irena Grubor, Charlotte Edvardsson, Roger Siemund and Peter Siesjö
Skane University Hospital, Departments of Neurosurgery and Diagnostic Radiology, Skane University Hospital, Lund, Sweden,

Abstract

Background

Laser interstitial thermal therapy (LITT) has emerged as an alternative to open surgery for both primary and secondary brain tumors. Additionally, thermal ablation by laser can be used to eradicate epileptic foci and to treat radiation necrosis. During the procedure, a laser catheter has to be placed in the targeted lesion under navigation guidance. To control temperature during ablation MR thermography is utilized, thus the ablation procedure is commonly performed inside a dedicated intraoperative MR. As most catheter insertions are performed outside the MR camera, shorter or longer transports with the indwelling laser catheter are needed. This poses a potential hazard for unintentional catheter dislodgment during transport. Navigation procedures outside the MR camera can also result in misplacement of the catheter which can lead to abandonment of the procedure or return to the operative suite. Currently used catheters for thermal ablation necessitates a cooling procedure after ablation imposing additional risks and logistics. To minimize the above stated hazards, we here present a workflow where both catheter placement and ablation are performed inside a diagnostic MR suite using a new laser catheter without cooling.

Methods

In an open-label, pilot, exploratory, single centre, early feasibility and safety clinical phase 1-2 trial, patients with recurrent glioblastoma were included after informed consent. Patients 18-80 years with lesions < 30 mm were eligible. Single or multiple ablations were performed in a diagnostic MR suite using a MR compatible navigation system (ClearPoint® Neuro Navigation System) together with a new uncooled laser catheter and MR thermography (Tranberg Thermal Therapy System and Thermoguide Workstation).

Results

5 patients with recurrent glioblastoma fulfilling all inclusion criteria and no exclusion criteria were treated with single or multiple laser thermal ablations in a diagnostic MR suite.  Laser effects between 2 and 4 W were used with ablation times between 270 and 570 seconds. The workflow was executable and sustainable without any treatment related side effects or device mis performance noted. Details of the workflow will be presented.

Conclusions

LITT using a non-cooled laser catheter inside an outpatient MRI suite was feasible and reproducible. The procedure may reduce risks associated with LITT procedures.

 


Hjalmar BJARTMARZ (Lund, Sweden)
14:25 - 14:30 #36123 - OP034 Frameless brain tumor biopsies: combining optical tissue characteristics and imaging.
OP034 Frameless brain tumor biopsies: combining optical tissue characteristics and imaging.

Introduction
The standard frameless biopsy procedure is guided solely by preoperative images. Consequently, the procedure is associated with adverse events such as inconclusive results and hemorrhage. Intraoperative feedback relying on tissue fluorescence has been suggested [1]. Our group has previously presented an optical probe system [2] integrated into the biopsy needle. The system provides feedback on tissue characteristics in situ before the tissue sample is taken. However, further information could be gained through a multimodal approach. This study aimed to evaluate a pipeline that connects the in situ optical information to the pre-, intra-, and postoperative image information and neuropathological results for postoperative analysis.

Methods
Six patients planned for frameless needle biopsies were included in the study (written informed consent, EPM-2020-01404, mean age: 59, range: 18-78, two women). Inclusion was based on suspected malignant intracerebral tumors as identified by contrast enhancement on preoperative 3T MRI. An oral dose of Gliolan (20 mg/kg, Medac GmbH, Germany) was administered to the patient 2-3 h before anesthesia. Trajectory planning and frameless navigation were performed using the StealthStation® (S8, Medtronic Inc, USA). After burr-hole trephination and opening of the dura, the optical probe was placed in the modified outer cannula of the biopsy needle (Passive Biopsy Needle Kit, Medtronic Inc). Then, the probe-needle kit was secured in the AutoGuide® (Medtronic Inc). Errors between the preoperative images and the patient’s physical anatomy (i.e., registration) as well as between the locked and planned trajectory (i.e., targeting) were noted. Tissue fluorescence, perfusion, and gray-whiteness were measured in millimeter steps along the trajectory and displayed to the surgeon in real time. The corresponding coordinates on preoperative MRI were logged. When fluorescence peaks at 635 nm were registered at or in the vicinity of the precalculated target, the probe was replaced by the inner cannula of the biopsy needle, and tissue samples were taken. Postoperative images (CT or MRI) were acquired within 12 h of surgery on which final entry and biopsy positions were defined.

A pipeline for postoperative analysis of secondary outcomes and comparison of planned and actual trajectories was constructed. The pipeline combines pre-, intra-, and postoperative data and presents all data in preoperative navigation image space.

Results and Discussion
Real-time feedback on tissue fluorescence, perfusion, and light intensity was obtained in 70 locations. In six patients, tissue fluorescence was found (14 locations) and pathology results confirmed tissue samples to be tumorous after 30-60 minutes. In one patient, no fluorescence peak was detected; the tissue sample was confirmed to be non-tumor. For this patient, high perfusion signals were recorded before tissue sampling. Postoperative imaging confirmed a local (asymptomatic) hemorrhage. Final CNS WHO 2021 diagnoses included Glioblastoma IDH-wildtype, grade 4; Astrocytoma IDH-wildtype, high-grade; and Primary diffuse large B-cell lymphoma.

The registration and targeting errors were 1.3-2.1 mm and 0.1-0.5, respectively. The average shift between pre- and postoperative positions was 3.85 (±2.63) mm. This shift is believed to be a combination of errors during registration of the preoperative images to the patient’s physical anatomy, changed conditions (e.g., brain shift), and potential errors in the image coregistration process.

We present a pipeline combining pre-, intra-, and postoperative data. The pipeline allows postoperative analysis of secondary outcomes by combining optical signals, final biopsy positions, and neuropathology. This multimodal approach could give further insights into tumor location beyond navigation on preoperative MRI.

References
[1] Millesi, M.; Kiesel, B.; Wöhrer, A.; Mercea, P.A.; Bissolo, M.; Roetzer, T.; Wolfsberger, S.; Furtner, J.; Knosp, E.; Widhalm, G. Is Intraoperative Pathology Needed If 5-Aminolevulinic-Acid-Induced Tissue Fluorescence Is Found in Stereotactic Brain Tumor Biopsy? Neurosurgery 2020, 86, 366–373.
[2] Klint E, Mauritzon S, Ragnemalm B, Richter J, Wårdell K. FluoRa - a system for combined fluorescence and microcirculation measurements in brain tumor surgery. Annu Int Conf IEEE Eng Med Biol Soc. 2021;2021:1512-1515.


Elisabeth KLINT (Linköping, Sweden), Johan RICHTER, Karin WÅRDELL
14:30 - 14:40 #36127 - OP035 Gamma-Knife Icon: 3 years of clinical follow up of patients with tumors in close proximity to the optic pathways, our preliminary experience and literature review.
OP035 Gamma-Knife Icon: 3 years of clinical follow up of patients with tumors in close proximity to the optic pathways, our preliminary experience and literature review.

Background: Gamma Knife Radiosurgery (GKRS) has traditionally been considered the gold standard therapy for single-fraction high-dose irradiation of relatively small brain lesions. Despite the steep radiation dose gradient  used in the GK treatment, eloquent structures that lie within 2 to 5 mm from targets are considered at risk. Fractionated stereotactic radiosurgery (fSRS) delivered over 3 to 5 days, is used to treat tumors located next to critical structures such as the optic pathways in order to minimize healthy tissue toxicity.  In many centers an invasive Leksell pin-based frame system is still used with GKRS . It  represents an advantage in terms of accuracy and precision of the treatment, but it involves also a negative aspect in terms of treatment compliance.  The new generation of GKRS: “Leksell Gamma Knife Icon (GK Icon)”, utilizes a frameless immobilization system associated with cone-beam computed tomography (CBCT) to evaluate motion error. 

Objective: Analyze the feasibility of fractionated stereotactic radiosurgery with GK Icon system for the treatment of benign lesions in close proximity to the optical apparatus.  

Methods: Patients were treated with GK Icon system applying the combination of fGKRS and a frameless immobilization system. Clinical and radiological follow-up was performed and the incidence of side effects was compared to reported data about patients treated with fGKRS using a traditional frame to immobilize the patient’s head (qui va detto il punto forte del vostro studio). also Importantly, we studied the error in the daily repositioning of the patient in the X, Y, Z axes, for both rotation and translation in order to evaluate the accuracy of the repositioning.

Results: Radiological control was achieved in 99% of tumors. Most patients had stable clinical symptoms, while we observed improvement of initial symptoms in 3 patients (8,1%). Out of the 37 symptomatic patients at onset, 5 of them reported worsening symptoms (13,5%). None of asymptomatic patients become symptomatic. Overall the percentage of clinical worsening was 6%.

Conclusion:  fGKRS Icon combines accuracy, significantly steeper gradients, and lower total body dose of the GKRS with the flexibility of fractionated treatment combined with the frameless immobilization system.


Karol MIGLIORATI, Giorgio SPATOLA (Brescia, Italy), Chiara BASSETTI, Lodoviga GIUDICE, Matteo CHIEREGATO, Mario BIGNARDI, Oscar VIVALDI, Cesare GIORGI, Corrado D'ARRIGO, Alberto Bernardo FRANZIN
14:40 - 14:50 #36135 - OP036 Modeling post-treatment edema in Gamma Knife radiosurgery of meningiomas with explainable machine learning.
OP036 Modeling post-treatment edema in Gamma Knife radiosurgery of meningiomas with explainable machine learning.

Meningiomas located near a sinus or draining vein can cause  venous congestion and lead to the development of edema around the tumour. Stereotactic radiosurgery treatment may aggravate existing edema or induce delayed edema formation in a significant percentage of patients (5%- 10%). In this study, we developed a machine learning model to predict the occurrence of new edemas after Gamma Knife radiosurgery for meningiomas. Our model integrates radiomics features extracted from the pre- treatment MRI scans with clinical information and dosimetric data from the treatment plans. Data imbalance is taken into account with machine learning methods.  The model is explainable  globally and at single patient level with game theoretical Shapley values. Counterfactuals restricted to change only the dosimetric part are used to gain further insights on the predictions. 


Matteo CHIEREGATO, Karol MIGLIORATI, Rosaria MAIO, Bassetti CHIARA, Mauro MORASSI, Alberto Bernardo FRANZIN, Milena COBELLI, Giorgio SPATOLA (Brescia, Italy)
14:50 - 14:55 #36151 - OP037 Optical brain biopsy: frame-based one-insertion method.
OP037 Optical brain biopsy: frame-based one-insertion method.

Background: Neurosurgical stereotactic biopsies are afflicted by hemorrhage, neurological impairment, or inconclusive neuropathological results. Therefore, it is imperative to reach the tissue sampling site safely and precisely with minimum needle insertions. A system was designed for intraoperative feedback on the brain tissue and of 5-aminolevulinic acid (5-ALA) fluorescence and for blood vessel detection during stereotactic needle biopsies [1]. 

Methods: A probe with optical fibers was designed to fit into the outer cannula of a Sedan Side-Cutting Biopsy Kit 2 for the Leksell stereotactic system (Elekta, Sweden). An opening at the tip of the cannula allows emitting and receiving light while moving forward through untouched tissue by our in-house developed mechanical insertion device [2]. The probe simultaneously detects microvascular blood flow, gray-whiteness of the brain tissue, and 5-ALA fluorescence spectra along the trajectory. The probe is connected to the FluoRa system [3] for sampling, storage, and real-time display of the optical information in the OR.

Stereotactic biopsies were performed in three consecutive cases, males aged 45 to 68, with suspected malignant intracerebral tumors on MRI. Written consent was obtained. The patients were given 20 mg/kg 5-ALA (Gliolan®, Medac, Germany) 3-4 hours preoperatively. The stereotactic frame was applied under anesthesia. A 3D-MRI (Ingenia 3T, Philips) including T1wGd-, T2w-, and FLAIR-sequences was acquired and registered in the stereotactic planning system (StealthStation S8, Medtronic, USA). Biopsy positions and trajectories were defined in each case. Through a burr hole trephination and a minimal dura mater incision, the biopsy needle with the optical probe inside was forwarded to the target points in millimeter steps while recording gray-whiteness (Total Light Intensity; TLI), microvascular blood flow (perfusion) and fluorescence (FL). The real-time measurements of the different modalities were displayed next to the stereotactic navigation system screen.

Results: The variations of the TLI matched the pathways through the brain tissue, from gray to white and darker in the tumor. No high perfusion was registered. The FL showed high peaks at 635 nm at the targets, confirming malignant tumor. The optical probe was then replaced by the inner cannula of the biopsy needle and tissue samples were taken from the spots of the highest fluorescence. The corresponding pathological findings were Glioblastoma in two cases and lymphoma in one case. 

Conclusions: Optical monitoring of the trajectory and identification of the target is safe and can reduce the number of needle insertions in stereotactic biopsies and shorten the procedure.

References:

[1] Richter J, Haj-Hosseini N, Milos P, Hallbeck M, Wårdell K. Optical brain biopsy with a fluorescence and vessel tracing probe. Oper Neurosurg. 2021;21(4):217-224. 

[2] Klint E, Mauritzon S, Ragnemalm B, Richter J, Wårdell K. FluoRa - a system for combined fluorescence and microcirculation measurements in brain tumor surgery. Annu Int Conf IEEE Eng Med Biol Soc. 2021;2021:1512-1515. 

[3] Wårdell K, Hemm-Ode S, Rejmstad P, Zsigmond P. High-resolution laser Doppler measurements of microcirculation in the deep brain structures: a method for potential vessel tracking. Stereotact Funct Neurosurg. 2016;94(1):1-9. 


Johan RICHTER (Linköping, Sweden), Peter MILOS, Elisabeth KLINT, Karin WÅRDELL
14:55 - 15:00 #36163 - OP038 A novel integrated module for cognitive cortico-subcortical mapping.
OP038 A novel integrated module for cognitive cortico-subcortical mapping.

INTRODUCTION

During awake surgery mapping of cognitive functions with the current standards,  inaccuracies, and redundant communication can occur by lack of clear testing methodology.

The neat definition and hence reproducibility of stimulation points, the asynchronous stimulation and task presentation, the kind of tasks where, are important criteria to obtain a precise and reliable cortical mapping.

Concerning subcortical mapping, there seems to develop a consensus about the need for continuous multimodal testing with time constraint and intermittent stimulation.

Avoidance of time gaps is essential.

 

METHODS

Cortical mapping should be analytical, with maximal specificity, while subcortical testing needs to be more ad hoc with maximally sensitive tasks. So we developed a module for both cortical and subcortical testing, adaptable to any team.

 

The cortical cognitive mapping module integrates in 1 screen (with all steps simultaneously available) :

 

1.           selection and presentation of tasks by neuro-psycho/linguist ,

2.           stimulation parameters,

3.           observation of patient’s face,

4.           visualisation of the stimulated cortex with overlay grid of stimulated points,

5.           evaluation of the results and its registration,

6.           recording of all the events (video)

 

For the subcortical testing, navigation data are integrated in the screen, coinciding with the resecting navigated CUSA-tip.

A dedicated multimodal task,  with simultaneous motor testing on touch screen for the patient,  is basically proposed.

In case of negative testing, CUSA-resection is performed within the checked area; the positive points are registered directly within the navigation.

As well for cortical as for subcortical mapping, stress is put on the sequencing of continuous  task presentation and stimulation (intermittent, synchronous with task,). When the bipolar stimulation is  provided by CUSA-tip and suction tip, time gaps are avoided.

 

RESULTS

A significant increase in accuracy and ergonomy is noted: in cortical mapping, the surgeon has to stimulate the indicated cortical preselected point, and the neuro-psycho/linguist evaluates with a simple mouse click – correct or not.

During subcortical testing, the accuracy of resection is enhanced since performed in a delimited stimulated area.

Since no time gaps occur,  an important gain of time is obtained; it is a closed loop system, with exclusion of communication errors.

The modules are versatile and adaptable to each team.

 

CONCLUSION

A module is proposed yielding an exhaustive corticosubcortical mapping, by which all relevant data are synthetised and integrated in one screen, intra- or postoperative re-evaluation is easy to obtain when the mapping is recorded, also valuable in redo-surgery and as future database.

 

 

 


David COLLE (Gent, Belgium), Tybault HOLLANDERS, Henry COLLE, Bonny NOENS, Peter MULLER, Erik ROBERT, Annelies AERTS

15:00 - 15:30 COFFEE BREAK - FLASH POSTERS SESSION 2 - EXHIBITION
15:30
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A28
PARALLEL SESSION 4
Movement Disorders 2

PARALLEL SESSION 4
Movement Disorders 2

Moderators: Volker COENEN (Head of Department) (Freiburg, Germany), Emmanuel CUNY (puph) (bordeaux, France), Brigitte GATTERBAUER (Gamma Knife) (Vienna, Austria)
15:30 - 15:40 #35635 - OP039 SPECTRE imaging - DBS implantation based on individual MR connectivity of the subthalamic nucleus.
OP039 SPECTRE imaging - DBS implantation based on individual MR connectivity of the subthalamic nucleus.

Objective: To investigate whether motor improvement after STN-DBS can be associated with individual structural connectivity analyzed by Subject sPEcific brain Connectivity display in the Target REgion (SPECTRE).

Methods: Patients from our DBS-Registry with Parkinson’s disease were selected for analysis, if the following was available: (1.) preoperative MedOFF and postoperative follow-up MedOFF StimON values of MDS-UPDRS-III, (2.) preoperative 3T-MRI including dMRI, (3.) Bilateral volumes of activated tissue (VAT, simulated with Brainlab Guide XT) contained STN (segmented with an in-house trained convolutional neural network) at a proportion ≥0.4.

For the generation of SPECTRE maps limbic/motor/associative (green/blue/red) cortical schemes defined in MNI space are warped to subject space, and in a tract weighting approach 500 probabilistic streamlines per voxel are seeded in the VATs to compute their cortical associations (Figure 1). The overall maximum of the motor connectivity (blue) of both VATs (left/right) is used to predict motor performance.

Postoperatively remaining relative motor disability (RRMD) was calculated as the ratio of follow-up divided by preOP UPDRS-values.

Linear regression analysis was calculated to estimate the relation between maximum individual motor connectivity, VAT size and RRMD.

Results: 30 patients were included in the analysis. Regression analysis found a significant effect (F(2, 27)=4.919, p=.015, R²=.27) where individual motor connectivity of the VAT was inversely associated with remaining relative motor disability (t=-2.95, p=0.006, Figure 2) while VAT size was not a significant predictor (t=1.73, p=.095).

Conclusion: SPECTRE imaging can explain treatment effects based on connectivity on a single subject level and has the potential to improve image-based DBS programming and targeting for DBS implantation.


Bastian Elmar Alexander SAJONZ (Freiburg, Germany), Marco REISERT, Marlies BÖCK, Justus V. GRITZMANN, Nadja JARC, Thomas PROKOP, Nils SCHRÖTER, Michel RIJNTJES, Horst URBACH, Wolfgang H. JOST, Volker Arnd COENEN
15:40 - 15:50 #35645 - OP040 Evaluating functional connectivity differences between DBS on/off states in essential tremor.
OP040 Evaluating functional connectivity differences between DBS on/off states in essential tremor.

Objectives:  Deep brain stimulation (DBS) targeting the ventral intermediate (Vim) nucleus of the thalamus is an effective treatment for essential tremor (ET).  Yet, it remains unclear which functional connections are most influential in impacting tremor control and/or concomitant gait ataxia. We studied ET patients undergoing DBSto a major input/output tract of the Vim, the dentato-rubro-thalamic tract (DRTt), using resting state functional MRI (rsfMRI) to evaluate connectivity differences between DBS ON and OFF and elucidate significant regions.

 

Methods: We enrolled fifteen ET patients who had previously undergone DRTt DBS. Anatomical/functional 1.5T MRIs were acquired and replicated for each DBS state. Tremor severity using The Essential Tremor Rating and Assessment Scale (TETRAS) and gait ataxia severity using the Scale for Assessment and Rating of Ataxia (SARA, items 1-3) was scored with DBS ON at optimal stimulation parameters and immediately upon DBS OFF. Regions of interest (ROI) were pre-defined as the bilateral Vim thalamus, pre-central gyrus, superior and inferior parietal lobules (SPL/IPL), dentate nucleus (DN), and cerebellar nodule. Connection strength between each of the 11 ROIs was measured using z-scores of correlation coefficient differences between DBS ON/OFF and correspondent p-value computed by using Fisher’s method, which represents change on individual level.  Effect of DBS treatment at group level was measured by averaging z-scores over all 15 patients between each ROI. Pearson correlation analysis was performed between z-score and tremor duration to see effect of tremor duration on connectivity change. Subgroups of patients with higher SARA scores were also compared. 

 

Results: All 15 patients had significant differences in tremor between DBS ON/OFF (p<0.001). Group analysis revealed that, with threshold p<0.05,  in DBS ON vs. OFF longer tremor duration was significantly correlated to decrease in connectivity between L SPL and R Vim (R=0.73, p=0.002) and increase in connectivity between R IPL and R pre-central gyrus (R=0.62, p=0.014).  Overall, patients with greater pre-operative ataxia had significantly decreased functional connectivity between multiple ROIs, including DN and cerebellar nodule, when DBS was ON compared to OFF (z-score<4). 

 

Conclusions: Stimulation of the DRTt and concordant improvement of tremor and ataxia resulted in connectivity decreases seen in multiple regions outside the motor network thought to be involved with tremor pathology. Such functional engagement of the SPL/IPL in tremor and cerebellum in ataxia, when combined with both structural and electrophysiologic connectivity, may help serve as a biomarker to improve DBS targeting and possibly predict outcome.


Albert FENOY (Great Neck, USA), Z. David CHU, Stephen KRALIK
15:50 - 16:00 #35992 - OP041 Asleep DBS for Essential Tremor using a AI approach for targeting: results of a phase-2 clinical trial (OPTIVIM).
OP041 Asleep DBS for Essential Tremor using a AI approach for targeting: results of a phase-2 clinical trial (OPTIVIM).

Background:

DBS of the VIM nucleus is an efficacious treatment for refractory essential tremor, although targeting the intra-thalamic nuclei remains challenging. We developped an AI approach to predict a clinical target for DBS in essential tremor (VIM/PSA). The learning database consisted in clinical and radiological features of patients previously operated on with optimal outcomes. The OPTIVIM trial (NCT03760406) aims to validate this approach.

Patients and Methods:

In this prospective bi-centric (Lyon and Bordeaux), non-comparative, phase-2 clinical trial, we included 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. Leads and targeting localisations were studied using leadBDS, Suretune and Guide XT.

The target was planned by OptimDBS RebrAIn software, 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:

Twenty-two patients underwent surgery under general anaesthesia with direct insertion of the leads at the target without clinical per-operative evaluation between June 2019 and February 2023 (9M/13F, mean age 63 (+- 11) years old).

The (pre-operative / post-operative) FTM scale means were 51.3/20. The mean improvement of the tremor was 61% on the FTM scale. These scores were confirmed by accelerometry.

The (pre-operative / post-operative) SARA means were 5/3,8. Two patients worsened their SARA.

The (pre-operative / post-operative) mPDQ39 means were 43/21. The mean improvement of quality of life were 50% on the mPDQ39.

The mean distance between the target and the electrode surface was 0,9mm (min 0, max 2.2).

Conclusions:

Asleep DBS for essential tremor using our machine-learning model for targeting the VIM/PSA may be a safe, efficient procedure leading to outcomes comparable to those published in the literature for standard awake DBS surgery.


Julien ENGELHARDT, Emile SIMON, Nejib ZEMZEMI, Dominique GUEHL, Stephane THOBOIS, Nathalie DAMON-PERRIERE, Teodor DANAILA, Camille DALLIENS, Chloe LAURENCIN, Louis NADAL, Pierre BRIAU, Olivier BRANCHARD, Nicolas AUZOU, Marie BONNET, Wassilios MEISSNER, Pierre BURBAUD, Polo GUSTAVO, Patrick MERTENS, Emmanuel CUNY (bordeaux)
16:00 - 16:10 #36111 - OP042 Modulating a subthalamic nucleus related network is associated with motor response following Deep Brain Stimulation.
OP042 Modulating a subthalamic nucleus related network is associated with motor response following Deep Brain Stimulation.

 

Objective

Chronic Deep Brain Stimulation of the subthalamic nucleus (STN-DBS) has been shown to improve the motor symptoms of Parkinson’s Disease and reduce levodopa requirement (1). The network topography associated with the therapeutic effects of STN DBS are not well described. FDG PET has been used to study disease and treatment related networks in PD (2, 3). The goal of this study was to identify a network associated with the therapeutic effects of STN DBS

 

Methods

We studied 13 PD patients with implanted STN-DBS electrodes (24 hemispheres) with FDG PET off medication in the on and off stimulation condition. To derive a brain network, we applied ordinal trend canonical variates analysis (OrT/CVA) to the ON/OFF scan data for each hemisphere (4). Further validation was assessed by quantifying stimulation mediated changes in an independent cohort of 13 STN DBS patients (26 hemispheres) acquired at the San Raffaele Scientific Institute, Italy (5). We assessed relationships between changes in pattern expression and UPDRS motor ratings in the derivation and validation STN DBS samples, and evaluated changes in network pattern in other therapeutic interventions.

 

Results

We identified a significant hemispheric spatial covariance pattern characterized by stimulation mediated increases in the subthalamic nucleus, ventral thalamus, supplementary motor area and pontine nuclei and decreases in the postcentral gyrus, cerebellar vermis and paravermian region (Fig 1). Subject scores exhibited consistent increases in the ON vs OFF conditions across hemispheres (p < 0.001, permutation test) (Fig 2). Increases in pattern expression across subjects correlated with improvement in UPDRS motor ratings for contralateral limbs (R= 0.6, p < 0.005) (Fig 3(a)). Similar findings were seen in the validation sample, with increased pattern expression in the ON condition (p < 0.05, paired t-test) and significant correlations with motor improvement (R = 0.66, p < 0.05) (Fig 3(b)).
Significant increases in pattern expression were observed with STN stimulation but not Levodopa infusion of comparable efficacy (Fig 4). Less pronounced increases were seen with GPi DBS whereas decreases were present following unilateral subthalamotomy and microlesion (Fig 4). In the absence of treatment, pattern expression was stable in PD patients and healthy controls. Pattern expression from preoperative (R= -0.55, p < 0.05) & OFF (DBS and Levodopa) (R= -0.55, p < 0.005) PET correlated with motor improvements in UPDRS after stimulation (Fig 3(c & d)).

 

Conclusions

STN-DBS modulates a significant motor related network which correlates with the therapeutic benefit. In contrast to previously characterized PD-related networks, this treatment induced pattern is modulated specifically by STN-DBS but not by other surgical interventions or dopaminergic treatment. Baseline network expression has the potential to predict stimulation associated therapeutic benefit. 

References

1.       1. Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A, Horak FB, Okun MS, Foote KD, Krack P, Pahwa R. Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Archives of neurology. 2011 Feb 14;68(2):165-.

2.       2. Perovnik M, Rus T, Schindlbeck KA, Eidelberg D. Functional brain networks in the evaluation of patients with neurodegenerative disorders. Nature Reviews Neurology. 2023 Feb;19(2):73-90.

3.       3. Schindlbeck KA, Eidelberg D. Network imaging biomarkers: insights and clinical applications in Parkinson's disease. The Lancet Neurology. 2018 Jul 1;17(7):629-40.

4.      4.Habeck C, Krakauer JW, Ghez C, Sackeim HA, Eidelberg D, Stern Y, Moeller JR. A new approach to spatial covariance modeling of functional brain imaging data: ordinal trend analysis. Neural computation. 2005 Jul 1;17(7):1602-45.

5.      5.Volonté MA, Garibotto V, Spagnolo F, Panzacchi A, Picozzi P, Franzin A, Giovannini E, Leocani L, Cursi M, Comi G, Perani D. Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced parkinson's disease. Parkinsonism & Related Disorders. 2012 Jul 1;18(6):770-4.


Prashin UNADKAT (New York, USA), Yilong MA, Shichun PENG, An VO, Chris TANG, Silvia CAMINITI, Daniela PERANI, David EIDELBERG
16:10 - 16:15 #36115 - OP043 Advanced personalized image analysis for neural modulation targeting.
OP043 Advanced personalized image analysis for neural modulation targeting.

Background: Tremor is a highly disabling symptom common in both Essential tremor (ET) and Parkinson’s disease (PD), conjugate with the dramatic reduction in quality of life, alongside social exclusion, embarrassment, and immense difficulty in performing routine tasks. Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) is an emerging non-invasive technology that utilizes sound waves energy to induce a focal thermal lesion with sub-millimeter precision to treat patients with tremor. The ventral intermediate nucleus of the thalamus (VIM) is a well-studied target for tremor reduction. However, since the VIM can’t be visualized radiologically, different targeting methods were developed. Indirect targeting is the most common approach for VIM targeting based on patients’ anatomy using the anterior-posterior commissure (AC-PC) as a reference point. However, it is correlated with suboptimal tremor control up to 20%, inconsistency of the treatment’s outcome especially regarding the long-term effect, and side effects such as ataxia, sensory deficits and dysarthria. Moreover, inaccurate targeting causes a longer procedure with excessive sonications that can affect the treatment’s outcome and the adverse events.

Aim: Utilization of advanced analysis methods as a targeting approach for personalized treatment and superior clinical outcomes.

Methods: Pre- and post-operative magnetic resonance imaging (MRI) scans were acquired from 56 patients who underwent MRgFUS. Using the preoperative diffusion tensor imaging (DTI) MRI sequence, three tracts (pyramidal tract [PT], medial lemniscus [ML], and dentatorubrothalamic tract [DRTT]) were located for each patient using tractography. These patients' postoperative T1 weighted images were used for segmentation and volume calculation of the lesion. Geometrical measurements were performed, such as the distance and overlap between the lesion and each of the tracts. To detect the factors affecting the treatment’s outcome, statistical and machine learning tools were applied to find correlations between the postoperative clinical evaluations (up to 2 years followup) and the image analysis.

Results: The overlap of the lesion with a specific region of the DRT, the distance of the lesion from the ML and PT, and the total overlap between the lesion and each tract were shown to have a significant correlation to the treatment’s outcome.

Conclusion:

The optimal treatment target within the VIM can be defined according to the correlations discovered. We suggest an innovative personalized method to detect the “sweet spot” for eliminating tremor using MRgFUS. This technique tailors the target localization to a specific patient based on the patient’s functional anatomy—the spatial locations of the patient’s tracts to improve tremor control and avoid adverse effects.


Shalem NOAM, Sinai ALON, Zur GIL, Carmely GAL, Eran AYELET, Schlesinger ILANA, Lev-Tov LIOR (Haifa, Israel)
16:15 - 16:25 #36126 - OP044 7-Tesla MRI Subthalamic Network Analysis in Deep Brain Stimulation for Parkinson’s disease.
OP044 7-Tesla MRI Subthalamic Network Analysis in Deep Brain Stimulation for Parkinson’s disease.

Background: Deep brain stimulation (DBS) of the nucleus subthalamicus (STN) is an effective surgical treatment for the patients with advanced Parkinson's disease (PD). However, individual improvement (response) after DBS remains variable and average (UPDRS) motor improvement in our  centre for the past ten years has been stable; averaging 46%. The effect of DBS relies on the modulation of malfunctioning brain networks by delivering electrical pulses within the STN. So far, visualizing the multiple brain networks in this small nucleus for DBS surgery has been challenging and prevented electrode placement guided by its cortical (motor) projections. By using structural 7-Tesla MRI (7T MRI) connectivity to visualize (malfunctioning) brain networks, DBS-electrode placement and activation can be individualized and network guided.

Methods: This is a single center prospective observational study. The primary outcome measure is the change in motor symptoms as measured by the disease-specific Unified Parkinson's Disease Rating Scale (UPDRS-III) after six months of DBS. Before DBS surgery, the STN and its cortical connections are visualized using 7T T2-weighted and diffusion weighted imaging. The three major projections of the STN are identified (using probabilistic connectivity): projections connecting to primary and supplementary motor cortex (motor), projections to the prefrontal cortex (associative) and projections to the basofrontal cortex (limbic). Electrode placement is aimed at the motor STN (part of the STN showing highest density of motor projections). 

Results: In 20 PD patients (representing 40 STNs) visualisation of cortical projections originating in the STN using 7T MRI was performed before DBS surgery. The 7T MRI subthalamic network map, showing the (colored) motor STN for each patient, was subsequently imported in de DBS planning software and electrode placement was aimed at this part. Average UPDRS improvement was 57% (range 40% - 83%).

Conclusion: Electrode placement guided by 7T MRI subthalamic network analysis enhanced the effectiveness in DBS for PD. After six months of DBS an average of 57% UPDRS improvement was seen; over 10% more compared to the past 10 years. Variability in motor improvement decreased; all patients had a response (>30% improvement). Current analysis will be extended as enrollment is ongoing and secondary outcome measures (Amsterdam linear disability score, quality of life as measured by PDQ-39, Starkstein apathy scale, motor complication score) will be included.


Maarten BOT (Amsterdam, The Netherlands), Niels RIJKS, Yarit WIGGERTS, Wietske VAN DER ZWAAG, Rob DE BIE, Martijn BEUDEL, Thuy-Anh K NGUYEN, Pepijn VAN DEN MUNCKHOF, Rick SCHUURMAN
16:25 - 16:30 #36169 - OP045 Susceptability weighted imaging for direct targeting globus pallidum interna in deep brain stimulation.
OP045 Susceptability weighted imaging for direct targeting globus pallidum interna in deep brain stimulation.

Background: Deep brain stimulation (DBS) is commonly used practise  for treating various neurological and psychiatric disorders to this day. Stimulation of GPi is an effective treatment for cardinal symptoms of Parkinson Disease, treatment resistant dystonia, dyskinesia, and other hyperkinetic movement disorders. Conventional T1 and T2 weighed MRIs are being used for targeting GPi in general practise but using susceptibility weighted imaging (SWI), proton density (PD) and fast gray matter acquisition T1 inversion recovery (FGATIR) sequences is rather recently debated. In this study, we explored the compatibility of the SWI modality for targeting GPi as we compared the CNR rates of the T2 and SWI acquisitions of the Parkinson patents and used SWI images for preoperative targeting modality for bilateral GPi DBS surgery for one Parkinson patient.

Methods: Between 2019 and 2023, cranial MRI scans and SWI acquisitions of the patients diagnosed with idiopathic PD more than 4 years ago, have collected without them being a candidate for DBS surgery. 20 patients included in the study regarding to their time of diagnosis (mean 4 years) but surgical intervention for treatment augmentation have not been required for 19 patients. Patients’ preoperative T2 weighted MRIs and SWI scans were investigated for detectability of the region of interest (GPi) and adjacent structures were identified for defining the borders. All the GPi structures were identified radiologically as inferior border set to be optic tracts, medial border met by internal capsule, lateral border met by internal lamina and Globus Pallidum externum.

 Results: In T2 and SWI acquisitions, GPi structures harboured different intensities within the same nucleus and both nuclei differed from each other morphologically and radiologically even in the same patient. CNR differences between the structures in T2 and SWI acquisitions revealed that in T2 and SWI, ventral and lateral CNR are similar bur medial border significantly more distinguishable in SWI acquisition. (SWI ventral: 47,25 and lateral :28,5 ;T2 ventral:52 and lateral:31,65)  but medial borders were significantly more distinguishable in SWI acquisition in which CNR scores 59,775 for SWI and 21,3 for T2. One patient operated successfully using SWI sequence as main frame to stereo-planning.

Conclusions: Comparison of the CNR scores of the borders of the GPi between conventional, T2 weighted MR scans and SWI acquisitions favours SWI scans as the contrast between tissues are more significant and visibility values scored higher in SWI scans. Targeting motor subregions of the GPi to achieve best clinical outcome with lower side effect profile is a challenging technique and requires expertise in the field considering the fact that each nucleus has an intensity variation within and each other.


Yahya Efe GUNER (ANKARA, Turkey), Anil ERAY, Ali SAVAS

15:30-16:30
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B28
PARALLEL SESSION 5
Psychiatry 2

PARALLEL SESSION 5
Psychiatry 2

Moderators: Pablo ANDRADE (Consultant Neurosurgeon) (Cologne, Germany), Roman LISCAK (head) (PRAGUE, Czech Republic), Claudio POLLO (Chief Deputy) (Bern, Switzerland)
15:30 - 15:40 #34301 - OP046 Deep brain stimulation: where should we stimulate in obsessive compulsive disorders?
OP046 Deep brain stimulation: where should we stimulate in obsessive compulsive disorders?

Objective

It has been suggested that the hyperdirect pathway, connecting the medial STN and the prefrontal cortex might be the structure to be stimulated in obsessive compulsive disorders. However, this fiber tract takes course over a long distance from the diencephalon to the prefrontal cortex. Several targets on or nearby this path have been tried in deep brain stimulation like the ventral anterior tegmentum (VAT), anteromedial subthalamic nucleus (amSTN), inferior thalamic peduncle (ITP) and the bed nucleus of the stria terminalis (BNST).  In our study we investigated whether these stimulation sites are connected to the hyperdirect pathway exclusively or if other fiber tracts are involved?

 

Methods

16 cerebral hemispheres in 8 patients with obsessive compulsive disorders were investigated. Three different regions of interest (ROI) were defined as seed regions for fiber tracking: the ventral anterior tegmentum (VAT),  the anteromedial subthalamic nucleus (amSTN) and the bed nucleus of the stria terminalis (BNST). Tractography was executed on diffusion weighted images with 64 gradient directions from a 3T scanner and the patients under general anesthesia.

 

Results

The seed region in the BNST provided the most circumscribed depiction of the hyperdirect pathway and the stria terminalis with a limited amount of additional fibers and cortical and subcortical projection areas. Seed regions in the VAT and the amSTN included the dentate-rubro-thalamic tract and fibers in the posterior and anterior limb of the internal capsule, projecting to large areas of the frontal and the motor cortex.

 

Conclusion

In deep brain stimulation the challenge is to find a well circumscribed target with maximum effect on symptom alleviation and no side effects. If the hyperdirect pathway, connecting the medial STN and the prefrontal cortex was indeed the sole structure to be stimulated in obsessive compulsive disorders, the BNST seems to be the best option. The BNST connects mainly and most exclusively to the hyperdirect pathway and the stria terminalis, whereas stimulation sites in the diencephalon involve significantly more fiber tracts and larger cortical projection areas.


Juergen SCHLAIER (Regensburg, Germany), Valeria DEMMEL, Daniel DEUTER, Nils Ole SCHMIDT, Berthold LANGGUTH
15:40 - 15:45 #34464 - OP047 Genomics of severe and treatment-resistant obsessive-compulsive disorder treated with deep brain stimulation: a preliminary investigation.
OP047 Genomics of severe and treatment-resistant obsessive-compulsive disorder treated with deep brain stimulation: a preliminary investigation.

Individuals with severe and treatment-resistant obsessive-compulsive disorder (trOCD) represent a small but severely disabled group of patients. Since trOCD cases eligible for deep brain stimulation (DBS) probably comprise the most severe end of the OCD spectrum, we hypothesize that they may be more likely to have substantial detectable genetic contributions. Therefore, while the worldwide population of DBS-treated cases may be small (~300), screening these individuals with modern genomic methods may accelerate gene discovery in OCD. As such, we have begun to collect DNA from trOCD cases who qualify for DBS, and here we report results from whole exome sequencing and microarray genotyping of our first five cases. All participants had previously received DBS in the bed nucleus of stria terminalis (BNST), with two patients responding to the surgery and one showing a partial response. Our analyses focused on gene-disruptive rare variants (GDRVs; rare, predicted-deleterious single-nucleotide variants or copy number variants overlapping protein-coding genes). Three of the five cases carried a GDRV, including a missense variant in the ion transporter domain of KCNB1, a deletion at 15q11.2, and a duplication at 15q26.1. The KCNB1 variant (hg19 chr20-47991077-C-T, NM_004975.3:c.1020G>A, p.Met340Ile) causes substitution of methionine for isoleucine in the trans-membrane region of neuronal potassium voltage-gated ion channel KV2.1. This KCNB1 substitution (Met340Ile) is located in a highly constrained region of the protein where other rare missense variants have previously been associated with neurodevelopmental disorders. The patient carrying the Met340Ile variant responded to DBS, which suggests that genetic factors could potentially be predictors of treatment response in DBS for OCD. In sum, we have established a protocol for recruiting and genomically characterizing trOCD cases. Preliminary results suggest that this will be an informative strategy for finding risk genes in OCD.


Long-Long CHEN (Stockholm, Sweden), Anders FYTAGORIDIS, Diana PASCAL
15:45 - 15:55 #35747 - OP048 Morphometric brain analysis of OCD patients treated with DBS based on disease severity and clinical outcome.
OP048 Morphometric brain analysis of OCD patients treated with DBS based on disease severity and clinical outcome.

Introduction:

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized by intrusive thoughts (obsessions) and repetitive routines or mental rituals (compulsions). Standard therapy involves psychotherapy and pharmacotherapy. Deep brain stimulation (DBS) can be considered for therapy refractory OCD. In a recent meta-analysis, 66% of OCD patients treated with DBS were considered full responders. In the past, several biomarkers have been analyzed as potential predictive factors for clinical improvement. In this retrospective analysis, we aimed to identify morphometric biomarkers that could correlate with disease severity and clinical outcome after DBS.

 

Methods:

We retrospectively analyzed the clinical outcome of 45 OCD patients treated with DBS at our center. All patients received bilateral electrodes in the nucleus accumbens/anterior limb of the capsula interna (Nacc/ALIC). T1 sequences of preoperative MRIs were used for morphometric analysis. Voxel-based morphometry analysis of the subcortical structures was carried out using cat12 SPM12-toolbox. For the voxel-based analysis of the cortical surface, FreeSurfer was used. Clinical improvement of the patients was measured using the Yale-Brown Obsessive-Compulsive Scale (YBOCS) before surgery and after one year of DBS.

 

Results:

There was a moderate correlation between the preoperative YBOCS and the cortical thickness in the right medial orbitofrontal cortex (OFC) (rho = 0.22), the right insula (rho = -0.25), the right transverse temporal gyrus (rho = 0.23) and the left temporal pole (rho = 0.21). None of these correlations were statistically significant. There was a moderate positive correlation between the clinical improvement measured on the YBOCS and the cortical thickness in the left caudal middle frontal gyrus (rho = 0.23), the left rostral anterior cingulate gyrus (rho = 0.21), the right lateral OFC (rho = 0.21) and the left medial OFC (rho = 0.30). The correlation between the clinical improvement and the cortical thickness in the left OFC was statistically significant (p = 0.045).

 

Discussion:

We found a significant positive correlation between improvement on the YBOCS during Nacc/ALIC DBS and the cortical thickness of the left OFC. A correlation between the clinical improvement of the patients and the size of the Nacc, as reported on previous studies, could not be shown in our cohort.


Petra HEIDEN (Cologne, Germany), Ricardo LOUÇÃO, Kyprianos AROTIS, Veerle VISSER-VANDEWALLE, Juan Carlos BALDERMANN, Pablo ANDRADE
15:55 - 16:00 #35985 - OP049 Tic-related cortical-thalamic activity modulation in Tourette syndrome by thalamic deep brain stimulation and tic suppression.
OP049 Tic-related cortical-thalamic activity modulation in Tourette syndrome by thalamic deep brain stimulation and tic suppression.

Objectives:

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and vocal tics, which are typically preceded by a premonitory urge. Although it is generally recognized that the phenomenology of TS symptoms is rooted in dysfunction of the cortico-thalamic network, the precise neural correlates of urges and tics are still poorly understood, as are the neurophysiological effects of voluntary tic suppression and deep brain stimulation (DBS). Our aim was to uncover electrophysiological markers of urge and tic that may be used to inform future studies aiming to develop closed-loop DBS for TS.

 

Methods:

We recorded combined postoperative EEG and local field potential (LFP) data derived from implanted leads in 8 patients with TS who underwent thalamic DBS, using the Percept PC system (Medtronic). Additional accelerometer and video recordings were used for tic detection. Recordings were performed under a tic-free and a tic-suppression condition in which patients were asked to suppress tics as best as possible. This paradigm was conducted once with DBS ON and once with DBS OFF. Afterwards, tic-related spectral power (activity around tic onset) of EEG and LFP as well as coherence between thalamic and cortical signals was calculated.

 

Results:

Our study showed decreased left and right thalamic alpha activity (8-12 Hz) compared to baseline starting 1500ms before tic onset with a gradual increase thereafter, leading to a large peak between 500ms to 1000ms after tic onset, when the patients were allowed to tic freely. A similar and even more pronounced activity pattern was observed in left and right parietal cortical regions. Single-subject based analysis indicated that tic-related changes in alpha power were accompanied by decreased coherence between thalamic and parietal regions before tic onset and an increase afterwards in the same frequency band. Interestingly, thalamic as well as cortical alpha activity was modulated by both tic suppression and DBS.

 

Conclusion:

The present results suggest that an unbalance in low-frequency (alpha) activity of a broad thalamic-parietal-cortical network in patients with TS may contribute to the tic generation and possibly even the urge phenomenology. Reduced low-frequency activity before tic onset might function as an electrophysiological marker for closed-loop DBS for TS.


Laura WEHMEYER, Juan BALDERMANN, Thomas SCHÜLLER, Petra HEIDEN, Alek POGOSYAN, Veerle VISSER-VANDEWALLE, Huiling TAN, Pablo ANDRADE (Cologne, Germany)
16:00 - 16:05 #36015 - OP050 Effect on personality traits in patients with obsessive-compulsive disorder treated with deep brain stimulation.
OP050 Effect on personality traits in patients with obsessive-compulsive disorder treated with deep brain stimulation.

Introduction

As the research on psychosurgical procedures continues to widen, there is a worry about adverse effects. Especially negative effects on personality is a common concern among potential patients and medical professionals.

Aim

Our study aimed to evaluate whether or not treatment of obsessive-compulsive disorder (OCD) with deep brain stimulation (DBS) in striatal targets, specifically here, the bed nucleus of the stria terminalis (BNST) and the nucleus accumbens (NA), has any effect on personality.

Method

In this study, we look at patients suffering from severe OCD treated with DBS in striatal targets, the BNST in ten patients and the NA in one. A self-assessment questionnaire (DIP-Q) was filled out before surgery ("baseline") and at least 12 months afterwards ("endpoint"). According to the DSM-IV, the personality disorders in the questionnaire are divided into clusters (A, B and C). Individual changes in the number of criteria fulfilled were statistically analysed through a reliable change index.

Result

Nine out of eleven patients had sufficiently filled out the DIP-Q questionnaire for analysis. The mean±SD Yale-Brown obsessive compulsive scale score at baseline was 32±3 and one year after surgery 22±7.

On a group level, no significant change in personality traits was found. Although individually, we found significant changes in 11% of the data analysed. Most of these changes were found in Cluster A, although the highest amount of fulfilled scores at baseline and endpoint were found in Cluster C and borderline personality disorder.

Conclusion

We found no indication that DBS would have any detrimental effect on personality traits. On a group level, no change of statistical significance was found. However, the sample size was small, with some individual patients scoring reliably different at the endpoint than baseline, emphasising the need for more extensive studies in the future.


Matilda NAESSTRÖM (Umeå, Sweden), Patric BLOMSTEDT, Carlberg OSCAR, Owe BODLUND
16:05 - 16:15 #36062 - OP051 Patients´ experience of treatment of obsessive-compulsive disorder with deep brain stimulation.
OP051 Patients´ experience of treatment of obsessive-compulsive disorder with deep brain stimulation.

Background

The outcome of Deep Brain Stimulation (DBS) in patients with obsessive-compulsive disorder (OCD) is usually evaluated using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). However, this scale does not address the broader impact at the personal level. Little is known about patients´ everyday life experiences after DBS for OCD. Here we aim to explore patients´ perception of daily life following DBS.

 

Methods

Out of 12 OCD patients in a pilot study of DBS in the bed nucleus of stria terminalis area, six patients (4 women), operated between 2010 and 2017 accepted to undergo in-depth semi-structured interviews. The mean±SD pre-operative YBOCS score was 32±3, at the time of the interview the mean score was 15±10. The interviews were audiotaped and transcribed verbatim, and the data were analysed according to the grounded theory.

Results

Patients described that DBS had opened the door to the world after being isolated in their homes or an institution. As one patient describes it: “I would without hesitation recommend them to go through the operation, if they get the chance, I absolutely think it was worth it… because without this I would probably still be lying in my bed.”

This change in functioning led to possibilities to start new relationships and social activities or to get back to work or studies, despite some obstacles to adapting to the new life after DBS.

The path toward changes in daily life differed among patients. Some noticed first the reduction of anxiety, some the reduction in depressive symptoms or obsessions and compulsions. All patients described that their OCD eventually improved.

Conclusions

In-depth interviews and qualitative evaluation of patients´ perspectives on DBS for OCD and its impact on their daily life contribute to a broader understanding of the effects of that treatment beyond the traditional symptomatic outcome according to scales. 


Marianne MELANDER (Umeå, Sweden), Gun-Marie HARIZ, Viktoria JOHANSSON, Patric BLOMSTEDT, Matilda NAESSTRÖM
16:15 - 16:25 #36131 - OP052 Structural network analysis using diffusion MRI tractography in OCD patients treated with gamma knife anterior capsulotomy.
OP052 Structural network analysis using diffusion MRI tractography in OCD patients treated with gamma knife anterior capsulotomy.

Objective: Obsessive-compulsive disorder (OCD) is a severe psychiatric condition. The authors present the changes induced by Gamma Knife radiosurgery anterior capsulotomy on DWI images in patients with OCD resistant to any medical therapy.

Methods: Patients with severe OCD resistant to all pharmacological and psychiatric treatments who were treated with anterior GKRS capsulotomy were retrospectively reviewed. These patients were submitted to a physical, neurological, and neuropsychological examination together with structural and functional MRI before and after GKRS treatment. Strict study inclusion criteria were applied. Radiosurgical capsulotomy was performed using two 4-mm isocenters targeted at the midputaminal point of the anterior limb of the capsule. A maximal dose of 120 Gy was prescribed for each side. OCD symptoms were determined by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Diffusion weighted images of OCD patients pre and 1 year post Gamma Kinfe radiosurgery were analysed and compared using a fixel based analysis to estimate changes in fibre density and cross-section.

Results: Eight patients were included in this study. We found a significant bilateral density reduction of fibre bundles traversing trough the anterior limb of internal capsula, projecting from thalamus to prefrontal cortex. Additional fibre cross section reduction was observed in the lower part of the frontal lobe withe matter. The results were correlated to Y-bocs improvement at 1 year follow-up for all patients and to later Y-bocs score in patients with longer follow-up. Five patients (62.5%) were considered as responders at 1 year (Y-bocs reduction >30%).


Conclusions: GKRS anterior capsulotomy is effective and well tolerated with a maximal dose of 120 Gy. It works as other lesional techniques in disrupting the fibers passing the anterior limb of the internal capsule and give a sort of neuromodulation in the limbic circuit if compared to preoperative Tractography.


Giorgio SPATOLA (Brescia, Italy), Paul TRIEBKORN, Raphaelle RICHIERI, Jean FARISSE, Viktor JIRSA, Jean Marie REGIS
16:25 - 16:30 #36175 - OP053 Deep brain stimulation of the anterior limb of the internal capsule in patients with obsessive-compulsive disorder: what is the ideal anatomical location?
OP053 Deep brain stimulation of the anterior limb of the internal capsule in patients with obsessive-compulsive disorder: what is the ideal anatomical location?

Introduction:

Deep brain stimulation (DBS) can be offered to patients with treatment refractory obsessive-compulsive disorder (OCD) as a last resort therapy. Since the first published case in 1999, several possible stimulation targets emerged: the nucleus accumbens (Nacc), the anterior limb of the internal capsule (ALIC), the subthalamic nucleus (STN) or the bed nucleus of stria terminalis (BNST). In recent studies a novel, unified connectomic target has been suggested, which links all the targets and projects to the orbitofrontal cortex. The aim of this study was to analyze the clinical outcome of the patients based on the anatomical location of the stimulated area.

 

Methods:

We retrospectively analyzed the clinical outcome of 23 OCD patients who were treated with bilateral Nacc/ALIC DBS at our clinic. Lead localization was reconstructed based on the preoperative MRI and the postoperative CT using Lead-DBS. The electric field profile was calculated based on the stimulation parameters 12 months after the surgery. Clinical improvement of the patients was measured using the Yale-Brown Obsessive-Compulsive Scale (YBOCS) before the surgery and after one year of DBS.

 

Results:

The electric fields generated by the active contacts were more central in the coronal plane within the ALIC in responders than in non-responders on the left side. There was no difference between the two groups in the anterior-posterior or dorsal-ventral location of the electric fields within the ALIC. There was a significant correlation between the overlap of the VTAs and the ”positive” unified pathway published by Li et al (2020) and the clinical outcome, on the right side rho = 0.33 and on the left side rho = 0.40.

 

Discussion:

Stimulation of the central ALIC on the left side seems to be associated with a better clinical outcome in patients with treatment refractory OCD. A correlation between clinical improvement and more dorsal and posterior location of the stimulation fields, as reported in previous studies, could not be shown in our cohort. We found a positive correlation between improvement on the YBOCS after DBS and overlap of the VTAs with the unified pathway reported by Li et al (2020)


Petra HEIDEN (Cologne, Germany), Ricardo LOUÇÃO, Veerle VISSER-VANDEWALLE, Juan Carlos BALDERMANN, Pablo ANDRADE

15:30-16:30
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C28
PARALLEL SESSION 6
Neurophysiology

PARALLEL SESSION 6
Neurophysiology

Moderators: Linda ACKERMANS (Neurosurgeon) (Maastricht, The Netherlands), Hagai BERGMAN (Prof) (Jerusalem, Israel), Suneil KALIA (Associate Professor) (Toronto, Canada, Canada)
15:30 - 15:35 #35653 - OP054 EEG-based evoked potentials as electrophysiological sweetspot for Parkinson’s disease patients with a deep brain stimulator.
OP054 EEG-based evoked potentials as electrophysiological sweetspot for Parkinson’s disease patients with a deep brain stimulator.

Background: Subthalamic (STN) deep brain stimulation (DBS) is an established neurosurgical therapy to treat movement disorders such as Parkinson’s disease (PD). The wide parameter space and time constraints can make the programming of patients challenging. Clinical effect mapping to determine sweetspots have been investigated to objectify programming. Previously, we have investigated EEG-based evoked potentials (EPs) as a biomarker to guide programming. We found that a 3-millisecond peak (P3) could predict the best DBS-contact configuration, while a 10-millisecond peak (P10) was related to substantia nigra-related side effects. Here, we propose to use EPs to generate electrophysiological sweetspot maps to further facilitate programming.

Methods: Stimulation was delivered at 10Hz for 50s at each contact of a directional lead, while EPs were recorded using EEG. Next, EPs were mapped into the patients’ individual space and then transformed to MNI standard space. P3- and P10- hotspots and coldspots were determined. Lastly, we performed two cross-validation analyses: a permutation analysis and a leave-one-patient-out analysis.

Results: 13 patients (18 hemispheres) were included in the analysis. The P3-hotspot covered parts of the dorsolateral STN but extended to its medial surroundings (see upper panels of Figure 1). The P10-hotspot covered parts of the substantia nigra (see lower panels of Figure 1). Only the P10-hotspot survived the permutation analysis. The leave-one-patient-out analysis showed positive, significant relationships between stimulation overlap with the P3-hotspot and P3-peak amplitudes (p<0.0001) and between P10-hotspot to P10-peak amplitudes (p<0.0001), while negative, significant relationships were found between stimulation overlap between the P3-coldspot and P3-peak amplitudes (p<0.0001) and between P10-coldspots to P10-peak amplitudes (p<0.0001) (see Figure 2).

Conclusion: This study investigated EP-based sweetspot mapping in PD patients. This approach revealed a P3-hotspot in line with hyperdirect pathway stimulation and P10-hotspot related to nigral stimulation that may facilitate DBS programming of PD patients. Ultimately, the use of sweetspot mapping may guide programming in a more objective manner.


Jana PEETERS, Till DEMBEK, Tine VAN BOGAERT (Leuven, Belgium), Alexandra BOOGERS, Robin GRANSIER, Jan WOUTERS, Philippe DE VLOO, Bart NUTTIN, Myles MC LAUGHLIN
15:35 - 15:40 #35750 - OP055 Investigating the Contributions of Deep Brain Structures to Speech Decoding Using Stereotactic Electroencephalography.
OP055 Investigating the Contributions of Deep Brain Structures to Speech Decoding Using Stereotactic Electroencephalography.

Introduction: Language impairments often arise from severe neurological disorders, prompting the development of neural prosthetics based on electrophysiological signals for the restoration of comprehensible language information. Previous decoding efforts have focused exclusively on signals from the cerebral cortex, neglecting the potential contributions of deeper brain structures to speech decoding in brain-computer interfaces (BCIs). This study aims to explore the role of deep brain structures in speech decoding by utilizing stereotactic electroencephalography (sEEG).

Materials and Methods: Five native Mandarin Chinese speakers with pharmaco-resistant epilepsy participated in this experiment. sEEG contacts were primarily located in the superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, postcentral gyrus, precentral gyrus, thalamus, hippocampus, fusiform gyrus, and basal ganglia. The participants were asked to read the Chinese materials displayed on a screen after receiving prompts. These materials included 407 Chinese characters (covering all Chinese syllables), 300 sentences, and several Chinese stories. A deep learning model based on long short-term memory (LSTM) was developed to encode speech and EEG data collected simultaneously. The power of 4-30 Hz and 70-150 Hz frequency bands were used as key features.

Results: We first established a database comprising approximately 100 hours of high-quality Chinese speech and sEEG signals. Prediction of the characteristics (tuning, place, manner, and voicing) of vowels and consonants within single words based on the selected features and electrode contacts, and an average accuracy of 48.75% (deep structure signals only), 53.56% (cortical signals only), and 58.35% (both deep structure and cortical signals) were achieved, all significantly exceeding chance levels (p < 0.001). Interestingly, utilizing deep structure signals to predict the tone of individual characters resulted in significantly (p = 0.015) higher accuracy compared to cortical signals (59.23% and 51.07% respectively), and the accuracy reached 62.87% using both deep structure and cortical signals. Then, we estimated spectral coefficients to reconstruct audible waveforms, obtaining correlations of up to 0.80 between original and reconstructed speech spectrograms, which were significantly above chance levels for all participants (p < 0.001).

Conclusions: Our findings indicate that electrophysiological signals obtained from deep brain structures offers valuable input to speech decoding performance, and pave ways to future speech BCIs.


Chen FENG (Hangzhou, China), Lu CAO, Xiaowei JIANG, Ting WANG, Jie YANG, Mohamad SAWAN, Junming ZHU, Yue ZHANG, Hemmings WU
15:40 - 15:50 #35769 - OP056 Electromyography-assisted posterior subthalamic area deep brain stimulation (EMG-PSA-DBS) for tremor: 2-year prospective study.
OP056 Electromyography-assisted posterior subthalamic area deep brain stimulation (EMG-PSA-DBS) for tremor: 2-year prospective study.

Title: Electromyography-assisted posterior subthalamic area deep brain stimulation for tremor: 2-year prospective study

Methods:  Prospective observational study of essential tremor (ET) and tremor-dominant Parkinson's disease (TDPD) patients undergoing unilateral electromyography-assisted posterior subthalamic area deep brain stimulation (EMG-PSA-DBS). EMG recordings from neck and limb muscles contralateral to the side of brain electrode implantation were obtained. Tremor activity was categorised as ‘clinical tremor’ (CT) if it could be detected by clinical inspection or using the gyroscope and ‘sub-clinical tremor’ (ST) if it manifested only as EMG spike clusters with frequencies corresponding to ET or PD tremor. A conventional unilateral PSA-DBS was performed. Macrostimulation was used to locate the PSA region of maximal CT suppression. The location was then adjusted until ST activity decreased by 90% or more at a stimulation amplitude of 1mA or less (60 microseconds, 100Hz) with minimal or no stimulation-induced side effects at 4.5mA. The macroelectrode was exchanged for a permanent brain electrode (Medtronic 3389-40) under X-ray guidance. The distalmost contact of the permanent electrode was placed at the site of greatest ST suppression. Finally, the electrodes were connected to an implantable pulse generator (IPG. Medtronic Activa PC/ RC). Tremor assessments for the treated side (Treated tremor score; TTS) were obtained 6-, 12- and 24-months after surgery with the IPG switched ON and OFF.

Results: 40 patients (20 ET, 20 TDPD) participated. The TTS in ET and TDPD patients before surgery were 24.80 ±6.86 and 20.00 ±5.76 respectively. At 6-, 12- and 24- months the TTS with the IPG ON was 1.05 ±1.73, 1.25 ±2.05 and 2.20 ± 3.65 in ET and 0.45 ± 1.36, 0.45 ± 1.00 ,and 0.20 ± 0.52 in TDPD patients. This corresponded to a tremor reduction of 91-96% in ET and 98-99% in TDPD patients compared to baseline. Inactivation of the IPG resulted in a worsening of the TTS by 35-55% but tremor control was still better than before surgery. EMG-PSA-DBS therefore suppresses tremor both by neuromodulation and a microlesioning effect that persists for up to 2 years from surgery. Due to microlesioning, 20% of patients have no tremor at 2- years even when the IPG is turned off. The average stimulation parameters are 1.5V, 73.5 microseconds, 111.5Hz.  We also demonstrated that the tremorgenic fibres in the PSA exhibit mediolateral somatotopy.

Conclusions:  EMG-PSA-DBS results in excellent tremor control from a combination of neuromodulation and chronic microlesioning. The PSA exhibits somatotopy.


Hu Liang LOW (London, United Kingdom), Sally CUTLER, Gary DOYLE, Christopher HONEY
15:50 - 15:55 #35850 - OP057 Increased electrode impedance as a marker for early detection of Deep Brain Stimulation (DBS) hardware Infection: an in-vitro study.
OP057 Increased electrode impedance as a marker for early detection of Deep Brain Stimulation (DBS) hardware Infection: an in-vitro study.

Introduction 
When deep brain stimulation (DBS) infections are identified, they are often too advanced to treat without complete hardware removal. Newer objective markers to identify DBS infections are needed. In our experience from a patient with GPi (Globus Pallidus-interna) DBS whose hardware was ex-planted following an infection,  retrospectively we realised that the increasing impedance values were an early clue to a hardware infection. We decided to recreate these conditions in a controlled environment; to accurately analyze the pattern of changing of electrical impedance following  a hardware infection. 

 

Methods 
A stainless steel culture chamber containing 1% brain heart infusion agar was used (Figure 1) A DBS electrode was dipped in peptone water containing S. aureus and subsequently introduced into the chamber. The apparatus was incubated at 37°C. The lead was connected to an Activa PC DBS Implantable Pulse Generator (IPG) (Figure 1) and impedance was measured using the N’vision #8840 patient programmer at 30 Hz and 1.5 V (Medtronic MN, USA). 

Linezolid solution was added to the chamber at day 3. Impedance was measured at 24hr intervals for 6 days. A control experiment without S.aureus inoculation was also performed.

 

Results
In the in-vitro study involving hardware infection, baseline impedance was recorded on day 1; the mean monopolar impedance was 751.8 ± 23.8  and the mean bipolar impedance was 1310.8 ± 85.8 Ω. A biofilm formation could be observed around the DBS lead by day 2, and florid growth around the lead was seen by day 3 (Figure 2). On day 3, the mean monopolar impedance was 1004.8 ± 68.7 , and the mean bipolar impedance was 1405.7 ± 63.8 . A 33.7% increase in mean monopolar impedance (p=0.007) and a 7.2% increase in bipolar impedance (p = 0.005), compared to the baseline, was observed following a biofilm formation from day 1–3.  

 

Linezolid was added to the culture chamber on day 3, and impedance values were recorded again. The addition of the linezolid solution led to subtle decrease in the impedance values; however, they were not statistically significant (p=0.739). The mean monopolar impedance by day 6 was 842.3±17.5Ω and the mean bipolar impedance was 1376.3±49.5Ω. A 15.9% decrease in monopolar impedance(p=0.003) and a 2.7% decrease in bipolar impedance (p=0.025) was observed between day 3–6 following the addition of linezolid solution on day 3These impedance values are summarized in Figure 3(a),4.

 

In the control experiment, there was a 1.6% decrease in the mean monopolar impedance from day 1 to day 3 (p=0.113), a 0.5% decrease following addition of linezolid solution on day 3 (p=0.074), and a 0.7% decrease from day 3 to day 6 (p=0.063). There was a 1.4% decrease in the mean bipolar impedance from day 1 to day 3 (p=0.062), a 0.1% decrease following addition of linezolid solution on day 3 (p=0.082) and a 0.9% decrease from day 3 to day 6 (p=0.091) (Figure 3(b)).

 

 

Conclusion
Our study provides an insight into impedance trends following a hardware infection in DBS. Increased impedance outside expected norms may be useful for early prediction of infection.  Furthermore, timely management using antibiotics might reduce the frequency of infection-related explant surgeries.


Hargunbir SINGH (Boston, USA), Shivani ARJUN, Divij SINGHAL, Nishit SAWAL, Vipin GUPTA, John ROLSTON, Michaela STAMM, Varsha GUPTA
15:55 - 16:05 #36018 - OP058 Electrophysiological navigation to the posterior subthalamic area in essential tremor patients.
OP058 Electrophysiological navigation to the posterior subthalamic area in essential tremor patients.

Background:

Essential Tremor (ET) is a prevalent movement disorder, impacting around 5% of the global population. While pharmacological treatments benefit many ET patients, those with severe and unresponsive symptoms often require surgical intervention, such as ablation or deep brain stimulation (DBS). Traditionally, the ventral intermediate (Vim) nucleus of the thalamus has been targeted for ET-DBS. However, Vim DBS can lead to adverse effects like speech disturbances, ataxia, and progressive reduced effectiveness in suppressing tremors. To address this, the posterior subthalamic area (PSA) has emerged as a promising alternative target with a lower risk of such adverse effects. Since the PSA lacks clear electrophysiological markers and is challenging to target due to its small size and white matter composition, our study explores the adjacent subthalamic nucleus (STN) as a navigational reference to reach the PSA, given its strong electrophysiological signature.

 

Methods:

Simultaneously inserting two recording electrodes into the brain, one in the anterior lateral BenGun location targeting the STN and the other in the central BenGun location targeting the PSA, we leverage the distinct STN characteristics of increased background noise and high density firing, as measured by root mean square (RMS), to identify the entrance and exit points of the STN. Confirmation of PSA location is achieved by stimulating at the depth equivalent to the bottom of the STN and assessing the therapeutic window. We then compare the electrophysiological data from ET patients' STN (n=12 patients, 18 trajectories) with that of Parkinson's disease (PD) patients (n=35 patients, 62 trajectories).

 

Results:

We successfully target the PSA by utilizing the electrophysiological signature of the STN as a reference. The STN of ET patients exhibited a different frequency distribution and lower RMS compared to PD patients' STN. Additionally, while the total length of the STN in ET patients was shorter, there was no difference in the percentage determined as the motor sub-region.

 

Conclusion:

By capitalizing on the highly distinctive electrophysiological characteristics of the STN and its proximity to the PSA, we enable electrophysiological navigation to precisely target the PSA in ET patients undergoing DBS surgery. Further investigation into the electrophysiological differences between the STN of ET and PD patients is warranted.


Halen BAKER ERDMAN (Jerusalem, Israel), Juan F LEÓN, Stefanie GLOWINSKY, Sami HEYMANN, Hagai BERGMAN, Zvi ISRAEL
16:05 - 16:15 #36040 - OP059 The Effect of Deep Brain Stimulation on Neurovascular Coupling in Human Intracranial Recordings of Basal Ganglia.
OP059 The Effect of Deep Brain Stimulation on Neurovascular Coupling in Human Intracranial Recordings of Basal Ganglia.

Background: Deep brain stimulation (DBS) targeting the basal ganglia has emerged as a promising therapy for a range of neurological and psychiatric disorders, including Parkinson's disease. However, the precise biological mechanisms responsible for its effects are not yet fully understood. Neurovascular coupling (NVC) is a crucial process that orchestrates the coordination between neural activity and cerebral blood flow in a spatiotemporal manner. While it is clear that DBS interacts with NVC, there has been a little research to accurately assess the impact of DBS on vascular responses within the human brain.

Objective: This study aims to investigate the effect of high-frequency microstimulation on vascular responses by examining the cardiac artifacts found in microelectrode recordings during brain mapping procedures for DBS implantation surgeries.

Methods: We investigated the influence of subthalamic nucleus (STN), globus pallidus internus (GPi), and ventral intermediate nucleus (VIM) microstimulation on cardiac artifact prominence from single-neuron recordings before and after 100 Hz stimulation (≥ 2 s) applied and recorded through microelectrodes placed 600 μm apart. We measured the amplitude of the artifact on the MER recording and used it as an indirect marker of neurovascular coupling. Pre- and post-stimulation intervals were compared using linear mixed models to ascertain the effect of stimulation. We further categorized the effect of microstimulation on intracranial vessel dynamics based on the percentage change of cardiac artifact prominence.

Results: Deep brain stimulation (DBS) notably enhanced vascular response in various brain regions, with an average increase of 4.2-fold in the VIM, 3.4-fold in the subthalamic nucleus STN, and 1.5-fold in the GPi following stimulation (p < 0.001). This augmentation was detected on the recording electrode but not on the stimulation electrode, implying a localized impact on neurovascular coupling. Furthermore, the study assessed the distribution of segments exhibiting increased, decreased, or unaltered cardiac artifact prominence post-stimulation, uncovering some variability across the examined brain regions.

Conclusion: Our findings reveal a significant impact of electrical stimulation on neurovascular coupling in the VIM, STN, and GPi brain regions, highlighting the potential therapeutic implications of DBS for neurological and psychiatric disorders, as well as neurovascular diseases. Further research is warranted to investigate the underlying mechanisms, optimize DBS parameters, and explore novel applications in treating brain disorders involving impaired neurovascular function.


Artur VETKAS (Toronto, Canada), Srdjan SUMARAC, Samantha CHAU, Emily HANIFF, Hodaie MOJGAN, Kalia SUNEIL, Andres M LOZANO, Bill HUTCHISON, Luka MILOSEVIC
16:15 - 16:20 #36116 - OP060 Curved trajectories in stereotactic neurosurgery – First results of an interdisciplinary approach.
OP060 Curved trajectories in stereotactic neurosurgery – First results of an interdisciplinary approach.

Introduction: One major limitation of stereotactic procedures is the dependence on straight trajectories for surgical planning. For difficult demanding regions such as insular or pineal area or for multiple target locations in deep brain stimulation, approaches using curved trajectories to the target could enlarge the surgical options. Here the authors present their first results of a collaborative research project supported by the German Research Foundation (DFG).

 

Methods: An interdisciplinary team of engineers, mathematicians and neurosurgeons is investigating the potential application of an actuation system for curved cannulas in stereotactic neurosurgery with concentric tube continuum robots (CTCRs). A system for mechanical actuation of the CTCR allowing an easy exchange of tubes, precise actuation at the tubes’ base and precise measurements of the robot’s backbone w.r.t. time were used. Validation was performed with a photogrammetric measurement system. Target precision and follow-the-leader-deviations by movements of the cannulas were assessed. For a set of automatically planned configurations by numerical optimization, the real curved cannula behavior was compared to state-of-the-art models of the elastostatic behavior. The key contribution is the investigation of the precision of target accuracy in a neurosurgical setting, evaluation of metal artifacts of the actuation system and of the nickel-titanium curved cannulas within predefined targets. A CT-device using a stereotactic head model and in a second step porcine cadaver brains were used..

 

Results: The actuation system’s artifacts did not disturb the image quality of the region of interest. CT-scans identifying the conduct of the curved cannula within the brain parenchyma did not show signs of marked tearing of the porcine brain, but a higher degree of interfering artifacts of the cannula was found increasing with the amount of porcine cadaver tissue surrounding the cannula tip. However, despite optimal target point accuracy in the planned configurations by numerical optimization, first practical applications of curved cannulas had a target point deviation of up to 4 mm. Further optimization of the stereotactic apparatus for curved trajectory planning allowed a further reduction of target point deviation reaching an accuracy and reproducibility in an acceptable range.

 

Conclusion: The authors present first results with the application of curved cannulas in their model of stereotactic procedures. While there is significant progress from a theoretical point of view particularly in mechanical engineering and mathematic modeling, a medical application of CTCRs is still in its infancy. Further refinement of the technique is required before a clinical application can be thought of. Hence, while the proposed methodology seems to be very promising from a conceptual point of view, further research towards a refined technique is required to make it applicable for first pre-clinical tests/experiments.

 


Joachim Manfred Karl OERTEL (Homburg, Germany), Mohamed HENIA, Julian MÜHLENHOFF, Thomas SATTEL, Willem ESTERHUIZEN, Matthias Karl HOFFMANN, Kathrin FLASSKAMP, Zhaoheng DING, Karl WORTHMANN, Doerthe KEINER
16:20 - 16:30 #36162 - OP061 Next-generation platform technology for absolute serotonin concentration recordings during brain stimulation: Multifunctional Apparatus for Voltammetry, Electrophysiology and Neuromodulation (MAVEN).
OP061 Next-generation platform technology for absolute serotonin concentration recordings during brain stimulation: Multifunctional Apparatus for Voltammetry, Electrophysiology and Neuromodulation (MAVEN).

Background: Within the central nervous system (CNS), serotonin (5-HT) is involved in mood regulation and is a key regulator in neuropsychiatric conditions like major depressive disorder, addiction, and schizophrenia. Thus, in vivo measurements of CNS 5-HT are relevant to investigating the pathogenesis, progression, and treatment response of neuropsychiatric conditions. The applicability of current existing technologies for measuring 5-HT concentration levels in vivo is limited in humans. The Mayo Clinic Neural Engineering Laboratories and Division of Engineering developed a next-generation platform technology for human neurochemical recordings: Multifunctional Apparatus for Voltammetry, Electrophysiology and Neuromodulation (MAVEN). Herein, we present our early investigative studies of 5-HT recordings in a rodent with escitalopram treatments.

Methods: Optimized for the detection of serotonin, N-shaped fast scan cyclic voltammetry (N-FSCV) and N-shaped multiple cyclic voltammetry (N-MCSWV) were performed using MAVEN. N-FSCV waveform scanned from a resting potential of +0.2 V to +1.0 V, then to -0.1 V and back to +0.2 V, at a rate of 1000 V/second. N-MCSWV waveform configuration was ESW = 0.4 V, EHolding = 0.2 V, EInitial = −0.1 V, switching potential = 1.3 V, EStaircase = 0.0125 V, τ = 1 ms, and the number of CSWs = 7 with 0.1 Hz repetition frequency accordingly. Proof-of principle tests included flow injection analysis for N-FSCV, beaker setups for N-MCSWV and in-vivo recordings in the rat brain with electrical stimulation evoked serotonin release and pharmacological validation with escitalopram treatments.

Results: Flow cell injection analysis and beaker setups demonstrated that the N-FSCV and N-MCSWV applied to the carbon fiber microelectrodes and successfully recorded the phasic and tonic serotonin signals. In vivo serotonin recordings, MAVEN reliably detected phasic serotonin changes following the electrical stimulation with N-FSCV, as well as tonic serotonin changes after escitalopram treatment. 

Conclusions: Many neuropsychiatric disease treatments require long-term monitoring to examine their efficacy. MAVEN allows real-time quantification of 5-HT concentrations that may serve as biomarkers in the treatment of neuropsychiatric disorders. It is our expectation that MAVEN will greatly expand our understanding of the effects of stimulation and drive new ways to treat neuropsychiatric disorders.


Kendall LEE, Kristen SCHEITLER (Rochester, USA), Abhinav GOYAL, Juan ROJAS-CABRARA, Aaron RUSHEEN, Jason YUEN, Christopher KIMBLE, Graham CAMERON, Dennis WARREN, Diane EAKER, Joshua BOESCHE, Basel SHARAF, Dong-Pyo JANG, Charles BLAHA, Kevin BENNET, Yoonbae OH, Hojin SHIN

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A29
PARALLEL SESSION 7
Movement Disorders 3

PARALLEL SESSION 7
Movement Disorders 3

Moderators: Yildiz DEGIRMENCI (Movement Disorders Specialist) (Istanbul, Turkey), Mojgan HODAIE (Attending Neurosurgeon) (Toronto, Canada, Canada), Rick SCHUURMAN (neurosurgeon) (Amsterdam, The Netherlands)
16:30 - 16:35 #35756 - OP062 Outcomes following Asleep versus Awake DBS – A Quantitative and Patient Reported Outcomes Analysis.
OP062 Outcomes following Asleep versus Awake DBS – A Quantitative and Patient Reported Outcomes Analysis.

Introduction

Advances in high-resolution intra-operative computed tomography and magnetic resonance neuroimaging technologies have resulted in a shift towards deep brain stimulation (DBS) lead implantation under general anesthesia, termed “Asleep” DBS. Initial studies comparing asleep DBS to traditional implantation techniques using microelectrode recording under light sedation -termed “Awake” DBS - have shown similar outcomes in both lead placement and early clinical response. However, data to date on differences in the patient surgical experience and longer-term outcomes is limited. We present a single center, single surgeon outcomes study, evaluating clinical and patient-reported outcomes after undergoing Awake or Asleep DBS lead placement in STN or GPI.

Methods

We conducted a retrospective review of 92 patients who underwent DBS surgery, either Asleep or Awake, for the treatment of PD and/or dystonia between 2018 and 2022. Surgical targets included globus pallidus internus (GPi) and subthalamic nucleus (STN), with overall cohort breakdowns as follows: 19 patients GPi/Asleep, 19 patients GPi/Awake, 29 patients STN/Asleep, 25 patients STN/Awake. Phone surveys were conducted using a modified quality of life survey (Euro-QoL-5D-5L) to assess patient-reported functional and clinical outcomes following DBS surgery. A chart review was performed to assess for objective differences among Awake and Asleep cohorts in parameters including pre- and post-operative clinical scales and medication dosing.  Six, 12, and 24 month post-operative time points were included as feasible. Comparison between patient-reported outcomes in asleep and awake cohorts, for both surgical targets, were analyzed.

Results

Across stimulation targets there were no significant differences between Awake and Asleep cohorts in the degree which DBS improved quality of life or whether patients would choose to undergo surgery again. The aggregate Asleep and Awake cohorts reported statistically significant improvements in walking, difficulty with activities of daily living, difficulty with performing work/leisure activities, and pain or discomfort due to their symptoms. The Awake cohort also reported significant improvements in anxiety or depression after DBS surgery, whereas the Asleep cohort did not. The Asleep STN had a statistically significant difference in experience of the surgical procedure, consistently reporting a better experience than the Awake STN subgroup.  No significant differences were found in the surgical experience between Awake versus Asleep GPi cohorts.

Conclusion

Asleep and Awake DBS techniques achieve similar outcomes across multiple domains. Asleep STN DBS patients report a more favorable surgical experience. Further studies with larger patient cohorts will continue to delineate patient outcomes differences between these two surgical approaches.


Christina SWAN, Jacob MAZZA (Chicago, USA), Vijay PALAKUZHY, Madison WEDDING, Sandra RAMOS, Neepa PATEL, Sepehr SANI
16:35 - 16:40 #35983 - OP063 The efficacy of asleep deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease.
OP063 The efficacy of asleep deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease.

Background

 

The development of visualization techniques enabled surgeons to target structures for deep brain stimulation directly. However, the number of studies comparing the efficacy of asleep and awake DBS is limited.

 

Aim

 

The purpose of the present study was to compare the efficacy and safety of asleep vs awake DBS of the subthalamic nucleus in patients with Parkinson’s disease.

 

Material and methods

 

We conducted a randomized controlled trial to assess the efficacy of asleep STN-DBS in patients with Parkinson’s disease. The main group included 20 patients that had been operated on based on direct 3T MRI targeting (T1 SPGR, high-resolution T2, T2-FLAIR, and SWAN sequences) and intraoperative CT, while 20 patients of the control group have been operated on with the implementation of direct 3T MRI targeting, microelectrode recording, and intraoperative stimulation. The primary endpoints were: 1) the difference in motor improvement between the two groups measured as the decrease in the UPDRS III scores postoperatively, and 2) the difference in the rate of serious intra- and postoperative complications. Changes in quality of life, activities of daily living, levodopa therapy-induced complications, levodopa equivalent daily dose, and mild adverse events were chosen as the secondary endpoints. The follow-up period made up for 1 year.

 

Results

 

Both groups demonstrated significant improvement in motor function 1 year postoperatively. The UPDRS III OFF score decreased from 53.0 points to 13.5 points in the main group and from 52.5 points to 16.5 points in the control group. In the ON-medication state, these numbers were 16.5 and 10.5 in the main group and 16.5 и 8.0 in the control group. Levodopa-induced dyskinesias and fluctuations were reduced by 6 points in both groups assessed by UPDRS IV. Activities of daily living evaluated by the Schwab-England scale increased from 50 to 80% and from 40 to 70% in the main and control groups, respectively. No significant differences were found between the groups (Mann-Whitney U Test, p>0,05).

 

There were no serious intra- and postoperative complications in the present study. Stimulation-related complications were presented by stimulation dysarthria, which occurred in 4 patients of the main group and 3 patients of the control group. The noted differences were not significantly relevant (Pearson's chi-squared test, p0671), though the test power wasn't big enough due to a small number of cases.

 

Conclusion

 

Asleep deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease can be performed with the same efficacy and safety as the standard awake DBS with the use of high-quality 3T MRI and intraoperative CT.


Svetlana ASRIYANTS (Moscow, Russia), Alexey TOMSKIY, Anna GAMALEYA, Anna PODDUBSKAYA, Alexey SEDOV, Igor PRONIN
16:40 - 16:50 #36149 - OP064 Image guided asleep DBS surgery improves motor outcomes and is more effective compared to micro-electrode guided awake surgery in Parkinson’s disease.
OP064 Image guided asleep DBS surgery improves motor outcomes and is more effective compared to micro-electrode guided awake surgery in Parkinson’s disease.

Background: A golden standard surgical method for STN-DBS surgery in Parkinson’s disease includes T2 weighted planar (mostly axial) MRI -based planning, awake multi-trajectory MER, intraoperative test stimulations and implantation of quadripolar electrode with “ring” contacts. Image guided asleep implantation with electronic brain -assisted 3D planning and segmented leads has been proposed as an alternative method. Objective: Here we aimed to compare outcomes between two completely different surgical approaches in a single center in Parkinson’s disease: planar image based awake surgery with MER and ring electrodes (PWMR) (n=65) and 3D electronic brain assisted planning and asleep surgery with segmented leads (EBSS) (n=35). Methods: Motor UPDRS scores (preoperative levodopa-OFF, preoperative levodopa-ON and postoperative levodopa-ON/DBS-ON) and levodopa equivalent doses before and 4-6 months after surgery were collected retrospectively at Tampere University Hospital between 2009 and 2022. PWMR was planned using Elekta Surgiplan / Medtronic S7 software and EBSS using Brainlab Elements software. Deviations from initial surgical trajectory either by selecting another trajectory for final electrode or enabling steering mode programming postoperatively were analyzed. The time spent in operation room (OR) was also compared. Results: Age, time from diagnosis or preoperative motor UPDRS did not differ between PWMR and EBSS groups either in levodopa OFF (38.1±10.4 and 38.1±10.4) or ON (13.0±6.1 and 12.6±8.6) conditions. Significantly lower motor UPDRS in levodopa ON - DBS ON condition was observed after EBSS compared to PWMR (4.5±5.8 and 14.0±8.8; p<0.001, independent samples t-test). Slightly greater reduction in levodopa equivalent dose was observed after PWMR compared to EBSS (59.1±21.2% and 51.7±21.6%), but difference was not statistically significant. The time spent in OR was significantly shorter in EBSS than PWMR (281±34min and 408±57min, p<0.001, independent samples t-test). One of the anterior trajectories (anterolateral, anterior or anteromedial) was chosen in 42.1% of trajectories in PWMR group instead of central trajectory. Current steering was used in 61.8% of the leads in EBSS group. Discussion: According to our experience, electronic brain -assisted delineations suggest slightly more cranial location of STN than comprehended earlier based on T2 axial images alone, where the surgical target was probably placed slightly more inferior and lateral in the area of most prominent low intensity T2 signal. Furthermore, MER might facilitate selection of more anterior trajectory and/or more deep final implantation depths due to MER signal characteristics. Conclusions: Different surgical approaches probably result in slight differences in final DBS lead location, where MER guided implants lie more anterior and inferior with respect to STN while image guided method results in more superficially placed leads in STN. Slightly greater levodopa decrease was observed after MER guided awake surgery, while greater reduction in motor symptoms was observed after image guided asleep surgery with frequently employed current steering possibility. Timewise, asleep surgery was far more effective.


Ilona HENRIKSSON, Mika KOSKINEN, Timo MÖTTÖNEN, Joonas HAAPASALO, Markus POLVIVAARA, Kai LEHTIMÄKI (Tampere, Finland)
16:50 - 17:00 #36171 - OP65 OP06( Awake and asleep Deep Brain Stimulation targeting caudal Zona incerta for Essential Tremor.
OP06( Awake and asleep Deep Brain Stimulation targeting caudal Zona incerta for Essential Tremor.

Background: With the improvements in imaging and perioperative techniques of target verification, more Deep Brain Stimulation-surgeries (DBS) are performed with the patient under general anaesthesia (GA). While this is increasingly common regarding DBS in the pallidum and subthalamic nucleus, there are few published works regarding thalamic/subthalamic DBS for tremor in this manner.

Method: A retrospective comparison of the one-year outcome in our last 30 lead implantations targeting caudal Zona incerta (cZi) performed under local anaesthesia (LA) with the first 30 lead implantations under GA.  LA-DBS was performed with visual anatomical targeting on preoperative MRI, followed by intraoperative macrostimulation for target verification. In GA-DBS only visual anatomical targeting was performed. All patients were put under GA for the implantation of the extension cables and IPG. 11 were bilateral procedures but each side was individually evaluated with the other side turned off at follow-up. Postoperative CT-scans were performed for all patients. All patients were evaluated using the Essential Tremor Rating Scale (ETRS) on/off stimulation 1 year after surgery. Friedmans non-parametric test with Wilcoxon signed rank test as a post-hoc analysis was used for within-group analysis. Mann-Whitney U test was used as a between-group test.

Results: In the LA-group, total ETRS improved from a median of 52 at baseline to 20 (62%) on unilateral stimulation 1 year after surgery (table 2). Contralateral (Cl.) tremor and hand function improved from a median of 7 to 0 and 9 to 1, respectively. In the GA-group, total ETRS improved from 48 at baseline to 20 on stimulation 1 year after surgery (58%). Median cl. tremor and hand function improved from 6 to 0 and from 11 to 3, respectively. All within-group improvements were statistically significant and between-group tests did not show any significant differences between the groups.

Most common postoperative adverse events in both groups were transient speech and gait disturbances. One patient began LA-DBS but had to be rescheduled to undergo GA-DBS due to difficulties in mounting the frame because of severe head tremor. One patient in the GA-group developed small pulmonary embolisms after surgery without long-term effects on physical activity. No other serious events were recorded. Three patients in the LA-group had to undergo revision due to straining extension cables/IPG. 6 patients in the LA-group had an additional lead passage due to side effects intraoperatively whilst no leads in the GA-group were moved.   

The mean pulse effective voltage (PEV) and mean frequency (Hz) were lower in the GA-group (p<0.05, table 3). There was a trend towards lower amplitude and pulse width as well (ns).

Location of the active cathode in relation to the midcommissural point (MCP) was 12.4 mm lateral in the LA-group and 12.3mm in the GA-group, 6.7mm posterior in both groups and 1.9mm and 1.6mm inferior, respectively (ns).

Ordinal regression using contralateral tremor as the dependent variable and grouping (LA/GA) and months after first surgery (as a measure of the surgeons increasing experience) as independent variables found no significant odds ratios.

Conclusion: This retrospective comparison of awake and asleep cZi-DBS found no difference in clinical outcome on tremor or mean electrode location.


Rasmus STENMARK P. (Umeå, Sweden), Patric BLOMSTEDT
17:00 - 17:10 #35803 - OP066 A diagnostic marker for delayed therapy escape after thalamic deep brain stimulation for essential tremor.
OP066 A diagnostic marker for delayed therapy escape after thalamic deep brain stimulation for essential tremor.

Objective: Delayed therapy escape is a serious yet frequent condition after thalamic deep brain stimulation (DBS) for essential tremor. It is a complex phenomenon and often associated with ataxia-like symptoms that leads to a significant decrease in quality of life. Due to the gradual evolution of these deficits, early recognition remains difficult. Hence, we aim to identify a diagnostic marker for delayed therapy escape to improve diagnosis and improve patient outcomes.

Methods: 31 patients with bilateral thalamic DBS for essential tremor gave informed consent and were included. Tremor, ataxia, and gait were assessed through operationalized and quantitative analyses including video-based motion capture and Fahn-Tolosa-Marin-Tremor-Rating Scale (FTMTRS) the Scale for the assessment and rating of ataxia (SARA). Examinations were carried out with activated DBS (ON) and directly after deactivation (OFF). We focussed on quantitative tremor analysis from the left arm, as the majority of patients were more affected on the left hand. If available preOP FTMTRS values were obtained. A higher FTMTRS more than 12 months after surgery compared to the score before DBS implantation indicated delayed therapy escape. To identify potential hallmarks of therapy escape, exploratory correlation analyses were conducted using a Pearson’s product-moment correlation coefficient between quantitative tremor features and clinical scores indicating therapy escape and ataxia. Test validity was assessed by computing receiver operating characteristics (ROC) curves. 

Results: PreOP FTMTRS scores were available for 16 patients, among them 5 patients with therapy escape. High values for the ratio of FTMTRS now versus preOP were associated with higher total power of postural tremor at OFF (r=0.779) and lower tremor frequency at OFF (r=-0.625), both on the left side (Fig1). The ratio of these two parameters (Power LOFF/Freq LOFF) yielded the highest pearson’s correlation coefficient (r=0.791) and an area under the curve of 0.89 in the ROC analysis (p=0.0149) (Fig2). Further, it correlated with high SARA values (r=0.694) and decreased step length (r=-0.784) at ON, both signs of ataxia (Fig1).

Conclusion: Frequency of postural tremor at OFF was previously suggested as an indicator of therapy escape (Sajonz et al. 2022). Here a low-frequent and high-power postural tremor at OFF using the ratio of Power LOFF/Freq LOFF was superior for identifying therapy escapers and might be a valuable diagnostic tool in the future. 

 

REFERENCES

1.     Sajonz, B.E.A., et al. NeuroImage: Clinical, 2022. 36: 103150.


Marvin Lucas FROMMER, Isabelle WALZ, Nils SCHRÖTER, Christoph MAURER, Michel RJINTJES, Brigitte GUSCHLBAUER, Franz AIPLE, Volker Arnd COENEN, Bastian E.a. SAJONZ (Freiburg, Germany)
17:10 - 17:15 #35864 - OP067 20 Years Follow-up of Thalamotomy for Tremor.
OP067 20 Years Follow-up of Thalamotomy for Tremor.

Background

The current focus in thalamic lesioning and deep brain stimulation surgery (DBS) is on brain networks rather than separate nuclei. Understanding these networks is necessary for further unraveling pathophysiology and personalizing treatment in tremor. Long term effect of thalamotomy possibly offers insight in the optimal area for brain network modulation.

Methods

Our electronic database was used to identify tremor patients who underwent thalamotomy between 1990 and 2005 in our centre. Standardized questionnaires and neurological assessments (video recorded) were used for evaluating long term effect on tremor, possible side effects, additional lesioning/DBS surgeries and the use of tremor suppressing medicine.  Long term effect was determined by using the TETRAS (severity scale from 0 to 4); one year after surgery and on the day of the questionnaire.

Results

A total of 171 tremor patients underwent (unilateral) thalamotomy;  24 patients could be reached and were included. These were predominantly Parkinson’s disease and essential tremor patients. Average duration after thalamotomy was 21 years. One year after surgery 21 patients showed improvement in tremor; 19 patients improved ≥ 2 points. Of these 19 patients, 17 patients had a lasting tremor suppressing effect on the day of the questionnaire. In 13 patients adverse effects were seen; most reported (7) was transient dysarthria. Additional lesioning and/or DBS surgery was performed in 14 patients. In the subgroup of patients with Parkinson’s Disease the additional lesioning/or DBS surgery was seen most frequent (6 out of 8).  

Conclusion

This study shows that thalamotomy can have a long lasting tremor suppressing effect; extending up to 30 years. Compared to DBS surgery, lesioning does not entail brain implants and requires less demanding follow up; possibly making this a more accessible treatment for tremor. Currently 7 Tesla MRI scans are performed in a subgroup of the tremor patients in order to perform brain network (probabilistic structural connectivity) analyses. These analyses are used to correlate tremor networks, the location of the lesion within the networks and the long lasting tremor suppressing effect. 


Sterre JOOR (Amsterdam, The Netherlands), Rick SCHUURMAN, Pepijn VAN DEN MUNCKHOF, Rob DE BIE, Maarten BOT
17:15 - 17:25 #34989 - OP068 Ventro-dorsal position of ablation impacts efficacy and safety in magnetic resonance guided focused ultrasound thalamotomy for tremor.
OP068 Ventro-dorsal position of ablation impacts efficacy and safety in magnetic resonance guided focused ultrasound thalamotomy for tremor.

Objective: Optimal target selection is even more essential for the success of thalamotomy for tremor that it is for non-ablative procedures as effect and side-effect persist and may not be influenced after the procedure.

Methods: In a consecutive series of 52 patients with pharmacotherapy resistant tremor disorders treated with magnetic resonance guided high-intensity focused ultrasound (MRgHiFUS) thamalotomy of the contralateral ventral intermediate (Vim) nucleus of the thalamus we switched our targeting practice from a site derived from DBS experience located 2 mm above the anterior-posterior (AC-PC) level to another site exactly at AC-PC level. No other parameters of the treatment were adjusted. The outcome was evaluated using standardized video-documented assessments and safety outcomes at baseline and 6 months after intervention.

Results: We identified a higher incidence of sensory disturbances at 6 months in the patient group treated 2 mm above AC-PC level (25% vs. 11%, p=.007). There were no significant differences regarding gait impairment (24% vs. 11%) and tremor suppression rates were similar (63.6% vs. 60.2%). The general patient satisfaction was high (87% would undergo MRgHiFUS treatment again).

Conclusion: While MRgHiFUS being equally effective regarding tremor control in both treatment groups, the more ventral target at AC-PC level was associated with a better risk-profile. In contrast to the general assumption of a safer target dorsally in the Vim regarding gait disorders we found referring to this no differences in both groups.


Lennart STIEGLITZ (Zurich, Switzerland), Markus OERTEL, Sujitha MAHENDRAN, Mechthild UHL, Carola FREUDINGER, Christian BAUMANN, Fabian BÜCHELE
17:25 - 17:30 #35768 - OP069 Treatment and outcome trends among 200 consecutive MRgFUS treatments: a single center experience.
OP069 Treatment and outcome trends among 200 consecutive MRgFUS treatments: a single center experience.

Introduction:

This study is a comprehensive analysis of the first 200 cases from a newly established Magnetic Resonance-guided Focused Ultrasound (MRgFUS) program for treating essential tremor (ET) and tremor dominant Parkinson’s disease (tdPD). Despite significant promise, MRgFUS is a relatively new technology and improvement in technique, outcomes, and reduction of complications over time have not been studied. Herein, we review trends in treatments and outcomes over time to assess if there is a positive trend with increased familiarity with MRgFUS.

Methods:

This retrospective study evaluated 200 consecutive unilateral MRgFUS treated patients with the diagnosis of ET and tdPD. Clinical outcomes were assessed at baseline and 6-month follow-up using standardized questionnaires and Clinical Rating Scale for Tremor (CRST) scores of the treated hand. Trends in outcome and treatment parameters over time were assessed. Logistic and linear regressions were utilized to formally assess trends in variables studied.

Results:

The majority of patients were male (67.9%) with an average age of 73 ± 9.0. ET was the dominant diagnosis (80.2%). Mean disease duration was 19.1 ± 15.9 years. Average skull score was 0.53 ± 0.1 with cavitation occurring in 27.8% of the cases. Mean number of sonications was 6.9 ± 1.5. Mean average and peak temperatures were 57.3 ± 2.3 °C and 61.6 ± 3.0 °C, respectively. Mean energy delivered per sonication was 16.8 ± 9.5 kJ. Mean treatment duration was 2.8 ± 0.8 hours. At 6-month follow-up, 89.5% of patients demonstrated greater than 50% reduction in CRST scores of treated hand. Side effects included decreased balance (20.8%), taste changes (7.7%), numbness (6.2%), speech changes (10.0%), and impaired cognition (6.9%). Notably, 51.9% of patients had no side effects.

Logistic regression analyses revealed an increase in reported taste side effects over time. Diagnosis of tdPD was associated with a significantly higher rate of speech (OR 3.95, p = 0.030) and cognitive (OR 4.89, p = 0.027) side effects at 6 months as compared with ET. No association was found between the rostral AC-PC target z-coordinate and side effect profile. Results are summarized in Table 1.

Conclusion:

MRgFUS is effective with an acceptable risk profile. Higher observation of taste changes across treatments is likely secondary to more focused examinations. More rostral targeting may not predict lower likelihood of side effects. tdPD patients are more likely to report post-treatment speech and cognitive changes. 


Daniel WOLFSON, Jacob MAZZA, Ryan KELLY, Lucinda CHIU, John PEARCE (Chicago, USA), Julia MUELLER, Dustin KIM, Daniel ZHANG, Neepa PATEL, Sepehr SANI
17:30 - 17:35 #36000 - OP070 Successful MRgFUS treatment of tremor in patients with a skull density ratio below 0.4.
OP070 Successful MRgFUS treatment of tremor in patients with a skull density ratio below 0.4.

Objective: The use of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor related disorders and other novel indications has been limited by guidelines advocating treatment of patients with a skull density ratio (SDR) above 0.45±0.05 despite reports of successful outcomes in low SDR (LSDR) patients. Our goal was to retrospectively analyze the sonication strategies, adverse effects, clinical and imaging outcomes in patients with SDR below 0.4 treated for tremor with MRgFUS.

Methods: Clinical outcomes and adverse effects were assessed at 3- and 12-months after MRgFUS. Outcomes, lesion location, volume, and shape characteristics (elongation and eccentricity) were compared between the SDR groups.

Results: 102 consecutive patients were included in the analysis, of whom 39 had SDR ≤0.4. No patient was excluded from treatment because of low SDR, with the lowest being 0.22. Lesioning temperatures (>52° C) and therapeutic ablations were achieved in all patients. There was no significant difference in clinical outcome, adverse effects, lesion location and volume between patients with SDR above 0.4 and the LSDR group. The SDR was significantly associated with total energy (rho = -0.459, p < 0.001), heating efficiency (rho = 0.605, p < 0.001), and peak temperature (rho = 0.222, p = 0.025).

Conclusions: Our results show that treatment of tremor in LSDR patients using MRgFUS is technically possible leading to a safe and lasting therapeutic effect. Limiting the number of sonications, adjusting the energy, and duration to achieve the required temperature early during the treatment are suitable strategies in LSDR patients.


Artur VETKAS (Toronto, Canada), Alexandre BOUTET, Sarica CAN, Jürgen GERMANN, Nardin SAMUEL, Brendan SANTYR, Stefan LANG, Alfonso FASANO, Kalia SUNEIL, Andres M LOZANO
17:35 - 17:40 #36103 - OP071 Digital phenotyping of patients undergoing focused ultrasound thalamotomy for essential tremor.
OP071 Digital phenotyping of patients undergoing focused ultrasound thalamotomy for essential tremor.

Introduction

No prior study has longitudinally assessed Essential Tremor (ET) using passively collected smartphone accelerometer data. Given the ubiquitous nature of smartphones, such a measure could be valuable for clinical care and therapeutic development.

 

Objective

To measure tremor outcomes in ET patients undergoing MRI-guided focused ultrasound (MRgFUS) thalamotomy using 1) active postural tremor surveys and 2) passive continuously measured smartphone accelerometer data from everyday phone use.

 

Methods

Patients with ET scheduled for MRgFUS installed the Beiwe application which continuously sampled smartphone accelerometers at 100 Hz. Outcomes per the Clinical Rating Scale for Tremor (CRST) were assessed at enrollment, day before and following MRgFUS, and at 3-month follow-up. Active postural tremor surveys using smartphones were conducted twice per week. Tremor in continuously measured smartphone accelerometer data was detected using a TensorFlow SPICE pitch estimation model. Spectral power was assessed in detected tremor events by evaluating the energy of the fundamental frequency and harmonic overtones.

 

Results

In a prospective study, 28 patients were included between December 2022 and April 2023, 9 patients have undergone MRgFUS thalamotomy as of abstract submission. Clinically rated postural tremor significantly decreased by 88% from baseline on the day following MRgFUS (p < 0.01). Average spectral power measured during active postural tremor surveys decreased by 90% following MRgFUS (p < 0.01). For tremor detected in passively collected accelerometer data using pitch detection, spectral power decreased by an average 80% following MRgFUS (p < 0.01). Postural tremor (CRST Part A) correlated with spectral power in active postural surveys, and with spectral power in passive data tremor events.

 

Conclusion

Tremor intensity could be monitored without patient input on a day-by-day basis. Further validation may allow accurate monitoring of tremor severity and treatment response to medications and surgical intervention completely passively.

 


Jakob V. E. GERSTL, Jakob V. E. GERSTL (Boston, USA), C. Gustaf A. VON GROTHUSEN, David J. SEGAR, Hassan Y. DAWOOD, Patrick EMEDOM-NNAMDI, Jukka-Pekka ONNELA, Timothy R. SMITH, John D. ROLSTON, G. Rees COSGROVE
17:40 - 17:45 #35707 - OP072 Safety and efficacy of unilateral MRI-guided laser inte, rstitial thermal therapy thalamotomy for patients with medically intractable essential tremor: a single-center, single-blind, pilot trial.
OP072 Safety and efficacy of unilateral MRI-guided laser inte, rstitial thermal therapy thalamotomy for patients with medically intractable essential tremor: a single-center, single-blind, pilot trial.

Introduction

 Medically intractable Essential Tremor (ET) is a challenging condition. Thalamic deep brain stimulation (DBS) is effective, but not all patients are eligible or willing to undergo this procedure. Less invasive neurosurgical procedures such as radiosurgery and MRI-guided focused ultrasound have emerged as second-line options for creating thalamotomy. Recently, a minimally invasive technology called MRI-guided Laser Interstitial Thermal Therapy (MRIg-LITT) has shown promising results in the treatment of epilepsy and tumors. Here, we report a prospective pilot study to investigate the safety and efficacy of unilateral MRIg-LITT thalamotomy in patients with medically intractable ET.

Methods

The procedure involved placing a laser probe in the ventral intermediate nucleus of the thalamus using the ROSA robot system under general anesthesia. Targeting and trajectory planning were established using the ROSANA planning software, which allowed for automatic image fusion between preoperative MRI and CT scan images. Intraoperative guidance was provided by CT scans and microelectrode recording. After placing the probe, a single MRIg-LITT thalamotomy was performed using the Visualase system equipped with a diode laser.

The Fahn-Tolosa-Marin (FTM) scale was used to evaluate improvement of upper limb tremor at 3 and 12 months postoperatively, as assessed blindly by an external expert neurologist. Quality of life was assessed using the Quality of Life in Essential Tremor Questionnaire (QUEST), and cognitive performance was evaluated using the MMSE and the MoCA. Adverse effects were assessed through open-ended questioning and neurological examinations.

Results

Nine patients with medically intractable ET underwent unilateral MRIg-LITT thalamotomy. M age was 68.0±11.67 years, mean duration of tremor was 31.22±18.75 years. The study found significant improvement in tremor in the treated hand, as measured blindly on the FTM, from a mean baseline score of 15.33±2.12 to a score of 4.0±2.50 (p=0.008) at 3 months and 2.56±1.13 (p=0.007) at 12 months. Patients’ perceptions of their quality of life on the QUEST also improved significantly from a mean baseline score of 45.77±11.53 to a score of 16.54±14.88 (p=0.011) at 3 months and 11.79±10.51 (p=0.008) at 12 months. There was no significant difference in cognitive performance, as assessed by the MMSE and the MoCA, before and 12 months after the thalamotomy (p=0.672 and 0.263, respectively). However, dysarthria, proprioceptive disturbances, and gait balance issues were the most frequent adverse events, occurring in 55%, 55%, and 77% of patients, respectively. Nonetheless, these adverse effects were mostly transient and spontaneously resolved in less than a month. No serious adverse effects were reported, and no hospital readmissions were necessary.

Discussion

Unilateral MRIg-LITT thalamotomy seems to be an effective and safe technique to treat upper limb tremor in patients with medically intractable ET who are considered unsuitable or unwilling to undergo DBS surgery. In our opinion, using MRIg-LITT in conjunction with a stereotactic robot and intraoperative electrophysiological testing has multiple advantages over other methods such as DBS, radiosurgery, or MRIg-FUS for creating precise and small lesions like thalamotomies: (1) no hardware is required, (2) no titration is needed, (3) results are obtained quickly, (4) intra-operative patient participation is not required, (5) incisions are minimal, (6) recovery time is minimal, (7) real-time image guidance is available during lesion creation, (8) maximum accuracy is achieved based on the patient's own anatomy rather than an anatomical atlas, (9) head shaving is not required, and (10) there is no interference from skull-density. Additionally, MRIg-LITT thalamotomy seems to have only a few contraindications: (1) patients who cannot receive general anesthesia, (2) patients who are unable to undergo an MRI, and (3) patients who cannot temporarily discontinue anticoagulant or antiplatelet therapy. The preliminary safety and efficacy data presented here lay the foundation for a future trial with a larger cohort and represent an important step towards new treatment possibilities for ET.


Mickael AUBIGNAT (Amiens), Melissa TIR, Martial OUENDO, Salem BOUSSIDA, Jean-Marc CONSTANS, Michel LEFRANC
17:45 - 17:50 #35990 - OP073 MR Imaging and MR Spectroscopy follow-up of patients treated by LITT for pharmacoresistant tremor.
OP073 MR Imaging and MR Spectroscopy follow-up of patients treated by LITT for pharmacoresistant tremor.

Context and purpose: Pharmacoresistant tremors can cause multiple functional handicaps. Thalamotomy by Laser Interstitial Thermal Therapy (LITT) guided and monitored by Magnetic Resonance Imaging (MRI) is one of the recent alternatives to improve the quality of life of these patients. Although practiced since 2019 in the USA and Europe, no study of the spectroscopic and metabolic changes after thalamotomy by LITT has been published. The main objective of this prospective study was to combine MRI and proton Magnetic Resonance Spectroscopy (MRS) to follow up the morphologic, spectroscopic and metabolic features of the treated Ventral intermediate nucleus (VIM) thalamic region after LITT thalamotomy.

Methods: Follow-up from 23 patients, treated by LITT at Amiens-Picardie University Hospital (from March 2019 to date), consisted of MRI (T1, T2 FLAIR, T2*, Diffusion, Perfusion and 3DT1) and MRS (PRESS sequence with 3 Echo Times of 35 ms, 144 ms and 288 ms) data that were collected pre-operatively, at immediate post-operative, at D2/D7 post-operative, at M6 and M12 post-operative. 

Results: MRI results (from 23 patients at immediate postoperative, 21 patients at D2-D7 postoperative, 19 patients at M6 postoperative, and 9 patients at M12 postoperative) were based on the calculation of volumes of FLAIR and Diffusion hypersignals from the VIM region and yielded: the presence of small volumes of hypersignal at immediate postoperative on T2-FLAIR (mean: 0.104 ± 0.062 cm3) and on diffusion (mean: 0.225 ±0.118 cm3) sequences. These hypersignals increased in 100% of patients between D2 and D7 on T2 FLAIR (mean: 3.302 ±1.712 cm3) and on diffusion (mean: 1.455 v 0.806 cm3). These hypersignals then decreased by more than 98% on average in the long term M6-M12 on T2 FLAIR (mean M6: 0.061 ±0.042 cm3, mean M12: 0.026±0.029 cm3) and on diffusion (mean M6: 0.020 ±0.036 cm3, mean M12: 0.016 ±0.032 cm3). MRS results yielded spectroscopic and metabolic changes that were based on the calculation of metabolites ratios from 7/23 patients [Metabolites: Cr: Creatine, NAA: N-acetyl-aspartate, Cho: Choline, mI: Myo-inositol, Lac: Lactate]. We mainly noted that mI/Cr ratio was found to be increased in 100% of patients at immediate postoperative measurements and then tended to progressively decrease. Lac/Cr ratio was increased in 85% of patients at immediate postoperative time and/or at D2-D7, and then continuously decreased, although a persistent residual quantity of lactate was measured at the long term in 71% of patients.

Discussion and conclusion: The present results provide a comprehensive overview of the morphologic, spectroscopic and metabolic changes evolution of the LITT-treated VIM thalamic region. These changes were marked mainly by a fluctuation followed by a stabilization at the long term after (a low-intensity and short-duration LASER parameters) LITT thalamotomy. Thanks to the higher sensivity of MRS (compared to MRI), the strategy of combining MRI and MRS showed an added-value in the evaluation of LITT efficiency then the use of only MRI. Further investigations with a larger data follow-up, as well as an evaluation of the effect of thalamotomy on distant motor regions will be carried out. MRI and MRS features will be also correlated to clinical data in order to improve the implementation, analysis, interpretation and monitoring of this new innovative LITT thalamotomy.


David LAYANI, Salem BOUSSIDA, Mickael AUBIGNAT, Aurélien LAMBERT, Adrien PANERO, Romain DRAILY, Amandine OSAER, Simon BERNARD, Melissa TIR, Michel LEFRANC, Jean-Marc CONSTANS (AMIENS)
17:50 - 18:00 #35684 - OP074 Novel hybrid computational MR imaging for use in functional neurosurgery.
OP074 Novel hybrid computational MR imaging for use in functional neurosurgery.

Background: Patient specific targeting of the Ventral intermediate nucleus (Vim) of the thalamus can be acquired based on patterns of cortical and cerebellar connectivity. Although tractography based targeting methods have shown promise in visualising distinct thalamic nuclei, there are several drawbacks. 

Objective: To develop/present a new hybrid, high resolution and high-fidelity imaging modality; and to evaluate its accuracy in Vim-targeting. 

Materials and Methods:  Imaging and outcome data of 35 consecutive refractory tremor patients who had undergone 43 connectivity guided deep brain stimulation (DBS) and/or radiofrequency thermocoagulation (RF-T) between 2013 and 2021 were used. A novel, high fidelity computational MRI map which has both, diffusion and anatomical contrasts was created using individual preoperative connectivity MRI. The map shows intrathalmic contrast for individual thalamic nuclei. Post-hoc analysis was carried out of the degree of overlap between the newly created Vim-target, and the volume of tissue activation (VTA, in case of DBS) or lesion volume (in case of RF-T). This degree of overlap was compared between outcome groups: Outcomes were measured by experts blinded for imaging data at latest follow-up using a Clinical Global Impression-Improvement score (CGI-I), based on a combination of the Fahn-Tolosa-Marin tremor rating scale (FTMTRS) and noted functional tremor improvements, where a CGI-I score of 1-2 (i.e. FTMTRS improvement of ≥50%) was considered favourable.

Results: In 36 of the 43 (84%) performed surgeries (24 DBS and 19 RF-T), direct Vim-targeting was possible using the new hybrid map. For those with a favourable outcome (71% of the patients at a median follow-up of 13 months), the mean amount of overlap between the new Vim-target and the VTA or lesion was 42% (±13), versus only 17% (±15) for patients with an unfavourable outcome (MD 25%, 95% CI 14 – 35, p<0.0001). Retrospective use of this Vim-targeting method used as a tool to predict outcome had a sensitivity of 90%, specificity of 80%, positive predictive value of 90% and negative predictive value of 80%.

Conclusion: We present a new, high resolution and high-fidelity imaging modality, providing a fast and efficacious way of targeting the ventral intermediate nucleus of the thalamus. In this study, this new targeting method was highly accurate in predicting outcomes after deep brain stimulation and radiofrequency thalamotomy when compared to connectivity derived targeting.


Taco GOEDEMANS (Amsterdam, The Netherlands), Francisca FERREIRA, Thomas WIRTH, Lonneke VAN DER WEERD, Marie T. KRÜGER, Ashkan PAKZAD, Thomas FOLTYNIE, Patricia LIMOUSIN, Maarten BOT, Pepijn VAN DEN MUNCKHOF, P. Rick SCHUURMAN, Ludvic ZRINZO, Harith AKRAM

16:30-17:30
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B29
PARALLEL SESSION 8
Psychiatry 3

PARALLEL SESSION 8
Psychiatry 3

Moderators: Pawel SOKAL (head of department) (Bydgoszcz, Poland), Veerle VISSER-VANDEWALLE (Head of Dep. of Ster. and Funct. NS) (Cologne, Germany), Hemmings WU (Neurosurgeon, Assistant Professor) (Hangzhou, China)
16:30 - 16:40 #35628 - OP075 Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial.
OP075 Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial.

Introduction:

Treatment resistance in alcohol use disorders (AUD) is a major problem for affected individuals and for society. In the search of new

treatment options, few case studies using deep brain stimulation (DBS) of the nucleus accumbens have indicated positive effects in

AUD.

Material & Methods:

Here we report a double-blind randomized controlled trial comparing active DBS (“DBS-EARLY ON”) against sham stimulation

(“DBS-LATE ON”) over 6 months in n = 12 AUD inpatients. This 6-month blind phase was followed by a 12-month unblinded period

in which all patients received active DBS. Continuous abstinence (primary outcome), alcohol use, alcohol craving, depressiveness,

anxiety, anhedonia and quality of life served as outcome parameters.

Results:

A total of n=12 patients  out of n=30 planned participants could be recruited to this study. The primary intention-to-treat analysis, comparing continuous abstinence between treatment groups, did not yield statistically significant results, most likely due to the restricted number of participants. In light of the resulting limited statistical power, there is the question of whether DBS effects on secondary outcomes

can nonetheless be interpreted as indicative of an therapeutic effect. Analyses of secondary outcomes provide evidence for this,

demonstrating a significantly higher proportion of abstinent days, lower alcohol craving and anhedonia in the DBS-EARLY ON

group 6 months after randomization. Exploratory responder analyses indicated that patients with high baseline alcohol craving,

depressiveness and anhedonia responded to DBS.

Conclusions:

The results of this first randomized controlled trial are suggestive of beneficial effects of DBS in treatment-resistant AUD and encourage a replication in larger samples. Additional reserach as to the exact location of (beneficial) stimulation and future refinement of the surgical approach to DBS for alcohol use disorder is currently under way.


Karl MANN, Jürgen VOGES, Veerle VISSER-VANDEWALLE, Karl KIENING, Jens KUHN, Martin JAKOBS (Heidelberg, Germany)
16:40 - 16:50 #35708 - OP076 Optimal connectivity profile for successful deep brain stimulation in anorexia nervosa.
OP076 Optimal connectivity profile for successful deep brain stimulation in anorexia nervosa.

Background:

Anorexia nervosa (AN) is one of the most debilitating psychiatric disorders with very few effective treatments. It becomes severe and enduring in a third of cases and an associated mortality rate that Is over five times that of the general population. Deep brain stimulation (DBS) has been gaining ground in psychiatry, for example in obsessive-compulsive disorder (OCD), yet few studies have investigated DBS for AN. Here, we identify the functional connectivity profile of effective DBS to the nucleus accumbens (NAcc) and test its ability to predict outcome in AN.

Methods:

In this study, DBS electrodes from AN patient (N = 7), who underwent DBS to the NAcc/anterior limb of the internal capsule were reconstructed and the resultant volume of activate tissue (VAT) were calculated using Lead-DBS (Horn et al., 2019). The DBS network mapping method, using resting state data from 1000 healthy patients, was then used to map their functional DBS network with clinical improvement in eating disorder psychopathology scores at 12 months. Permutation tests and leave one out cross-validation were used to estimate the validity of the subsequent AN-DBS functional network. Voxel-wise, VAT-region of interest connectivity was calculated based on resting state network parcellations (Yeo et al. 2011).

Results:

Connectivity between the DBS electrode VAT and a distributed network of brain regions correlated with clinical response across eating disorder psychopathology scores. In particular, normative functional connectivity to the ventromedial prefrontal cortex, temporal pole and hypothalamus was associated with improvement in Eating Disorder Evaluation (EDE), Yale-Brown-Cornell Eating Disorder Scale (YBC-EDS) and Snaith-Hamilton Pleasure Scale (SHAPS) (false discovery rate (FDR) corrected, alpha < 0.05). Connectivity to the same regions correlate with improvement in body mass index but this did not survive FDR correction. In leave-one-out cross-validation, this network connectivity significantly predicted DBS response for EDE (R=0.82, p=0.026), YBC-EDS (R=0.77, p=0.047) and SHAPS (R=0.88, p=0.017). Reduction in EDE correlated with VAT connectivity to the limbic network (R=0.69, p=0.043, Bonferroni corrected) and the somatomotor network (R=0.68, p=0.048, Bonferroni corrected). Reduction in SHAPS also correlated with limbic network connectivity (R=0.80, p=0.004, Bonferroni corrected).

Conclusion

Response to NAcc DBS for AN is associated with a specific connectivity profile that overlaps with the limbic network. These results indicate that a high proportion of variability in treatment response can be explained by between subject variability in electrode connectivity profile; this can inform future surgical planning and stimulation paradigms in clinical trials of DBS for AN.


John ERAIFEJ (Oxford, United Kingdom), Nanditha RAJAMANI, Jessica SCAIFE, Amir Puyan DIVANBEIGHI ZAND, Ningfei LI, Bassam AL-FATLY, Rebecca PARK, Andreas HORN, Alexander L GREEN
16:50 - 16:55 #35743 - OP077 Connectivity patterns in patients with deep brain stimulation for self-injurious behavior.
OP077 Connectivity patterns in patients with deep brain stimulation for self-injurious behavior.

Objectives:

Self-injurious behavior (SIB) is associated with a number of psychiatric disorders like autism, Tourette syndrome or psychosis, especially in combination with cognitive impairment. Conservative treatment consists of behavioral therapy and pharmacological treatment with neuroleptic medication. For SIB refractory to conservative treatment deep brain stimulation (DBS) can be considered. Depending on the primary disorder of the patient different DBS targets could be considered. We analyzed the long-term follow-up outcome of patients with SIB treated with DBS at our center. Further, we investigated the connectivity patterns of the involved fibers in order to correlate the modulated cortical areas with the outcome of these patients.

 

Methods:

We included 10 patients with SIB with diverse primary disorders (Tourette syndrome, autism and psychosis after brain injury) that received bilateral DBS for SIB at our center between 2005 and the present. Stimulation targets were chosen depending on their primary disorders, and consisted of the nucleus accumbens, amygdala, posterior hypothalamus, medial thalamus and ventrolateral thalamus. Clinical outcome was measured using the Early Rehabilitation Barthel Index (ERBI) and time of restraint. The connectivity patterns of the stimulated areas in different patients were visualized using normative connectome.

 

Results:

Our study showed a significant improvement in the functionality of the patients measured on the ERBI (p<0.005) and time of restraint (p<0.01) after 6 months of DBS in patients with SIB. The analysis of the connectivity patterns showed a stimulation of the ipsilateral superior frontal lobe, the orbitofrontal lobe, the precentral area and the amygdala in all patients. There was a significant correlation between the clinical improvement and the connectivity of the stimulated tissue to the amygdala and to the hippocampus.

 

Conclusion:

DBS is a promising treatment option for patients with intractable SIB, with varying targets depending on the primary disease. Furthermore, the results of our connectivity pattern analysis could be a useful tool for preoperative target planning.


Petra HEIDEN (Cologne, Germany), Daniel WEIGEL, Ricardo LOUÇÃO, Veerle VISSER-VANDEWALLE, Pablo ANDRADE
16:55 - 17:00 #35840 - OP078 Significant Weight Gain and Long-Term Increase in Quality-Of-Life in Two Consecutive Cases of Severe Bulimic Anorexia Nervosa treated by Deep Brain Stimulation of the Nucleus Accumbens.
OP078 Significant Weight Gain and Long-Term Increase in Quality-Of-Life in Two Consecutive Cases of Severe Bulimic Anorexia Nervosa treated by Deep Brain Stimulation of the Nucleus Accumbens.

 Background:

Anorexia nervosa (AN) severely impacts individual’s mental and physical health as well as quality of life. In 21% of cases no durable response to conservative treatment can be obtained (1). The serious course of the disease justifies the use of invasive treatment options, as AN has the highest mortality rate among psychiatric disorders. Deep Brain Stimulation (DBS) of the reward system of the brain, has been FDA approved as a treatment option for chronic obsessive-compulsive disorder since 2009. The Nucleus Accumbens (NAcc) pertains to the reward system of the brain, which is believed to be affected in AN. We hypothesize that bulimic-type AN is part of the spectrum of obsessive-compulsive disorders and as such can be treated by stimulation of the NAcc. We hereafter describe two consecutive cases of patients suffering of a severe form of bulimic AN, treated by DBS of the NAcc, showing an increase in weight and an impressive durable gain in quality-of-life. 

Cases:

Ms E. was 46 years-old when she was presented by here psychiatrist to our outpatient clinic. For a hight of 1.60m, she was barely weighting 27 Kg. The muscle wasting led to an inability to walk without aid and even breathing was visibly exhausting to the patient. Her kidney function had deteriorated over the years and finally the patient developed a complete renal failure. She had been suffering of severe bulimic AN since the age of 16. She had sought medical treatment in various psychiatric institutions, but the disease kept getting worse. The patient finally gave her consent for the implantation of a NAcc DBS. She was implanted with a Medtronic® ACTIVA RC Stimulator and Medtronic® SenSight electrodes. The exact position of the electrodes was of major interest for the postoperative programming of the stimulation fields. Lead DBS (2), an open-source software, was used for computational reconstruction of the exact location of the electrodes in the patients’ brain. In Lead DBS, PaCER algorithm was used for automated electrode trajectory and contact reconstruction (3). The patient did not develop any postoperative complications. The months after surgery, the patients' weight increased gradually (Figure 1). So did her overall fitness. The patient regained enough muscle strength to walk by herself. She was transferred to the psychiatric ward, where she spent several months after surgery under close monitoring. The symptoms of bulimia decreased significantly. She went from vomiting 20 to 30 times a day, making her life unbearable, to vomiting up to 5 times a day. A close psychiatric follow up was necessary to overcome the psychological challenges the patient was facing. Finally, the patient was discharged to supervised housing, where she could take up activities of daily living. At 21 months follow-up, the patient presented a spectacular increase in weight of 13 Kg, as well as an undeniable increase in quality-of-life. She took up dancing and sports classes and was even cooking for herself and friends. She reports still presenting binge-eating and vomiting behavior in the evening, with up to five episodes daily.

Ms E. was the second patient suffering of bulimic type AN presenting an impressive weight gain after Nacc DBS treated at our institution. Our first patient gradually gained 15 Kg during the months after surgery and was even able to go back to her job as a schoolteacher. The weight stayed stable even after explanation of the stimulator for wound infection (4).

Conclusion:

Nacc DBS must be considered a treatment option for severe bulimic AN resistant to non-invasive treatment. DBS is a safe, minimal-invasive surgical technique with a low complication rate, showing promising results in the treatment of severe forms of bulimic AN. However, the fact that AN patients are susceptible to specific complications related to their illness, like postoperative wound healing disturbances and refeeding syndrome, has to be kept in mind. Also, a close psychiatric follow-up must be assured, to allow for a successful therapy. Multidisciplinary patient management before and after surgery must be warranted. A prospective multicenter trial including a larger patient number will be necessary to confirm our results. We advocate, that in this stage of knowledge, if the life of the patient is at risk, there might be an indication for NAcc DBS, if alternative treatment modalities recommended by evidence-based guidelines, could not durably alleviate the patients’ suffering.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


Isabel FERNANDES ARROTEIA (Luxembourg, Luxembourg), Andreas HUSCH, Frank HERTEL
17:00 - 17:05 #35987 - OP079 Morphometric brain analysis of patients with Tourette syndrome treated with DBS based on disease severity and clinical outcome.
OP079 Morphometric brain analysis of patients with Tourette syndrome treated with DBS based on disease severity and clinical outcome.

Objectives:

Deep brain stimulation (DBS) is an effective therapy option for patients with treatment refractory Tourette syndrome (TS). A recent meta-analysis including different stimulation targets, showed that about 69% of the patients experience a significant tic-reduction with at least 50% improvement measured on the YGTSS (Yale Global Tic Severity Score) after one year [1]. The identification of biomarkers to estimate patients’ response to DBS is a crucial step for individualized therapy in TS patients. We aimed to identify morphometric biomarkers that could correlate with disease severity and clinical outcome in TS patients after DBS.

 

Methods:

We retrospectively analyzed the clinical outcome of 26 TS patients treated with DBS at the University Hospital of Cologne or at the Carlo Besta Neurological Institute in Milan. All patients received bilateral electrodes either in the centromedial nucleus/nucleus ventrooralis (CM/Voi), the CM/parafascicular nucleus (CM/Pf) or the anteromedial globus pallidus internus (amGPi). T1 sequences of preoperative MRIs were used for morphometric analysis. Voxel-based morphometry analysis of the subcortical structures was carried out using cat12 SPM12-toolbox. For the voxel-based analysis of the cortical surface, FreeSurfer was used. Clinical improvement of the patients was measured using the YGTSS before and one year after sugery.

 

Results:

There was a statistically significant, moderate positive correlation between the preoperative YGTSS and the size of the left (rho=0.43, p=0.029) and the right pallidum (rho=0.43, p=0.028). There was a strong negative correlation between the cortical thickness in the right middle temporal gyrus (rho=-0.65, p<0.001) and the right posterior cingulate gyrus (rho=-0.53, p=0.005) and the YGTSS. There was a moderate positive correlation between the improvement on YGTSS and the size of the right pallidum (rho=-0.45, p=0.021). We also observed a strong, statistically significant positive correlation between the cortical thickness in the left inferior temporal gyrus and clinical improvement (rho=0.65, p<0.001). Moreover, a moderate correlation between the improvement on YGTSS and the cortical thickness in the left middle temporal gyrus (rho=0.45, p=0.021) and the right inferior temporal gyrus (rho=0.41, p=0.037) was observed.

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           

Conclusion:

We found significant positive correlations between the cortical thickness of the left and right inferior temporal gyrus and the left middle gyrus and clinical improvement measured on the YGTSS. Interestingly, there was a positive correlation between the size of the left and right pallidum and the preoperative YGTSS. However, clinical improvement showed a negative correlation to the size of the right pallidum.

 

[1] Wehmeyer L, et al. Target-Specific Effects of Deep Brain Stimulation for Tourette Syndrome: A Systematic Review and Meta-Analysis. Front Neurol 2021;12:769275.


Pablo ANDRADE (Cologne, Germany), Heiden PETRA, Tommaso GALBIATI, Ricardo LOUÇAO, Juan BALDERMANN, Domenico SERVELLO, Veerle VISSER-VANDEWALLE
17:05 - 17:10 #35988 - OP080 Neuromodulation for aggressiveness and self-injurious behavior – a case report and review of the literature.
OP080 Neuromodulation for aggressiveness and self-injurious behavior – a case report and review of the literature.

Objectives:

Patients with pathological aggressiveness display stereotypical behavior that can manifest through aggressive language/sound, damaging objects or hurting other people (hetero-aggression) or themselves (auto-aggression). Conventional treatment consists of psychotropic medication, behavioral therapy and electroconvulsive therapy. For patients with refractory aggressive behavior, functional neurosurgery could be considered. In this study, we describe the case of a patient with mental retardation and severe hetero-, and auto-aggressive behavior treated with stereotactic ablative lesions in the anterior limb of the internal capsule (ALIC) and the posteromedial hypothalamus. Further, we performed a systematic literature review of the effects of functional neurosurgery in pathological aggressiveness.

 

Methods:

The 24-year-old female patient with a congenital genetical disorder displayed progressive aggressive behavior since early childhood, where conservative therapy showed no clinical effect. We performed simultaneous bilateral stereotactic ALIC capsulotomy and posteromedial hypothalamotomy. Clinical assessment was performed prior to surgery and 6 weeks, 6 months and 12 months after the intervention. Level of aggressiveness was assessed using the Modified Overt Aggression Scale (MOAS; 0-40 points, higher scores represent worse condition) and level of functionality was assessed using the Global Assessment of Functioning Scale (GAF; higher scores represent better functioning). To review existing literature on functional neurosurgery in pathological aggressiveness, we performed a systematic literature review using PubMed according to the PRISMA criteria.

 

Results:

There was a significant improvement of the functionality of the patient from 10 points on GAF prior to surgery, to 61 points 6 months after the intervention. There was also a relevant improvement on the MOAS from 33 points prior to surgery to 10 points after 6 months. After 12 months the aggressive behavior slightly increased to 12 points on MOAS and there was a worsening of functionality to 51 points on GAF. In total, 42 studies could be included in the review, 27 studies with lesioning procedures and 15 with deep brain stimulation (DBS). The amygdala was the most common target for stereotactic lesioning, followed by the posteromedial hypothalamus. The most common target for DBS was the hypothalamus, followed by the nucleus accumbens. Measurement of the clinical outcome was very heterogenous, however most studies described a significant improvement in over 50% of the patients.  

 

Conclusion:

Bilateral stereotactic capsulotomy and hypothalamotomy proved to be an effective treatment in this case. Review of the existing literature showed a heterogenous treatment of patients with pathological aggressiveness.


Pablo ANDRADE (Cologne, Germany), Sarah SAREM-ASLANI, Petra HEIDEN, Ricardo LOUÇAO, Veerle VISSER-VANDEWALLE
17:10 - 17:20 #36164 - OP081 Focused Ultrasound Neuromodulation Reduces Drug Cravings and Use in Patients with Substance Use Disorders.
OP081 Focused Ultrasound Neuromodulation Reduces Drug Cravings and Use in Patients with Substance Use Disorders.

Introduction

Despite advances in medical/behavioral treatments for substance use disorder (SUD), success rates remain low.  Novel therapeutic strategies are needed to address the addiction epidemic especially given the >107,000 drug overdose deaths in 2021, most of which involved opioids. Low-intensity focused ultrasound (LIFU) is a non-invasive procedure being investigated as a novel neuromodulation approach. We initiated a proof-of-concept study investigating LIFU neuromodulation targeting the nucleus accumbens (NAc) in participants with severe opioid and co-occurring SUDs. We initiated first in human FDA-approved study to investigate the safety, feasibility and the effects of NAc LIFU on substance craving and use in participants with SUD.

 

 

Methods

Six participants with SUD received sham LIFU followed by 10-20 minutes of active LIFU. The NAc target was selected using a combination of MRI and tractography. Safety and impact on drug cravings were assessed during the procedure and throughout the 90-day follow-up.  

 

Results

NAc LIFU neuromodulation was safe and well-tolerated in all participants. Sham LIFU resulted in no appreciable craving changes (p>0.05). Active LIFU reduced cravings for all substances during and immediately following sonication (mean reduction: >50%). Substance craving reduction was sustained for up to 90 days during follow-up (p=0.004). Moreover, there was a reduction in self-reported substance use, verified via urine toxicology during follow-up visits. 

 

Conclusion

This is the first in human report of LIFU neuromodulation targeting the NAc in patients with SUD. The procedure was safe and well-tolerated. LIFU neuromodulation acutely reduced substance craving during sonication and was sustained through to long-term follow up of 90-days. While promising, NAc LIFU requires further investigation in a randomized, controlled trial with a larger cohort of participants.

 

 


Ali REZAI (Morgantown, USA), Manish RANJAN, Pierre-Francois D’HAESE, Thompson-Lake DAISY, Jeffrey CARPENTER, Berry JAMES, Victor FINOMORE, Sally HODDER, James MAHONEY
17:20 - 17:30 VESTIBULAR SCHWANNOMA: UPFRONT RADIOSURGERY OR EXPECTATION. THE V-REX STUDY. Morten LUND-JOHANSEN (Professor, Consultant) (Bergen, Norway)

16:30-17:30
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C29
PARALLEL SESSION 9
Rehabilitation

PARALLEL SESSION 9
Rehabilitation

Moderators: Jocelyne BLOCH (Médecin Cadre) (Lausanne, Switzerland), Lorand EROSS (Director of the institute) (Budapest, Hungary), Marina RAGUŽ (M.D. Ph.D. Neurosurgeon) (Zagreb, Croatia)
16:30 - 16:40 #34518 - OP083 Deep brain stimulation to improve neurological recovery from spinal cord injury.
OP083 Deep brain stimulation to improve neurological recovery from spinal cord injury.

We conducted a whole brain survey in preclinical model of spinal cord injury (SCI) that revealed the critical role of the lateral hypothalamus in the recovery of walking following incomplete SCI. The delivery of deep brain stimulation (DBS) in the lateral hypothalamus immediately and durably improved walking in mice. Here, we tested the safety and preliminary efficacy of DBS delivered in the lateral hypothalamus of humans to improve neurological recovery following incomplete SCI. Two individuals with chronic incomplete SCI underwent the implantation of DBS electrodes in the left and right lateral hypothalamus. To guide the surgical implantation of the DBS leads, we implemented a pre-operative planning strategy that aimed to determine the optimal target region in the lateral hypothalamus. First, we collected functional magnetic resonance imaging (fMRI) data during attempted movements of the lower limbs. Second, we acquired diffusion tensor imaging (DTI) data to localize the region of the lateral hypothalamus from which nerve fiber bundles projecting to the reticular formation originate. We found that DBS delivered in the lateral hypothalamus instantly evoked sensory perception originating from the paralyzed muscles. Increasing the intensity of the stimulation elicited the urge to walk. As early as the first session post-operatively, DBS of the lateral hypothalamus augmented the vigor of muscle activity, which translated into the facilitation of walking between parallel bars. Rehabilitation augmented by DBS (3x3 hours of training per week) improved lower extremity motor scores, even when DBS was turned off. This neurological recovery resulted in improvement of the 10-meter walk test and 6-minute walk test. These preliminary data suggest that DBS of the lateral hypothalamus is a safe and efficacious strategy to improve the recovery of lower limb functions after SCI. These results expose a previously unknown involvement of the lateral hypothalamus in the production of walking in humans.


Viviana AURELI (Lausanne, Switzerland), Lea BOLE-FEYSOT, Newton CHO, Nicolas HANKOV, Nadine INTERING, Camille VARESCON, Nadia BERARD, Bogdan DRAGANSKI, Robin DEMESMAEKER, Leonie ASBOTH, Jordan SQUAIR, Gregoire COURTINE, Jocelyne BLOCH
16:40 - 16:45 #35642 - OP084 MRI morphometric and diffusion tensor imaging parameters as potential predictive factors in evaluation of patients with disorders of consciousness prior to deep brain stimulation.
OP084 MRI morphometric and diffusion tensor imaging parameters as potential predictive factors in evaluation of patients with disorders of consciousness prior to deep brain stimulation.

Background: Neuroimaging progress has yielded new tools which, potentially, can be applied to improve the diagnosis of neurological disorders and predict outcome. The disorders of consciousness (DOC) is limited to subjective assessment and objective measurements of behavior, with an emerging role for neuroimaging techniques. The aim of the study was to investigate the clinical application of MRI morphometric analysis and imaging indicators of diffusion tensor imaging (DTI) for the DOC patients.

Methods: MRI with obtaining high resolution T1 MPRAGE and DWI was done in twenty patient with a clinical diagnosis of DOC admitted at Department of Neurosurgery Dubrava University Hospital in order to perform neurophysiological testing to confirm whether is the patient candidate for deep brain stimulation. Morphometric analysis was done using Freesurfer software. The data for the imaging indicators, fractional anisotropy (FA) and mean diffusivity (MD), were separately collected from three relevant regions of interest (ROIs): brainstem, thalamus, and subcortex.

Results: The indicators were statistically analyzed, and correlation analyses were conducted for the results of morphometric study and mean values of FA and MD in the ROIs evaluated through clinical Rappaport Disability Rating, Coma/Near Coma scale and Coma Recovery Scale-Revised scores. Morphometric analysis revealed that level of brain volume decrease is correlated with severity of DOC. Furthermore, the more severe the DOC, the higher the MD value and the lower the FA value. The FA and MD values in the ROIs correlated with CRS-R scores, particularly in the thalamus.

Conclusion: Both volumetric and DTI analysis has proved to be a powerful tool as it grants insight into the pathogenesis and specific grey and white matter abnormalities underlying different comatose states, casting light on the neural basis of consciousness and the clinical features associated with DOC.


Marina RAGUŽ (Zagreb, Croatia), Marin LAKIC, Darko ORESKOVIC, Andelo KASTELANCIC, Petar MARCINKOVIC, Fadi ALMAHARIQ, Dominik ROMIC, Domagoj DLAKA, Nataša KATAVIĆ, Igor FUCKAN, Vedran DELETIS, Darko CHUDY
16:45 - 16:50 #35643 - OP085 Optimal targets, connectivity, and tissue integrity for deep brain stimulation in patients with disorders of consciousness.
OP085 Optimal targets, connectivity, and tissue integrity for deep brain stimulation in patients with disorders of consciousness.

Introduction: Disorders of consciousness (DOC) are characterized by alterations in arousal and/or awareness resulting from brain injuries. Deep brain stimulation (DBS) is an emerging treatment to restore arousal/awareness in DOC. However, little is known about optimal targets and whether outcomes depend on brain connectivity, tissue integrity, or reorganization potential.

Objective: To determine whether DBS outcomes in DOC are associated with stimulation locations, connectivity of stimulation sites, and MRI measures of brain tissue integrity.

Methods: Retrospective analysis of 38 patients with DOC who underwent unilateral DBS targeting thalamic centromedian nucleus (ages=12-65 years). DOC resulted from anoxic (n=26) or traumatic (n=12) injuries. Patients were classified as ‘responders’ or ‘non-responders’ using Coma/Near Coma and Coma Recovery Scales. Volumes of tissue activated (VTAs) assessed DBS locations associated with favorable response. Correlations were also performed with age, regional brain volumes from pre-operative MRI, and structural connectivity calculated from patients’ VTAs using normative diffusion MRI.

Results: 8/38 patients were responders and 24/38 non-responders; outcomes are pending in 6/38 patients due to <3 months follow-up. Favorable response was associated with younger age (median age=19 years in responders, 42 years in non-responders) and greater volumes of whole-brain grey matter and subcortical regions including putamen, pallidum, caudate, and cerebellum (Figure-1). Responders also tended to have deeper and more medial implantations, with VTAs engaging parafascicular nucleus, reticular nucleus, and peri-midbrain red nucleus (Figure-2). In responders, VTA connectivity was higher with superior frontal gyrus, caudate, pallidum, and cerebellum, and lower with sensorimotor and occipital cortex (Figure-3).

Conclusions: Efficacious DBS for DOC is linked to younger age, greater preservation of whole-brain grey-matter, greater volumes of and connectivity with select subcortical areas (pallidum, caudate, cerebellum), stronger connectivity with superior frontal gyrus, and stimulation of locations inferomedial to the centromedian nucleus. Findings may assist with optimizing patient selection, DBS targeting, and post-implantation programming.


Aaron E.l WARREN, Marina RAGUŽ (Zagreb, Croatia), Darko CHUDY, John D. ROLSTON
16:50 - 16:55 #35729 - OP086 Putamen Atrophy as a predictive factor of efficacy of Deep Brain Stimulation in Post-Anoxic Encephalopathy.
OP086 Putamen Atrophy as a predictive factor of efficacy of Deep Brain Stimulation in Post-Anoxic Encephalopathy.

Background:

A major cause of mortality and morbidity in term newborns is perinatal asphyxia, which had a prevalence of 1-6 per 1000 births live in high-incomes countries and 5-10 per 1000 live births in developing countries. The most important consequence of perinatal asphyxia is the occurrence of brain injury, seen on conventional MRI and including ventrolateral thalami and posterior putamina damages and white mater injury. These lesions result in adverse neurological sequelae such as tetraparetic motor deficit associated with dystono-dyskinetic syndrome. Deep Brain stimulation is one of the therapeutic options, but the outcomes in this population are insufficient.

Methods:

We conducted a retrospective study on 71 patients treated by Deep Brain Stimulation (DBS) of Globus Pallidus intern (GPi) for a secondary dysto-dyskinetic syndrome due to a post-anoxic encephalopathy (EP). We described on the pre-operative MRI the presence or not of deep grey nuclei, white matter and cerebellum damages. Patient’s clinical condition was evaluated with the Burke-Fahn Marsden Dystonia Rating Scale. Correlation between brain lesions identified on MRI and the clinical severity was analyzed.

Results:

Among the 71 patients included, 42 had putamen atrophy. Patients with putamen atrophy were clinically most severe that patients without putamen atrophy before surgery (p = 0,0289 for the motor part and P <0,0003 for the functional part of BFMDRS). We also reported that patients with putamen atrophy had a poor outcome in comparison to patients without putamen atrophy at 1 year post-DBS. (p= 0,0384 for the motor part and p < 0,0001 for the functional part of BFMDRS). No significant difference was found regarding on lesions in the other parts of the brain.

Conclusion

We described the importance of the analysis of brain lesions on the pre-operative MRI for patients with post-anoxic encephalopathy. Atrophy of the motor putamen can be used as a predictive factor of a poor outcome of bilateral GPi DBS.


Marylou GRASSO, Emilie CHAN-SENG, Philippe COUBES, Gaëtan POULEN (MONTPELLIER)
16:55 - 17:00 #36114 - OP087 Loss of ipsilateral motor representation in contralateral-projecting corticospinal neurons during motor learning.
OP087 Loss of ipsilateral motor representation in contralateral-projecting corticospinal neurons during motor learning.

Introduction

Corticospinal tract injury causes damage to the corticospinal neurons (CSNs), which often leads to motor impairment. During motor function recovery, the CSNs on the intact side play an important compensatory role. However, CSNs mostly project to motor neurons in the contralateral spinal cord to control the contralateral limb movement. Whether the contralateral-projecting CSNs (cpCSNs) obtain motor information of the ipsilateral limb remains understudied. Here, we aim to investigate whether the cpCSNs process motor information of the ipsilateral forelimb, and how its representation of the bilateral motor information evolves during motor learning.

Materials and Methods

Using cre-dependent adeno-associated virus and genetically encoded calcium indicator GCaMP6f, we conduct two-photon calcium imaging of cpCSNs in mice learning a bilateral lever-press task. Behavioral data and calcium signals in the apical dendrites of cpCSNs were recorded simultaneously. Then we classify cpCSNs into subsets based on the difference in neuronal activity between ipsilateral and contralateral movements, and calculate the laterality index to assess the preference and dynamics in the laterality of cpCSNs during motor learning.

Results

The population activity of cpCSNs is significantly different in the three stages of ipsilateral motor learning, substantially stronger in the early stage (mean ΔF/F=0.033) than in the latter two stages (mean ΔF/F=0.001, and 0.002). On the contrary, the populational activity shows no significant change during contralateral motor learning. Laterality in cpCSNs shows an ipsilateral bias in the early stage, contralateral bias in the middle stage, and neutral in the late stage. The individual activity of cpCSNs shows correlation with ipsilateral forelimb movements, which changes during learning. 82% of movement-related cpCSNs are active in ipsilateral movements in the early stage, while this number decreased to 64% and 73% in the middle and late stages of learning, respectively. In contrast, 62%, 75%, and 44% of movement-related cpCSNs are active in contralateral movements in the early, middle, and late stages of motor learning, respectively.

Conclusions

Our findings suggest that cpCSNs are involved in the ipsilateral forelimb movements as it does in the contralateral side. Their involvement in the ipsilateral motor learning, however, drastically decreases over time. It further supports the hypothesis that cpCSNs in one hemisphere contain ipsilateral motor information as a backup for the other hemisphere, and dumps this information after a motor task is learned. Maintaining the ipsilateral involvement of cpCSNs may be crucial during motor function rehabilitation.


Jiawei HAN, Jumming ZHU, Shaomin ZHANG, Hemmings WU (Hangzhou, China)
17:00 - 17:10 #36125 - OP088 Deep brain stimulation for disorders of consciousness and diminished motivation.
OP088 Deep brain stimulation for disorders of consciousness and diminished motivation.

Rationale: Some patients develop prolonged disorders of consciousness or signs of severe diminished motivation after experiencing severe brain injury. There are currently little evidence-based therapies for improvement of behavioral performance in these patients. Experimental DBS of the intralaminar thalamus (centromedian-parafascicular complex, CM-Pf) has previously been performed to increase arousal and restore purposeful behavior in a selected group of these severely injured patients. However, the mechanism of action of DBS still remains unknown.  
Objective: To explore the (neurophysiological) mechanisms of action and efficacy of CM-Pf DBS in patients with prolonged disorders of consciousness and diminished motivation.
Methods: Six patients with a minimally conscious state (MCS) without improvement >24 months after traumatic brain injury and several patients with severe disorders of diminished motivation (akinetic mutism) will undergo experimental CM-Pf DBS. Neurophysiological changes between the DBS OFF and ON state will be measured using magnetoencephalography (MEG) and different stimulation paradigms (low- and high-frequency stimulation) will be tested. Moreover, CRS-R (coma) scores and MOCA tests will be used to objectify clinical outcome.
Results/conclusion: Preliminary results show that CM-Pf DBS is able to alter pathological levels of functional connectivity throughout the brain that have developed in response to brain injury and limit brain functions. DBS, especially when used in a low-frequency form, restores functional connectivity towards a healthier baseline, which allows for the return of functional networks. This is paralleled by some signs of clinical improvement. The neurophysiological/MEG results will be shown, as well as some amazing ‘awakening’ effects of DBS through OFF and ON videos.


Hisse ARNTS (Nijmegen, The Netherlands), Rick SCHUURMAN, Pepijn VAN DEN MUNCKHOF
17:10 - 17:15 #36142 - OP089 Tibial nerve stimulation in neurogenic bladder and defecation dysfunction – single center case series.
OP089 Tibial nerve stimulation in neurogenic bladder and defecation dysfunction – single center case series.

Introduction

Symptoms of neurogenic bladder and defecation dysfunction are common sequel of spinal cord injury caused by trauma or spinal tumor. Defecation disturbances, symptoms of dysfunction of bladder’s detrusor and sphincter are extremely tiresome for patients and reduce quality of life. Conservative methods of treatment are frequently not effective. Non-invasive neuromodulation procedures are commonly prescribed. One of the attractive alternatives methods is tibial nerve stimulation which can be non-invasive or invasive. 

The aim of our study was to evaluate effects of tibial nerve stimulation use in patients with functional disorders of bladder and rectum.

Methods

In 3 patients right tibial nerve stimulation was applied with the use of surgically implanted lead stimulator Freedom 4 (Stimwave, Curonix, Ca, USA).

We have assessed the effects of function self assessed by patients and the quality of life with follow-up to 1 year.

Results

In follow-up of 1 year in all 3 individuals, positive results were noted. Ultimately, all patients were programmed with burst stimulation. All patients had a good response to intraoperative stimulation. Each patient had a significant improvement in micturition control and defecation. In the case of one patient, retention of urine, confirmed by urodynamic examination, persisted in the volume of 80 ml.

In one patient, stimulation with a program with an amplitude of 1.5 mA and a frequency of 1500 Hz significantly reduced pain in the perineum. In addition, there was an improvement in sexual function expressed in the form of the ability to have sexual intercourse and the elimination of premature ejaculation. In the remaining patients, almost complete sensation in the area of the perineum and buttocks returned. Simultaneously, in one patient, stimulation of the tibial nerve resulted in a reduction in contracture of the toes of both feet, which occurred as a consequence of a spinal cord injury.

Conclusion

Tibial nerve stimulation using the application is a minimally invasive procedure, and its primary goal is to reduce the symptoms of urgency, frequency and episodes of urinary and stool incontinence. It enables convenient stimulation daily and improves function of muscles of bladder and anus. In addition, it is a minimally invasive method, very well tolerated, and does not burden the patient with the risk of side effects associated with taking medications.


Paweł SOKAL, Aleksandra MAJ-KĘSICKA, Magdalena JABŁOŃSKA (Bydgoszcz, Poland), Oskar PUK, Sara KIEROŃSKA, Renata JABŁOŃSKA, Damian PALUS
17:15 - 17:25 #36172 - OP090 Sensory-substitution-based perception interface using spinal cord stimulation applied for hearing aid.
OP090 Sensory-substitution-based perception interface using spinal cord stimulation applied for hearing aid.

The World Health Organisation estimates that nearly 466 million people are suffering from disabling hearing loss (2019) – 7 % of them children. While not all individuals with hearing impairments can benefit from cochlear implants, using sensory substitution principles, such as non-invasive vibrotactile techniques, can be used to assist hearing-impaired patients.

In this study our objective was to systematically establish a proof of concept in hearing adults demonstrating that a sensory-substitution-based perception interface using spinal cord stimulation (SCS) can replicate the functioning principle of a cochlear implant.

We calibrated personalized stimulation settings to generate distinctive and reproducible sensations in 9 patients who had recently undergone spinal cord stimulator (SCS) implantation, and used these sensations as inputs in pattern discrimination tasks.

Sound samples (voices, warning sounds) with a fixed duration of 7 seconds and normalized volume translated into stimulation patterns were used in a forced-choice design, with the patient having to discern these (groups of 4 sound examples are presented with 3 random choices) after a learning phase purely on the basis of the spinal stimulation-induced percepts. Each set contained one confusion pair with similar cadence patterns but fine differences to ensure patients can differentiate beyond mere rhythm (e.g. a fire alarm vs. a car siren).

We managed to establish computer-to-brain communication in 7 out of 9 patients. The learning phase lasted no more than 10 minutes. Out of the 7 patients who completed the discrimination tasks, 6 could distinguish between the sound samples above chance level, with an overall mean performance of 70%. The performance range varied from 42 to 87%, with the chance level set at 1/3. 

This study demonstrates the potential of utilizing sensory-substitution-based perception interfaces through spinal cord stimulation as a promising approach for hearing-impaired individuals. The achieved proof of concept opens up new possibilities for interventions that could enhance auditory perception and improve the quality of life for those who are unable to benefit from traditional cochlear implants. Further research is needed to refine the sound-encoding and signal transferring methods employed in this approach. Additionally, future investigations should focus on expanding the sample size and including a more diverse range of patients to assess the generalizability of our findings. 


Halasz LASZLO (Budapest, Hungary), Balint VARKUTI, Gabriella MIKLOS, Saman HAGH GOOIE, Emilia TOTH, Max HASSELBERGER, Gijs VAN ELSWIJK, Lorand EROSS

17:30
Friday 29 September
Time ROOM A1 ROOM C1-C2 ROOM C3 ROOM C4
08:30
08:30-10:00
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A25
PLENARY SESSION 3

PLENARY SESSION 3

Moderators: Jocelyne BLOCH (Médecin Cadre) (Lausanne, Switzerland), Stephan CHABARDÈS (head of the department) (GRENOBLE, France)
08:30 - 08:50 Infrared stimulation : preclinical & clinical preliminary experience. Stephan CHABARDÈS (head of the department) (GRENOBLE, France)
08:50 - 09:10 Pain Surgery. Konstantin V. SLAVIN (professor) (Chicago, USA)
09:10 - 09:25 Evaluating functional connectivity differences between DBS on/off states in essential tremor. Albert FENOY (neurosurgery) (Great Neck, USA)
09:25 - 09:40 #34068 - PL02 Gamma knife central latheral thalamotomy for neuropathic pain: a single-center retrospective study.
PL02 Gamma knife central latheral thalamotomy for neuropathic pain: a single-center retrospective study.

Background: Chronic neuropathic pain can be severely disabling and is difficult to treat. The medial thalamus is thought to be involved in the processing of the affective-motivational dimension of pain and lesioning of the medial thalamus has been used as a potential treatment for neuropathic pain. Within the medial thalamus, the central lateral nucleus has been considered as a target for stereotactic lesioning.

 

Objective: To study the safety and efficacy of central lateral thalamotomy using Gamma Knife radiosurgery (GKRS) for the treatment of neuropathic pain.

 

Methods: We retrospectively reviewed all patients with neuropathic pain who underwent central lateral thalamotomy using GKRS. We report on patient outcomes, including changes in pain scores using the Numeric Pain Rating Scale and Barrow Neurological Institute pain intensity score, and adverse events.

 

Results: Twenty-one patients underwent central lateral thalamotomy using GKRS between 2014 and 2021. Meaningful pain reduction occurred in 12 patients (57%) after a median period of 3 months  and persisted in seven patients (33%) at last follow-up (median follow-up was 28 months). Rates of pain reduction at 1, 2, 3, and 5 years were 48%, 48%, 19%, and 19%, respectively. Meaningful pain reduction occurred more frequently in patients with trigeminal deafferentation pain compared to all other patients (P = .009). No patient had treatment-related adverse events.

 

Conclusions: Central lateral thalamotomy using GKRS is remarkably safe. Pain reduction following this procedure occurs in a subset of patients and is more frequent in those with trigeminal deafferentation pain; however, pain recurs frequently over time.


Piero PICOZZI, Andrea FRANZINI (Milano, Italy)
09:40 - 10:00 High-dimensional neuroprosthetic control using a generative model of hand biomechanics. Conor KEOGH (Clinical Research Fellow) (Oxford, United Kingdom)

10:00 - 10:30 COFFEE BREAK - FLASH POSTERS SESSION 3 - EXHIBITION
10:30
10:30-12:00
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A31
PLENARY SESSION 4

PLENARY SESSION 4

Moderators: Alexandre CAMPOS (Doctor) (São Paulo, Brazil), Patrick CHAUVEL (Professor of Neurology) (Pittsburgh, USA), Kai LEHTIMÄKI (Associate Professor in Neurosurgery) (Tampere, Finland)
10:30 - 10:50 #33989 - PL03 Statistical Anatomical mapping of DBS of the anterior Nucleus of the Thalamus for intractable epilepsies.
PL03 Statistical Anatomical mapping of DBS of the anterior Nucleus of the Thalamus for intractable epilepsies.

Background : The prospective trial SANTE have demonstrated the benefit of the stimulation of the anterior nucleus of the thalamus (ANT) in intractable epilepsies not remediable by resective surgery. The precise topography of the best target offering the optimum safety efficacy ratio is still a matter of debate.

 

Material and method : In 46 patients operated in the frame of the prospective multicentric trial « France » and followed at least 2 years with all the anatomical and clinical pre and postoperative data available. The topography of the stimulating contact, the volume of tissue activated (VTA), the recruited fiber tracts were cross matched with seizure reduction and side effects.

Results : Comparison between pre and postoperative seizure frequency is demonstrating at two years a mean seizure reduction rate of 35% with  17, 21 & 8 patients respectively responders, improved and not improved. The analyses of the position of the stimulating contact is showing that in the best responders its location is more posterior and inferior. The study of the VTA is demonstrating that the probability to be improved is correlating on the left with a larger coverage of MD (MedioDorsal nucleus) and on the right side with a larger coverage of AV (Ventral part of the ANT) and MD plus a lower coverage of IL (Internal medullary lamina).  The dynamic of the response in time depends on the category of response to the stimulation. The site for the best response and the probability of best response seems to be depending on the location of the epileptogenic zone.

 

Conclusion : The white fibers postero-inferior at the AV and specially the mammilo-thalamic tract is turning out to be the main optimum target of DBS for intractable epilepsies. The ANT per se may not be the main target.


Jean REGIS (MARSEILLE), Hamdi HUSSEIN, Milan MAJTANIK, Jurgen MAY, Claire HAEGELEN, Fabrice BARTOLOMEI, Sylvain RHEIMS, Emmanuel CUNY, Sophie COLNAT, Louis MAILLARD, Philippe KAHANE, Stéphane CLEMENCEAU, Romain CARRON, Bertrand DEVAUX, Marc GUENOT, Guillaume PENCHET, Denis FONTAINE, Nica ANCA, Lorella MINOTTI, Sandra DAVID-TCHOUDA
10:50 - 11:10 #33939 - PL04 Patterns of pulvinar-cortical coupling in posterior quadrant epilepsies evaluated by SEEG methodology.
PL04 Patterns of pulvinar-cortical coupling in posterior quadrant epilepsies evaluated by SEEG methodology.

By considering the role of the subcortical regions in the organization of the epileptiform activity, such as the thalamus, clinical outcomes can be improved through more accurate diagnosis and focused therapeutic intervention that aims to modulate the abnormal epileptic network. In the present study, we investigated stereoelectroencephalographic (SEEG) recordings in drug-resistant epilepsy patients to qualitatively and quantitatively analyze the ictal pulvinar activity as well as its synchronization with the different cortical areas, with special attention to the posterior quadrant cortical areas. 

Between March 2020 to March 2022, 18 patients with medically refractory partial epilepsy (MRE), who underwent SEEG exploration at the University of Pittsburgh, were prospectively selected for the study, among a series of 62 SEEG patients operated during the same period. The study has been approved by the University of Pittsburgh Institutional Review Board (protocol #20070113). During ictal recordings, Phase-locking value (PLV) was applied to quantify synchronization of oscillatory activity between the EZ and the Pulvinar nucleus of the thalamus (Lachaux 1999). To calc