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EP01
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Eposters
BASIC SCIENCE

00:00 - 00:00 #24072 - Changes in the patient’s cognitive status at the spinal cord stimulation.
Changes in the patient’s cognitive status at the spinal cord stimulation.

The high social significance and prevalence of cognitive impairment determines the relevance of the search for new ways to correct these conditions, but existing pharmacological methods that improve the functional state of the central nervous system do not always meet the expectations of both doctors and patients. In clinical practice, a combination of moderate cognitive impairment of vascular origin with chronic pain syndromes is quite often noted.

The aim of the study was to study changes in cognitive status in patients with trial and chronic epidural spinal cord electrical stimulation.

Materials and methods. The study was conducted on 46 patients hospitalized and operated on at the Department of Functional Neurosurgery of the Federal Centre of Neurosurgery (Tyumen) from January 2015 to December 2019. The average age of the patients at the time of the study was 59.5±2.9 years. In all patients the indication for surgical treatment was a severe drug-resistant pain that developed as a result of various surgical interventions on the lumbar spine. Cognitive status was assessed using the SAGE test before the trial stimulation of the spinal cord, on day 5, immediately after the end of the trial period of electrical stimulation and after 3 months after implantation of the chronic epidural spinal cord electrostimulation system (EON C (St. Jude Medical Inc., USA). The study included patients over the age of 50 years with moderate cognitive deficiency of vascular origin (10-16 scores on the SAGE scale). Epidural electrodes in all patients were located at Th9-Th10 level. Stimulation parameters were selected individually and varied from 60 to 80 Hz, pulse widths from 300 to 500 μs, amplitude from 2.5 to 6 mA. The control group was represented by 28 patients of the spinal surgery department with chronic vertebrogenic pain syndromes. The age, gender distribution, and initial cognitive status of these patients corresponded to the main clinical group.

Results. All patients of the main clinical group on the background of electrical stimulation subjectively described improvement in well-being, normalization of sleep, and a decrease in the level of anxiety and depression. On the 5th day of the trial stimulation of the spinal cord in patients of this group, an improvement in cognitive status on the SAGE scale from 13.5±0.8 to 17.1±0.7 scores (P<0.05) was objectively observed. The average test execution time decreased from 18.36±1.18 min to 13.09±1.62 min (P <0.05). These changes significantly differed from the indicators of the control group, where in the postoperative period there was no significant change in cognitive status (except for the time of the repeated test). At the control examination (after 3 months) against the background of chronic epidural electrical stimulation of the spinal cord, the SAGE test scores were 17.4±0.6  (P<0.05 compared with the initial level), the average test time was 13.18±0.79 min (P<0.05 compared to baseline). All patients both in the early and in the distant postoperative period showed an improvement in cerebral circulation according to MRI and CT perfusion of the brain.

Conclusion. Our data show that chronic epidural spinal cord stimulation is accompanied by a persistent improvement in cognitive status in patients with moderate cognitive deficiency of vascular origin.

Andrei SHAPKIN (Tyumen, Russia), Albert SUFIANOV, Galina SUFIANOVA
00:00 - 00:00 #26256 - Effects of high frequency stimulation of the subthalamic nucleus in Parkinsonian mice on the acetylcholinergic system of the pedunculopontine nucleus.
Effects of high frequency stimulation of the subthalamic nucleus in Parkinsonian mice on the acetylcholinergic system of the pedunculopontine nucleus.

Introduction

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is standard care for motor symptoms of Parkinson’s disease. However, a challenge of DBS remains improving gait and balance disturbances. The control of gait and balance has been associated with the acetylcholine system in the pedunculopontine nucleus (PPN). In this study we investigated the effects of STN DBS on the PPN acetylcholine system in a Parkinsonian mouse model by immunohistochemistry.

 

Materials and Methods

Mice received intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline. This was followed by bilateral STN electrode implantation. The animals underwent chronic STN DBS or sham stimulation. Motor behaviour was assessed by the automated Catwalk gait analysis. After transcardial perfusion brains were sectioned and processed for tyrosine hydroxylase (TH), choline acetyltransferase (ChAT) and c-Fos immunohistochemistry. Neuronal expression of these markers was evaluated by stereological analysis.

 

Results

MPTP treated mice showed static and dynamic gait impairments in the Catwalk analysis compared to saline treated animals. These impairments were reversed by STN DBS. MPTP treated mice resulted in a significant reduction of dopaminergic neurons in the substantia nigra pars compacta and PPN acetylcholinergic neurons by TH and ChAT immunohistochemistry respectively. STN DBS did not alter the number of PPN ChAT neurons expressing the neuronal activation marker c-Fos.

 

Conclusion

MPTP injections resulted in motor and gait impairments as well as a degeneration of the PPN acetylcholine system. Although STN DBS improved gait and balance in the automated Catwalk this was not associated with an activation of PPN acetylcholine neurons, as immunohistochemical double labelling for ChAT and c-Fos was not changed by STN DBS. Motor and gait effects of STN DBS are therefore less likely to be mediated by a STN-PPN connection.

Sonny TAN (Aachen, Germany), Victoria WITZIG, Faisal ALOSAIMI, Hans CLUSMANN, Yasin TEMEL, Ali JAHANSHAHI
00:00 - 00:00 #23349 - Influence of DBS-like electric stimulation on inflammatory mediators in-vitro.
Influence of DBS-like electric stimulation on inflammatory mediators in-vitro.

Objective: Deep brain simulation (DBS) is a neurosurgical therapy especially for movement disorders but also psychiatric diseases as depressions with a therapy-refractory course are rising. Even if the therapeutic results are mostly satisfactory, the mechanism of action is not completely understood. Possibly the effect of DBS is partly based on changed cytokine/ chemokine concentrations of the surrounding brain cells. Thus, in this study we established an in vivo adapted in vitro model of DBS and analyzed the influence of an electric stimulation on different brain cells.

Methods: According to conditions used in DBS patients, we established an in vitro model to electrically stimulate SVGA- (Astrocytes), HMC3- (Microglia) and SH-SY5Y-cells (Neurons). To exclude an influence on apoptosis or proliferation rates, cells were stained by TUNEL-Assay and proliferation rates were determined by cell counting compared to control samples, respectively. Additionally, we stimulated brain cells with 2mV for 24 hours and measured the expression of different cytokines and chemokines (CXCL12, CXCL16, CCL2, CCL20, IL1β, IL6) by qrtPCR and verified significant expression differences by fluorescence staining.

Results: The in vivo adapted in vitro DBS-model was established successfully. An influence on cell proliferation and apoptosis rates was not observed. mRNA expression of IL1β in SH-SY5Y-cells and CXCL12 in SVGA-cells were significantly induced, and these results were confirmed by fluorescence staining.  

Conclusion: The mechanism of action of DBS seems to be very complex and its influence on the expression of cytokines and chemokines should be further explored. The establishment of this DBS-model could lead to a better understanding of these effects.

Henri MOLKEWEHRUM, Carolin KUBELT, Michael SYNOWITZ, Janka HELD-FEINDT, Ann-Kristin HELMERS (Kiel, Germany)
00:00 - 00:00 #25856 - Minimising post-op micro-hemorrhages in the milieu of the DBS electrode by using bipolar stimulation – an in-vitro experiment.
Minimising post-op micro-hemorrhages in the milieu of the DBS electrode by using bipolar stimulation – an in-vitro experiment.

Background: Introducing the Deep Brain Stimulation (DBS) Electrode into the target may cause peri-electrode edema which can present from 6 hours to 120 Days postoperatively, with symptoms ranging from confusional states, neurological deficits to seizures and dyskinetic storms.[1-3]  A postulated mechanism of peri-electrode edema is Microhaemorrhages due to lead implantation.[2] In a prospective study by Borellini et al., all patients who underwent DBS implantation showed asymptomatic peri-lead edema on postoperative MRI imaging, with 30% having microhemorrhages.[4] Microhemorrhages and edema around the lead can result in postoperative as well as the long term changes in tissue impedance.[5] Therefore, an ideal Lead-Tissue interface, i.e. one with minimal post-operative edema, is essential to prevent post-operative complications as well as to improve long term outcome of stimulation.

Material and Methods: In our in-vitro experiment, two DBS electrodes were introduced into two test tubes, each containing 5 ml of freshly drawn venous blood. One electrode was turned on with a bipolar pattern of stimulation, and the other acted as a control. Clotting time was observed in both the test tubes.[Fig 1] The experiment was repeated with increasing increments of stimulation voltage from 0.5 to 4.5 Volts. The experiment was conducted at a constant temperature of 25°C.

 

Results: There was a 44.4% decrease in the clotting time with the bipolar stimulation turned on as compared to the control electrode.[Table 1] No change in clotting time was observed after increasing the stimulation voltage beyond 2.0 V. After blood in both test tubes had clotted (at 5 minutes), there was visible clotting on the electrode with the stimulation turned on, while the control electrode was clean. [Fig 2]

 

Conclusions: Turning on the stimulation significantly reduced the clotting time around the DBS electrode in our in-vitro experiment. We believe these findings will prove to be beneficial in an operative setting. Till date, no evidence based guidelines exist on when to begin the stimulation after a DBS surgery, with most centres turning on the stimulation after 4 weeks of the implantation. [6] We hypothesise that turning on the DBS electrodes immediately after implantation would help reduce Microhemorrhages and Edema by expediting the hemostasis. We believe a bipolar stimulation [Fig 3] at 2.0 V for 3 minutes would ensure adequate hemostasis, thereby minimising peri-lead edema. This would ensure a better lead-tissue interface for future stimulation purposes.

 

References:

1.     Lee JJ, Daniels B, Austerman RJ, Dalm BD. Symptomatic, left-sided deep brain stimulation lead edema 6 h after bilateral subthalamic nucleus lead placement. Surg Neurol Int. 2019 Apr;10:68.

2.     Deogaonkar M, Nazzaro JM, Machado A, Rezai A. Transient, symptomatic, post-operative, non-infectious hypodensity around the deep brain stimulation (DBS) electrode. J Clin Neurosci. 2011 Jul;18(7):910–5.

3.     K. Hooper A, M. Ellis T, D. Foote K, Zeilman P, S. Okun M. Dyskinetic Storm Induced by Intra-Operative Deep Brain Stimulator Placement. The Open Neurosurgery Journal. 2009 Feb [cited 2021 Apr 15]. ;2(1). Available from: http://benthamopen.com/contents/pdf/TONEUROSJ/TONEUROSJ-2-1.pdf

4.     Borellini L, Ardolino G, Carrabba G, Locatelli M, Rampini P, Sbaraini S, et al. Peri-lead edema after deep brain stimulation surgery for Parkinson’s disease: a prospective magnetic resonance imaging study. Eur J Neurol. 2019 Mar;26(3):533–9.

5.     Hartmann CJ, Wojtecki L, Vesper J, Volkmann J, Groiss SJ, Schnitzler A, et al. Long-term evaluation of impedance levels and clinical development in subthalamic deep brain stimulation for Parkinson’s disease. Parkinsonism Relat Disord. 2015 Oct;21(10):1247–50.

6.     Picillo M, Lozano AM, Kou N, Puppi Munhoz R, Fasano A. Programming Deep Brain Stimulation for Parkinson’s Disease: The Toronto Western Hospital Algorithms. Brain Stimul. 2016 May;9(3):425–37.

Hargunbir SINGH (Chandigarh, India), Nishit SAWAL, Arnav MITTAL, Divij SINGHAL, Adhish BERI, Gurmehar HUNDAL, Saloni Rani KUMAR, Ansh CHAWLA
00:00 - 00:00 #24071 - Renal hemodynamic and excretory function at spinal cord stimulation.
Renal hemodynamic and excretory function at spinal cord stimulation.

Pain is a strong stressful irritant that has a huge impact on almost all organs and systems of a patient, while a pain reaction through a reflex mechanism can cause impaired renal hemodynamics. Changes in renal blood flow, in turn, is accompanied by impaired homeostasis, disorders of the water-electrolyte balance, impaired neuroendocrine regulation, causing and exacerbating dysfunction of the cardiovascular system. Considering the known peripheral hemodynamic effects of spinal cord stimulation, a similar positive effect of this treatment on blood circulation and kidney function can be assumed.

Purpose of the study. To study the effect of epidural electrical stimulation of the spinal cord on renal blood flow and excretory function.

Materials and methods. We examined 18 male patients aged 50 to 65 years who were treated at the Federal Center of Neurosurgery (Russia,Tyumen). In all patients, regardless of the nature and severity of the clinical picture of the underlying disease, the indication for surgical treatment was a severe drug-resistant pain syndrome that developed as a result of various surgical interventions on the cervical and lumbar spine. Temporary epidural electrodes were implanted in all patients, respectively, at the cervical (C3-C6, N = 8) or lower thoracic (Th9-Th10, N = 10) levels. The stimulation parameters were selected individually, the pulse frequency was 80 Hz, the pulse width was 500 μs, and the amplitude was from 2 to 6 mA. The period of temporary epidural electrical stimulation of the spinal cord was 5-7 days. Assessment of renal blood flow was carried out on an ultrasound machine Toshiba Aplio 500 before implantation of the trial epidural electrode and 5-7 days after surgery. Peak systolic (PSV), end-diastolic blood flow velocities (EDV) and resistance index (RI) were studied in the renal artery, segmental, interlobar and arciform arteries and in the renal veins. To assess the excretory renal function in the concentration of creatinine, urea and residual nitrogen in the blood serum were evaluated.

Results. With spinal cord stimulation at the Th9-Th10 level, all patients showed a statistically significant increase in peak systolic renal blood flow velocity by 20-35%. The greatest hemodynamic changes were recorded in the renal artery and interlobar arteries, where the increase in PSV was 30.8%, respectively (from 0.74±0.01 m/s to 0.98±0.03 m/s, P<0.01) and 39.62% (from 0.32±0.03 m/s to 0.44±0.04 m/s, P<0.05). Peak systolic blood flow velocity in segmental and arciform arteries increased by 24.4%, respectively (from 0.56±0.06 m/s to 0.71±0.07 m/s, P<0.05) and 28% ( from 0.23±0.03 m/s to 0.29±0.02 m/s, P<0.05). Moreover, statistically significant changes in the diameter of the arteries (the diameter of the renal artery was 6.3-6.8 mm) and RI (0.33-0.4) were not observed. In the analysis of biochemical parameters, a decrease in the serum level of urea (from 6.48±0.45 mmol/L to 4.74±0.4 mmol/L, P<0.01), residual nitrogen (from 26.6±1.36 mmol/L to 21.42±1.2 mmol/L, P<0.01) and creatinine (from 76.8±2.3 μmol/L to 72.4±2.2 μmol/L, P<0.05), which indicates an increase in glomerular filtration rate. When stimulating the spinal cord at the level of the cervical thickening, statistically significant changes in the renal hemodynamics and biochemical blood parameters were not observed. In both groups, there was a tendency to a decrease in average daily heart rate and systolic blood pressure.

Conclusion. Spinal cord stimulation is accompanied by an increase in the functional and speed indicators of renal hemodynamics, which is of interest for using this method in cases of impaired renal blood flow and filtration-excretory renal function of various genesis, this study is also promising with the aim of using the method of electrical stimulation of the spinal cord for renal arterial hypertension.

Andrei SHAPKIN (Tyumen, Russia), Albert SUFIANOV, Galina SUFIANOVA, Olga SADYKOVA, Tamara ISHENKO
00:00 - 00:00 #23500 - Stereo-EEG with microelectrodes: Single neurons in human medial temporal lobe encode ego- and allocentric direction during virtual spatial navigation.
Stereo-EEG with microelectrodes: Single neurons in human medial temporal lobe encode ego- and allocentric direction during virtual spatial navigation.

Background: Successful spatial navigation requires a detailed neural representation of the spatial environment. Allocentric representations encode spatial information in a world-centered reference frame, whereas egocentric representations encode spatial variables relative to the observer. 

 

Methods: To demonstrate the coexistence of ego- and allocentric representations of direction in the human brain, we recorded from medial temporal lobe neurons in neurosurgical epilepsy patients performing a virtual navigation task. 498 medial temporal lobe neurons were recorded via 45 stereotactically implanted depth electrodes outfitted with 8 microelectrodes each (Behnke-Fried electrodes). Neurons were extracted using spike sorting and clustering algorithms and their activity was related to the patients' behavioral performance in the virtual environment. 

 

Results: We describe a new class of neurons whose activity varies as a function of egocentric direction towards local reference points of the spatial environment (“anchor cells”), complementary to neurons coding for allocentric location or global direction. Anchor cells were particularly prevalent in parahippocampal cortex and overrepresented the environmental center as a local reference point.

 

Conclusion: Our results provide first evidence for neural codes of egocentric space in the human brain and support the two-system model of parallel egocentric and allocentric representations in spatial memory and navigation.

 

Fig. 1: Task, behavioral performance, and illustration of anchor-cell identification. 

A, Patients performed an object–location memory task in a virtual environment. In each trial, a given object (“cue”) had to be placed at its correct location (“retrieval”). Patients received feedback depending on response accuracy (“feedback”) and re-encoded the object location afterwards (“re-encoding”).

B, Bird’s eye view of the environment. Blue compass, allocentric direction; green compass, egocentric direction (given the patient is facing “northeast”). A (B; L; R), ahead (behind; to the left; to the right) of the subject.

C, Histogram of spatial memory performance values across all trials from all patients (n=1890 trials). Red dotted line, chance level.

D, Change in spatial memory performance between the first and the last trial (n=18 sessions from n=14 patients). Blue line, mean across subjects.

E, Illustration of anchor bearing, which is the angular difference between the allocentric heading angle and the angle of the vector from the subject’s location to the anchor point.

F, Left, candidate anchor points. Right, illustrative tuning curve for one candidate point depicting firing rate as a function of bearing towards this point. Significance of each point is tested via surrogate statistics.

G, Cluster-based permutation testing identifies the largest cluster of significant candidate points (“anchor field”). The “anchor point” is the center of mass of the anchor field.  

Peter C. REINACHER (Freiburg, Germany), Lukas KUNZ, Bernhard P. STARESINA, Armin BRANDT, Nora A. HERWEG, Melina TSITSIKLIS, Michael J. KAHANA, Joshua JACOBS, Andreas SCHULZE-BONHAGE
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EP02
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Eposters
EPILEPSY

00:00 - 00:00 #26155 - Angiocentric Glioma – a case report of a rare entity.
Angiocentric Glioma – a case report of a rare entity.

Introduction

Angiocentric Glioma (AG) was first described in 2005 as a distinct lesion and recently classified as a WHO Grade I tumour. According to the literature and available case reports (around 100 cases described worldwide) these lesions are predominantly seen in children or young adults with intractable or drug-resistant epilepsy.

Case report

A 17 year old boy presented with progressively worsening episodes of sudden leftward rotation of the head, without impaired awareness   He underwent vídeo-EEG monitoring which revealed ictal pattern projection in the right frontal region, and interictal epileptiform discharges in the right fronto-central region and less frequently in the contralateral homologous region. An MRI scan revealed a T2 hyperintense lesion adjacent to the right pre-central gyrus measuring approximately 8mm x 22mm x 6mm. The lesion involved the cortex and subcortical white matter, resembling a focal cortical dyplasia with the transmantle sign but with discrete gadolinium enhancement and a thin ( After a multidisciplinary discussion the patient was indicated for surgery with intraoperative electrocorticography (EcoG) and neurophysiologic motor mapping. The lesion was resected after a right frontal craniotomy and sent for histopathological evaluation. Epileptiform discharges were recorded over the lesional area and the surrounding tissue. The analysis revealed elongated glial cells involving the cortex and subcortical white matter aggregated around blood vessels. The neoplastic cells were positive for Glial fibrillary acidic protein (GFAP) and no Ki-67 or IDH-1 expression identified. 5 months after surgery the patient remains seizure-free (Engel Ia according to the Engel classification).

Conclusion

AG is a slow-growing primary lesion of the central nervous system, usually discovered during the investigation of a drug-resistant epilepsy. The main differential diagnosis includes dysembryoplastic neuroepithelial tumor (DNET), oligodendrogliomas, and gangliogliomas. Being a WHO grade I with excellent prognosis after ressective surgery with minimal or no adjunctive therapy, a prompt evaluation for surgery should be pursued in every case.

António CUCO (Lisbon, Portugal), Alexandra SANTOS, Francisca SÁ, José Paulo MONTEIRO, Nuno CANAS, Jose Carlos FERREIRA, Mrinalini HONAVAR, Pedro CABRAL, Jose CABRAL
00:00 - 00:00 #22509 - Deep brain stimulation of the anterior nuclei of the thalamus relieves basal ganglia dysfunction in monkeys with temporal lobe epilepsy.
Deep brain stimulation of the anterior nuclei of the thalamus relieves basal ganglia dysfunction in monkeys with temporal lobe epilepsy.

Background: Deep brain stimulation of the anterior nuclei of the thalamus (ANT-DBS) is effective in treating temporal lobe epilepsy (TLE). Previous studies have shown that the basal ganglia involved in seizure propagation in TLE, but the effects of ANT-DBS on the basal ganglia have not been clarified.

Methods: Chronic ANT stimulation was applied to monkeys with kainic-acid-induced TLE using a robot-assisted system. Their behavior was monitored continuously. Immunofluorescence analysis and western blotting were used to estimate the basal ganglia and the effects of ANT stimulation. 

Results: The electrodes were accurately implanted into the ANT, and the seizure frequency decreased after ANT-DBS. The expression of the D1 and D2 receptors in the putamen and caudate was higher in the ANT-DBS group than in the epilepsy (EP) model. Neuronal loss and apoptosis were less severe in the ANT-DBS group. Glutamate receptor 1 (GluR1) in the nucleus accumbens (NAc) shell increased in the EP group but decreased after ANT-DBS, and similar changes in GluR1 expression were observed in the globus pallidus internus (GPi). γ-Aminobutyric acid receptor A (GABAA-R) also decreased and glutamate decarboxylase 67 (GAD67) increased in the GPi of the EP group, whereas the reverse tendencies were observed after ANT-DBS.

Conclusion: Chronic ANT-DBS exerts neuroprotective effects on the caudate and putamen and enhances D1 and D2 receptor expression. GPi overactivation was downregulated by ANT-DBS, which enhanced the antiepileptic effect of the basal ganglia in the NHP-TLE model. Our findings provide further insight into the molecular mechanism of ANT-DBS therapy for TLE.

Guanyu ZHU (Beijing, China), Chen YINGCHUAN, Tingting DU, Jianguo ZHANG
00:00 - 00:00 #21777 - First experience of endoscopic transsphenoidal resection of hypothalamic hamartoma.
First experience of endoscopic transsphenoidal resection of hypothalamic hamartoma.

This article discusses two clinical cases of hypothalamic hamartoma (HH) which have not yet been described in any Russian or international papers, and presents the details of endoscopic resection technique with a transsphenoidal approach.

Materials and methods. Patient R., 16 years old male with a 9-year history of epileptic seizures was admitted to a hospital with a complaint of epileptic seizures every 5-6 days.  Magnetic resonance imaging (MRI) showed 1.5 х 1.4 х 1.4 cm HH, focal cortical dysplasia of the right occipital lobe. Three complex partial seizures with secondary generalization were detected during 3-days scalp video-EEG monitoring.

Patient M., 23 years old female with a 16-year history of illness was admitted to a hospital with a complaint of epileptic seizures once in a week.  MRI showed 2.44 х 2.79 х 2.68 cm HH. Two complex partial seizures with secondary generalization were detected during 4-days scalp video-EEG monitoring. In both cases surgical excision by transsphenoidal endoscopic approach was performed.

First patient was discharged in satisfactory condition on the 7th day after surgery, and didn’t have neurological deficit, electrolyte disorders (hypo- or hypernatremia, polyuria, polydipsia), visual disorders ( hemianopsia or reduced visual acuity).

Second patient in the early postoperative period had electrolyte disorders (hyponatremia), which were reversed after using hypo-osmolar solutions and mineralocorticoids. There were no visual impairments (hemianopia or visual acuity reduction). The patient was discharged in satisfactory condition on the 7th day after the surgery. In 18 months after surgery both patients are seizure free (Engel I).

Results. Clinical observation data suggest that transsphenoidal resection of HH in patients with drug-resistant epilepsy is possible.

Conclusion. Our experience shows that refractory epilepsy associated with HH can be safely and effectively treated with transsphenoidal resection of HH, with the possibility of radical cure and disease control.

Vladimir KRYLOV, Igor TRIFONOV (Moscou, Russia), Guekht ALLA, Mikhail SINKIN, Igor KAĬMOVSKIĬ, Andrey GRYGORIEV, Elena GRYGORIEVA
00:00 - 00:00 #23926 - Initial experience of an O-Arm®-based neuronavigated and Vertek®-assisted stereo-electroencephalography for drug-resistant epilepsy.
Initial experience of an O-Arm®-based neuronavigated and Vertek®-assisted stereo-electroencephalography for drug-resistant epilepsy.

Background

Evidence suggests O-Arm®-based neuronavigation assisted by a Vertek® passive articulated arm is an effective strategy for stereo-electroencephalograhy (SEEG) deep brain electrodes implantation and a valid alternative for robotic arm assisted methods.

 

Methods

We retrospectively review our center’s initial experience with O-Arm®-based neuronavigated and Vertek®-assisted sEEG (OV-SEEG).

 

Results

From May 2019 to February 2020 we performed OV-SEEG in 5 cases of adult drug-resistant epilepsy. Mean age at procedure was 39.8 years, varying from 18 to 54. All patients were female. A total of 61 leads were implanted, varying from 10 to 14 per patient. Procedure total duration averaged 24 minutes per lead. Mean intracranial trajectory length was 42.7±13.8mm. Mean trajectory error was 2.7±2.0mm. Trajectory errors were predominantly anterior lead skew (observed in 46% of trajectory errors). No correlation was observed between intracranial trajectory length and trajectory error (Person correlation coefficient of 0.104, p=0.674). Trajectory error was significantly larger in the first procedure when compared to the subsequent four (6.2±0.8mm vs 2.0±1.5mm, p<0.001). 

 

Conclusion

OV-SEEG is a valid tool for the diagnosis of drug-resistant epilepsy and our experience further suggests this is a precise and time-effective SEEG solution.

Vasco PINTO, Sérgio SOUSA, Eduardo CUNHA (Porto, Portugal), Carla SILVA, Rui RANGEL, Alfredo CALHEIROS
00:00 - 00:00 #21775 - Invasive EEG monitoring for presurgical evaluation in patients with drug resistant form of epilepsy.
Invasive EEG monitoring for presurgical evaluation in patients with drug resistant form of epilepsy.

Purpose: resective epilepsy surgery based on an invasive EEG (iEEG), performed with subdural grids or depth electrodes is considered to be the best option towards achieving seizure-free state in drug-resistant epilepsy.
Method: prospective analysis of 79 patients with drug-resistant epilepsy who underwent iEEG monitoring for the presurgical evaluation before resective surgery.
Results: 31 patients (39%) – were MRI negative, 48 (61%) – MRI positive. For all patients were made scalp EEG (sEEG). During sEEG in 55 patients (69%) seizure onset zone (SOZ) was bilateral. In 24 (31%) patients results of MRI and sEEG were not concordance. In patients with bilateral SOZ by sEEG, on iEGG we found: 6 (13%) patients had bilateral SOZ and in 49 (87%) seizure began in one side. In patients, with non-concordance MRI/scalp EEG: 3 patients (9%) didn’t have epileptiphorm activity on sEEG, but had it on iEEG; in 3 patients (9%) – sEEG was not concordance with iEEG and in 18 patients SOZ were detected only by iEEG. For all patients were made resective surgery. Outcomes were evaluated 12 months after surgery in 60 patients (76%): 32 patients (53%) became seizure free: 26 patients (43%) – Engel Ia, 2– Engel Ic, 4 – Engel Id. Eleven (18%) - Engel II: one - Engel IIa, 7 – Engel IIb, one – Engel IIc, 2 – Engel IId. The unsatisfactory result of treatment were noted at 13 patient (21%): 3 – Engel IIIa, one - Engel Iva, 9 – Engel IVb. There was no mortality in our group. The complications developed in 7 (11%) patients: 2 – had intracerebral hematoma in the area of electrode placement (without indications for surgical treatment), 4 patients had status epilepticus and one - wound liquorrhea.

Conclusion: Our results confirmed efficiency and safety of iEEG as presurgical procedure in patients with drug resistant form of epilepsy. 53 % patients become «seizure free» 12 months after surgical treatment.

Vladimir KRYLOV, Igor TRIFONOV (Moscou, Russia), Guekht ALLA, Mikhail SINKIN, Igor KAĬMOVSKIĬ
00:00 - 00:00 #23986 - Neurocognitive outcome after laser interstitial ablation for temporal lobe epilepsy, a systematic review and meta analysis.
Neurocognitive outcome after laser interstitial ablation for temporal lobe epilepsy, a systematic review and meta analysis.

Introduction:

Epilepsy is a common condition that  affects  4 to 10 per 1000 people around the world. About one third of patients with epilepsy become medically refractory. Temporal lobe epilepsy encompass the most common cause of refraction to medication

Anterior temporal lobectomy  (ATL) became the golden standard  after the land mark study by Wiebe et al was published in 2001 and showed clear evidence of superiority of surgical treatment over medical treatment alone for temporal lobe epilepsy. Minimally invasive options such as Laser interstitial laser therapy (LITT) are becoming attractive options particularly in older patients or those with multiple co-morbidities. In this systematic review and meta analysis we aim to summarize the current evidence on neurocognitive outcome after LITT.  We provide a summary estimate of memory and naming outcome. 

 

Methods:

This study was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed and OVID Midline were systematically searched for all indexed publications in the English language up to May 2020. Search was limited to human studies. The search strategy combined the following search terms: (seizure OR epilepsy OR intractable epilepsy OR intractable seizure OR mesial temporal sclerosis ) AND (laser interstitial thermal therapy OR laser-induced thermal therapy OR laser ablation OR laser interstitial thermal OR stereotactic laser OR neuroblate OR visualase OR MRIgLITT OR lesioning) AND (prognosis OR prognostic OR outcome OR follow up OR cognitive OR memory OR IQ). Additional strategies included manual searches of articles that were not included in the electronic search and screening bibliography  of collected studies. 

 

Results:

This meta-analysis included 10  studies with 181 candidates. Regardless of the side of the procedure the rate of verbal memory loss is 50% (CI 19.5%-80.5%). For left sided procedure the rate is 50.3% ( CI 28.5%-71.19%) while for right sides procedure the rare is 23.7% ( CI 6.3%-59%). For visual memory regardless of the laterality, the rate of loss is 47.4% (CI 26.8%-68.9%), while 42.9% (CI 20.6%-68.4%)  and 26.9% (CI 4.1%-75.9%) after left and right sided procedures respectively. 

For naming regardless of procedure laterality the loss rate is 17.8% (CI 7%-38.6%), while 26.5% (CI13.3-45.9%) and 22.8% ( CI 8.7%-47.6%) after left and right sided procedures respectively. 

 

Conclusion: 

Similar to open temporal lobectomy left sided LITT carries higher rate of adverse effect on neurocognitive outcome including, verbal memory, visual memory and naming. The rate of verbal memory loss is more than double after left sided procedure compared to right sided one.

 

Soha A ALOMAR (Jeddah, Saudi Arabia), Rana MOSHREF, Leena MOSHREF, Abdulrahman SABBAGH
00:00 - 00:00 #25795 - Quality of life after deep brain stimulation for epilepsy.
Quality of life after deep brain stimulation for epilepsy.

Quality of life after deep brain stimulation for epilepsy

 

Jacco Smeets, MSc1, Linda Ackermans, MD, PhD2,3,6, Ghislaine van Mastrigt, PhD4, Rob Rouhl, MD, PhD3,5, Louis Wagner, MD3,6, Sander van Kuijk, PhD7, Jeske Nelissen5, Ilse van Straaten, MD, PhD8, Kuan Kho, MD9, Francesca Snoeijen-Schouwenaars, MD, PhD6, Anne-Marthe Meppelink, MD, PhD10, Sylvia Klinkenberg, MD, PhD5,6, Kim Rijkers, MD, PhD2,3,6, Marian Majoie, MD, PhD3,5,6

 

1 Faculty of Health, Medicine and Life Sciences, Maastricht University

2 Department of Neurosurgery, Maastricht University Medical Center

3 School for Mental Health & Neuroscience, Maastricht University Medical Center

4 CAPHRI: Care and Public Health Research Institute, Maastricht University

5 Department of Neurology, Maastricht University Medical Center

6 ACE: Academic Center for Epileptology

7 Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University

   Medical Center

8 Department of Neurology, Amsterdam University Medical Center, location VUmc

9 Department of Neurosurgery, Medisch Spectrum Twente

10 SEIN: Centre of Excellence for Epilepsy and Sleep Medicine

 

Topic: epilepsy

 

Key words: epilepsy, quality of life (QoL), neuromodulation

 

Objective

Epilepsy, one of the most frequently occurring chronic neurological disorders, is associated with reduced quality of life (QoL). Epilepsy is generally treated with anti-epileptic drugs, however, 30% of epilepsy patients are medically refractory, meaning that they continue to have seizures despite adequately dosed medication. For these medically refractory patients, neuromodulation can be an option, especially when resective epilepsy surgery is not an option or did not have a significant effect. Two types of neurosurgical neuromodulation are currently accepted in The Netherlands: Deep Brain Stimulation of the Anterior Nucleus of the Thalamus (ANT-DBS) and Vagus Nerve Stimulation (VNS). VNS has been used for over 20 years in The Netherlands, DBS since 5 years. The effectiveness in terms of seizure control of DBS and VNS are quite similar. Observational studies show that DBS and VNS lead to a seizure reduction of 50% or more after 2 years in respectively 54% and 33% of patients. QoL in epilepsy heavily depends on seizure control. Few small previous studies show that neuromodulation in epilepsy increases QoL. However, there is no data on QoL changes after neuromodulation for epilepsy in the Netherlands. We therefor aim at determining the change in QoL in medically refractory epilepsy patients treated with DBS or VNS.

 

Methods

Included are all adult patients and children above 15 years of age referred for DBS or VNS to one of the three participating hospitals; Maastricht University Medical Center, Amsterdam University Medical Center and Medisch Spectrum Twente. After informed consent they receive the Quality of Life in Epilepsy Inventory (QOLIE-31) questionnaire and the EQ-5D-5L questionnaire on health-related QoL at baseline and after 3, 6, 12, 24, and 60 months.

Data on seizure frequency are derived from the patient charts where treating neurologists record seizure frequency based on seizure diaries.

 

Results

We expect that medically refractory epilepsy patients will report a better QoL after treatment with DBS or VNS. Thus, we expect a clinically relevant increase in QOLIE-31 score, which is an increase of at least 5.19 points, and an increase in EQ-5D-5L score. Treatment with DBS of VNS for epilepsy usually leads to less seizures, instead of a complete disappearance of seizures. When patients report a better QoL after DBS or VNS, even though they still report seizures, the treatment can be seen as useful. This is especially true when patients are able to participate in society again, to a greater extent than before treatment. 

 

Conclusions

Previous research shows that neuromodulation might lead to an increase in QoL in patients with medically refractory epilepsy. We expect that this prospective study will lead to similar results.

Jacco SMEETS, Linda ACKERMANS (Maastricht, The Netherlands), Ghislaine VAN MASTRIGT, Rob ROUHL, Louis WAGNER, Sander VAN KUIJK, Jeske NELISSEN, Ilse VAN STRAATEN, Kuan KHO, Francesca SNOEIJEN-SCHOUWENAARS, Anne-Marthe MEPPELINK, Sylvia KLINKENBERG, Kim RIJKERS, Marian MAJOIE
00:00 - 00:00 #21776 - Types of epileptogenic lesions in patients with drug-resistant forms of epilepsy.
Types of epileptogenic lesions in patients with drug-resistant forms of epilepsy.

Purpose: to evaluate pathomorphological types of epileptogenic lesions in patients with drug-resistant epilepsy.
Method: prospective analysis of 270 patients with drug-resistant epilepsy, who had undergone resective surgery in University Clinic of Moscow State University of Medicine and Dentistry between 01.01.2014 and 12.12.2019.

Results: According to MRI data 49 (18%) patients were MRI negative and 221 patients (82%) – MRI positive.  Data of the pathohistological results were: FCD Ia – 14 patients, FCD Ic – 37, FCD IIa – 34, FCD IIb – 3, FCD IIIa – 117, FCD IIIb – 11, FCD IIIc – 5, FCD IIId – 28, LGG – 10,  HS – 3, AVM – 4,  HH – 3, LGG+HS – 1. Based on the histology data, the main type of pathology was FCD IIIa – 117 patients (43%). In group of patients with FCD IIIa, the accompanying pathology with HS was: FCD Ia – in 12 patients, FCD Ib – 2, FCD Ic – 32, FCD IIa – 52, FCD IIb – 19. In analysis patients with MRI positive and negative forms the following results were obtained: in MRI positive forms the main type of epileptogenic lesion was FCD IIIa – 50%, in MRI negative – FCD Ic – 32% and FCD IIId – 26%. No statistically important relationship between outcomes of surgical treatment and pathomorphology was found in our study.

Conclusion: the results obtained in our series revealed that the main type of epileptogenic lesions were FCD – 43% and in MRI positive forms  - FCD IIIa – 50%, in MRI negative – FCD Ic – 32% and FCD IIId – 26%.

Vladimir KRYLOV, Igor TRIFONOV (Moscou, Russia), Guekht ALLA, Anna LEBEDEVA, Mikhail SINKIN, Igor KAĬMOVSKIĬ
00:00 - 00:00 #21774 - VNS - second chance after failed resective epilepsy surgery.
VNS - second chance after failed resective epilepsy surgery.

Purpose: to evaluate the effectiveness of  vagus nerve stimulation (VNS) after failed resective epilepsy surgery.

Method: All the patients who had persistent seizures after resective surgery who subsequently underwent VNS placement at our institution from 2016 to 2019 were included in the study. Twenty-one consecutive patient (14 women and 7 men) were enrolled and followed for the outcome.  Seizure outcomes were based on modified Engel classification (I: seizure-free/rare simple partial seizures; II: >90% seizure reduction (SR), III: 50-90% SR, IV: <50% SR; classes I to III (>50% SR)=favorable outcome).

Results:  The patient's average year old was – 31,15, the duration of the epilepsy was 17,6 years,

Temporal lobe epilepsy was diagnosed in 5 patients, temporal plus (temporal+frontal) - 8 patients, 6 - patients had bilateral lesions and 2 – multifocal. All patients in this group previously had resective surgery: 20 patients -  anterior medial temporal lobectomy (AMTLE) and one patient – AMTLE plus exTLE.  10 (47%) patients were evaluated 12 months after surgery: 2 (20%) had a modified Engel class I outcome, 4 (40%) had class II, 4 (40%) had class III. Data of the pathohistology results were: FCD Ia – 2, FCD Ic – 4, FCD IIa – 1, FCD IIIa-10, FCD IIId – 4. There was no surgical mortality. Side effects of VNS were detected: hoarseness -10 (47%) patients, cough during stimulation – 3 (14%).

Conclusion: VNS therapy in patients who have failed surgical therapies only provides improvement in seizure control in all 100% patients in our series. We confirmed its efficacy and safety: 20 % patients become «seizure free», 40% - had >90% seizure reduction and 40% - 50-90% SR 12 months after surgical treatment.

Vladimir KRYLOV, Igor TRIFONOV (Moscou, Russia), Guekht ALLA, Mikhail SINKIN, Igor KAĬMOVSKIĬ
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00:00 - 00:00 #23952 - "e;Utility of volume of tissue activated-modeling for clinical stimulation parameters in DBS patients.
"e;Utility of volume of tissue activated-modeling for clinical stimulation parameters in DBS patients.

Introduction: Deep brain stimulation (DBS) is an established treatment for a number of movement disorders, including Parkinson's disease (PD), essential tremor (ET), and dystonia. DBS surgery is widely recognized as depending essentially on precision for clinical efficacy. There is an inherent difficulty in accurately determining electrode positions post-operatively due to factors such as brain shift and co-registration limitations. Novel methods,
 for visualizing post-operative results on individual- and (importantly) on group-level, include the open-source Lead-DBS suit which uses a custom image-processing pipeline to normalize individual patient images to MNI-space, thereby enabling accurate anatomical electrode visualization. Here, we build onto what other groups have indicated: the potential for using 3D neuro-modeling as a guide to post-operative stimulator programming and anatomical analysis.

Method: 20 patients with 1-2 electrodes each (amounting to 30 electrodes) were included in the analysis. These were a subset in a cohort of patients treated with DBS at Sahlgrenska University Hospital, Sweden, with a diagnosis of either PD or ET. The Lead-DBS pipeline consists of (1) co-registration of pre-operative and post-operative images, (2) normalization to MNI-space, (3) registration of electrode positions, (4) VTA (volume of tissue activated) simulation using clinically stable stimulator parameters (1 year post-op) and finally (5) statistical analysis.

Results: Of the 20 patients included, 11 had PD and 9 had ET. Median distance to the closest voxel within the target structure (STN/VIM) was 1.64, 0.38, 0.53 and 1.11 mm for contacts 0-3 (ventral to dorsal) respectively. Distances smaller than 1 mm were dee med within the target structure. With this definition, 76 of 120 contacts (63,3%) resided within the target structure. Visual 2- and 3-dimensional evaluation revealed a clear difference between the STN and VIM leads: the former most often incorporated either contact 1 (40.0%), 2 (35.0%) or both (60.0%) whereas the latter was most often located above the active contacts suggesting that, at least in part, white matter tracts in the subthalamus may be stimulated in these patients. Indeed, contact 3 was the closest on average (median 0.12 mm to nearest voxel within the VIM). The median VTA/target overlap was 13.9 mm2. Approximately a third (median 28%) of the VTA was occupied by the motor subdivision of the STN in patients with PD.

Conclusion: Neuroimaging-based visual and statistical analysis provides useful data. The present small-sample study suggests utility in facilitating patient-specific programming and in patient-to-patient anatomical comparison.

Linus KOESTER (Gothenburg, Sweden), Thomas SKOGLUND, Johan LJUNQVIST
00:00 - 00:00 #23886 - Assessing the accuracy of intraoperative 3D fluoroscopy to predict correct electrode position during deep brain stimulation surgery.
Assessing the accuracy of intraoperative 3D fluoroscopy to predict correct electrode position during deep brain stimulation surgery.

Background/Goal

The effectiveness of deep brain stimulation (DBS) surgery is critically dependent on accurate electrode position. Microelectode recording and microstimulation are invaluable tools to fine-tune the location to target. However, an anatomical post-implantation confirmation of the true electrode position is required to exclude unwanted shifts during definitive electrode implantation. Intraoperative confirmation of real electrode position is usually performed with lateral 2D fluoroscopy or intraoperative CT/MRI, methods which lack high accuracy or easy accessibility, respectively. The goal of the current work is to assesses the accuracy of intraoperative 3D fluoroscopy (3DF), a quick, inexpensive, radiation-light method, in estimating the final electrode location.

 

Methods 

This study included 28 patients submitted to DBS surgery, and a total of 52 electrodes implanted (24 Parkinson’s disease patients implanted bilaterally in the subthalamic nucleus and 4 chronic pain patients implanted in the left ventral posterolateral thalamic nucleus). All patients underwent intraoperative fluoroscopic imaging acquisition and 3D reconstruction with a C-arm system (Ziehm) after implantation of the definitive electrodes. The acquired 3DF images and 48h post-operative CT images were fused with preoperative MRI using the StealthStation S8 system (Medtronic). The Euclidean coordinates of the electrode tip in the 3DF and CT images were extracted and used to calculate their distance. Radiation exposure from 3D fluoroscopy and post-operative CT was also compared.

 

Results/Discussion

The difference between the electrode position estimated by 3DF and CT was 0.90 mm (p>0.05). The brain shift effect on final electrode position was minimal, possibly because deeper structures are less affected by brain shift. Total radiation exposure was significantly lower with 3D fluoroscopy compared to CT (p<0.05).

 

Conclusion

Intraoperative 3D fluoroscopy accurately predicts final lead position after DBS surgery. We believe its advantages - less expensive, less radiation exposure, opportunity to correct electrode position during the same operative period, shorter operative time and  earlier hospital discharge -  render it a valuable tool to replace post-operative CT imaging.

Manuel PINTO (Porto, Portugal), Clara CHAMADOIRA, Rui VAZ
00:00 - 00:00 #23909 - BrainCubes - MRI histology of the human reward system.
BrainCubes - MRI histology of the human reward system.

Objective: Bridging the gap between the microstructural scale, accessible via optical techniques, and the millimeter scale, observable by modern whole brain imaging techniques, is one of the major challenges of modern neuroscience. Microscopy techniques offer rich detail, however, massive tracing of individual neuronal structures (e.g. sub-bundles) over large distances at this moment is impossible. Full brain imaging techniques like diffusion-weighted MRT can give the full view, but due to the coarse resolution the information content is more of statistical nature and tractographic reconstructions provide rather a sketch than the true picture of whole brain connectivity. In this project we want to contribute to fill this gap by comparing high resolution MR-imaging (including tractography) and histological investigations of cadaver specimens by  building a high-throughput MRT scanning pipeline and applying it in the same coordinate system. Our focus is the human reward system, especially the limbic midbrain.  

 

Methods: Fixed postmortem human brains are cut regularly into cubes such that they can be scanned by small-animal MR-scanners at resolutions of 50µm to 200µm. Here we propose preliminary data acquired at a Bruker Biospec 7T. The specimen (midbrain) was cut to an approx. 60mm, 40mm, 40mm cube, embedded in phosphate buffered saline and scanned with a 3D spinecho scan at a resolution of 200 micron in-plane and slice-thickness of 300 micron. The b-value was chosen to be 4000 s/mm² with 50 gradient directions. The probe was acquired in three slabs using partial excitation and afterwards digitally stitched to achieve full coverage. The scantime of one slab was around 21 hours. For further preprocessing a denoising (1) and Gibbs-artifact correction (2) was applied. Simple tensor analysis revealed diffusion coefficient of around 0.2 µm²/ms and fractional anisotropy values of around 0.3 in highly anisotropic areas, which is sufficient for tractographic approaches. We applied global tractography (3) on the dataset and rendered directional streamline densities, which are shown in the accompanying figure at a closeup around the nucleus ruber. 

 

Results: In a first example specimen we were able to successfully perform fiber tractography at high resolution in a postmortem brain. Comparison between MR-imaging and histological staining of the specimen allowed to discover local topographical anatomy in the human limbic midbrain. Especially the ventral tegmental area (VTA), the retroflex fascicle of Meynert, the superolateral (sl) and inferomedial medial (im) forebrain bundles (MFB) could be differentiated at an unprecedented detail. 

 

Conclusion: The proposed technique might help to understand local connectivity and bridge the gap to classical anatomical methods like histologica workup and staining. It appears to be a valuable adjunct to interpreting the long distance depiction of the human brain’s connectome.

 

References:

  1. Lemberskiy, Gregory, and Dmitry S. Novikov. 2019. “Achieving Sub-Mm Clinical Diffusion MRI Resolution by Removing Noise during Reconstruction Using Random Matrix Theory.” In ISMRM Proceedings 2019.

  2. Kellner, E., B. Dhital, V.G. Kiselev, and M. Reisert. 2015. “Gibbs-Ringing Artifact Removal Based on Local Subvoxel-Shifts.” Magnetic Resonance in Medicine, n/a-n/a. https://doi.org/10.1002/mrm.26054.

  3. Reisert, Marco, Irina Mader, Constantin Anastasopoulos, Matthias Weigel, Susanne Schnell, and Valerij Kiselev. 2011. “Global Fiber Reconstruction Becomes Practical.” Neuroimage 54 (2): 955–962.

Marco REISERT (Freiburg, Germany), Shi Jia TEO, Andrea WESSOLLECK, Máté DÖBRÖSSY, Andreas VLACHOS, Volker Arnd COENEN
00:00 - 00:00 #24000 - C1C2 puncture under FP navigation: a safe and useful procedure.
C1C2 puncture under FP navigation: a safe and useful procedure.

Background and purpose: The C1C2 intrathecal puncture is performed when lumbar puncture is not feasible or usable. Since cervical vertebra are adjacent to the spinal cord and blood vessels, the puncture risk is high and requires high accuracy. We present the FP navigation method with preoperative planning and various indications.

Material and method. The goal of preoperative planning was to accurately localize the target, the high risk structures and an identifiable fixed key point during the planning and the procedure. The CT scan was the most accurate method.

Preoperative imagery allowed to localize VA (vertebral artery) and PICA (postero inferior cerebellar artery) which normally were not located in the C1C2 posterior space.

The key point was the localization of the F point (Peckham “flare“ point), an osseous landmark which represents the triangular “flaring” of the posterior C1 arch at its junction with the anterior arch, corresponding to the VA groove. FP was 0.2 _ 0.5 mm posterior to the dorsal spinal cord margin (Peckham 2018).

The target was located in the high part of the C1C2 space, at the middle between the perpendicular to the F point and the spinous line. Usual navigation procedure was performed in relationship to FP even if the cervical junction position was different.

Results. C1C2 punctures were performed for various procedures, notably to implant intrathecal catheters connected to a subcutaneous pump in pain and spasticity treatment.

Discussion: C1C2 puncture with FP neuronavigation was a safe procedure. Posterior spinal cord piamater and posterior veinous plexus were avoided thanks to an accurate procedure. Development of intrathecal cervical catheter was still ongoing.

Hayat BELAÏD (PARIS), Jean-Baptiste THIÉBAUT, Vincent D'HARDEMARE, Pierre BOURDILLON, Alister ROGERS, Philippe AUTRET, Claire-Marie RANGON, Catherine VIART
00:00 - 00:00 #26262 - DBviS – A visualization tool of DBS research data.
DBviS – A visualization tool of DBS research data.

The most common method for estimating the spatial effect of deep brain stimulation (DBS) is by using electric field simulation. The outputs can be used to evaluate a patient specific response but also on a group level to create probabilistic improvement or side disorder maps for intuitive visualization of the result and possible prediction of new data. Further, several theoretical studies are available showing the impact of different parameters in the simulations. To spread information of the simulation technology and study results we are implementing a visualization tool, DBviS, where the user can look through datasets from studies and compare with own results.

DBviS is a software based on 3DSlicer (https://www.slicer.org/) for visualization of DBS research data. It utilizes all the default 3DSlicer functions for visualization and measurements. In this platform, we have gathered data from several different types of studies. One is an anatomical normalization study of 19 patients, which generated an atlas of substructures in Thalamus and the subthalamic area [1]. Other studies include probabilistic stimulation maps for clinical improvement or side effects in different diseases (Parkinson’s disease, essential tremor, Tourette, OCD etc.) [2, 3]. Further, information from theoretical studies is included to visualize the effect of different modelling choices, like including the brain tissue anisotropy [4, 5]. Other examples are comparisons of the stimulation effect when using microelectrode recording with the implanted DBS lead [6] and electric field simulation related to tractography reconstruction [5].

The plan for future development is that highly skilled users can transform their own simulations to the different scenes and compare their clinical result with published data. This can also be supported by using our other apps, ELMA (based on MATLAB, The Mathworks Inc., USA) for brain conductivity modelling, and DBSim (based on COMSOL Multiphysics, Sweden) for electric field simulations [7]. These are stand-alone applications that can be downloaded for free from the webpage of the Neuroengineering group at Linköping University (https://liu.se/en/research/neuroengineering-lab) for performing patient-specific electric field simulations.

*Research is financially supported by the Swedish Foundation for Strategic Research (BD15-0032)

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

[2] A. Shah et al., Stimulation maps: visualization of results of quantitative intraoperative testing for deep brain stimulation surgery, Medical & Biological Engineering & Computing 58(4) (2020) 771-784.

[3] R. Stenmark Persson et al., Deep Brain Stimulation of caudal Zona Incerta for Parkinson’s disease; one-year follow-up and electric field simulations, Submitted  (2021).

[4] T. Nordin et al., The Effect of Anisotropy on the Impedance and Electric Field Distribution in Deep Brain Stimulation, in: T. Jarm, A. Cvetkoska, S. Mahnič-Kalamiza, D. Miklavcic (Eds.) 8th European Medical and Biological Engineering Conference, Springer International Publishing, Cham, 2021, pp. 1069-1077.

[5] T. Nordin et al., White matter tracing combined with electric field simulation - A patient-specific approach for deep brain stimulation, Neuroimage Clin 24 (2019) 102026.

[6] F. Alonso et al., Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems-A Simulation Study, Brain sciences 8(2):28 (2018).

[7] J.D. Johansson et al., Patient-Specific Simulations of Deep Brain Stimulation Electric Field with Aid of In-house Software ELMA, 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), IEEE, Berlin, Germany, 2019, pp. 5212-5216.

Teresa NORDIN (Linköping, Sweden), Fabiola ALONSO, Dorian VOGEL, Johannes JOHANSSON, Simone HEMM, Karin WÅRDELL
00:00 - 00:00 #23936 - Does cable-bound stimulation and recording of neuronal activity affect rat`s wellbeing?
Does cable-bound stimulation and recording of neuronal activity affect rat`s wellbeing?

Chronic stimulation and recording of neuronal activity in different rodent models for movement disorders and neuropsychiatric disturbances is carried out via a cable with a swivel that allows relative free movement of the rat without twisting of the cable. Nevertheless, it is still semi-restraining and may therefore impose stress and confound to the animal.

We here subcutaneously implanted transmitters for contactless recording of heart rate and activity of rats during cable-bound stimulation and recording of neuronal activity, which was compared to the perioperative period of intracranial electrode implantation.

Male Sprague Dawley rats (n=8, 180 g) were implanted with electrodes in the subthalamic nucleus (STN) under general anesthesia with local anesthesia and perioperative pain management with non-steroidal anti-inflammatory drugs. Two weeks after the electrode implantation the threshold for stimulation-induced side effects were determined in each rat. Thereafter, a five-day sham-stimulation period started with only the cable connected to the rat’s electrode head stage but no current applied.  Finally, the cables were disconnected and rats were allowed to move freely in their cages for another two days. In addition to continuous monitoring of heart rate and activity via a subcutaneously implanted transmitter, the rats’ well-being and general health condition were monitored by daily body weight measures and clinical scoring.

Clinical scoring and weight measures during the course of the study did not show any substantial alterations. Right after electrode implantation, heart rate was elevated, however, without reaching the level of significance. Only the first two days of cable-bound sham-stimulation resulted in decreased locomotor activity (p<0.05) as compared to pre- and post-stimulation values, whereas heart rate measures were not affected.

Electrode implantation and semi-restraint caused by tethered electrodes had only a transient and mild effect on rat`s activity. Since so far, even advanced and fully implantable devices do not allow flexible switching between recording and electric stimulation with different settings, as e.g., needed for adaptive “closed loop” stimulation, our stimulation/recording setup may be valid and ethically justifiable in neuroscience rat models.

Laura WASSERMANN, Ann-Kristin RIEDESEL, Simeon HELGERS, Mesbah ALAM, Christine HÄGER, Joachim KRAUSS, Kerstin SCHWABE (Hannover, Germany)
00:00 - 00:00 #26087 - Effect of the Trajectory Angle on Idiopathic Delayed Onset Edema in DBS.
Effect of the Trajectory Angle on Idiopathic Delayed Onset Edema in DBS.

Background: Symptomatic idiopathic delayed onset edema (IDE) is a complication which can occur after DBS electrode placement. Due to the potential duration and severity of neurological deficits, it can cause a heavy burden on the patient. The location of the cortical area used for electrode entrance could be related to the development of symptomatic IDE.

Objective: To evaluate possible influence of cortical entry of DBS electrodes on symptomatic IDE occurrence in patients from 2014 until 2021.

Methods: DBS electrode cortical entry in Brodmann areas 6 (divided in pre-supplementary motor area and supplementary motor area, pre-SMA and SMA) and 8. Symptomatic IDE occurred in ten Parkinson's disease (PD) patients, three tremor patients and one pain patient (IDE group, representing 27 trajectories). The cortical entry and edema volume of the trajectories were determined. A group of PD patients after DBS without IDE (non-IDE, 243 trajectories in 122 patients) was used for comparison. Edema volume was measured using CT, Brodmann areas were determined using MRI.

Results: Average edema volume was 9.4 cm³ and 11.8 cm³ for right and left trajectories, respectively. In the IDE group, 74% (20/27) of the electrodes entered the brain in Brodmann area 6 (52% pre-SMA, 22% SMA) and 26% (7/27) in area 8. In the non-IDE group 40% (97/243) of the electrodes had area 6  as entry (30% pre-SMA, 10% SMA) and 60% entered the brain through area 8 (146/243).

Conclusion: In the IDE group, Brodmann area 6 was used more often as DBS entry compared to the non-IDE group. Possibly this area is more susceptible for the development of symptomatic IDE due to its neuronal architecture and its contributions in linking cognition to action. The current analysis will be extended with non-IDE tremor and pain patients that underwent DBS. Adding these patients for analyses could provide more insight in the relation between the occurrence of symptomatic IDE, cortical entry, diagnosis and DBS target.

Patrick O'DONNELL (Amsterdam, The Netherlands), Pepijn VAN DEN MUNCKHOF, Catherine M.k.e DE CUBA, Rob M.a. DE BIE, P. Richard SCHUURMAN, Maarten BOT
00:00 - 00:00 #23904 - Expanding applicability of intraoperative cone beam (O-arm) CT in stereotactic neurosurgery.
Expanding applicability of intraoperative cone beam (O-arm) CT in stereotactic neurosurgery.

Background: Implementation of intraoperative cone beam CT (‘the O-arm system’) for navigation in neurosurgery is expanding. The O-arm is known to enable navigation-guided screw placement in spine surgery and is also increasingly being applied in intracranial procedures, such as deep brain stimulation. In frame-based stereotactic procedures, it has  more potential applications.
Objective: To describe the technical details and advantages of the O-arm in common stereotactic neurosurgical procedures.
Methods: Frame-based stereotaxy using the O-arm was applied in four different neurosurgical procedures: ventricular catheter placement for hydrocephalus in idiopathic intracranial hypertension, catheter placement for cystic suprasellar tumor drainage, pediatric supratentorial, and infratentorial tumor biopsy.
Results: The O-arm enabled fast acquisition, high stereotactic registration accuracy, and direct intraoperative evaluation of probe location.

Conclusion: The O-arm system can be conveniently implemented for both supra- and infratentorial frame-based stereotactic procedures, as well as catheter placement and tumor biopsies, in both pediatric and adult cases, further expanding its applicability in neurosurgery.

Hisse ARNTS (Amsterdam, The Netherlands), Rick SCHUURMAN, Jantien HOOGMOED, Pepijn VAN DEN MUNCKHOF, Maarten BOT
00:00 - 00:00 #26283 - Frameless stereotactic brain biopsy: A prospective study on robot‐assisted brain biopsies performed on 32 patients by using the RONNA G4 system.
Frameless stereotactic brain biopsy: A prospective study on robot‐assisted brain biopsies performed on 32 patients by using the RONNA G4 system.

Aims: We present a novel robotic neuronavigation system, RONNA G4, used for precise preoperative planning and frameless neuronavigation. The system has been developed by a research group from the University of Zagreb and a team of neurosurgeons from the University Hospital Dubrava, Zagreb, Croatia. The aim of this study is to provide a comprehensive error measurement analysis of the system used for brain biopsy procedures.

Methods: Frameless stereotactic robot-assisted biopsies were performed on thirty-two consecutive patients. Post-operative computerized tomography (CT) and magnetic resonance imaging (MRI) scans were assessed to precisely measure the target point error (TPE) and the entry point error (EPE). All clinical data, the learning curve, and the influence of the trajectory angle on targeting accuracy were measured and evaluated.

Results: The application accuracy of the RONNA system for the TPE was 1.95 ± 1.11 mm, while for the EPE was 1.42 ± 0.74 mm. In our cohort, only one pathohistological diagnosis was inconclusive; thus, the total diagnostic yield was 96.87%. Linear regression showed statistical significance between the TPE and EPE and the angle of the trajectory on the bone (p=0.026, p=0.010). The learning curve analysis showed statistical significance, especially for one neurosurgeon who performed most of the procedures (p<0.001). The operation duration was significantly reduced over time, as shown by comparing the first ten procedures with the last ten procedures (p=0.0007).

Conclusion: According to the results of our comprehensive analysis of TPE and EPE, the RONNA G4 robotic system is a precise and highly accurate autonomous neurosurgical assistant in performing frameless brain biopsies. Greater trajectory angles were associated with larger EPE and TPE.

Domagoj DLAKA (Zagreb, Croatia), Švaco MARKO, Darko CHUDY, Jerbić BOJAN, Šekoranja BOJAN, Šuligoj FILIP, Vidaković JOSIP, Dominik ROMIC, Marina RAGUŽ
00:00 - 00:00 #23337 - MRI 3T Multi-channel Radiofrequency Safety Assessment of DBS Systems.
MRI 3T Multi-channel Radiofrequency Safety Assessment of DBS Systems.

Introduction: More than 60% of patients implanted with a deep brain stimulation (DBS) system need an MRI within 10 years after implantation [1]. Furthermore, MRI is an important research tool to develop better understanding of DBS therapy, to improve outcome in existing indications and expand therapy with new indications.

1.5T and 3T MRI scanners comprise 80+% of installed base, with the share of 3T scanners increasing [2]. ISO/TS 10974:2018 “Assessment of the Safety of MRI for Patients with an AIMD” provides detailed guidelines for hazards that can occur with 1.5T MR scanners; however, considerations of hazards for 3T scanners are not currently in scope of the test specification.

Primary challenges at 3T compared to 1.5T stem from the diversity of MRI radiofrequency (RF) fields that can be generated by modern 3T MRI scanners. Traditional circularly-polarized quadrature excitation (CP) may fail to produce uniform image contrast at 3T (128MHz) due to electromagnetic (EM) wave-interference effects, therefore most modern 3T MRI scanners employ radiofrequency (RF) shimming with two-channel whole-body transmit coils (MC-2) to alleviate these artifacts [3]. Impact of MC-2 on RF-field distributions on AIMD need to be accurately evaluated at 3T for evaluation of hazards related to RF-fields.

 

Problem Statement: RF-field distribution and excitation mode optimization procedure may vary depending on the imaging location, subject size, transmit coil design, proprietary algorithms employed by different MR vendors, and future developments in the MRI technology. Therefore, from a neurostimulator manufacturer standpoint, entire RF-field shim space needs to be thoroughly analyzed for both RF lead heating and RF induced voltage levels. If not performed properly, risk of device malfunction, unintended tissue stimulation and risk of thermal injury due to interactions with AIMD and RF-field may be underestimated.

 

Discussion: Two different MC-2 RF excitations that produce similar magnetic-field uniformity may demonstrate distinct E-field distributions (Figure 1). Either one of these two shim solutions might be employed by an MRI scanner depending on vendor-specific 3T shim algorithm selection. Tangential E-field distributions of a DBS system implanted within the annotated region of Figure 1 can be significantly different (Figure 2), and thereby causing more than 10-times higher RF lead heating and 3-times higher RF induced voltage due to Shim A excitation compared to Shim B.

 

Conclusion:  RF shimming introduces complexity to 3T MRI safety assessments.  This type of RF excitation needs to be considered carefully to appropriately evaluate potential RF effects in safety assessments.

 

References:

  1. Falowski et al. Stereotact Func Neurosurg 2016;94:147-153.

  2. IMV Benchmark Report, 2017 MR.

  3. Harvey PR, Hoogeveen RM. Multi transmit parallel RF transmission technology. Philips Healthcare. 2009.

M. Arcan ERTURK, Mark CONROY, Thomas BRIONNE (Tolochenaz, Switzerland), Jacob CHATTERTON, S. Riki BANERJEE
00:00 - 00:00 #26133 - Optical guidance tool for frameless brain tumour needle biopsy.
Optical guidance tool for frameless brain tumour needle biopsy.

Background

Needle brain tumour biopsies are performed to tailor therapy when resection is not an option. Secondary outcomes of the procedure include inconclusive results (5-7% of cases [1-2]), and haemorrhage (5% of cases [2]). 5 aminolaevulinic acid (5-ALA) induced fluorescence has previously been suggested for decreasing the negative biopsy rate in frame-based biopsies [3]. The method demonstrates that fluorescence can indicate tumour tissue and, if combined with laser Doppler flowmetry (LDF), also act as a “vessel alarm” [4]. As a next step the method is transferred to frameless navigation, integrating an updated fluorescence and LDF system with an optical probe into the navigation procedure. The aim of the study is to present the first clinical measurements during brain tumour needle biopsy using the new concept.

 

Methods

The FluoRa 1.0 system [5] consists of four parts: a commercial LDF module, an inhouse fluorescence module, a LabVIEW (National Instruments, USA) software, and an optical probe. The LDF module (PF 5000, 780 nm, Perimed AB, SWE) records tissue perfusion (i.e., microcirculation [6]). The fluorescence module emits blue laser light (405 nm, Z-laser GmbH, DE) that is collected (AVASpect-ULS2048L-EVO, Avantes BV, NL) after tissue interaction. All signals are presented in real time in the FluoRa software, simultaneously with a ratio that illustrates the relation between tissue autofluorescence at 510 nm and fluorescence at 635 nm [7].

The optical probe consists of one sending and one receiving fibre for the fluorescence and LDF module, respectively. Each source fibre transports light from one laser to the tissue, and each detector fibre transports backscattered light to the corresponding module for signal digitization. The outer dimensions of the probe were adapted to the biopsy needle (Passive Biopsy Needle, Medtronic, Inc., USA). To allow for forward-looking measurements of the tissue, the needle was modified with an aperture at the tip. The probe was sterilized using the STERRAD® protocol. The system was tested experimentally and, following risk analysis, approved for use by Linköping University Hospital.

A patient with suspected malignant brain tumour referred for needle biopsy was included in the study (written informed consent, EPM-2020-01404). Preoperative MR images (T1-Gd, 3T Skyra, Siemens Healthcare, DE) were used for planning and optical guidance with the StealthStation® (S8, Medtronic, Inc., USA). An oral dose of 5-ALA (20 mg/kg) was administered 4 hours before intraoperative measurements. The optical probe was inserted in the modified needle. Stepwise insertion along two planned trajectories was combined with LDF (5-10 s) and fluorescence (3x200 ms) measurements presented in real time. When in target position, the probe was removed from the outer part of the needle and the inner biopsy needle was inserted. Biopsies were taken at -6, -3 and 0 mm according to standard clinical protocol.

 

Results and Discussion

Fluorescence and LDF were recorded in 79 points. A temporary increase in perfusion was observed at 2 sites. A fluorescence peak was visible in 15 of the 79 points. Biopsy sites coincided with fluorescence peaks. Intraoperative histopathology confirmed presence of malignant tumour tissue from the marginal zone. The postoperative diagnosis on frozen tissue samples confirmed glioblastoma WHO grade IV IDH wild-type.

Further clinical evaluation is needed to investigate the benefits of the integrated optical probe system for frameless needle biopsies, as well as for resections. The next step is to link the optical measurements to different MRI protocols, including tractography, microdiffusion and 3D visualization of results.

In conclusion, this clinical case illustrates the feasibility of real time identification of malignant tumour tissue through optical guidance, with both fluorescence and LDF, in frameless brain needle biopsy.

The study was financially supported by the Swedish Foundation for Strategic Research (RMX18-0056).

 

Disclosure

JR and KW are inventors of related patents and hold shares in FluoLink AB, Sweden.

 

References

[1] Kesserwan MA, et al, Surg Neurol Int. 2021.

[2] Livermore LJ, et al, Br J Neurosurg. 2014.

[3] Richter JCO, et al, Operative Neurosurgery, Accepted, 2021.

[4] Zsigmond P, et al, Stereotact Func Neurosurg, 2018.

[5] Klint E, et al, 43rd IEEE EMBC, Submitted, 2021.

[6] Wårdell K, et al, Operative Neurosurgery, 2013.

[7] Haj-Hosseini N, et al, Laser in Surgery and Medicine, 2010.

Elisabeth KLINT (Linköping, Sweden), Johan RICHTER, Karin WÅRDELL
00:00 - 00:00 #26260 - Orientation detection of deep brain stimulation electrodes based on neuronavigation with an embedded magnetic sensor.
Orientation detection of deep brain stimulation electrodes based on neuronavigation with an embedded magnetic sensor.

Background: Recently, directional leads (D-leads) have been introduced. The horizontal current steering allows an adaptation of the stimulated volume leading to a reduction of induced side effects. Indeed, the identification of the orientation of the DBS lead and of the position of the different lead segments within the anatomical structures represents an important basis for stimulation parameter tuning. Therefore, the control of their orientation during surgery gains in importance compared to conventional DBS leads.

While the positioning of DBS leads using electromagnetic tracking (EMT) has recently been investigated [1][4], their orientation is still not completely handled. Orientation detection currently relies on postoperative electrode artefact analysis on Computed Tomography (CT) images [3] implying additional radiation dose and remaining time consuming. It has been reported that D-leads can exhibit large deviations from the intended implantation direction [2]. Previous published results with an EMT system under development have shown a mean absolute error (MAE) of 2.46° on the angle of interest (yaw angle) for D-leads detection [5]. The aim of the present work is to evaluate the accuracy of angle detection with a 3D magnetic sensor providing a higher sensitivity than the one reported in [5].

Materials and Methods: A magnetic field generator, which consists of a single coil (3B Scientific GmbH, Germany) arranged sequentially in three orientations, was used to create field changes below 100 uT within the tracking volume. In addition, a single 3D magnetic field sensor (MMC5603NJ, MEMSIC Inc. USA, sensitivity of 6.25 nT per LSB) was integrated at the tip of a carbon tube mimicking the DBS electrode (Fig. A). Due to prototyping constraints, the tip was designed with a 2.5 mm diameter. The tracking algorithm was based on Kuipers’ resolution method. The outcomes of our algorithm were compared to the stereotactic Leksell system (Elekta, Sweden) used as reference to control the rotation over each axis. Each rotation was measured separately with different measuring steps and ranges (Roll rotation: 0-90° by 5° step; Pitch rotation: 0-110° by 10° step; Yaw rotation: 0-280° by 20° step) due to the stereotactic arc dimension.

Results: The rotations over roll, pitch and yaw showed a MAE of respectively 0.24°, 0.86°, and 1.66° (Fig. B) (Root mean square error (RMSE) of 0.29°, 0.99° and 1.85°). The measurement uncertainties varied according to the angles from 0.5° for roll angle to 2° for yaw angle, which corresponds to the uncertainties introduced while reading the true angles on the arc’s graduation.

Discussion and outlook: The results obtained are similar to those obtained through post-CT artefact analysis, which have been reported to be 1.5° [3] (RMSE). In comparison to the previous results, the use of a sensor with higher sensitivity leads to an improvement on the angular resolution. In parallel with the position tracking already put forward in previous works [4], the neuronavigation based on an embedded 3D magnetic sensor could provide a full tracking of DBS leads. The robustness of the system, especially to magnetic perturbations, is under investigation, and the performance obtained in presence of a stereotactic system are encouraging. This system should provide a new approach to intra-operative verification of the DBS electrode orientation and relevant information to tune the stimulation parameters accordingly. Considering the dimensions of the presented magnetic sensor (0.8 x 0.8 x 0.4 mm), further miniaturization steps will allow us to reach the dimension of DBS electrodes (1.27 - 1.4 mm diameter).

References:

[1] Burchiel et al. Verification of the Deep Brain Stimulation Electrode Position Using Intraoperative Electromagnetic Localization. Stereotact Funct Neurosurg. 2020
[2] Dembek et al. Directional DBS leads show large deviations from their intended implantation orientation. Parkinsonism Relat Disord. 2019
[3] Hellerbach et al. DiODe: Directional Orientation Detection of Segmented Deep Brain Stimulation Leads: A Sequential Algorithm Based on CT Imaging. Stereotact Funct Neurosurg. 2018
[4] Quirin, et al. Towards Tracking of Deep Brain Stimulation Electrodes Using an Integrated Magnetometer. Sensors 2021
[5] Vergne et al. Tracking the Orientation of Deep Brain Stimulation Electrodes Using an Embedded Magnetic Sensor. 10th IEEE EMBS Conference on Neural Engineering, online, 2021

Celine VERGNE (Muttenz, Switzerland), Morgan MADEC, Joris PASCAL, Simone HEMM
00:00 - 00:00 #23971 - Perivascular spaces as a potential risk marker for intracerebral hemorrhage in DBS surgery – a retrospective investigation.
Perivascular spaces as a potential risk marker for intracerebral hemorrhage in DBS surgery – a retrospective investigation.

Objective: Intracerebral hemorrhage (ICH) poses the most devastating complication of DBS surgery and is associated with higher age and the use of microelectrode recording. In the preOP MRI we encountered wide perivascular spaces (PVS) in cases with ICH during electrode implantation at our department. This aspect has not been described in the literature before. However, PVS enlargement is associated with occurrence of spontaneous intracerebral hemorrhage (Raposo et al. 2019, Duperron et al. 2019) and may reflect a general vascular vulnerability. Here we aimed to explore the role of enlarged PVS as a risk indicator for ICH during DBS electrode implantation.

Methods: The data of 330 consecutive patients (01/2013-11/2019) were analysed. Preoperative imaging includes a 3T T1-MPRAGE and T2-Space sequence with 1mm isotropic resolution. Unsuitable MR images were excluded (movement artefacts, <3 Tesla, WMH of non-vascular origin e.g. multiple sclerosis, preexisting DBS, tumor resection), resulting in 242 MRIs. Prior to PVS burden quantification, T1 und T2 images were coregistered using SPM12 and the T1 image was segmented using SPM12’s segmentation algorithm in WM/GM/CSF. For normalization of the T2 contrast a smooth T2 CSF reference image was computed by 1) masking out the all signal non-CSF in the T2 image (using SPM’s CSF-T1 segmentation), and 2) extending the CSF signal to adjacent regions by a broad Gaussian smooth. The raw T2 is then divided by this reference image to obtain comparable contrasts. PVS burden was computed by the commonly used Frangi-filter for tubular structures (smin=0,4mm, smax=2,0mm, scale ratio=2, α=0,1, β=1, c=0,01) on the normalised T2 (Frangi et al. 1998). All responses in non-WM were excluded. Finally, PVS index was computed by a simple summation of all non-negative filter responses within white matter.

A score was set up representing the most invasive implantation method applied in each patient: intraoperative clinical testing with stimulation via blunt tip probe (1) or via macroelectrodes with retracted microelectrodes (2); microelectrode recording (3). Metric data (age and PVS index) were dichotomised using the median.

The Fisher exact test was applied with a level of significance at p < .05 to compare the incidence of ICH in patients with a high and low index of PVS. Further exploratory analyses were conducted (Fisher exact test for known risk factors age, and invasivity; correlation analyses for the metric data age and PVS index).  

Results: 8 intracerebral hemorrhages occurred during implantation of 649 electrodes in 336 operations (2.4 %) in 330 patients. Relevant neurological deficits resolved in all but one of the affected patients. ICHs occurred more often in patients with high PVS enlargement (p = .029, 2-sided).. As expected, exploratory analyses showed a higher incidence of ICH in patients of higher age (p = .019, 2-sided) and with increasing invasivity index (p = .008, 2-sided). As expected, we found significant positive correlations of age and the PVS index.

Discussion: Enlarged PVS may serve as an additional risk indicator for ICH in DBS surgery and help to mitigate invasivity (e.g. avoid microelectrodes) in patients at risk. The presented results are preliminary and further analyses are in preparation to address the sparse data bias (Greenland et al. 2016) due to low incidence of ICH.

 

References:

Nicolas Raposo and others, ‘Enlarged Perivascular Spaces and Florbetapir Uptake in Patients with Intracerebral Hemorrhage’, European Journal of Nuclear Medicine and Molecular Imaging, 46.11 (2019), 2339–47 <https://doi.org/10.1007/s00259-019-04441-1>.

Marie-Gabrielle Duperron and others, ‘High Dilated Perivascular Space Burden: A New MRI Marker for Risk of Intracerebral Hemorrhage’, Neurobiology of Aging, 84 (2019), 158–65 <https://doi.org/10.1016/j.neurobiolaging.2019.08.031>.

Alejandro F. Frangi and others, ‘Multiscale Vessel Enhancement Filtering’, in Medical Image Computing and Computer-Assisted Intervention — MICCAI’98, ed. by William M. Wells, Alan Colchester, and Scott Delp (Berlin, Heidelberg: Springer Berlin Heidelberg, 1998), mcdxcvi, 130–37 <https://doi.org/10.1007/BFb0056195>.

Sander Greenland, Mohammad Ali Mansournia, and Douglas G Altman, ‘Sparse Data Bias: A Problem Hiding in Plain Sight’, BMJ, 2016, i1981 <https://doi.org/10.1136/bmj.i1981>.

Timo Sebastian BRUGGER, Marco REISERT, Christoph KALLER, Egger KARL, Volker Arnd COENEN, Bastian Elmar Alexander SAJONZ (Freiburg, Germany)
00:00 - 00:00 #26250 - StereoSlicer, a plugin for 3DSlicer to handle data from stereotactic surgeries.
StereoSlicer, a plugin for 3DSlicer to handle data from stereotactic surgeries.

Background:

When performing analysis of data related to stereotactic neurosurgery, one of the first operations is to extract image data from the clinical software systems. This step can become quite problematic, due to a gap in 3D reference space between software used in clinical practice and image analysis environment. Leksell arc settings (Leksell G Frame, Elekta AB, Sweden) for trajectories are an example: they are of great importance in functional neurosurgery but importing these to research-oriented software can become a complex task since the reference of the coordinates is based on the N-shaped marker of the Coordinate Frame (Elekta AB, Sweden) embedded in the 3D image. Our aim is to minimize the burden from this gap in an automatic and user-friendly way.

In this paper, StereoSlicer, a plugin easing the use of Leksell arc settings in the medical image visualization and processing software 3DSlicer (slicer.org) is presented.

Method:

The plugin consists of three modules. The first module is responsible for the detection of the N-shaped markers in the images: histogram-based intensity thresholding is used to isolate their contrast band from the background and from the patient. Then the resulting objects are filtered based on their size and position. Once the markers are identified, their 3D representation is generated. An ideal model of the markers in a known orientation can then be generated with the user interface. This orientation corresponds to the marker plates normal to the vectors describing the Right-Anterior-Superior (RAS) space.

The two models (segmented and ideal) are then registered using iterative closest point surface-to-surface registration. The resulting affine transformation describes the position of the Coordinate Frame within the patient images. In the second module, the Leksell arc settings are first converted to an affine transform describing the position of the trajectory in RAS space. By combining it with the previous transform, the Leksell arc settings can be used to place the trajectory in the original patient images. To use trajectories in generic research software, points can also be transformed to voxel indices in image space.

With the third module, the standard slice views from 3DSlicer can be oriented orthogonal to the trajectory rather than the anatomical directions. The result is a “probe view” similar to what is available in clinical software.

The two first modules were validated separately. The segmentation module was tested with CT data from 19 patients originating from the university hospital in Clermont-Ferrand in France (2011-A00774-34/AU905). The segmentation was run for each patient and the proper detection of the marker was checked visually. The validity of the affine transforms calculated was tested with the placement of trajectories at known locations in the Leksell coordinate system, namely along the bars of the marker. Parallel trajectories corresponding to the use of the Ben Gun were added in order to validate conversion from the arc settings to an affine transformation. The transform between Leksell space and the patient space was then tested by checking that the same trajectories indeed align with the markers visible in the CT contrast and the 3D model based on segmentation. Lastly, a fake trajectory was created in Brainlab iPlan Stereotaxy with the anterior commissure (AC) and posterior commissure (PC) labeled by the neurosurgeon as entry and target points. The resulting arc settings were used in StereoSlicer and the position of AC and PC points were calculated and compared to the anatomy.

Results:

In each of the 19 patients, all N-shaped marker were correctly identified, the registration between the surfaces of the segmented and ideal fiducials was successful and allowed to place trajectories with Leksell settings which aligned with the artifacts of the marker in the CT image in patient space. In all the patients, each end of the fake trajectory coincided with AC and PC on the MRI in StereoSlicer with a sub-voxel precision.

Conclusion:

StereoSlicer provides automatic N-shaped marker segmentation and allows to use Leksell arc settings within the popular, open-source 3DSlicer platform. It was tested with CT images from a single center. Further testing is needed with images from other centers and other imaging modalities such as MRI. To that end, the source of the plugin will be open-sourced and submitted to the Slicer Extension Index.

Dorian VOGEL (Basel, Switzerland), Johansson JOHANNES, Nordin TERESA, Karin WÅRDELL, Simone HEMM
00:00 - 00:00 #26123 - Tractography Alterations in the Arcuate and Uncinate Fasciculi in Post-Stroke Aphasia modulated by tDCS.
Tractography Alterations in the Arcuate and Uncinate Fasciculi in Post-Stroke Aphasia modulated by tDCS.

Fiber tractography based on diffuse tensor imaging (DTI) can reveal three-dimensional white matter connectivity of the human brain. Tractography is a non-invasive method of visualizing cerebral white matter structures in vivo, including neural pathways surrounding the ischemic area. DTI may be useful for elucidating alterations in brain connectivity resulting from neuroplasticity after stroke. We present a case of a male patient who developed significant mixed aphasia following ischemic stroke. 

The patient had been treated by mechanical thrombectomy followed by an early rehabilitation, in conjunction with transcranial direct current stimulation (tDCS). DTI was used to examine the arcuate fasciculus and uncinate fasciculus upon admission and again at three months post-stroke.

Results showed an improvement in the patient’s symptoms of aphasia, which was associated with changes in the volume and numbers of tracts in the uncinate fasciculus and the arcuate fasciculus.

This case report demonstrated DTI with tractography as an MRI technique used to detect the microstructural changes and difference in the anatomy and morphology of fiber tracts in patients after ischemic stroke which corresponded with improvement in the patient’s clinical functioning.

Sara KIEROŃSKA (Bydgoszcz, Poland), Milena ŚWITOŃSKA, Paweł SOKAL
00:00 - 00:00 #26122 - Tractography changes in the forceps minor and superior longitudinal fasciculus after cingulotomy in patient with obsessive-compulsive disorder.
Tractography changes in the forceps minor and superior longitudinal fasciculus after cingulotomy in patient with obsessive-compulsive disorder.

After stereotactic procedure, the brain is known to be reorganized especially in the associate cortex. We report a case to show changes in the forceps minor and superior longitudinal fasciculus in a patient with obsessive-compulsive disorder underwent cingulotomy using diffusion tensor imaging. 

A 45-year-old man with obsessive-compulsive disorder history since 12 years in the form of uncontrolled hand washing pharmacologically treated with unsatisfactory effect was qualified to bilateral cingulotomy. 

The anterior part of gyrus cingulum 25 mm above of the frontal horn of lateral ventricles was chosen as the target bilaterally. The procedure of cingulotomy was undertaken without adverse events.

An initial brain magnetic resonance imaging with a diffusion tensor imaging was performed before and 3 months after cingulotomy procedure. After 3-months follow up we observed changes in forceps minor and superior longitudinal fasciculus comparing in increase of tracts volume from 18-22% and increase of numbers of tracts from 15-20% comparing with baseline DTI. Moreover fractional anisotrophy (FA) after 3 months follow up has been increased up to 25% in forceps minor and up to 20% in superior longitudinal fasciculus

At 3-months follow-up, there was also  more than 60 % reduction in OCD symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale.

Results showed an improvement in the patient’s symptoms of OCD, which was associated with changes in the volume and numbers of tracts in the forceps minor and the superior longitudinal fasciculusThis case report suggests that diffusion tensor imaging tractography could be a useful method to understand cortex reorganization after cingulotomy in OCD. 

 

Sara KIEROŃSKA (Bydgoszcz, Poland), Paweł SOKAL, Marcin RUDAŚ, Banasiak ANNA, Marcin RUSINEK
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00:00 - 00:00 #26189 - 3T Magnetic Resonance-guided Focused Ultrasound (MRgFUS) unilateral thalamotomy of Vim (ventral intermediate nucleus) in patients with essenzial tremor: three-years clinical experience of a single center.
3T Magnetic Resonance-guided Focused Ultrasound (MRgFUS) unilateral thalamotomy of Vim (ventral intermediate nucleus) in patients with essenzial tremor: three-years clinical experience of a single center.

Background and Aims. Magnetic resonance-guided focused ultrasound (MRgFUS) unilateral thalamotomy of the ventralis intermedius (Vim) nucleus is emerging as a minimally invasive treatment for patients with disabling and medication-refractory essential tremor (ET). We report our preliminary three-year experience on 52 patients with ET treated from January 2018 to December 2020 in a single center (University Hospital of Verona).

Methods. From January 2018 to December 2020, 52 patients (31 men, 21 women, age: 73.5 ± 7.8 years) underwent MRgFUS thalamotomy of the Vim nucleus for disabling and refractory ET (tremor duration: 22.6 ± 12.1 years) with a 3T magnetic resonance scanner (MRgFUS Insightec Exablate 4000) at Verona University Hospital.

Results. At baseline the total Clinical Rating Scale for Tremor (CRST) score was 45.8 ± 15.6, and the Quality of Life in Essential Tremor Questionnaire (QUEST) score was 40.8 ± 13.8. At one-month follow-up, the total CRST score was 12.8 ± 6.3 and the QUEST score was 10.5 ± 4.1. Response persisted in the majority of patients at three-month, six-month, one-year, two-year and three-year follow-up.        Side effects related to Vim nucleus thalamotomy included ataxia, speech disturbances, ballism, paraesthesia, and lower extremity weakness. These side effects were mild and transient in most patients.

Conclusions. Our data confirm that MRgFUS thalamotomy of the Vim nucleus is an effective and safe treatment for disabling and refractory ET and its effects are long-lasting.

Giorgia BULGARELLI (Verona, Italy), Stefano TAMBURIN, Giuseppe Kenneth RICCIARDI, Michele LONGHI, Emanuele ZIVELONGHI, Tommaso BOVI, Stefania MONTEMEZZI, Roberto FORONI, Antonio NICOLATO
00:00 - 00:00 #23965 - ACTIVA systems for deep brain stimulation: an analysis on a prospective, multicenter Product Surveillance Registry (PSR) to meet the reimbursement requirements of the French Haute Autorité de Santé (HAS).
ACTIVA systems for deep brain stimulation: an analysis on a prospective, multicenter Product Surveillance Registry (PSR) to meet the reimbursement requirements of the French Haute Autorité de Santé (HAS).

Following reimbursement of ACTIVATM DBS systems, the French Haute Autorité de Santé (HAS) via the Commission Nationale d’Evaluation des Dispositifs Médicaux et des Technologies de Santé (CNEDiMTS) requested a five-year follow-up registry of implanted DBS patients to maintain the reimbursement of the devices. The aim of the study was to characterize adverse events and quality of life measures by DBS indication.

A prospective, non-randomized, observational, multicenter study was conducted, as part of the Product Surveillance Registry (PSR), an ongoing, prospective, long-term multi-center registry. Patients were enrolled from June 2013 until October 2018. A sampling of patients (n=400) from 7 representative French implanting centers would be pooled with data from other global centers enrolling in the PSR. Testing for homogeneity would be performed to ensure poolability of data. The eligible centers in France were analyzed by quartiles representing implant volume (very large, large, average, and small sites to be representative of real-world use). To limit bias, changes in EQ-5D score were analyzed for therapy-naïve PSR patients who completed both baseline and follow-up questionnaires (matched pairs).

At the time of the final study report in June 2019, 2 537 patients were enrolled at 38 global sites, including 491 (19,4%) from France. The majority of patients were treated for Parkinson’s disease (PD) (64,2%) and Essential Tremor (22,9%). The average length of follow-up time was 31 months (0 – 106,7 months). France enrolled a higher proportion of PD patients (71,1% vs 58,3%; p<0,0001) and patients receiving a replacement device (45,6% vs 36,7%; p<0,0001). There was no statistically significant difference in enrolled patients from France versus patients from other geographies in age and gender. Overall, 1 427 events were reported for 768 patients (30,2%). Of those, 381 events were classified as serious (26,7%) for 294 patients (11,6%). A total of 331 events were reported for 197 French patients (40,1%). Of those, 109 events were classified as serious (32,9%) for 89 patients (18,1%). The rates of adverse events and serious adverse events in France were not significantly different from other European countries. Overall, 693 hospitalizations were reported (376 in France). Of these 221 (31,9%) were due to events. The most common adverse events related to hospitalizations were for medical device site or wound infections, worsening tremors or dyskinesia, high impedance, psychiatric disorders (e.g. depression, anxiety), gait disturbances, and device migrations. There was a difference in hospitalization rates between patients in France and other geographies, that may be attributable to regional variation in care patterns (e.g more hospitalizations in France for device re-programming vs. outpatient care).  Overall, there were 171 deaths (6,7%) and 17 deaths (3,5%) in France. None of deaths were reported as a direct result of a product performance event. Patients from France and other geographies showed a statistically significant improvement in EQ-5D index and VAS scores through first follow-up. For therapy-naïve PD patients from France (N=135), change across time was statistically significant with average improvements between baseline and first follow-up (6 or 12 months) of 0,12 in EQ-5D index score (p<0,0001) and a significant improvement in EQ-5D VAS score of 12,4 units or 22,9% change between baseline and first follow-up.

The results of this five years follow-up study support the continued safety and effectiveness of the DBS systems for their intended use in real world conditions. Thus, HAS approved the renewal of reimbursement of ACTIVATM DBS systems in France.

Stéphane PALFI (PARIS), Emmanuel CUNY, Jean-Philippe AZULAY, Luc DEFEBVRE, Soledad NAVARRO, Philippe COUBES, Franck DURIF, Apolline ADE, Pierre-Antoine GROHARD, Christian AUBLANT, Thomas BRIONNE, Keisha SANDBERG, Todd WEAVER
00:00 - 00:00 #26099 - Awake versus asleep STN-DBS for Parkinson’s disease: asleep as a feasible alternative.
Awake versus asleep STN-DBS for Parkinson’s disease: asleep as a feasible alternative.

Introduction
Bilateral deep brain stimulation (DBS) of the nucleus subthalamicus (STN) has been proven to be a successful treatment for Parkinson’s disease. The success of DBS correlates with the anatomical accuracy of the implanted electrodes. Generally, this procedure is performed under local anesthesia (LA) to enable microelectrode recording (MER) and intraoperative macrostimulation. The correct location of the implanted electrode is verified during the test stimulation. Nowadays, general anesthesia (GA) is a feasible alternative, due to technical improvements in direct targeting employing high field MRI and intraoperative CT imaging (iCT) (Medtronic O-arm). The verification method relies on intraoperative imaging with or without MER. The impact on the patient is less severe while using GA, as it is perceived as more accessible and comfortable. The success of this technique is independent of cooperation of the patient.

Material and Methods
Five patients with Parkinson’s disease were treated with bilateral DBS of the STN under GA. Preoperative 3T MRI T2 and T1 MPRAGE with gadolinium sequences images (Siemens Skyra 3T MRI) were made under GA. Direct targeting through visualization of the STN in T2 images was done. After attachment of a Cosman-Roberts-Wells frame (Integra CRW stereotactic system), CT guided stereotactic images were made and fused with the preoperative MRI. Boston Scientific Vercise Cartesia directional leads were stereotactically implanted and linked to BS Vercise Gevia battery. Intraoperative MER was used to verify the correct electrophysiological location. Intraoperative verification of the anatomical lead positions was done with iCT. There were no postoperative infections or hemorrhages.


Results
All lead positions were within 2mm radius of the planned trajectory. The postoperative motor effect was comparable with STN DBS under LA. Long term follow-up showed a lasting result.

Conclusion
We can confirm similar results on the postoperative improvement between LA and GA for STN DBS.

Sarah HENDRICKX (Ghent, Belgium), Stijn VANDAMME, Frederik CLEMENT, Jeroen VAN LERBEIRGHE, Dimitri VANHAUWAERT, Olivier VAN DAMME
00:00 - 00:00 #23930 - Bilateral deep brain stimulation of the internal globus pallidus for severe refractory tardive syndromes: multicentric experience and evidence-based recommendations.
Bilateral deep brain stimulation of the internal globus pallidus for severe refractory tardive syndromes: multicentric experience and evidence-based recommendations.

TITLE

Bilateral deep brain stimulation of the internal globus pallidus for severe refractory tardive syndromes: multicentric experience and evidence-based recommendations. 

 

 

AUTHORS

Oscar Andrés Escobar Vidarte. MD. FACS.

Associate Professor, Neurosurgery Section, Universidad del Valle, Cali, Colombia.

Professor, Department of Medical Clinics, Pontificia Universidad Javeriana, Cali, Colombia.   

Coordinator Neorosurgery Service, Comfandi Amiga Clinic, Cali, Colombia.

Functional Neurosurgeon, Castellana Clinic, Cali, Colombia.

Functional Neurosurgeon, Latin American Institute of Neurology and the Nervous System (ILANS), Bogotá, Colombia.

First author and speaker.

 

Javier Orozco Mera. MD. FACS.

Professor, Neurosurgery Section, Universidad del Valle, Cali, Colombia. 

Neurosurgeon of Tumors and Skull Base Surgery, Neurosurgery Service, Comfandi Amiga Clinic, Cali. 

 

Gabriel José Arango Uribe. MD.

Movement Disorders Neurologist.

Latin American Institute of Neurology and the Nervous System (ILANS), Bogotá, Colombia. 

Marly Clinic, Bogotá, Colombia. 

 

Juan David Rivera. MD.

Neurosurgery Program Specialization Resident. 

Neurosurgery Section, Universidad del Valle, Cali, Colombia.

 

 

TOPIC

Movement disorders.

 

 

 

KIND OF COMMUNICATION

Poster presentation.

 

 

KEY WORDS

Tardive syndromes, deep brain stimulation, internal globus pallidus.

 

 

INTRODUCTION

Tardive Syndromes (TS) are characterized by the appearance of involuntary dystonic and/or dyskinetic movements after chronic use of some medications (3-6 months). Deep brain stimulation (DBS) of the Internal Globus Pallidus (GPi) has been used to treat severe and refractory cases.

 

OBJECTIVE

To describe and analyze the impact of DBS GPi on the severity of the movements in patients with severe and refractory TS, and to review the available evidence to recommend this procedure.

 

METHODS

Eleven patients with severe and refractory TS were driven to GPi bilateral DBS, the series analysis was performed by results evaluation with a minimum 1-year follow-up using preoperative Burke-Fahn-Marsden Dystonia motor scale (BFM) value and postoperative value during the last follow-up visit.

 

RESULTS

Patients were followed during a period of 1 to 7 years, with an average preoperative score of the BFM scale of 36,7 and postoperative score of 9,3, obtaining an average improvement of 74,7%. An extension cord rupture, a surgical wound infection and a case of persistent moderate dysarthria were documented. When performing a literature review a meta-analysis published in 2018 was found and such work showed an average improvement in the severity of the BFM scale of 76% in patient driven to a DBS because of TS.

 

CONCLUSION

GPi DBS for severe and refractory TS can be considered as a tratment for movement control, being recommended by expert groups as a safe and reproducible procedure.

Oscar ESCOBAR (Cali, Colombia), Javier OROZCO, Gabriel ARANGO, Juan RIVERA
00:00 - 00:00 #23964 - Bilateral double beta peaks in a PD-patient with STN-electrodes and „brainsensing“.
Bilateral double beta peaks in a PD-patient with STN-electrodes and „brainsensing“.

Objective: Subthalamic (STN) local field potentials (LFPs) in the beta band are considered as potential powerful biomarkers for for the current physiological” status” of the patient and might therefore be used for “brainsensing” and consecutive adaptive, closed-loop deep brain stimulation. Our goal was to investigate the subthalamic beta band peak amplitudes in a Parkinson’s disease patient over an extended period of time under various „conditions“ (movement tasks, stim on/stim off, med on/med off) by using a novel and commercially available implantable neurostimulator with permanent sensing capability for the first time.

Methods: We recorded LFPs within the STN using the novel, now commercially available implantable neurostimulator at rest and during physical activity (gait) and the respective response to various stimulation protocols and stim-off. Gait performance was continuously monitored with sensors attached to the shanks, thighs, arms and chest, and step length, cadence and foot clearing were measured. Gait recordings and LFPs were synchronized by detecting the impulses of a transcutaneous electric nerve stimulator (TENS) triggered by the gait recording devices. The exact timing and amplitude of stimulation was recorded by the stimulator and transferred to atablet computer.

Results: We found a double-peaked beta activity on both sides. Increasing stimulation and physical activity (walking) resulted in a decreased beta band amplitude, but was accompanied by the appearance of a second, and previously unrecognized peak at 13 Hz in the right hemisphere.

Conclusion In summary, our results will support the investigation of patient-specific individual LFP patterns (LFP ‘fingerprints’) and aid the development of LFP-based feedback signals. In addition, our exploratory study highlights the potential of dual deep brain stimulation and recording devices (DBS/R) for the study of LFPs.

 

Jan MEHRKENS (München, Germany), Thomas KÖGLSPERGER, Kai BÖTZEL
00:00 - 00:00 #26115 - Cerebellar and sensorimotor cortical connectivity predicts outcomes of pedunculopontine nucleus stimulation in Parkinson's disease.
Cerebellar and sensorimotor cortical connectivity predicts outcomes of pedunculopontine nucleus stimulation in Parkinson's disease.

Background

Deep brain stimulation of the pedunculopontine nucleus is a promising surgical procedure for the treatment of Parkinsonian gait and balance dysfunction. It has, however, produced mixed clinical results that are poorly understood. We used tractography with the aim to rationalise this heterogeneity.

Methods

A cohort of eight patients with postural instability and gait disturbance (Parkinson’s disease subtype) underwent pre-operative structural and diffusion MRI, then progressed to deep brain stimulation targeting the pedunculopontine nucleus. Pre-operative and follow-up assessments were carried out using the Gait and Falls Questionnaire, and Freezing of Gait Questionnaire. Probabilistic diffusion tensor tractography was carried out between the stimulating electrodes and both cortical and cerebellar regions of a priori interest.

Results

Five of eight patients showed improvement at follow-up (median = 12 months, Q1–Q3: 12–16 months). Structural connectivity between stimulating electrode and precentral gyrus (r = 0.81, p = 0.01), Brodmann areas 1 (r = 0.78, p = 0.02) and 2 (r = 0.76, p = 0.03) were correlated with clinical improvement. A negative correlation was also observed for the superior cerebellar peduncle (r = −0.76, p = 0.03). 

Conclusions

Both motor and sensory structural connectivity of the stimulated surgical target characterises the clinical benefit, or lack thereof, from surgery. In what is a challenging region of brainstem to effectively target, these results provide insights into how this can be better achieved. Considering both electrode coordinates and connectivity patterns, we conclude that stimulating the most caudal and lateral part of the pedunculopontine nucleus may offer the best chance of relieving symptoms, whereas, stimulating the superior cerebellar peduncle medially may worsen them. The mechanisms of action remain unclear, but our results support both motor and sensory components, commensurate with the probable nature of the underlying dysfunction.

Ashley RAGHU (Oxford, United Kingdom), Tariq PARKER, John STEIN, Jesper ANDERSSON, Stephen PAYNE, Tipu AZIZ, Alex GREEN
00:00 - 00:00 #23784 - Clinical deep brain stimulation targeting based on an inverse problem approach. The artificial intelligence solution.
Clinical deep brain stimulation targeting based on an inverse problem approach. The artificial intelligence solution.

Targeting in deep brain stimulation (DBS) procedures remains controversial, mainly because research into the relationship between improvement and electrode location requires correction for anatomical variations leading to poorly controlled errors.

Thus, it is difficult to present the following forward problem in simple terms: From a preoperative clinical status, we must define the targets to be reached in order to obtain a good result, the result obtained with the stimulation, the precise location of the electrodes and the correlation between all of these items.

From a mathematical perspective, when it is difficult to solve a forward problem, a solution can be found by considering the inverse problem.

By identifying patients with a good clinical outcome after DBS, we correlated active contacts of electrodes with simple MRI landmarks around this contact. We thus describe the location of the electrode by the Euclidian distance and the vector of each landmark. We produced a metamodel that expresses the position of active and clinically effective contacts depending on the position of MRI landmarks. We applied this metamodel to new patients to predict the effective location of active contacts by identifying MRI landmarks. After verification of the consistency and the robustness of the model, we verified its clinical effectiveness through trials where electrodes were directly inserted at the predicted target without any microrecording or MRI correction.

We first applied this method to the subthalamus nucleus (STN) in Parkinson’s disease (PD). We selected 22 PD patients who dramatically improved with STN DBS. The coordinates of the active contacts were correlated with 12 radiological landmarks around the electrode. We selected the 3 landmarks with the strongest correlation with the active contact and expressed the target coordinates as 3 equations of the corresponding regression line of these landmarks.

xT=0.44xlat hedge of the 3rd ventricle+10.71

yT=0.69ymammilothalamic tract+1.62

zT=0.72zthalamus height -16

In a second cohort of 9 patients, we verified the target accuracy (external validation) by calculating the Euclidian distance between the active contact location and the predicted target. Comparison of the internal error (calculated by leave-one-out cross-validation) of the first cohort and the external error confirmed the model’s coherence and robustness.

We conducted the PARKEO trial (NCT01817088), a prospective phase-2, open-label, single-centre, randomised non-comparative trial with two parallel groups: an asleep group without microrecording (20 patients) and an awake group with microrecording (10 patients). All patients were targeted on the clinical-based STN.

The mean motor improvement rates (mean [95% Confidence Interval]) on the UPDRS III between OFF and ON stimulation without medication was 52.3% [45.4% – 59.2%] and -18.8 [-31.6; -6.0] for the quality-of-life improvement evaluated by the decrease in PDQ39 in the asleep group 6 months after surgery.

We applied this method to the VIM in essential tremor (ET), but the selection of three landmarks, as for the STN target, failed to predict the active contact of the electrodes. We then constructed a learning data base from 15 patients (29 leads) who had undergone surgery with a median tremor improvement of 72% on the Fahn-Tolosa-Marin scale. All the patients underwent pre- and post-operative imaging from which the coordinates of 18 anatomical landmarks per side and of the active contacts were extracted. We used regression and deep learning methods (Artificial Intelligence). The models were statistically and anatomically validated, respectively, according to a leave-one-out cross-validation and the mean distance to VIM structure on the DISTAL atlas in the MNI space. Support Vector Regression (SVR) gave the best results with a mean error of 1.33 +/- 1.64mm between the predicted target and the active contact position.

We conducted the Opti-VIM trial (NCT03760406), a prospective phase-2, open-label, double-centre (Bordeaux and Lyon) single group trial on a group of 20 asleep patients without microrecording. Further preliminary results of stimulation of the optimized VIM target under general anaesthesia and without additional electrophysiological or MRI correction are presented.

Thus, the resolution of the inverse targeting problem by AI simplifies surgery by allowing interventions under general anaesthesia, without MER correction and with good outcomes.

Julien ENGELHARDT, François CAIRE, Nejib ZEMZEMI, Denis FONTAINE, Dominique GUEHL, Pierre BURBAUD, Nathalie DAMON-PERRIERE, Wassilios MEISSNER, Caroline GIORDANA, Michel BORG, Emmanuel CUNY (Bordeaux)
00:00 - 00:00 #23992 - Comparison of DBS devices lifespan for the treatment of Parkinson’s disease with corresponding meta-analysis of the literature.
Comparison of DBS devices lifespan for the treatment of Parkinson’s disease with corresponding meta-analysis of the literature.

Technological advances have permitted the manufacture of new generation of devices for deep brain stimulation. These devices need to be tested to demonstrate non inferiority both on clinical effectiveness associated complications and longevity of the device. Several studies have compared the lifespan o such devices using heterogeneous methods. The goal of this study is to determine whether there is a longevity difference between first and second generation of Medtronic© devices.  The second objective is to compare the longevity of the same implanted devices after its first implantation and after its replacement. PRISMA review methods were applied to construct a meta-analysis of similar studies.

 

Methods

60 consecutive patients implanted with DBS for Parkinson’s disease from 2010 to 2013, in whom the device was not later explanted for adverse effect reasons (i.e. infection), were followed and screened for device replacements from 2010 to the current date (01/01/2018). Thirty patients beneficiate from Kinetra® devices and thirty patients beneficiate from new stimulator model (at this time) ActivaPC®. Comparisons were made between the lifespan of these two different models. The longevity of same type of device used both for first implantation and then for replacement in the same patient was also compared and analysed.

 

Results

Average lifespan for the Kinetra® stimulator was 1711±478 days whereas for the ActivaPC® was 1691±289 days. The difference is not statistically significant (p=0,32 student t-test) . Kaplan Meyer statistics were calculated for these two models. Median survival for Kinetra® was 1611 days whereas for ActivaPC® was 1740 days. A log rank test showed this difference to be close to the statistical significance limit p=0.06.

Lifespan comparison between first and second implanted device showed a statistically significant difference in lifespan with a shorter lifespan of the second device (1699 vs 1435 days, p=0.02).

 

Discussion

Four similar studies were found and were candidates for meta-analysis. Using PRISMA review criteria none qualified for inclusion in the meta-analysis. Elements of each study are discussed and compared to the presented original study. .

 

Conclusions

In this study, no significant difference in longevity between the two devices Kinetra® and Activa® was shown. Replaced devices of both type, have shorter lifespan than first implant devices.

This independent study was not supported by any grants.

Andrei BRINZEU (Lyon), Theo BRUSSOLLE, Emile SIMON, Gustavo POLO, Teodor DANAILA, Chloe LAURENCIN, Stephane THOBOIS, Patrick MERTENS
00:00 - 00:00 #25487 - DBS Implantable Pulse Generator Trauma Protection Pad; a novel solution to reduce trauma induced IPG explantation.
DBS Implantable Pulse Generator Trauma Protection Pad; a novel solution to reduce trauma induced IPG explantation.

Background: Our centre is set in a tropical environment where the attire includes thin fabrics

which do not provide any cushioning/protection against trauma to the skin overlying the IPG.

Our study revolves around patients of low socio-economic strata, who preferred the cheaper

but bulkier non rechargeable IPG over its compactor but more expensive counterpart, the

rechargeable IPG. Patients who suffered from accidental trauma to the left infra clavicular

region had severe lacerations, leading to local infections and in some cases a complete loss of

battery function requiring immediate replacement.

Method: Amoldable memory foam embedded in a hydrophobic fabric with cooling properties,

was made to be placed over the IPG. A ferromagnetic catch is placed inside the foam to

articulate with a magnet. A neodymium magnet attached to a large sized button holds the DBS

IPG Trauma Protection Pad in place and it seconds as a brooch.

Result: The DBS IPG Trauma Protection Pad was successfully placed over the IPG and acted

as a shock absorber thereby reducing the chances of accidental trauma causing damage to the

IPG.

Conclusion: The Trauma Protection pad would reduce the damage caused by accidental

trauma and prevent local infection, thereby reducing patient morbidity as well as the rate of

trauma induced DBS battery explantation procedures.

Adhish BERI (Chandigarh, India), Hargunbir SINGH, Nishit SAWAL
00:00 - 00:00 #26127 - Decrease of daytime sleepiness by deep brain stimulation of pedunculopontine nucleus area in parkinsonian non-human primate.
Decrease of daytime sleepiness by deep brain stimulation of pedunculopontine nucleus area in parkinsonian non-human primate.

Introduction:

Less known than motor symptoms, excessive daytime sleepiness (EDS) is one of the most disabling non-motor symptoms reported by parkinsonian patients. EDS seriously affects the patients’s quality of life and is often worsened by current treatments, and justifies to explore new therapies such as deep brain stimulation (DBS). We aimed to evaluate the effect of pedunculopontine nucleus area (PPNa)-DBS, a key area of the brainstem arousal system, on daytime sleepiness in parkinsonian non-human primates (NHPs).

Methods:

Two NHPs (macaca fascicularis) were implanted with a polysomnographic telemetry equipment recording electro-encephalogram, electro-occulogram and electro-myogram signals in freely moving animals, synchronized with a video system to analyze the wake/sleep behavior. In addition, a quadripolar electrode, connected to a stimulator, was implanted into the PPNa to apply the stimulation. After a characterization of wake/sleep behavior by 12h daytime continuous recordings and an evaluation of the level of daytime wakefulness by a modified multiple sleep latency test in healthy and parkinsonian monkeys, the effect of PPNa-DBS at low (LFS) frequency was studied in the same experimentations mentioned previously.

Results:

First, we showed that wakefulness was significantly modified in parkinsonian monkeys resulting in a total disorganization of nap architecture with an increase in daytime sleepiness associated with sleep inertia in the morning. Second, we observed that PPNa-LFS counter-balanced these disturbances by reducing the total sleep duration (158.1 ± 43.18 min in DBS-OFF vs 87.36 ± 15.74 min in DBS-ON; p<0.05) and the sleep inertia (first sleep after wake: 12.64 ± 3.98 min DBS-OFF vs 63.74 ± 25.86 min DBS-ON; p<0.05). 

Conclusion:

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Our results show that the PPNa-LFS increases the daytime wakefulness in parkinsonian NHPs. This awakening effect observed in our study appears as an encouraging result which offers new perspectives to treat severe wake/sleep disorders.

Aurélie DAVIN (Grenoble), Stephan CHABARDES, Olivier DAVID, Napoléon TORRES-MARTINEZ, Brigitte PIALLAT
00:00 - 00:00 #22675 - Deep brain stimulation and lesioning surgery – a three year start in Bangladesh.
Deep brain stimulation and lesioning surgery – a three year start in Bangladesh.

Abstract: Idiopathic Parkinson’s Disease ( IPD ) is a chronic neurodegenerative disease results from degeneration of Dopaminergic neurons of substantia nigra  . It’s cardinal features are resting tremor , rigidity , akinesia and postural instability.The role of subthalamic nucleus in the development of Parkinsonian tremor and other cardinal features is not completely understood yet. However, previous studies in monkey, administration of MPTP( 1-methyle-4-phenyl-1.2.3.6.-tetrahydropyridine ) proved that sub thalamic nucleus has a direct role in the development of parkinsonian tremor and other features . Commonly, very disabling dyskinesia develop due to the side effects of dopaminergic drugs used in Parkinson's Disease.  Until recently in Bangladesh had no functional neurosurgery service. We report our very preliminary experience over the last three years.

Surgery is performed awake with image guided (MRI/CT Stereotaxy) assessing the effects of stimulation and lesioning on table. We have so far implanted 5 deep brain stimulators (PINS) and a pallidotomy with good effect. Patients were assessed at 6 weeks and up to one year after surgery. In the cases of STN DBS, the UPDRS was reduced by 63.33%( p<0.001) and dyskinesias by 70% after a pallidotomy.

There have been no infections or hemorrhages in this small pilot series.

Key words: Subthalamic Nucleus(STN), Deep Brain Stimulation(DBS) , Parkinson’s Disease(PD), Globus Pallidus Internus ( Gpi) 

1. *. Md. Zahid Raihan , Associate Professor & Head, Department of Neurosurgery, KuMC, DGHS,Dhaka . 1967zahidraihan.zr@gmail.com

 2. Professor Tipu Zahed Aziz, Professor of Functional Neurosurgery, Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford.

Hospital , University of Oxford , UK

Mohammad ZAHID RAIHAM (Dhaka, Bangladesh)
00:00 - 00:00 #23997 - Deep brain stimulation, subthalamic nucleus with its motor networks.
Deep brain stimulation, subthalamic nucleus with its motor networks.

INTRODUCTION

Deep brain stimulation (DBS) is a widely described technique, and very effective in Parkinson's disease (PD) resistant to drug management. Most authors agree that the target of choice is the subthalamic nucleus (STN) for the control of cardinal symptoms stiffness-tremor-bradykinesia. Advances in radiological imaging, such as the DTI, could play a fundamental role in the surgical planning of the STN.

 

OBJECTIVES

We report a clinical case with DBS at the STN level, and the relevance of tractography in planning.

 

METHODS

46-year-old woman with PD for 7 years, the last year she complain of stiffness, bradykinesia of the upper extremities and freeezing of gait; resistant to pharmacological treatment. L-dopa test (UPDRS III) OFF = 45, ON = 9. We proposed to perform the ECP at the NST level, the patient understood and accepted the consent.

A preoperative brain MRI was performed1.5T that included volumetric sequence T1, T2 and DTI. NST surgical planning was performed directly and adjusted by tractography connecting the dorsolateral region of the NST with the supplemental motor area / lateral premotor cortex (X: 11.7, Y: -2.8, Z: -4).

Under local anesthesia was performed micro-recording and micro-stimulation, was implanted definitive electrodes (Vercise Cartesia-Boston Scientific); Intraoperative CT confirming the correct lead placement, without complications. Immediately after general anesthesia, a pulse generator is implanted (Vercise Gevia-Boston Scientific). On the third day the stimulation was ON, and the fourth day post-surgical the patient was discharge.

 

RESULTS

Seven month after surgery, we observed a significant reduction in the Unified Parkinson Disease Rating Scale part III ON medication-ON stimualtion 8, reduction L-dopa equivalent daily dose in 70%.

Currently, programming stimulation is monopolar with ring (5-6-7) 1.5mA, 60mSec, 130Hz. The volume of tissue activated included the suplementary motor area, lateral premotor cortex, parcially primary motor cortex.

 

CONCLUSIONS

The planning of the STN in the first papers was based on indirect methods, currently with the resolution of the MRI we can perform directly visualizing the nucleus. However, tractography allows us to reconstruct the possible hyperdirect pathway connecting the STN and the motor cortex. This allows us to improve DBS targeting, identify the most effective lead contact, and programming with low intensity.

Luis Mariano ROJAS-MEDINA (Madrid, Spain), Lucia ESTEBAN-FERNANDEZ, Daniel LOURIDO-GARCÍA
00:00 - 00:00 #24031 - Deep brain stimulation-electrodes may rotate after implantation – an animal study.
Deep brain stimulation-electrodes may rotate after implantation – an animal study.

Background & Purpose: Directional Deep Brain Stimulation (dDBS) electrodes allow to steer the electrical field in a specific direction. When implanted with torque they may rotate for a certain time after implantation. Aim of this study was to evaluate whether and to which degree leads rotate in the first 24 hours after implantation using a sheep brain model. 

Methods: dDBS electrodes were implanted in 14 sheep heads and 3D rotational fluoroscopy (3D-RF) scans were acquired to visualize the orientation of the electrode leads according to Reinacher et al. 2017. Electrode leads were clockwise rotated just above the burrholes (180° n=6, 360° n=6, 2 controls) and 3D-RF scans were again acquired after three, six, 13, 17 and 24 hours, respectively.

Results: 180° rotated electrodes showed an initial rotation of 83.5° (range: 35.4°-128.3°) and a rotation of 114.0° (range: 57°-162°) after 24 hours. With 360° torsion, mean initial rotation was 201° (range: 3.3°-321.4°) and mean rotation after 24 hours 215.7° (range 31.9°-334.7°), respectively. 

Conclusion: Implantation of dDBS leads with torque (i.e.rotating the lead during implantation) should be avoided. Direct postoperative imaging may not be accurate for determining the rotation of dDBS electrodes if a torque is present.

 

Figure: Rotational deviation of implanted electrodes after applied torsion

180° applied torsion depicted in GREEN, 360° in RED and controls (0°) in BLUE 
A: Initial rotational deviation (timepoint 0h) and in follow-up. B: Absolute deviation in relation to the rotation after applied torsion. 

Peter C. REINACHER (Freiburg, Germany), Volker Arnd COENEN, Horst URBACH, Karl EGGER, Alexander RAU
00:00 - 00:00 #23995 - Deep brain stimulation: Shaving versus not shaving?
Deep brain stimulation: Shaving versus not shaving?

INTRODUCTION

Deep brain stimulation (DBS) is a widely described technique with excellent results for some movement disorders resistant to pharmacological treatment. The reported infection rates are less than 4%. Usually, shaving the scalp is widespread in surgical practice; however, there is conflicting evidence to decrease or increase the risk of infection.

 

OBJECTIVE

We report two cases not shaving all scalp, and we describe the technique step by step.

 

METHODS

We present two cases diagnosed with Parkinson's disease (PD) resistant to pharmacological treatment.

Casse 1. 59-year-old woman with PD for 12 years, the last 3 years worsening of simple motor fluctuations. Currently with Levodopa/Carbidopa, Rasagilene, Amantadine. L-dopa test (UPDRS III) OFF=62, ON=11.

 

Case 2. 46-year-old woman with PD for 7 years, last year worsening of upper limb stiffness, bradykinesia and freezing of gaitCurrently with Levodopa/Benserazide, Levodopa/Carbidopa, Safinamida, Opicapona. L-dopa test (UPDRS III) OFF=45, ON=9.

Taking into account symptoms and poor control with pharmacological treatment, we proposed to perform DBS in the bilateral subthalamic nucleus (STN). Patients understand and accept informed consent.

 

RESULTS

The night before and the morning of the surgery, the head is washed with povidone-iodine, the Leksell stereotaxic frame is placed, the intraoperative CT (AIRO) is obtained, for subsequent fusion with the brain MRI, and we obtained the coordinates. We shave only the incision area, the surgical field and transparent dressing are put on.

Bilateral frontal burr-hole were performed wiht local anesthesia, NST  micro-recording and micro-stimulation was obtened, improvement symptoms and without side effects, definitive electrodes were implanted; Intraoperative CT confirms the correct lead placement, without complications. Immediately after, under general anesthesia, a pulse generator is implanted. Antibiotic prophylaxis with Cefazolin 2gr IV, Vancomycin 500mg diluted in SSF 0.9% 500ml. On the third day the stimulation is ON, and  the fourth post-surgical day the patient is discharge.

During follow-up, mean 10.5 months, wounds in perfect condition, improvement of symptoms UPDRS III ON medication - ON stimulation: 9; Levodopa dose reduction of 70%.

 

CONCLUSIONS

In our hospital, we usually shave the head completely to perform DBS surgery; however, applying this protocol we have obtained very good results, without presenting infections or healing problems, and the patients preferred it for its aesthetic and psychological results in the postoperative period.

Luis Mariano ROJAS-MEDINA (Madrid, Spain), Lucia ESTEBAN-FERNANDEZ, Freddy SALGE-ARRIETA
00:00 - 00:00 #23462 - Directional Lead in Deep Brain Stimulation for Parkinson's Disease - Hong Kong Experience.
Directional Lead in Deep Brain Stimulation for Parkinson's Disease - Hong Kong Experience.

Deep Brain Stimulation (DBS) for Parkinson's Disease (PD) was first performed in Hong Kong in 1997.  More than 300 cases had been operated using conventional ring electrodes.  Directional Lead was introduced since March 2018.  Totally 9 patients with 17 directional leads had been implanted.  We reviewed the clinical outcome including UPDRS III moto scores, clinical assessment, system-related complication and drug dosage reduction.

Tak Lap POON (Hong Kong, Hong Kong)
00:00 - 00:00 #23911 - Emergency deep brain stimulation in a girl with dystonic storm due to GNAO1-associated hyperkinetic-dystonic movement disorder.
Emergency deep brain stimulation in a girl with dystonic storm due to GNAO1-associated hyperkinetic-dystonic movement disorder.

Background:

Mutations in the GNAO1 gene, encoding for a G-protein subunit, are associated with a hyperkinetic-dystonic movement disorder and mental retardation as well as an epileptic encephalopathy. Patients with the movement disorder show continuous hyperkinetic movements of variable degree with frequent exacerbations during minor illness, pain or surgery resulting in life-threatening dystonic storms. Various medications such as clonidine and tetrabenazine are used both to prevent exacerbations and as options in the acute treatment of dystonic storms. Sedation, analgesia and relaxation may be required to terminate the crisis. Deep Brain stimulation (DBS) has shown to be effective in preventing exacerbations. We report the case of an adolescent girl with refractory dystonic storm and emergency implantation of DBS.

Case report:

The 16 year old teenager presented repeatedly with dystonic states and rhabdomyolysis (max. CK 100.000 U/ml) requiring ICU treatment. In most events, balanced sedation with continuous hydromorphone, clonidine infusions and midazolam bolus plus oral clobazam and tetrabenazine was sufficient to control the hyperkinetic movements. During the last episode, even maximum doses of this treatment combination were insufficient to control the symptoms. As the patient developed impaired bowel passage and hemorrhagic colitis due to the prolonged dystonic storm, emergency stereotactic implantation of DBS electrodes in the globus pallidus internus (GPI) was performed. Shortly after activating the stimulator (manufacturer?), symptoms resolved and the medication could be tapered to zero over three weeks without recurrence of symptoms. Only low dose dronabinol was added to reduce spasticity.

Conclusion:

Emergency implantation of GPI DBS in dystonic state due to GNAO1 mutation is feasible and may be effective to terminate dystonic storms.

Assel SARYYEVA (Germany, Germany), Jan-Christoph SCHOENE-BAKE, Thomas JACK, Eva BUELTMANN, Hans HARTMANN, Joachim K. KRAUSS
00:00 - 00:00 #26270 - Evidence of possible bias in pre-surgical assessment of Parkinson’s disease using levodopa challenges.
Evidence of possible bias in pre-surgical assessment of Parkinson’s disease using levodopa challenges.

IntroductionParkinson’s disease (PD) patients who no longer reliably respond to medication may be treated with deep brain stimulation (DBS). Whether DBS is appropriate for a given patient is assessed, in part, by a levodopa challenge, in which a patient will undergo the MDS-Unified PD Rating Scale (MDS-UPDRS) part-3 assessments before and after taking levodopa. However, a significant fraction of patients do not benefit sufficiently from DBS to justify the attendant surgical risk and cost of the procedure. This suggests the process of selecting patients for DBS intervention could be improved. 

 

Because motor requires subjective ratings of disease severity, by unblinded clinicians, a rater bias could result in a patient receiving, or being denied, treatment inappropriately. We investigated whether there is an identifiable bias in levodopa challenges when conducted for the purpose of surgical pre-assessment, as compared to levodopa challenges conducted during clinical trials that do not involve patients being considered for surgical treatment. 

 

Method: The dataset consists of 180 levodopa challenges on 146 different patients, conducted at six different sites and by a variety of assessors, collected using the KELVIN-PD™ platform. Of these, 93 were conducted for pre-surgical assessment for DBS, while the remaining 87 were conducted as part of a pharmaceutical clinical trial (see Figure 1). 

 

The null hypothesis was that these two groups would see a similar level of improvement, as measured by the improvement in UPDRS part-3 score between the ‘off levodopa’ and ‘on levodopa’ assessments. We tested this hypothesis by two methods. 

 

Firstly, we considered whether a patient was undergoing pre-surgical assessment as a boolean variable (1 meaning they are, 0 otherwise), alongside the ‘off levodopa’ rating, within a linear regression model to predict the ‘on levodopa’ rating. The coefficient of this boolean being significantly different from zero would be consistent with the hypothesis that there exists a systematic bias when PD patients are assessed for DBS surgery.

 

Secondly, we computed the distribution of percentage improvements for both groups, and performed a Mann-Whitney test for difference in distributions. The Mann-Whitney test was chosen because as a non-parametric method for testing whether one distribution’s mean is significantly greater than another. 

 

For this second analysis we controlled for baseline disease severity (off levodopa UPDRS part-3), because we observed that percentage improvement had a weakly significant correlation with baseline rating (Pearson’s r = -0.149, p-value = 0.046). We controlled for this by conducting the analysis on a subset of 80 levodopa challenges, selected such that the distribution of baseline rating among patients was identical between the surgical and pharmaceutical trial groups (see Figure 2). 

 

Result:

The average improvement in UPDRS part-3 score was 40.9% among the pharmaceutical trial group, and 55.1% among the surgical assessment group. 

 

Our first test found the linear regression model coefficient of the surgical assessment boolean to be significantly different from zero (F1,178 = 10.2 , p < 0.01), with a mean estimated value of -5.3 (see Table 1).

 

Our second test found the difference between the distributions of these percentage improvements to be highly significant (Mann-Whitney’s U = 552, p-value < 0.01).

 

Conclusion:

While further work is required to exclude the possibility of systematic differences between pre-surgical and other patients, these results are consistent with there being a clinically significant bias in levodopa assessments when conducted on patients being considered for DBS, and that this bias equates to approximately a difference of 5.3 on the UPDRS part-3. 

 

Should further work bear this result out, it would suggest that extra care should be given to objectively assess patients who are being considered for DBS. 

 

Blinded rating might go some way towards removing any bias, although this may be logistically challenging. Alternatively, true objectivity may be achieved through algorithmic measurement of motor function. 

Gareth MORINAN, Jonathan O'KEEFFE (London, United Kingdom)
00:00 - 00:00 #23655 - Freezing of Gait as a Complication of Bilateral Pallidal Deep Brain Stimulation in a Patient with Tardive Dystonia.
Freezing of Gait as a Complication of Bilateral Pallidal Deep Brain Stimulation in a Patient with Tardive Dystonia.

Background

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective and well-tolerated treatment for different forms of generalized, focal and segmental dystonia. Impressive results have been reported in patients with tardive dystonia (TD). GPi DBS affects the pallidal outflow on normal limb function causing the bradykinetic symptoms seen often in patients especially in focal and segmental dystonia. The aim of this case report is to present a patient with TD who developed a bradykinetic symptom mainly freezing of gait due to bilateral monopolar GPi stimulation.

Methods

We present a patient who was treated by GPi DBS for TD. The patient underwent staged bilateral implantation of DBS leads (Medtronic, Minneapollis, Minnesota, USA).  The formal objective assessment included Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The patient was assessed preoperatively and at 3, 6, and regular 12 months postoperative visits. The follow-up reached 60 months.

Results

The patient gained significant improvement of his TD till 48 months. The motor part of BFMDRS scores when compared to baseline scores improved by 70 %, 84 % , 25 % at 3, 12 and 48 months, respectively. The functional part of BFMDRS scores when compared to baseline scores improved by 75 %, 82 % , 30 % at 3, 12 and 48 months, respectively. At nearly 48 months follow-up, the patient experienced rapid reoccurrence of TD. Skull, neck and chest  x-rays, as well impendence measurements were within normal range. Changing the stimulation polarity from bipolar to monopolar resulted in nearly complete resolution of TD. After 2 months of continuous bilateral monopolar GPi DBS this patient developed freezing of gait. This bradykinetic symptom is not bothersome to patient over the ensuing 2 years of follow-up. 

Conclusion

Although GPi DBS has shown its efficacy in patients with focal or segmental dystonia, the influence of GPi DBS on nondystonic body regions deserves further investigation. Probably the co-stimulation of pyramidal tracts by monopolar than bipolar stimulation polarity may cause bradykinetic symptoms in patients with focal, segmental dystonia who underwent GPi DBS.

Michał SOBSTYL (Warsaw, Poland), Angelika STAPIŃSKA-SYNIEC, Anna KUPRYJANIUK
00:00 - 00:00 #23960 - Globus pallidus internus deep brain stimulation for the treatment of axial dystonia.
Globus pallidus internus deep brain stimulation for the treatment of axial dystonia.

Introduction

 

Axial dystonia is a rare phenotype of segmental dystonia that predominantly affects the trunk with occasional contiguous spread to the cranio-cervical junction. It is usually medically refractory and poorly controlled with Botulinum toxin injection. The truncal dystonia causes major morbidity and significant impairment of quality of life. Based on the experience with deep brain stimulation (DBS) of the Globus Pallidus internus (GPi) for other forms of dystonia, we report three cases of axial dystonia from different aetiologies that benefited from bilateral GPi DBS

 

Methods

 

Three male adult patients with axial dystonia due to tardive dystonia, dystonia associated with Parkinson’s disease and idiopathic adult-onset axial dystonia underwent comprehensive multidisciplinary assessment prior to implantation of DBS systems. Dystonic symptoms severity was quantified using the Burke-Fahn-Marsden Dystonia Rating Scale Movement Score (BFMDRS-M). 

 

Results

The mean age at surgery was 52.6 years (48 – 55 years) and disease duration was in the range of 4 – 15 years. The follow-up period was between 9 and 141 months. In each case, significant control of truncal dystonic symptoms was achieved. The mean improvement in the BFMDRS-M scores was 79.3 % (71.2 – 88.9%). All patients also experienced significant improvements in their quality of life and were able to reintegrate into society. Rapid improvement (hours to days) was noted in blepharospasm and cervical dystonia with more delayed improvement (weeks to months) seen with truncal control.  Symptom control deteriorated when the implantable pulse generators were near or completely depleted. Only one patient had stimulation-related side effect which was managed with adjustments of the stimulation parameters.  

 

Conclusion

Bilateral GPi DBS is a viable surgical option the management of medically refractory axial dystonia irrespective of aetiology. Careful patient selection and management within a multidisciplinary team is crucial for ensuring best outcomes.

 

Kantharuby TAMBIRAJOO (London, United Kingdom), Luciano FURLANETTI, Michael SAMUEL, Keyoumars ASHKAN
00:00 - 00:00 #23895 - Imaging insights of isolated idiopathic dystonia: a voxel-based morphometry study and meta-analysis.
Imaging insights of isolated idiopathic dystonia: a voxel-based morphometry study and meta-analysis.

Background

Neuroimaging have demonstrated structural changes of wide-spread brain regions in patients with dystonia. However, the understanding of brain abnormalities across different isolated idiopathic dystonia and how they contribute to the clinical outcomes remains poorly understood.

Objectives

To investigate grey matter volume (GMV) abnormalities and their correlation with clinical outcomes in isolated idiopathic dystonia patients. 

Methods

We retrospect 73 isolated idiopathic dystonia patients using voxel-based morphometry (VBM) to investigate their GMV abnormalities and correlated with their clinical outcomes. In addition, a meta-analysis was conducted on 14 VBM studies.

Results

Our VBM study revealed decreased GMV in bilateral putamen shared in all types of dystonia compared to health controls. While increased GMV was observed in frontal, parahippocampa, middle temporal and inferior parietal gyrus. GMV increases were also observed in other regions, such as supramarginal, fusiform and lingual gyrus in subgroups. Left globus pallidus was the only increased region based on meta-analysis. Finally, there is a significant negative correlation between GMV and onset age. Trends of GMV increased in moderate-outcome group compared to superior-outcome group in several regions.

Conclusions

The shared abnormalities of putamen among all groups and globus pallidus from meta-analysis may indicate their pathophysiological roles. Altered brain regions, e.g. sensorimotor cortex, frontal and temporal cortex, were consistent with previous studies, which may likely be compensatory changes from our prospective. Future imaging predictors need to be further explored in those brain regions with multi-model imaging analysis.

Yunhao WU (Shanghai, China), Jie FENG, Yufei LI, Ming ZHANG, Chencheng ZHANG, Hongxia LI, Tao WANG, Bomin SUN, Yiwen WU, Dianyou LI, Hongjiang WEI
00:00 - 00:00 #26144 - Impact of subthalamic deep brain stimulation on motor and sensorimotor cortical oscillatory activity in free-moving hemiparkinsonian rats.
Impact of subthalamic deep brain stimulation on motor and sensorimotor cortical oscillatory activity in free-moving hemiparkinsonian rats.

Background

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

Objective

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

Methods

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

Results

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

Conclusion

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

Arif ABDULBAKI (Hannover, Germany), Theodor DOLL, Joachim K. KRAUSS, Kerstin SCHWABE, Mesbah ALAM
00:00 - 00:00 #22651 - Improving programming in Deep brain stimulation using the GuideXT Assisted Refinement and Optimisation Workflow (GROW).
Improving programming in Deep brain stimulation using the GuideXT Assisted Refinement and Optimisation Workflow (GROW).

Introduction

The best outcomes in Deep Brain Stimulation (DBS) are achieved when 3 factors align, appropriate patient selection, accurate lead placement, and optimal clinical programming. While advancements have been made in the identification of suitable candidates,  in the technology to plan surgery,   and  in the devices  to deliver stimulation,  only limited advances have been made to  improve the initial programming of DBS settings.  Additionally, with the advent of directional leads, clinical programming has become more complicated and is taking more time in clinical practice. In this study, we implement the use of GuideXT software, which enables us to virtually determine theoretical volumes of tissue activation (VTAs), to help refine and optimise programming in DBS patients.

Method

We used our GuideXT Assisted Refinement and Optimisation Workflow (GROW) on

16 patients with DBS for Sub thalamic nucleus  (STN) stimulation  who required refinement or optimisation. Eight were new implants, four patients had suboptimal outcome following DBS and four had good outcomes but were given the choice of further refinement using the software. The UPDRS and clinical side effects were noted pre and post refinement. All patients had directional DBS leads.

Results

New Implants

Five patients had intial DBS programming done without the use of the GuideXT software, the average time for initial programming was 90mins ±30. The average reduction in UPDRS 3 was 31   from 50 to 18, but there were issues with dyskinesia, inadequate tremor control, dystonia, and speech symptoms. Using the GuideXT software allowed resolution of these problems in 4 out of the 5 patients.

In three patients GuideXT was used before initial programming; this reduced the clinic time for initial programming from 90mins to 45mins ±15. However the patients did require further clinical refinement in all cases.

Suboptimal DBS

In this historical group, the patient had significant improvement following DBS implant but suffered from side effects (e.g. dystonia ). Using GuideXT the side effects were reduced in 3/4 patients.

Refine DBS

These patients were happy with their programming, average UPDRS 3 of 10, however, when offered to try an alternative program refined on GuideXT softeware. 2 out of the 4 patients chose the GuideXT refined program as their endpoint, reporting improvements in balance and speech symptoms.

 

Conclusion

GROW has shown to help salvage and optimise historical patients with significant side effects as well as refine and improve outcomes in patients who already have good outcomes. More importantly, GROW can reduce time taken to get to the optimal program by reducing programming time and number of visits required to get the optimal settings.

Mohammed HUSSAIN (Newcastle, United Kingdom)
00:00 - 00:00 #22508 - Is DBS really successful in Lance-Adams Syndrome?
Is DBS really successful in Lance-Adams Syndrome?

Lance-Adams syndrome(LAS) is the chronic type of posthypoxic myoclonus which occurs after succesful cardiopulmonary resuscitation. The detailed pathophysiology of chronic post-hypoxic myoclonus is still not well known. Here, we present a case of a 40-year-old woman who developed myoclonus after cardiopulmonary arrest (CPA) after her first cesarean delivery at age of 26. The patient underwent imlantation of bilateral GPi-DBS about 12th years into her disease course. Myoclonus in this patient was ameloriated with Gpi stimulation. In the literature, there have been worldwide around 100 patients who diagnosed LAS and only four cases of LAS treated with deep brain stimulation. Bilateral Gpi-DBS may offer a safe and effective treatment for refractory cases of LAS. Here, we present the fifth case of LAS after cardiopulmonary arrest during delivery, who was treated with DBS, and review all the cases in the light of the literature.     

Gulsah OZTURK (Istanbul, Turkey), Selcuk PEKER
00:00 - 00:00 #23785 - Long term recording of human STN local field potentials in Parkinson’s disease after deep brain stimulation.
Long term recording of human STN local field potentials in Parkinson’s disease after deep brain stimulation.

Objective: to describe the continuous recording of subthalamic nucleus (STN) local field potentials (LFPs) and their response to electrical stimulation and sleep in a Parkinsons disease (PD) patient after STN deep brain stimulation (DBS).

 

Background: STN DBS improves motor symptoms and quality of life in PD patients suffering from disabling motor complications under optimized medical therapy. Stimulation parameters are classically set during assessment of clinical benefits and adverse effects derived from the combination of several variables, namely selected contact and energy-related parameters. STN beta-band LFPs correlate with bradykinesia and rigidity in PD patients, suggesting their usefulness as clinical surrogate markers. However, real world data on this matter is currently scarce.

 

Methods: We describe new real world long term (>6 weeks) data concerning LFP recording and response to stimulation and sleep in a PD patient. A 70-year old female with PD motor symptoms for more than 10 years, and disabling motor complications under optimized medical therapy was offered STN DBS. The procedure was performed under local anesthesia. Final electrode location was selected after micro-electrode recording using 3 trajectories per hemisphere and assessment of clinical benefits derived from intra-operative stimulation. A new generation implantable pulse generator (IPG) incorporating the ability to sense and chronically record LFPs was placed in infraclavicular position. LFPs were recorded since the immediate post-operative period.

 

Results: LFPs were successfully recorded. During awake time, while off dopaminergic medication and off stimulation, the beta-band power is much higher. Turning on the stimulation causes an immediate decrement of beta-band power, and a “ceiling effect” is clearly seen as stimulation amplitude reaches a maximally suppressed beta level without further impact of stimulation escalation. Beta-band power is lower during sleep, even without night time dopaminergic drugs and presents an oscillatory pattern. All these findings are noticeable in both brain hemispheres.

 

Conclusions: real world LFP recording after STN DBS in PD is a straightforward process. Beta-band LFP power is clearly influenced by electrical stimulation parameters and sleep, and correlates with clinical benefits. Further research might provide valuable clues to guide the optimization of DBS parameters in these patients.

Manuel PINTO (Porto, Portugal), Ana OLIVEIRA, Clara CHAMADOIRA, Rui VAZ, João MASSANO
00:00 - 00:00 #21902 - Long-term Outcome of Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease.
Long-term Outcome of Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease.

Background

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been accepted as an effective treatment for severe Parkinson’s disease (PD). Randomized and controlled studies have demonstrated that STN DBS is more effective in advanced PD than medical treatment. Although there have been some reports of long-term efficacy and safety after deep brain stimulation (DBS) surgery for Parkinson’s disease (PD), little is known about the fate of all patients. We performed a follow-up of all patients who undergone bilateral subthalamic nucleus (STN) DBS surgery for PD before more than 10 years, and assessed the survival rate and long-term outcome of DBS.

Methods

We included all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to Mar 2008 at single institution. Whether or not the patients were alive or dead was investigated, and pre- and postoperative follow-up assessments including UPDRS score were analyzed. 

Results

The mean age at the time of surgery was 72 years (range, 27-82), and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from the DBS surgery to death was 110.46 ± 40.8 months (range, 0-155). Thirteen patients (37.1%) died because of disease progression, followed by 11 patients (31.4%) died due to pneumonia. The cumulative survival rate was as follows: 98.8 ± 1.2% (1 yr), 97.5 ± 1.7% (3 yr), 95.1 ± 2.4% (5 yr), and 79.0 ± 4.5% (10 yr). Of the 46 surviving patients (57%), 36 continued to receive follow-up assessment including the UPDRS scale, but 10 survivors denied follow-up at hospitals due to economic cause or inability to move. Twelve patients (14.8%) underwent revision surgery to correct the electrode location, and the mean interval period between DBS and revision surgery was 14.5 months.

Conclusions

STN DBS is a safe and effective treatment in selective patients with PD. This study was based on the long-term follow-up of large-scale patients, and would contribute to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD. 

Park HYERAN (SEOUL, Korea, Republic of)
00:00 - 00:00 #22502 - Management of Cervical Dystonia Patient with Deep Brain Stimulation During Pregnancy and Review of the Literature.
Management of Cervical Dystonia Patient with Deep Brain Stimulation During Pregnancy and Review of the Literature.

Deep brain stimulation(DBS) can provide psychosocial and functional improvement in medically refractory  cervical, segmental or generalised moderate to severe dystonia patients. After the DBS treatment of women with dystonia patients, becoming pregnant can be planned. There is a lack of certain published knowledge on pregnancy and DBS. We report  a 24-year-old female patient with cervical dystonia implanted with bilateral GPi-DBS who became pregnant during five years follow-up period after DBS surgery and delivered a healthy baby by caesarean  section under general anesthesia. We review the management of pregnancy in DBS treated dystonic patients with the other published cases in the literature. Based on this review  DBS with rechargeable battery system is effective and safe treatment method in dystonia  during pregnancy period.

Gulsah OZTURK (Istanbul, Turkey), Selcuk PEKER, Gokalp SILAV
00:00 - 00:00 #26186 - MDS UPDRS Item-Based Rigidity and Postural Stability Score Estimations: A Data-Driven Approach.
MDS UPDRS Item-Based Rigidity and Postural Stability Score Estimations: A Data-Driven Approach.

BACKGROUND AND OBJECTIVE

As the second most common chronic neurodegenerative disorder, Parkinson’s disease (PD) affects around 7-10 million people in the world. Patients with PD need to consult regularly for medical care, of which the access may be limited due to geographical and other socioecomonic issues. The telemedicine refers to the remote exchange of medical information for the purpose of providing medical care by means of telecommunication technology. Increasing evidence has suggested the feasibility of the telemedicine in PD. The ongoing global sanitary crisis of coronavirus disease 2019 also emphasizes the necessity of the popularization of the PD telemedicine. However, Among the disadvantages of telemedicine is the impossibility of the complete evaluation of the motor function for PD, as scored by the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III). Despite a modified version of the UPDRS removing rigidity and retropulsion items has been proposed2, its utilization has not been universally accepted. To overcome the difficulty of the scoring of rigidity and postural stability in the PD telemedicine, we investigated whether scores of rigidity and postural stability could be estimated by a combination of other items of MDS UPDRS-III through a data-driven approach. 

METHODS

The experimental dataset included 15763 MDS UPDRS score cases of 2131 patients obtained from the Parkinson’s Progression Markers Initiative (PPMI) database. We randomly selected 3322 cases of 426 patients as the external independent test set, and the remaining 12441 cases of 1705 patients were used for model training and validation. 27 scores of the other 16 items except rigidity and postural stability in the MDS UPDRS-III were taken as initial input features. Afterwards, we adopted a feature selection scheme based on a scoring system (DX score) to remove redundant irrelevant features. Finally, we used support vector machines (SVM) as classifiers to assess the scores of rigidity and postural stability. For the evaluation of model performance, we defined e as the absolute difference between the rater’s score and the predicted score. Due to the subjectivity of raters and inter-rater variability in clinical practice, the classification error of e ≤ 1 is considered acceptable.

RESULTS

There were no significant differences between the model training/validation dataset and the external independent dataset of PPMI regarding demographic and clinical features. The results of 5-fold cross-validation and independent test are shown in Table 1. In the model training and validation dataset, the predictive accuracy of the rigidity subscores was between 92.23% and 96.48% when e ≤ 1, and between 63.38% and 66.27% when e = 0. Similarly in the independent test set of PPMI, the accuracies of rigidity score predictions were between 90.70% and 96.27% when e ≤ 1, and between 59.87% and 67.82% when e = 0. The average accuracy of the rigidity total score estimation was 94.95% in the five-fold CV dataset and 93.32% in the independent dataset. For the postural stability score estimation, the predictive accuracy was 96.08% and 87.69 when e ≤ 1 and e = 0, respectively. Similar results were obtained in the independent test set of PPMI (95.64% and 87.63 when e ≤ 1 and e = 0, respectively). The best features selected by the optimal parameters of SVM for the corresponding rigidity subscore and retropulsion test score prediction were shown in Table 2. 

DISCUSSION

To the best of our knowledge, our study firstly demonstrated a data-driven algorithm to estimate the rigidity and postural stability scores of MDS UPDRS-III based on other items that could be evaluated visually and remotely. Our model respectively estimated the total score of rigidity and retropulsion test with an acceptable average accuracy.

CONCLUSION

The robustness of our algorithm warrants further refinement and validation in larger independent cohort and this model may be suitable for stiffness and retropulsion test score estimation in PD telemedicine in the future.

Zhengyu LIN (Shanghai/Lyon, China), Rui GUO, Chencheng ZHANG, Dianyou LI, Xiaohua QIAN, Bomin SUN
00:00 - 00:00 #23918 - Monitoring Cognitive and Emotional Functioning of Patients with Parkinson’s Disease after Unilateral Deep Brain Stimulation of the Subthalamic Nucleus – Preliminary Results from the 12-month Follow-up.
Monitoring Cognitive and Emotional Functioning of Patients with Parkinson’s Disease after Unilateral Deep Brain Stimulation of the Subthalamic Nucleus – Preliminary Results from the 12-month Follow-up.

Objective:

The primary goal of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with advanced Parkinson’s disease (PD) is the improvement of health-related quality of life by a significant reduction of motor symptoms. However the relationship between STN DBS and cognitive-emotional functioning of these patients are still not consistent. In some studies, patients’ cognition either improved or did not worsen, in other – progressively deteriorated. Some studies emphasize that unilateral STN DBS may represent a risk factor for decrements in cognition and mood.

The presented study aimed to determine the safety of unilateral STN DBS for emotional and cognitive functioning, using questionnaires and neuropsychological tests for attention, memory, and executive functions.

 

 

Methods:

The study gained approval from the local Bioethics Committee, and all PD patients gave their written informed consent prior to participation. Exclusion criteria included a history of other than PD neurological diseases, psychiatric disorders or significant cognitive decline (assessed with Addenbrooke’s Cognitive Examination III, ACE-III).

Study participants underwent clinical evaluation at baseline in the off and on medication states by applying Unified Parkinson’s Disease Rating Scale (UPDRS) part I to IV, Hoehn and Yahr scale (H/Y), Schwab and England scale (S/E) and Parkinson’s Disease Questionnaire – 39 (PDQ-39). They were also subjected to 3 neuropsychological assessments: one preoperative and 2 postoperative at 6, and 12 months since unilateral STN DBS. All neuropsychological assessments were performed in the on medication state and included: six tests from CANTAB battery (Motor Screening Task, MOT; Reaction Time, RTI; Rapid Visual Information Processing, RVP; Pattern Recognition Memory, PRM; Paired Associates Learning, PAL; Multitasking Test, MTT), Auditory Verbal Learning Test (AVLT), Digit Span from WAIS-R (DS), and Beck Depression Inventory (BDI).

 

Results

Among 38 PD patients with unilateral STN DBS, 26 patients completed the 6 months follow-up assessment, and 15  – the 12-month follow-up. There was one death unrelated to surgery within 6 months, and one patient required partial hardware removal due to an infection after 6 months.

The preliminary analyzes were performed in a group of 15 patients [8 males; mean age: 62.5, (SD - 7.1) years; mean ACE-III score: 91.4 (SD 8) points].

None of the cognitive tests used, revealed any significant deterioration in cognitive performance. Moreover, patients slightly but significantly improved in CANTAB RVP test [chi2(2) = 7.17, p = 0.028, Kendall W = 0.3].

Neither positive nor negative effects of unilateral STN DBS were observed in Beck Depression Inventory (chi2(2) = 1.33, p = 0.513, Kendall W = 0.06).

The analyses of postoperative clinical evaluations with UPDRS revealed significant improvements in the on medication state compared to baseline. The improvements were noted in part II [chi2(2) = 16.75, p = 0.001, Kendall W = 0.56] , and part III [chi2(2) = 23.16, p = 0.001, Kendall W = 0.77].  The UPDRS part IV showed significant decreased of complications of levodopa-induced dyskinesia [chi2(2) = 22.53, p = 0.001, Kendall W = 0.75]. Clinical and functional improvement as measured by H/Y and S/E scales, comparing the baseline and 12-month follow-up assessment was observed in 10 (67%) and 12 (80%) participants, respectively. However, self-evaluated functioning as measured by PDQ-39 seemed stable [chi2(2) = 2.09, p = 0.353, Kendall W = 0.09].

 

Conclusions:

Our preliminary results showed no significant cognitive and emotional decrement in 6 and 12 months follow up after unilateral DBS-STN. Interestingly in one cognitive measure assessing attention, and speed of information processing, a significant improvement was revealed. Like previous studies, our analyzes also confirmed significant motor and quality of life improvement after unilateral STN DBS in PD patients. The continuation of this study is warranted with longer follow-up and incorporation of more participants.

Szczepan IWAŃSKI (Warsaw, Poland), Katarzyna POLANOWSKA, Michał SOBSTYL, Angelika STAPIŃSKA-SYNIEC, Aleksandra ZIELIŃSKA, Marcin LEŚNIAK, Joanna SENIÓW
00:00 - 00:00 #23976 - MR-guided High Intensity Focus Ultrasound for treatment of post traumatic tremor: a case report.
MR-guided High Intensity Focus Ultrasound for treatment of post traumatic tremor: a case report.

Introduction: Posttraumatic tremor (PTT) does not represent a uniform syndrome and it refers to a series of atypical tremors that occur secondary to traumatic brain injury. The majority of tremors loosely defined as post-traumatic tremors (PTT) also fill the criteria for Holmes tremor (HT); HT has been defined as a low frequency tremor (below 4,5Hz), present at rest and exacerbated with posture and intensified with action and typically accompanied with ataxia and/or dysmetria, that appear up to 24 months after brain surgery, tumors, stroke or traumatic brain injury. Pharmacological treatment is usually unsuccessful in PTT, leaving stereotactic surgery as a rescue option. However reports on deep brain stimulation (DBS) for treatment of HT are odd, heterogeneous regarding effectiveness and lacking of information in target details and tremor semiology. MR-guided High Intensity Focus Ultrasound (MRgFUS) has recently gained interest as being a noninvasive alternative to conventional neurosurgery in treating essential and Parkinson tremor.

Material & methods: We present a case of 36 years old female, with past medical history of severe traumatic brain injury after a car accident at the age of four. Recovery was evident after 14 days, when she presented mild dysarthria, postural and kinetic tremor in left upper limb and spasticity according to previous medical notes. Her first neurological examination revealed scanning dysarthria, incoordination of both right upper limb with mild dysdiadochokinesia; postural and intention tremor was present in left upper limb. She had spasticity of both upper & lower limbs mainly on her left hemibody with pyramidal type of weakness. Her tandem walking was possible without ataxic gait. She didn´t have voice, mandible or cephalic tremor. Tremor didn´t influence in her daily basic activities but it made difference in her professional life as nurse assistant. The ventral intermedius nucleus (VIM) of the thalamus was the selected target to make a lesion with MRgFUS on 3 Tesla MRI (Insightec®); density skull score was calculated (0.45) with CT. A brain MRI 3T Siemens with T1 MPRAGE, T2 SPACE, T2 FLAIR and DTI scan sequences were used for location of corticospinal tract and dentatorubrothalamic tract (DRT) with SyngoVia® and Brainlab® softwares.

Sonications were carried out, obtaining an average temperature of 61ºC at target.

Results: There was a tremor reduction of 90% according to Clinical Rating Scale for Tremor (Section A 90%, section B 70% and section C 90%) at 6 months follow up. And a control brain MRI (T2 sequences) at this time, showed a lesion on right VIM of 0.022cm3 and changes on the DRT.

Conclusions; MRgFUS was effective and safe to treat PTT in our patient. This is to our knowledge the first case reported of PTT treated with MRgFUS. More studies should be needed to generalize this result as MRgFUS could be consider a noninvasive neurosurgical treatment for PTT.

Alana ARCADI (Pamplona, Spain), Jorge GURIDI, Iciar AVILES, Lain GONZALEZ-QUARANTE, María Cruz RODRÍGUEZ, María GOROSPE
00:00 - 00:00 #23981 - Pallidal Deep Brain Stimulation for involuntary movement afteranti-N-methyl-D-aspartate (NMDA) receptor encephalitis.
Pallidal Deep Brain Stimulation for involuntary movement afteranti-N-methyl-D-aspartate (NMDA) receptor encephalitis.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is caused by antibodies against NR1/NR2 heteromers and results in a characteristic neuropsychiatric syndrome. Dalmau et al. reported that 90 % of the patients are women, the majority of whom have ovarian teratomas. About 10 % of anti-NMDA receptor encephalitis patients are men. The tumor complication rate is low at 20 %. Most patients temporarily develop involuntary movements during the course of the disease. We report the effect of globus pallidus internus (GPi)-deep brain stimulation in a patient with postural dystonia of the limb with orofacial dystonic movements for more than five years after recurrence of anti-NMDA receptor encephalitis. A 13-year-old boy developed psychiatric symptoms such as polyphrasia and agitation at the age of 5 years. Cerebrospinal fluid examination revealed antibodies against NMDA receptors. No major complications including teratoma were evident. Therefore, the diagnosis of anti-NMDA receptor encephalitis was made and he received immunosuppressive therapy. He had residual epileptic seizures and, gradually developed left-side dominant postural dystonia. At the age of 8 years, he developed dysarthria and exacerbation of the left side symptoms. This was diagnosed as recurrence of encephalitis. Immunosuppressive therapy was administered again. However, his symptoms progressed and he also developed dystonia of the limb and trunk, orofacial dyskinesia including grimacing, masticatory-like movements, forceful jaw open-close, dysphonia, and seizures. Various medications were tried but their effects on his involuntary movements were minimal. Fluid-attenuated inversion recovery magnetic resonance imaging showed mixed high and low signals in the bilateral striatum and pallid spheres. 99 m Tc-ethyl-cysteinate dimer single-photon emission computed tomography examination showed hypoperfusion of the bilateral striatum and the insula gyrus. We diagnosed this as generalized dystonia due to the sequelae of encephalitis. The patient underwent bilateral GPi-DBS under general anesthesia with microelectrode recordings. The recordings during the trajectory revealed a general decrease in neural activity in the basal ganglia. We inserted electrodes from the coronal sutures and identified the optic tracts. Boston Scientific Vercise Cartesia Directional Leads were placed 2 mm apart from the optic tract bilaterally. The patient’s facial involuntary movements improved around 1 month postoperatively and his dystonia symptoms in the limbs also improved thereafter. Six months after surgery, his postural dystonic symptoms were mild and his weight had increased. The mechanism of involuntary movements in anti-NMDA receptor encephalitis is unknown in detail, and reports and effects of brain surgery for involuntary movements in anti-NMDA receptor encephalitis are limited. While these symptoms are temporary in most cases, synaptic disturbances result in a loss of control of motor circuits in some cases.Although the intraoperative microelectrode recording of the present case suggested neuronal shedding in the extensive basal ganglia region, DBS was effective even in such a condition. Seventy-five percent of anti-NMDA receptor encephalitis patients have a good prognosis and the disease goes into remission. Although further studies are needed to determine how this disease progresses, DBS appears to be an effective treatment option in cases of residual refractory involuntary movements.

Takefumi HIGASHIJIMA (Yokohama, Japan), Takashi KAWASAKI, Katsuo KIMURA, Yu TSUYUSAKI, Hitaru KISHIDA, Katsumi SAKATA, Tetsuya YAMAMOTO
00:00 - 00:00 #23821 - Preliminary experience with the use of robot assisted laser interstitial thermotherapy in functional neurosurgery.
Preliminary experience with the use of robot assisted laser interstitial thermotherapy in functional neurosurgery.

laser  interstitial thermotherapy (LITT) has been described in neurosurgery oncology to treat brain metastases, primary tumors and post-radiation necrosis with an excellent safety profile. The ILTT procedure appears as an alternative mini-invasive modality in functional neurosurgery. We report our preliminary results on the use of this procedure under robot-assisted stereotactic

Four patients benefited from this procedure in our center for indications in functional neurosurgery. The average age of the patients was 55.5 years (min: 35, max: 85 years). The indications were: hypothalamic hamartoma (n = 1), essential tremor (n = 1), hippocampal sclerosis (n = 1), chronic pain (n = 1). We do not observe any intraoperative or immediate postoperative complications in particular. No haemorrhagic or neurological deficit complication was noted. Postoperative recovery was rapid allowing a short hospital stay of 4.75 days (min: 2 days, max: 8 days). The ILTT procedure under assisted stereotactic seems to be an effective and safe method for indications in functional neurosurgery. 

Meshal JAREBI (Amiens), Michel LEFRANC, Johann PELTIER
00:00 - 00:00 #26080 - Quantifying stridor associated with parkinsonism and deep brain stimulation a case report.
Quantifying stridor associated with parkinsonism and deep brain stimulation a case report.

Stridor is a recognisable harsh and high pitched inspiratory sound associated with impaired vocal fold abduction. In patients with Parkinsonism, it raises the suspicion of Multiple System Atrophy (MSA). Stridor is uncommon in Parkinson’s disease (PD) although cases have been reported. We present the case of a 54 year old male diagnosed with idiopathic PD who presented with stridor. The stridor was variable throughout the day but worst during off periods. The patient was put forward for DBS due to medical refractory dyskinesias.  At time of initial assessment he reported a 4yr history of mild stridor. Following DBS the stridor progressed and become distressful for him on exertion and intrusive in speech. Vocal fold examination 6 months post DBS identified a maximum vocal fold abduction of 4-5mm, at 9 months this was limited to 2.5mm and the possibility of a tracheostomy was discussed.

As the stridor was known to be responsive to medication it was considered feasible that careful adjustment of stimulation might improve it there by delaying or preventing the need for a tracheostomy.  The patient was systematically assessed with and without medication.  A monopolar review aiming to reduce stridor while maintaining motor function was carried out, using both conventional (60 us & 130Hz) and novel approaches, including frequency modulation, the use of shorter pulse width (30us), and directional screening at the vertical level of the chronically used contacts. To quantify the severity of stridor, the patient read a short standard passage following a period of exertion. The laryngograph technique, commonly used in voice clinics was used to provide information on vocal fold behaviour throughout the opening closing cycle in each condition. An audio recording was rated using a perceptual speech assessment (DAB).

Inclusion of medication was found to mildly reduce vocal fold frequency irregularity (IFx 49.91% to 37.89%) caused by high frequency stridor and improved speech on the perceptual scale (14/42-25/42). Use of optimised stimulation settings were successful in markedly improving his speech further (24/44/ 30/42), reducing the stridor and eradicating it in high frequency regions (IFx % 49.91% to 21.91%). UPDRS-III scores on stimulation pre- and post-optimisation (off/on medication) were 28/18 and 25/17 respectively. The stridor in isolation was noted to become increasingly periodic across conditions. At 6 week review the patient reported an experienced reduction in stridor and improvement in speech but an elevated vocal pitch reflective increased vocal fold tone.  Examination of the vocal folds post optimisation of stimulation found the glottic gap to be 7-8mm. The improved glottic gap did not sustain however and at 10 months the patient required a tracheostomy. 

In the absence of any other features to meet diagnostic criteria for MSA, we are treating this gentleman as a patient who has PD with stridor but will continue to observe if he develops autonomic features or other signs more suggestive of MSA. While there have been previous reports of stridor being induced or exacerbated by STN-DBS in PD, to our knowledge this is the first reported case illustrating the utility of neuromodulation in alleviating this problematic symptom and delaying the need for a tracheostomy. Furthermore it illustrated the usefulness of the laryngograph in objectively quantifying stridor severity in a non-invasive manner.

Timothy GROVER (London, United Kingdom), Viswas DAYAL, Alexis DE ROQUMAUREL, Adrian FOUCIN, Patricia LIMOUSIN, Tom FOLTYNIE
00:00 - 00:00 #24081 - Reduced cerebellar lobule volumes in essential tremor.
Reduced cerebellar lobule volumes in essential tremor.

Background

Essential tremor (ET) has been linked to cerebellar neurodegeneration based on symptoms and autopsies. Previous voxel-based morphometric investigations have indicated signs of cerebellar atrophy. However, the involvement of specific cerebellar lobules remains unclarified. Novel automated pipelines allow for segmentation of cerebellar lobules based on magnetic resonance imaging (MRI).

Objective

To volumetrically compare cerebellar lobules and gray matter volumes of ET patients with healthy controls (HC) using the Cerebellar Segmentation (CERES) pipeline.

Methods

Cerebellar segmentations of structural MRI scans of age- and gender-matched HC (n=70; from database) and ET patients (n=70) were performed using the CERES pipeline. Lobule-specific volume and gray matter differences between ET and HC were determined using t-tests corrected for multiple testing.

Results

ET patients demonstrated reduced volumes of the cerebellar lobules I-II, Crus II and VIIB as compared to HC. Moreover, decreased gray matter volumes of the cerebellum and lobules VI, Crus I, Crus II and VIIB were observed in ET as compared to HC.

Conclusions

Patients with ET demonstrated decreased cerebellar volumes and gray matter volumes of regions related to the first motor representation and cognitive areas. The results support the view of a neurodegenerative etiology underlying ET.

Richard ÅGREN, Amar AWAD, Patric BLOMSTEDT, Anders FYTAGORIDIS (Stockholm, Sweden)
00:00 - 00:00 #23946 - Single-centre analysis of precision and precision-influencing factors in deep brain stimulation.
Single-centre analysis of precision and precision-influencing factors in deep brain stimulation.

Introduction: Deep brain stimulation (DBS) is a surgical method used in neurological
motor disease, especially Parkinson's disease (PD), essential tremor (ET) and dystonia. Precision
and accuracy are essential for clinical efficacy, and due to the multi-staged nature of the procedure,
errors accumulate at multiple points. The aim of the present study was to measure the precision of
DBS at one Swedish center (implementing image-guided frame-based DBS-surgery without micro-electrode recording) and
to confi rm and find factors influencing targeting error. Finally, this was put into a clinical context to
asses the eff ect of targeting error on clinical outcome in a subset of PD patients.

Method: We retrospectively examined all DBS operations at Sahlgrenska University Hospital between
2010 and 2020 which amounted to 188 electrodes in 139 patients. 87 patients with 133 electrodes were
included in the final analysis. Pre-operative MRI images were co-registered to post-operative MRI or CT
images using proprietary software (Suretune 3, Medtronic). Both radial and euclidean errors were
calculated and related to age, hemisphere, type of post-op image (as a quality indicator),
intra-operative patient inclination, use of dural sealant, order of sides and target structure. For a subset of 21
PD patients, clinical improvement, measured as Levodopa-equivalent dose (LED) reduction, was also
related to precision.

Results: Median radial error was 1.1 mm (IQR 0.9; 95% CI 1.0-1.2) and median euclidean error was
1.7 mm (IQR 1.0; 95% CI 1.6-1.9). There was a signifi cant diff erence in radial and euclidean error
between hemispheres in favor of right-sided leads (p < 0.01 and p < 0.05 respectively). There was no
signif icant correlation between age and error of any type. Modality of post-operative imaging, the use of
tissue glue and patient position did not signif cantly aff ect targeting error. There was no statistical
association between error magnitude and clinical outcome, although the LED reduction 3- and 6-
month as well as 1-year post-op was highly signifi cant (p < 0.001) compared to the pre-operative dosage.
On average, euclidean error tended to point in a medial (median 0.75 mm), posterior (median 0.52
mm) and inferior (median 0.49 mm) direction compared to the target, suggesting a slight systematic
error.

Conclusion: Targeting error at our center has a magnitude comparable to that of other centers. The
present study was able to confi rm some of the factors thought to aff ect precision in DBS, although
the stability of both positive and negative findings may be limited by sample size, especially for the
clinical subgroup.

Linus KOESTER (Gothenburg, Sweden), Thomas SKOGLUND, Johan LJUNQVIST
00:00 - 00:00 #24001 - Spinal cord stimulation in Parkinson’s disease and Parkinsonism: 10 years later, review of the litterature and future prospects.
Spinal cord stimulation in Parkinson’s disease and Parkinsonism: 10 years later, review of the litterature and future prospects.

Background and purpose: More than 10 years ago, a preclinical study (Fuentès 2009) reported the “restoration of locomotive function in Parkinson’s disease by spinal cord stimulation“. Since that, various case reports and pilot studies suggested that SCS may be used as a therapy for motor and gait dysfunction in parkinsonian states. Is there anything new today on this subject, it’s the goal of this presentation.

Material and method. Data sources for this relevant literature search included usual publishers. We selected the latest and most inovative publications.

Results. Various pilot studies were presented. First line analysed symptom was the “Freezing of gait“, but dystonias as camptocormy or Pisa syndrome could be relevant indications. A preclinical study (Zhang 2019) suggested interesting hypothesis on SCS mechanism in extrapyramidal gait disorders.

Discussion. No RCT were published on the subject. Some problems were not resolved: speed was probably not a good primary outcome. Idem for patient selection and stimulation settings. New technologies in gait studies (fi. muscle synergies study) and spinal cord stimulation (fi. burst stimulation) could be an opportunity to taylor a high level RCT. About the mechanism, SCS probably restored a proper functoning of the spinal CPG (central pattern generator). But is it enough to restore gait and balance.

Jean-Baptiste THIÉBAUT (PARIS), Vincent D'HARDEMARE, Jean-Philippe BRANDEL, Cécile HUBSCH, Didier PRADON, Laurent GOETZ, Nathalie PATTE-KARSENTI, Marc ZIEGLER
00:00 - 00:00 #23659 - Subcutaneous Pneumothorax in a Patient with Cervical Dystonia as a Rare Complication of Deep Brain Stimulation Procedure.
Subcutaneous Pneumothorax in a Patient with Cervical Dystonia as a Rare Complication of Deep Brain Stimulation Procedure.

Objectives:

Deep brain stimulation (DBS) procedure-related adverse events correspond usually to intracerebral haemorrhagic complications. These complications may cause transient or permanent neurological deficits or even death. The intracerebral haemorrhagic complications are related to introduction of microelectrodes or macroelectrodes to a stereotactic target. The another possible source of complication may be related to the internalization of DBS hardware during tunnelling of the connection cable in the neck region. 

Methods:

Here, we describe to our knowledge the first case of a patient who developed a subcutaneous pneumothorax due to passage of a tunneling tool for placement of a connection cable. The patient within 30 minutes after surgery developed a marked subcutaneous pneumothorax. The pneumothorax was related due to the right lung apex injury confirmed by chest radiological examinations. The formal preoperative objective assessment included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The postoperative TWSTRS assessments were done at 3, 6 months and 12 months postoperatively.

Results:

The subcutanoues pneumothorax spontaneously resolved within 5 days. During this time period the patient was carefully monitored in the neurointensive unit. The patient made a full recovery and did not required an urgent thoracic surgery. The resolution of pneumothorax was confirmed by thorax and neck computed tomography examinations. The patient made the full recovery. Bilateral GPi stimulation in this patient resulted in marked reduction of cervical dystonia. At 12 months follow-up visit, the severity, disability and pain scores of TWSTRS were improved by 55 %, 52 % and 45 % respectively.

Conclusions:

This case demonstrates that tunneling for permanent placement of a connection cable may injure some structures in the upper neck region like lung apex. Although an blunt tip for tunneling tool was used in this case we observed this rare complication. Routinely, we utilize only the blunt tips for tunneling a connection cable in the neck region. We do not advocate to utilize an sharp tip of a tunneling tool which is more prone to cause a vascular or another tissue injury.

Michał SOBSTYL (Warsaw, Poland), Angelika STAPIŃSKA-SYNIEC, Anna KUPRYJANIUK
00:00 - 00:00 #23957 - Subthalamic nucleus deep brain stimulation in post-infarct dystonia.
Subthalamic nucleus deep brain stimulation in post-infarct dystonia.

Background


Dystonia secondary to cerebral infarcts present months to years after the initial insult, is usually unilateral, causes significant morbidity and is considered to be the result of aberrant reorganisation of the motor network after brain injury. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is established as the most frequent target in the management of dystonic symptoms. We report our experience with subthalamic nucleus (STN) DBS in three patients with clinically significant refractory post-infarct dystonia, in whom the GPi DBS was not possible.


Methods

Preoperative and postoperative functional assessment data prospectively collected by a multidisciplinary movement disorders team, including imaging, medication and neuropsychology evaluations were analysed with regards to symptom improvement. Quantification of dystonic signs and symptoms was done at baseline and at last follow-up using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score and disability score. 

 

Results

Three patients (2 males) with a mean age of 19 years (range 18 – 21 years) underwent DBS implantation. Internal carotid artery dissection and post-viral encephalitis (in 2 patients) were the causes of the initial infarct. Mean proportion of life lived with dystonia (defined as dystonia duration/age at surgery) was 0.67 (range of 0.61 - 0.78). Two patients had unilateral STN DBS implantation whereas the third patient had bilateral STN DBS implantation for asymmetrical bilateral symptoms. Median follow up was 38.3 months (range of 36 – 43 months). Clinically valuable improvements in dystonic symptoms and pain control were seen in all patients despite variable improvements in the Burke-Fahn-Marsden dystonia rating scores (movement score improvements of 14-64%, disability score improvements of 11-33%), highlighting the inadequate sensitivity of the scale in measuring subtle but clinically meaningful changes. 

 

Conclusion

In the absence of large prospective studies and given the rare nature of stroke-related dystonia and the heterogeneous nature of the condition, the use of subthalamic nucleus deep brain stimulation could be an alternative in the management of patients with post-infarct dystonia with abnormal striatal anatomy which precludes GPi DBS.  

Kantharuby TAMBIRAJOO (London, United Kingdom), Luciano FURLANETTI, Michael SAMUEL, Keyoumars ASHKAN
00:00 - 00:00 #23941 - The Effect of Subthalamic Nucleus - Deep Brain Stimulation and Different Stimulation Frequencies on Cerebral Hemodynamics in Parkinson's Disease.
The Effect of Subthalamic Nucleus - Deep Brain Stimulation and Different Stimulation Frequencies on Cerebral Hemodynamics in Parkinson's Disease.

Objectives:

The effect of the deep brain stimulation of the subthalamic nucleus (STN-DBS) on cerebral hemodynamic parameters is still not clear. Our objectives are to investigate the effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) and to compare low-frequency versus high-frequency STN-DBS on hemodynamic parameters of the middle cerebral artery between patients with advanced Parkinson's disease and age-sex matched healthy controls.

Patients and Methods:

Eighteen patients with advanced Parkinson's disease (PD) who have bilateral STN-DBS and 18 control subjects underwent Transcranial Doppler Ultrasound (TCDU) were included in the study. The hemodynamic parameters including blood flow velocity (FV), pulsatility index (PI) and, resistance index (RI) of the right middle cerebral artery (MCA) were measured and compared during the phases using TCDU. The first DBSoff, the second low-frequency DBS of 60 Hz, and the third high-frequency DBS of 130 Hz were compared.

Results:

PD patients had significantly higher MCA-PI values compared with controls (0.99 ± 0.27 vs. 0.82 ± 0.14) (p = 0.031). Also, the MCA-PI values were higher in the low-frequency DBS (0.94 ± 0.14) and high-frequency DBS (0.93 ± 0.16) than in the controls (0.82 ± 0.14) (p = 0.022 and p = 0.041, respectively). There were no significant differences of FV and RI values among the DBS-on, DBS-off and, controls. The RI values were higher in the PD patients than in the controls, although these were not statistically significant. Also, PI values of the MCA decrease in different frequencies (60 Hz or 130 Hz).

Conclusion:

The results of this study showed that MCA-PI values are higher in advanced PD compared with controls. These indices indicate that MCA resistances and impedances are increased in advanced PD. Low- or high-frequency DBS treatment have beneficial effect to reduce high PI in advanced PD patients.

Atilla YILMAZ (Istanbul, Turkey), Orkun KOBAN, Mustafa Turgut YILDIZGOREN
00:00 - 00:00 #23979 - The role of sedation in patient’s ability to cooperate during DBS surgery. A pilot study.
The role of sedation in patient’s ability to cooperate during DBS surgery. A pilot study.

Purpose: Deep brain stimulation (DBS) is an effective treatment for several conditions including movement disorders. Several techniques have been utilized for acceptable operational conditions during awake state. Management of hemodynamic perturbations is crucial in preventing  complications such as intracranial bleeding. The present pilot study investigated the role of  monitored anaesthetic care during DBS electrode placement and  microelectrode recordings in relation to patients’ ability to cooperate.

Material  and Methods: Three patients with Parkinson’s Disease  who underwent surgery for DBS placement were included in the study. During DBS surgery, all patients received monitored anesthesia care (propofol 25–50 mcg/kg/min and/or remifentanil 0.02–0.05 mcg/kg/min). When the one burr hole was made only local anaesthetics were utilized, whereas in the second mild sedation was additionally used and vice versa. Comparisons between the two methods were made on level of alertness using the Modified Observer`s Assessment of Alertness/Sedation Score (MOAA/S) and hemodynamic parameters.

Results: Three patients (2 males, 1 female, mean age 64.6 years) were included in the study. No significant differences were found in MOAA/S score, mean arterial blood pressure, heart and respiratory rate and blood oxygen saturation levels between the two techniques used. Patient’s cooperation was satisfactory in all cases.

Conclusion: The present pilot study did not reveal any differences in alertness, when different anaesthetic management was utilized, for patients with PD that underwent DBS surgery.

Arian LENAS, George ALEXIOU (IOANNINA, Greece), Zigouris ANDREAS, Spyridon VOULGARIS
00:00 - 00:00 #23664 - Tremulous Cervical Dystonia Treated by Bilateral Pallidal Stimulation. Case Series Report.
Tremulous Cervical Dystonia Treated by Bilateral Pallidal Stimulation. Case Series Report.

Objectives:

The aim of the present study was to present a case series of 4 patients with longstanding debilitating tremulous cervical dystonia (CD). Pharmacological treatment including benzodiazepines as well botulinum toxin injections failed to adequately control dystonic jerking movements of the head and neck. The patients were referred for pallidal deep brain stimulation (DBS) surgery.

Methods:

Four patients underwent bilateral implantation of DBS leads into the posteroventrolateral segment of the globus pallidus internus (GPi). One patient received additional implantation of left lead in the nucleus ventralis intermedius of the thalamus (Vim). All surgeries were uneventful. The formal preoperative objective assessment included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the motor score of Tremor Rating Scale (TRS). The postoperative TWSTRS and TRS assessments were done at 3, 6 months and 12 months postoperatively up to 48 months after surgery.

Results:

At 3 months follow-up visit, the severity, disability and pain scores of TWSTRS were improved by 35 %, 48 % and 44 % respectively. The TRS improved by 68 % when compared to baseline TRS score. At the last follow-up visit, the severity, disability and pain scores of TWSTRS were improved by 51 %, 52 % and 56 % respectively. The TRS improved by 78 % when compared to baseline TRS score. There were no hardware-related complications over follow-up period.

Conclusions:

Our preliminary experience gathered in 4 patients indicates that bilateral pallidal DBS can be an effective treatment for disabling tremulous CD.

Michał SOBSTYL (Warsaw, Poland), Angelika STAPIŃSKA-SYNIEC, Anna KUPRYJANIUK
00:00 - 00:00 #24084 - Unilateral Vim and cZi DBS for treatment of spasmodic dysphonia and arm tremor.
Unilateral Vim and cZi DBS for treatment of spasmodic dysphonia and arm tremor.

Background

The key finding in patients with Spasmodic Dysphonia (SD) is repeated involuntary contractions of the laryngeal muscles during speech. This may severely impair the ability to communicate verbally, having phone conversations and in the long run decrease quality of life substantially. Patients are if necessary treated with repeated botulinum toxin injections (bo-tox) of the laryngeal muscles, but some patients may become refractory to this treatment. Promising result have been reported with unilateral thalamic DBS of the speech dominant hemisphere for a few patients with bo-tox refractory SD [1].

Objective

To analyze the effect of unilateral thalamic (Vim) and subthalamic (cZi) DBS for SD.

Methods

A 75 year old female patient with severely disabling and bo-tox refractory SD as well as concomitant kinetic tremor of both arms was treated with unilateral DBS of the Vim and cZi in order to address tremor of the dominant (right) arm and symptoms of SD.

Results

The patient has thus far only been interviewed by telephone due to the current Covid-19 pandemic. She experiences complete cessation of tremor in her right arm and is now able to have phone conversations with friends and relatives for the first time in many years. More detailed result will be presented at the congress.

Conclusions

Unilateral Vim and cZi DBS might be a beneficial treatment in severe and bo-tox refractory SD.

 

1 Poologaindran A, Ivanishvili Z, Morrison MD, Rammage LA, Sandhu MK, Polyhronopoulos NE, Honey CR: The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: Interrogating cerebellar and pallidal neural circuits. J Neurosurg 2018;128:575-582.

Bjartur SÆMUNDSSON, Catarina WERSCH, Ellika SCHALLING, Mathias SUNDGREN, Göran LIND, Anders FYTAGORIDIS (Stockholm, Sweden)
00:00 - 00:00 #23924 - Vim anatomical variability: an MRI structural connectivity study.
Vim anatomical variability: an MRI structural connectivity study.

Visualising brain structures using MRI to guide and verify targeting is of utmost importance in the success of functional neurosurgical procedures. This is possible for most established targets (e.g. the subthalamic nucleus, the internal pallidum) but not the thalamic Ventralis intermedius nucleus (Vim) target. This has led some to explore the use of structural connectivity to help better define this structure instead of solely relying on atlas-based coordinates adapted to the patient’s anatomy. The aim of this work is three-fold: 1) quantify Vim anatomical variability using the coordinates estimated by tractography 2) quantify the discrepancy between atlas-based and tractography-based coordinates 3) exclude methodological confounds to ensure found variability is truly anatomical. 

One hundred, state of-the-art diffusion MRI datasets of healthy individuals from the Human Connectome Project were processed. We reconstructed the dentato-rubro-thalamo-cortical tract (DRTCT) with probabilistic tractography, using a previously published method (Akram et al 2018)1. Intersections between the thalamus and the DRTCT were used as surrogate for the Vim. Confounding factors such as participant motion and regional brain volumes were explored to ensure the observed variability corresponded to true anatomical variability. We also examined the effect the volume of the superior cerebellar peduncle (SCP), being the narrowest structure the DRTCT crosses, has on the tractography results.

The tractography-based mean coordinate obtained for left Vim was x = -18.75 (anterior-posterior), y = -13.68 (medio-lateral), z = 2.67 (superior-inferior) mm, with standard deviations of 1.19, 1.25 and 1.33 mm, respectively. For right Vim, it was x = -17.59, y = 13.08, z = 4.00 mm, with standard deviations of 1.46, 1.14 and 1.60 mm, respectively. This contrasts significantly with Talairach atlas determined coordinates which are, for left Vim, x = -14.37 (anterior-posterior), y= -12 (medio-lateral), z= 0 (superior-inferior) and for right Vim x = -14.37, y = 12, z = 0. In our work, Vim locations were more variable on the right, and variation was overall more marked in an anterior-posterior direction. There was asymmetry in the connectivity profiles between the left and right sides. Motion and brain volumes had no significant impact on the results, however; left SCP volumes did indeed influence the tractography results, and the SCP was confirmed as a potential source of artificial variance.

This work confirms the disparity between connectivity based and atlas-based approaches in capturing individual Vim location. The significance of this will have to be assessed against patient outcomes in subsequent studies. The left-right asymmetry is a new finding that might be explained by lateralisation of specific functions withing the cerebellum, such as the increasingly recognised role that the cerebello-thalamo-cortical network plays in language processing and localisation as one hypothesis.

Tractography-based methods appear to provide a consistent measure of individual anatomy that could capture variability missed in traditional targeting. These methods are shown here to be robust to major confounds but could be further refined nonetheless in order to improve efficacy and reduce side-effects of thalamic surgery for tremor.

 

References

1. Akram H, Dayal V, Mahlknecht P, et al. Connectivity derived thalamic segmentation in deep brain stimulation for tremor. NeuroImage Clin. 2018. doi:10.1016/j.nicl.2018.01.008

Francisca FERREIRA (London, United Kingdom), Harith AKRAM, John ASHBURNER, Hui ZHANG, Ludvic ZRINZO, Christian LAMBERT
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EP06
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Eposters
NEUROPHYSIOLOGY

00:00 - 00:00 #26130 - Cortical activity in an acute rodent model of Parkinson: possible use for adaptive deep brain stimulation.
Cortical activity in an acute rodent model of Parkinson: possible use for adaptive deep brain stimulation.

Background: Oscillatory activity of local field potentials (LFPs) plays a central role in regulating different states of brain function. In neurological and neuropsychiatric disorders neuronal oscillatory activity between subcortical basal ganglia (BG) and cortical circuits are altered, which may be useful as biomarker for adaptive deep brain stimulation (DBS).

 

Objective: Here we investigate the changes in the spectral power of oscillatory activity in the motor cortex (MCtx) and the sensorimotor cortex (SMCtx) of rats after acute injection of the dopamine (DA) receptor antagonist haloperidol (HALO) and subsequent injection of the DA receptor agonist apomorphine (APO). Further, a convolutional neural network (CNN) model was implemented for classification of the different states of brain signals.

 

Methods: In six male Sprague Dawley rats (270-300g) a sixteen channel surface miro-electrocortigram (ECoG) recording array was placed under the dura above the MCtx and SMCtx areas of one hemisphere under general anaesthesia and perioperative pain management. Seven days after surgery, micro ECoG was recorded in individual free moving rats in three conditions: (1) basal activity, (2) after injection of HALO (0.5 mg/kg), and (3) with additional injection of APO (1mg/kg). Spontaneous basal oscillatory activity was analyzed in the MCtx and SMCtx area. Furthermore, a CNN consisting of 23,530 parameters was applied on the raw data. The network is constructed by stacking six convolutional layers followed by one hidden fully connected layer and one output layer.

 

 Results: Injection of HALO decreased oscillatory theta band activity (4-8Hz) and enhanced beta (12-30Hz) and gamma (30-100Hz) in both MCtx and SMCtx, which was compensated after APO injection (p <0.001). Evaluation of classification performance of the CNN model using the k-Fold method provided an accuracy of 92%, sensitivity of 90% and specificity of 93% on one-dimensional signals of 60s, thus minimizing the required information down to a single channel recording as an input.

 

Conclusion: Injection of HALO in free moving rats leads to changes in the spectral power of oscillatory activity in motor cortical areas that show similarities to those recorded in PD patients, including alleviation by DA receptor agonists. Using the CNN algorithm for classification of neuronal activity state-of-the-art performance was accomplished. The proposed model requires a minimum of sensory hardware and may be integrated into future research on therapeutic devices for Parkinson disease, such as adaptive closed loop stimulation, thus, possibly contributing to a more efficient way of treatment.

Mesbah ALAM (Hannover, Germany), Ali Abdul Nabi ALI, Simon KLEIN, Nicolai BEHMANN, Theodor DOLL, Holge BLUME, Joachim K. KRAUSS, Kerstin SCHWABE
00:00 - 00:00 #26297 - Effect of directional deep brain stimulation of the subthalamic nucleus on the behavior in healthy non-human primate.
Effect of directional deep brain stimulation of the subthalamic nucleus on the behavior in healthy non-human primate.

Introduction

Deep brain stimulation (DBS) of the motor Subthalamic nucleus (mSTN) has become the gold standard surgical treatment for Parkinson’s disease whereas DBS of the non motor part of the STN (noM-STN) has been also used to treat severe obsessive-compulsive disorders. However, the knowledge of the respective distribution of non motor versus motor STN is limited and it has been reported that mSTN- DBS can induce non motor symptoms and, at contrario, noM-STN DBS can show motor side effect such as dyskinesia. Thanks to the recent technological development of directional leads, it is now possible to steer the current toward the mSTN or the noM STN, depending on the mode of stimulation. Here, we investigated the effect of directional STN DBS on the motor and non motor behavior in healthy non-human primate (NHP).

 

Methods

One NHP was implanted with a directional DBS lead into the STN, using pre-operative MRI and per operative ventriculography and micro-recordings to select the best trajectory. In parallel, the NHP was trained to perform a switching task enabling the evaluation of different components of the behavior. Indeed, i) the reaction time evaluated the motor domain, ii) measurement of the error rate during the task discriminated the cognitive domain and, iii) the decisional time, to either check to gain information about the delivery of a large bonus reward or to continue with the default switching task, allowed the evaluation of the emotional domain. STN DBS, at 130 Hz, using a directional mode, was applied during the task to check if a single lead could have a differential effect on those 3 domains. 

 

Results

We observed that DBS of the dorsolateral territory of the STN decreased the reaction time (679±13 ms vs. 552±20 ms; p≤ 0.0001) without changing the error rate. Interestingly, the decisional time was lower for the stimulation of the dorsolateral territory and higher for the stimulation of the more ventral territories compared to the OFF-stimulation condition (841±73 ms for the dorsolateral territory, 1555±405 ms for the ventral ones compared to 1165±110 ms for the OFF-stimulation condition; p≤0.05).

 

Conclusion 

These results highlight that 1) STN DBS of the dorsolateral territory can significantly modify the motor performances, whereas DBS of the ventral territories can significantly impact the cognitive and emotive performances; 2) using the directional mode of stimulation, one can steer the current toward different sub-territories of the STN with motor or non motor effect depending on the subdomain of STN stimulated. A better knowledge of the sub-territories of the STN could help to understand the side effects of STN-DBS, and directional stimulation could help to optimize the effect of STN-DBS in relation to the main motor or non motor symptoms that require a treatment.

Mathilde BERTRAND (FRANCE), Stephan CHABARDES, Julien BASTIN, Brigitte PIALLAT
00:00 - 00:00 #23424 - Intraoperative electrophysiology during deep brain surgeries in disorders of consciousness.
Intraoperative electrophysiology during deep brain surgeries in disorders of consciousness.

The efficacy on deep brain stimulation in disorders of consciousness (DC) is inconclusive. We investigated bilateral 30-Hz low-frequency stimulation designed to overdrive neuronal activity by dual pallido-thalamic targeting to promote conscious behavior in five patients. Five adult patients (mean age 38 years old) were included: one unresponsive-wakefulness-syndrome male (traumatic brain injury); and four patients in a minimally conscious state, one male (traumatic brain injury) and three females (two hemorrhagic strokes and one traumatic brain injury). Pallido-thalamic electrode targeting were performed under sevoflurane general anesthesia with recording of extracellular muti-unit neuronal activity and local field potential (LFP). These data were compared with five GPi DBS implantations (three males) for Parkinson’s disease (n=4) or dystonia (59 years old) and three VIM DBS surgeries (two males) for Parkinson’s disease (n=1) or essential tremor (40 years old).

The electrode implantation was realized after electrophysiological mapping using an intraoperative electrophysiological system for functional neurosurgery (MicroGuide Pro, Alpha Omega Eng., Israel). For each brain hemisphere, the mapping was performed using two exploration electrodes (Alpha Omega Eng.) steered by rigid guide tubes: one on the planned track and a second one on the parallel track located posteriorly at 2mm. The characteristics of our electrophysiological approach were as follow: systematic recordings of the spontaneous neuronal activity every 1 mm during 30 seconds along the distal 8.2 mm (min: 5; max: 13 mm) in the pallidum and the thalamus previously labelled and manually outlined on stereotactic MRI.

Spikes were encountered for 50 out of 130 recordings in the pallidum (38.46%) and for 43 out of 185 (23.24%) in the thalamus of patients with disorders of consciousness. Concerning motor disease (MD) patients implanted under general anesthesia, spikes were found in 52 out of 150 recordings in the pallidum (34.66%) and for 54 out of 82 (65.85%) in the thalamus. Mean firing rate of neurons in the pallidum was 9.84 +/-8.71 Hz and 11.95 +/-10.31 Hz during surgery for patients with DC and MD respectively. Concerning Thalamus, mean firing rate was 3.78 +/-4.87 Hz versus 2.25 +/-2.15 Hz (DC vs MD).

Percentage of raw power spectral density of LFP was similar in GPi for patients with DC and MD. Delta (47.8%), Theta (19.5%) and Alpha (17.0%) bands were preponderant for DC, while Delta (37.2%), Alpha (29.1%) and Beta (17.0%) range were powerful for MD patients.

Pallidal neuronal activity is similar for patients under general anesthesia suffering from DC or MD. Differences were encountered for Thalamus: higher 7-30Hz frequency power was encountered for patients with MD and higher low (<7Hz) and high (>30Hz) band power was observed for DC.

Thalamic neuronal activity differs between MD and DC patients. Few records have been obtained and published for patients with impaired consciousness. These results should be considered with caution given the small number of patients in the study.

This clinical trial (NCT01718249) was funded by the Fondation de l’Avenir (ET1-615 2011; “Deroche Legacy” Grant BO4-001), the University Hospital of Clermont-Ferrand, the Centre Jean Perrin and Medtronic France.

DBS-Post-coma study group and clinical research protocol are detailed here: https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Facn3.648&file=acn3648-sup-0001-Suppinfo.docx

Jérôme COSTE (Clermont-Ferrand), Anna SONTHEIMER, Bénédicte PONTIER, Jean-Jacques LEMAIRE, Dbs-Post-Coma STUDY GROUP
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EP07
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Eposters
ONCOLOGY

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