Tuesday 27 June
Time Bellevue Potsdam I-III Tegel Kaminzimmer
07:30
07:30-08:15
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BS1
PARALLEL SESSIONS: BREAKFAST SESSIONS
CHALLENGING CASES IN NEUROMODULATION

PARALLEL SESSIONS: BREAKFAST SESSIONS
CHALLENGING CASES IN NEUROMODULATION

Moderators: Maximilian MEHDORN (retired) (Kiel, Germany), Fabian PIEDIMONTE (Buenos Aires, Argentina)
Keynote Speakers: Terry COYNE (Neurosurgeon) (Keynote Speaker, Brisbane, Australia), Paresh DOSHI (Neurosurgeon) (Keynote Speaker, mumbai, India), Shiro HORISAWA (neurosrugery) (Keynote Speaker, Shinjyuku, Japan)

07:30-08:15
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BS2
PARALLEL SESSIONS: BREAKFAST SESSIONS
IMAGING IN STEREOTACTIC AND FUNCTIONAL NEUROSURGERY

PARALLEL SESSIONS: BREAKFAST SESSIONS
IMAGING IN STEREOTACTIC AND FUNCTIONAL NEUROSURGERY

Moderators: Nader POURATIAN (Los Angeles, USA), Tejas SANKAR (Neurosurgeon) (Edmonton, Canada)
Keynote Speakers: Juan Antonio BARCIA (Neurosurgeon) (Keynote Speaker, Barcelona, Spain), Volker COENEN (Head of Department) (Keynote Speaker, Freiburg, Germany), Dario ENGLOT (Fellow/Trainee) (Keynote Speaker, Nashville, USA), Nader POURATIAN (Keynote Speaker, Los Angeles, USA)

07:30-08:15
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BS3
PARALLEL SESSIONS: BREAKFAST SESSIONS
MAXIMIZING THE SUCCESS OF YOUR RESEARCH PUBLICATION

PARALLEL SESSIONS: BREAKFAST SESSIONS
MAXIMIZING THE SUCCESS OF YOUR RESEARCH PUBLICATION

Moderators: Tipu AZIZ (Professor) (Oxford, United Kingdom), Philippe CORNU (PROFESSEUR) (PARIS, France)
Keynote Speakers: Tipu AZIZ (Professor) (Keynote Speaker, Oxford, United Kingdom), Stephan CHABARDÈS (head of the department) (Keynote Speaker, GRENOBLE, France), David ROBERTS (Keynote Speaker, Lebanon, USA)

08:30
08:30-09:00
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KL1
PLENARY SESSIONS: KEYNOTE LECTURES
WSSFN PRESIDENTIAL ADDRESS

PLENARY SESSIONS: KEYNOTE LECTURES
WSSFN PRESIDENTIAL ADDRESS

Plenary Speaker: Joachim K. KRAUSS (Chairman and Director) (Plenary Speaker, Hannover, Germany)

09:00
09:00-09:30
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KL2
PLENARY SESSIONS: KEYNOTE LECTURES
THE HISTORY OF STEREOTACTIC AND FUNCTIONAL NEUROSURGERY

PLENARY SESSIONS: KEYNOTE LECTURES
THE HISTORY OF STEREOTACTIC AND FUNCTIONAL NEUROSURGERY

Moderators: Ali R. REZAI (Ohio, USA), Juergen VOGES (Head of the Department) (Magdeburg, Germany)
Plenary Speaker: Marwan HARIZ (neurosurgeon) (Plenary Speaker, Umeå, Sweden)

09:30
09:30-10:30
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OPS01
OPS01 PLENARY SESSION: ORAL PRESENTATIONS

OPS01 PLENARY SESSION: ORAL PRESENTATIONS

Moderators: Ali R. REZAI (Ohio, USA), Juergen VOGES (Head of the Department) (Magdeburg, Germany)
09:42 - 09:54 #10259 - OP02 A randomised controlled trial of Deep Brain Stimulation in Severe Refractory Obsessive Compulsive Disorder.
A randomised controlled trial of Deep Brain Stimulation in Severe Refractory Obsessive Compulsive Disorder.

Objectives: A significant minority of patients with Obsessive Compulsive Disorder (OCD) remain severely affected despite high quality standard treatment. We present the clinical results of a double-blind randomised crossover pilot trial of deep brain stimulation (DBS) for OCD.

 

Methods: Six patients with severe refractory OCD were recruited. Minimum inclusion criteria were: symptoms refractory to ≥2 selective serotonin reuptake inhibitors for ≥ 12 weeks at optimal doses, ≥2 trials of cognitive behavioural therapy (CBT) involving Exposure and Response Prevention (> 10 hours) plus intensive inpatient treatment within a specialist unit; ≥ 10 years’ illness duration; ≥ 2 years of unremitting symptoms; ≥ 32 on the Yale-Brown Obsessive Compulsive Scale (YBOCS).

 

Bilateral anteromedial subthalamic nucleus (amSTN) and bilateral ventral capsule/ventral striatum (VC/VS) DBS leads were implanted in each patient using an MRI-guided & MRI-verified approach. Patients were randomised to amSTN or VC/VS stimulation. After 3 months, the stimulation site was switched for a further 3 months, then both sites were stimulated for 3 months. Following this, patients received open label DBS optimisation and CBT. Patients and psychiatrists were blinded to stimulation site during the randomisation phase. YBOCS and global assessment of function (GAF) scores were performed at key time points.

 

Results: There were no surgical complications. YBOCS improved from baseline by a mean of 45% with amSTN DBS, 53% with VC/VS DBS and 61% with DBS at both sites. Following open label DBS plus CBT, mean YBOCS reduction was 74%, 3 patients were in remission (YBOCS < 8), all patients were “responders” (defined as YBOCS decrease of >35%). GAF scores improved from 22 to 72. Effective contacts at the VC/VS target were within the ventral aspect of the anterior limb of the internal capsule, above the nucleus accumbens. During the course of the trial, DBS was associated with a number of transient mood and behavioural changes that required close supervision and stimulation adjustment.

 

Conclusion: DBS was safe and efficient at both sites with improvement in OCD symptoms that was also accompanied by improvements in quality of life scores. In this patient group, the VC target provided greater benefit than the amSTN target. It must be emphasised that DBS is a labour-intensive and lifelong therapy that requires close surgical and psychiatric follow up. 


Ludvic ZRINZO (London, UK, United Kingdom), Himanshu TYAGI, Tom FOLTYNIE, Patricia LIMOUSIN, Lynne DRUMMOND, Naomi FINEBERG, Keith MATTHEWS, Eileen JOYCE, Marwan HARIZ
09:54 - 10:06 #10804 - OP03 Stereotactic radiosurgery capsulotomy for refractory OCD: Lesion location and connectivity analysis in 30 patients.
Stereotactic radiosurgery capsulotomy for refractory OCD: Lesion location and connectivity analysis in 30 patients.

Background

Obsessive-compulsive disorder (OCD) affects 2-3% of the population, and approximately 20% of these patients are refractory to medical and behavioral therapy. These patients may be candidates for stereotactic radiosurgery capsulotomy (SRSC). In this study we identified SRSC lesion locations predicting favorable outcome, as well as lesion prefrontal connectivity.

Methods

SRSC Lesions were traced on T1 scans in 30 OCD patients, and transformed to standard imaging space. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) reduction was regressed against a threshold-free cluster enhanced voxel-wise analysis of lesions. Tractography was performed on 40 patients from the Human Connectome Project, using the significant cluster center as a seed.

Results

24 of the 30 participants (80%) were full responders. A cluster (Fig1), centered in the right internal capsule, correlated with outcomes (corrected p < 0.05). Tractography showed that fibers through this cluster radiate to inferior medial prefrontal cortex (Fig2).

Conclusions

SRSC remains an effective treatment for refractory OCD. These results suggest a specific area in the right ventral capsule whose inclusion increases the likelihood of response. This region demonstrates connectivity to the orbitofrontal and ventromedial prefrontal cortex, highlighting the importance of these regions in OCD pathophysiology. Further analysis of individual variability and connectivity will be essential for improving outcomes.


Garrett BANKS (New York, USA), Nicole MCLAUGHLIN, Pranav NANDA, Euripedes MIGUEL, Jason SHEEHAN, Zhiyuan XU, Antonio LOPES, Marcelo HOEXTER, Marcelo BASTISTUZZO, Danika PAULO, Noren GEORG, Benjamin GREENBERG, Steven RASMUSSEN, Sameer SHETH
10:06 - 10:18 #10149 - OP04 Deep Brain Stimulation of the Medial Forebrain Bundle: Marked Responses in Treatment Resistant Depression.
Deep Brain Stimulation of the Medial Forebrain Bundle: Marked Responses in Treatment Resistant Depression.

Background: Treatment resistant depression (TRD) is a serious and debilitating disorder. Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported by Schlaepfer et al. (2013) to lead to rapid anti-depressant effects. Here, we report the interim analysis of an ongoing pilot study investigating the efficacy of DBS- MFB in TRD. This report extends our recently published results (Fenoy et al., 2016).

Methods: We assessed the efficacy of MFB-DBS in a cohort of six TRD patients over a 52-week period using improvement on the Montgomery-Åsberg Depression Rating Scale (MADRS) as the primary outcome measure. Implanted patients entered a 4-week single-blinded sham stimulation period prior to stimulation initiation. Deterministic fiber tracking analysis was performed to compare modulated fiber tracts between patients.

Results: Upon stimulation at target intraoperatively, responders reported immediate increases in energy and motivation. During a 4 week sham stimulation phase, there was no significant mean change in mood. After initiating stimulation, 3 of 6 patients had a >50% decrease in MADRS scores relative to baseline at 7 days. The difference in MADRS score between baseline and week 1 of active stimulation was significant (mean change = 15 pts, 43% reduction, p = 0.005) as was the difference between baseline and week 2 (mean change = 17 pts, 49% reduction, p = 0.001). One patient withdrew from study participation for personal reasons. At 26 weeks, 4 of 5 patients have >75% decrease in MADRS scores relative to baseline. At 52 weeks, 2 of 3 remaining patients continue to have >80% decrease in MADRS scores; 2 patients have not yet completed their 52 week assessments. Evaluation of modulated fiber tracts reveals significant frontal connectivity to the target region in all 5 responder patients, but minimal connectivity in the non-responder at 26 weeks.

Conclusion: This study of MFB-DBS shows rapid anti-depressant effects within the first week of stimulation, as reported by Schlaepfer et al. (2013). The striking effects observed are very promising, but we await full completion of this pilot study before drawing further conclusions about efficacy. 


Albert FENOY (Houston, USA), Paul SCHULZ, Sudhakar SELVARAJ, Christina BURROWS, Giovana ZUNTA SOARES, Joao QUEVEDO, Jair SOARES
10:18 - 10:30 #10193 - OP05 Sweet Spot of antidystonic effect in pallidal neurostimulation: a European multicentre imaging study.
Sweet Spot of antidystonic effect in pallidal neurostimulation: a European multicentre imaging study.

Objective: We investigated Volumes of Tissue activated (VTA) in dystonia subjects under effective bilateral pallidal DBS. We aimed to disentangle the sweet spot for dystonia suppression within the pallidal region.

Background: GPi-DBS is an established therapy for generalized and cervical dystonia. Average improvement of dystonia severity amounts to 50-60%, but outcomes are often variable and clinical studies report up to 25% non-responders. Variability in electrode placement may account for a large proportion of outcome variability. So far no study has been able to identify an “optimal efficacy volume” within the GPi.

Methods: 85 subjects with dystonia (41 cervical mean TWSTRS 20.3±3.6 points/44 generalized dystonia, mean BFMDRS 45.8±20.5 points) under chronic bilateral GPi-DBS from 8 European DBS centres were stratified for chronic motor improvement (median reduction of 46.7(±27.7)% after 12.0 months in cervical / median reduction of 52.3(±35.9)% after 34.8 months in generalised dystonia). We simulated VTAs for each lead in subject’s related MRI space based on chronic stimulation parameters obtained from a chart review and associated with BFMDRS/TWSTRS improvement. All patient images were registered to a common average MRI. Only VTAs with a motor improvement >50% were taken for the visualisation of three different areas, defined by allegorizing only voxels that were overlapped by >15(green); >30(orange) VTAs and the “sweetspot”, overlap volume of  >50(red) VTAs.

Results: Wide variability of lead location, stimulation parameters and chronic motor improvement was observed in this cohort of 85 subjects. VTA size did not exhibit a significant correlation with improvement in motor symptoms. Model-based analysis of 108 responding VTAs showed a core mean volume (=”sweetspot”) located within and below the ventroposterior GPi. Stereotactic coordinates of the center of gravity were lateral: 20.0, anterior: 2.3 and inferior 2.6 (based on AC-PC in mm).

Conclusions: In this study, we showed that the magnitude of current injection is not decisive for the therapeutic DBS effect. In fact, the outcome is highly correlated with the precise location of neuromodulation within the region of interest. The most beneficial (sweet-)spot hints to a relevant contribution of subpallidal white matter, which could indicate a possible modulation of the ansa lenticularis for the anti-dystonic effect of DBS in addition to stimulation of the presumed sensorimotor region of the GPi.


Martin M REICH (Würzburg, Germany), Florian LANGE, Jonas ROOTHANS, Andreas HORN, Fritz WODARG, Joachim RUNGE, Mattias ÅSTRÖM, Nicolo POZZI, Frank STEIGERWALD, Karsten WITT, Robert NICKL, Philip PLETTIG, Matthias WITTSTOCK, Gerd-Helge SCHNEIDER, Volker Arnd COENEN, Philipp MAHLKNECHT, Werner POEWE, Wilhelm EISNER, Cordula MATTHIES, Volker STURM, Ioannis ISAIAS, Andrea KÜHN, Joachim K KRAUSS, Guenther DEUSCHL, Jens VOLKMANN *

10:45
10:45-11:45
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OPS02
OPS02 PLENARY SESSION: ORAL PRESENTATIONS

OPS02 PLENARY SESSION: ORAL PRESENTATIONS

Moderators: Emad ESKANDAR (Boston, USA), Joseph NEIMAT (Chairman) (Louisville, USA)
10:45 - 10:57 #10231 - OP06 A phase I pilot study of magnetic resonance-guided focused ultrasound pallidotomy for Parkinsonian dyskinesia.
A phase I pilot study of magnetic resonance-guided focused ultrasound pallidotomy for Parkinsonian dyskinesia.

Objectives: Recently, magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as an innovative treatment for numerous neurological disorders. This clinical trial was designed to identify the feasibility, effectiveness, and potential side effects of unilateral MRgFUS pallidotomy for the treatment of Parkinsonian dyskinesia.

Method: Ten patients with severe, medication-refractory Parkinson’s disease (PD) with motor fluctuation underwent unilateral MRgFUS pallidotomy using the Exablate 4000 device (Insightec, Israel) between December 2013 and May 2016. All patients provided written informed consent. Clinical assessments were conducted to evaluate the therapeutic effects after unilateral MRgFUS pallidotomy and according to our follow-up protocol. Technical failure and safety issues were also carefully assessed by monitoring all events during the study period.

Results: Seven of ten patients were followed-up for at least six months. Three patients were dropped from the study for various reasons. All patients who underwent MRgFUS pallidotomy experienced immediate and sustained improvements in dyskinesia, particularly in the treated hand. This reduction was accompanied by functional improvement in activities of daily living. However, thermal lesioning via MRgFUS also failed in several cases. In addition, several side effects were associated with MRgFUS, although no patient experienced persistent aftereffects.

Conclusion: In the present study, which marks the first phase I pilot study of unilateral MRgFUS pallidotomy for advanced PD, we demonstrated the benefits of unilateral MRgFUS pallidotomy in PD, as well as certain limitations of this technique associated with incomplete thermal lesioning of the globus pallidus interna.


Na Young JUNG (Seoul, Korea), Chang Kyu PARK, Si Woo LEE, Sang Keum PAK, Eun Jeong KWEON, Won Seok CHANG, Hyun Ho JUNG, Jin Woo CHANG
10:57 - 11:09 #10138 - OP07 Comparing 12 month treatment outcomes for intensive psychological therapy (ITP) and Anterior Cingulotomy (ACING) for severe OCD.
Comparing 12 month treatment outcomes for intensive psychological therapy (ITP) and Anterior Cingulotomy (ACING) for severe OCD.

Objectives To describe and compare the clinical outcomes for two consecutive series of patients within our clinical service receiving either intensive psychological therapy (ITP) or bilateral anterior cingulotomy (ACING) for chronic severe OCD.

Method We reviewed data from the 8 most recent patients completing our intensive treatment programme and also the 5 most recent patients treated neurosurgically (ACING).  All ACING patients had previously failed to achieve a sustained improvement from an intensive treatment programme. In controlled treatment trials, a decrease of greater than or equal to 35% on the Yale Brown Obsessive Compulsive Rating Scale (Y-BOCS) is generally considered a clinically meaningful treatment response, with a reduction of greater than or equal to 25% a significant, but lesser improvement.  Outcomes were examined at the following time-points: baseline (pre-treatment); immediate post treatment (discharge); and 12-months after treatment.

Results Prior to treatment, ITP group Y-BOCS severity scores were in the moderate to extreme range (30.25±5.4) whilst the ACING patients were in the severe to extreme range (32.4±5.7). At discharge, 50% of the ITP group achieved a clinically meaningful response to treatment; 13% achieved a lesser, but significant response; whilst 37% failed to benefit from treatment.   Of the ACING patients 40% achieved a clinically meaningful response, whilst the remaining 60% showed no response.  This equates to the ITP group experiencing an average 30.5% improvement in symptom severity (20.21±8), compared to 22.4% improvement for the ACING group (19.75±9.8). However, at 12 months the ITP group showed no change in response rates and maintained a 30.3% overall improvement in Y-BOCS severity scores (20.25±8.8), but the ACING group continued to progress with 60% of patients now achieving either a significant or a clinically meaningful response; with remaining patients, although not achieving a significant response, gaining a 20% overall reduction in their Y-BOCS severity scores (25.5±3.5).  This gives the ACING group an overall improvement at 12 months of 48.5%

Conclusions Improvements made on discharge by ITP patients were maximal, with no additional improvements over the following 12 month period. ACING patients, however, continued to improve.  This suggests that the trajectory of response following surgery may differ from that of ITP.


Karen WALKER (Dundee, United Kingdom), David CHRISTMAS, Keith MATTHEWS
11:09 - 11:21 #10623 - OP08 Gamma Knife subthalamotomy for Parkinson's disease: A prospective trial.
Gamma Knife subthalamotomy for Parkinson's disease: A prospective trial.

Objective: To assess the feasibility of Gamma Knife   subthalamotomy in Parkinson's disease

Background:   Chronic STN stimulation   is an established treatment for complicated PD. Bilateral subthalamotomy may   induce significant and long-lasting results when DBS is not available.   However, which alternative can be proposed for patients with surgical contraindications   for electrodes implantation? Gamma Knife (GK) thalamotomy is an effective   therapy for treating disabling tremor. This technique encounters very few   contraindications. We report the results of a prospective trial on GK Subthalamotomy   for patients with absolute contraindications for DBS. The primary endpoint was tolerance.

Methods: 14 PD patients (10men, mean age 66.4) with   severe motor complications were included. STN DBS was contraindicated because   of vasculopathy or anticoagulant treatment.  Patients were assessed before and quarterly   for at least 24 months after GK subthalmotomy. A unilateral GK subthalamotomy   on the most affected side was proposed first followed by contralateral   subthalamotomy after M12 if necessary. STN lesioning was performed with   Leksell Gamma unit with a single exposure through a 4mm collimator. Radiosurgical   dose was 110Grays.

Results:  12 patients were   assessed at 2 years. 2 patients died before M6 (stroke, suicide). 7 patients   had bilateral GK subthalamotomy, 5 unilateral (2 previous contralateral STN   DBS, 2 refusals, 1 unilateral disease). UPDRS motor score was improved by   17.6% at M24,  motor fluctuations by   18% and dyskinesia were reduced by 66%. Cognitive score was stable except for   one patient. No significant decrease in LEDD was observed. MRI STN lesion   appeared 9 months after radiosurgery. One patient was a hyporesponder and 4   had an hyperresponse with clinical consequences: Severe transient dyskinesia   (2), transient hemiparesia and delirium (1), permanent hemiplegia.

Conclusions: Apart from a   significant decrease in dyskinesias, the patients did not improve following   STN GK and several experienced adverse effects. Although the cohort is small and with high comorbidities,   this study does not indicate that GK subthalamotomy may be a good alternative to   DBS for advanced PD.


Jean REGIS (MARSEILLE), Romain CARRON, Alexandre EUSEBIO, Tatiana WITJAS
11:21 - 11:33 #10435 - OP09 Quantifying activation of the hyperdirect pathway during subthalamic deep brain stimulation.
Quantifying activation of the hyperdirect pathway during subthalamic deep brain stimulation.

Deep brain stimulation (DBS) of the subthalamic region is an established clinical therapy for the treatment of late stage Parkinson's disease. A fundamental biophysical effect of DBS is the generation of action potentials in axons surrounding the stimulating electrode. One axonal pathway of special interest is the corticofugal hyperdirect pathway to the subthalamic nucleus. Therefore, we developed a highly detailed patient-specific DBS model to study hyperdirect activation and action potential propagation. The DBS patient model was based on 7T MRI data. Subcortical nuclei were segmented from T1-weighted, T2-weighted, and susceptibility-weighted images. The hyperdirect pathway was reconstructed, as well as the internal capsule, with the assistance of tractography derived from diffusion-weighted images. Each of the 5000 axons reconstructed were modeled as a multi-compartment cable structure. The voltage distribution generated by the DBS electrode was calculated using a finite element method. This voltage distribution was then used to stimulate the model axons, and the response of the axons to DBS was quantified. We found that the hyperdirect pathway was robustly activated at the clinically effective stimulation parameters. In addition, we found that hyperdirect axons must be of especially large axon diameter (~10 um) to match the signal conduction velocity necessary to generate the cortical evoked potentials (~1 ms delay) recorded experimentally in DBS patients.


Kabilar GUNALAN, Bryan HOWELL, Cameron MCINTYRE (Cleveland, USA)
11:33 - 11:45 #10424 - OP10 Estimation of effective target area in the globus pallidus during deep brain stimulation for Tourette syndrome.
Estimation of effective target area in the globus pallidus during deep brain stimulation for Tourette syndrome.

Objectives: Deep brain stimulation (DBS) of the anteromedial globus pallidus internus (amGPi) is emerging as a helpful method for severe cases of Tourette syndrome (TS) in adult patients but the optimal target is still under investigation.

Method: Patient-specific finite element method simulations of affected voxels were made in 15 patients in order to determine which are associated with symptom improvement at latest follow up (17-82 months from surgery). The equation for steady currents was solved with electric conductivities estimated from tissue classification into grey matter, white matter and cerebrospinal fluid in T1-weighted preoperative images. Voxels experiencing an electric field intensity sufficient to trigger axons with a diameter of 2 µm were assumed to be activated and were co-registered with the MNI 152 averaged T1-weighted brain space in which linear regression between each voxel and the DBS outcome scores were performed.

Results and conclusion: Tics (YGTSS: p < 0.0001) and mood (BDI: p = 0.012) improved significantly by DBS while obsessive-compulsive behavior (OCB) improved for some severe cases but the improvements did not reach statistical significance for the whole group. It was found that an area of the anterior pallidum encompassing the medial medullary lamina between GPi and GPe, and at the level of the AC-PC line, was significantly related to tic improvement. Improvements in mood or OCB could not be significantly associated with any specific area.


Johannes JOHANSSON (Linköping, Sweden), Ladan AKBARIAN‐TEFAGHI, Harith AKRAM, Ludvic ZRINZO, Patricia LIMOUSIN, Eileen JOYCE, Marwan HARIZ, Karin WÅRDELL, Tom FOLTYNIE

11:45
11:45-12:30
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AW
PLENARY SESSION: AWARDS CEREMONY
WSSFN Distinguished Awards Ceremony and Presentations

PLENARY SESSION: AWARDS CEREMONY
WSSFN Distinguished Awards Ceremony and Presentations

Moderators: Emad ESKANDAR (Boston, USA), Joseph NEIMAT (Chairman) (Louisville, USA)
11:45 - 12:30 Spiegel and Wycis Award. Yves LAZORTHES (Plenary Speaker, Toulouse, France)
Introduced by Joachim K. Krauss
11:45 - 12:30 Spiegel and Wycis Award. Francisco VELASCO CAMPOS (SENIOR INVESTIGATOR) (Plenary Speaker, Mexico, Mexico)
Introduced by Michael Schulder
11:45 - 12:30 Tasker Award. David ROBERTS (Plenary Speaker, Lebanon, USA)
Introduced by Jin Woo Chang

12:30
12:30-13:30
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LIS1
LUNCH SYMPOSIUM - INDUSTRY SPONSORED

LUNCH SYMPOSIUM - INDUSTRY SPONSORED

13:30-14:30
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LIS2
LUNCH SYMPOSIUM - INDUSTRY SPONSORED

LUNCH SYMPOSIUM - INDUSTRY SPONSORED

12:30-14:30
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MEET2
WSSFN Board of Director's Meeting

WSSFN Board of Director's Meeting

14:30
14:30-15:00
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KL5
PARALLEL SESSIONS: KEYNOTE LECTURES
HIFU-FROM BLOOD BRAIN BARRIER TO FUNCTIONAL NEUROSURGERY

PARALLEL SESSIONS: KEYNOTE LECTURES
HIFU-FROM BLOOD BRAIN BARRIER TO FUNCTIONAL NEUROSURGERY

Moderators: Aviva ABOSCH (Denver, USA), Angelo LAVANO (Full Professor of Neurosurgery) (Catanzaro, Italy)
Plenary Speaker: Jin Woo CHANG (Plenary Speaker, Seoul, Korea)

14:30-15:00
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KL3
PARALLEL SESSIONS: KEYNOTE LECTURES
HISTORY OF PSYCHOSURGERY IN POSTWAR GERMANY

PARALLEL SESSIONS: KEYNOTE LECTURES
HISTORY OF PSYCHOSURGERY IN POSTWAR GERMANY

Moderators: Alex GREEN (Consultant Neurosurgeon) (Oxford, United Kingdom), Ali SAVAS (NA) (ANKARA, Turkey)
Plenary Speaker: Lara RZESNITZEK (psychiatrist) (Plenary Speaker, Berlin, Germany)

14:30-15:00
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KL4
PARALLEL SESSIONS: KEYNOTE LECTURES
LOCAL FIELD POTENTIALS IN MOVEMENT DISORDER SURGERY

PARALLEL SESSIONS: KEYNOTE LECTURES
LOCAL FIELD POTENTIALS IN MOVEMENT DISORDER SURGERY

Moderators: Jocelyne BLOCH (Médecin Cadre) (Lausanne, Switzerland), Alon MOGILNER (New York, USA)
Plenary Speaker: Andrea KUEHN (Plenary Speaker, Berlin, Germany)

15:00
15:00-16:00
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OPS04
OPS04 PARALLEL SESSIONS: ORAL PRESENTATIONS

OPS04 PARALLEL SESSIONS: ORAL PRESENTATIONS

Moderators: Aviva ABOSCH (Denver, USA), Angelo LAVANO (Full Professor of Neurosurgery) (Catanzaro, Italy)
15:00 - 15:12 #10453 - OP16 Deep brain stimulation in the caudal Zona incerta for essential head tremor: Long-term results.
Deep brain stimulation in the caudal Zona incerta for essential head tremor: Long-term results.

Background: Essential tremor (ET) is the most common adult movement disorder and is usually confined to the upper extremities. However, head and voice tremor is also common, with reports indicating the prevalence of head tremor to be around 50%.

Aim: The aim of this study was to analyse the short- and long-term results in a patient cohort with essential head tremor treated with DBS in the caudal Zona incerta(cZi).

Method: Retrospective analysis of patients fulfilling the following criteria: Essential tremor (ET); Unilateral or bilateral cZi-DBS without previous DBS or lesional surgery on either side; Completed evaluation with Essential Tremor Rating Scale (ETRS) at baseline before surgery and on/off stimulation at short-term follow-up 12 months after surgery, and at long-term follow-up, at least 24 months after surgery.

15 patients with unilateral and 2 with bilateral DBS, thus in total 19 leads were identified and included in the present study. The two bilaterally implanted patients were evaluated separately for each side and analysed as two unilateral procedures. Friedman test with Wilcoxon as a post hoc analysis was used for ordinal values. One-way ANOVA with repeated measurements with Bonferroni correction was used for continuous variables. A p-value<0.05 was considered significant.

Results: Of 36 unilateral and 12 bilateral DBS procedures fulfilling the inclusion criteria, 15 and 2, respectively, had head tremor. Nine were women and 12 men with a mean age at surgery of 70.4±9.3 years. Evaluations were done at a mean of 12 months and 35 months after surgery.

Total ETRS before surgery at baseline was 55.5±10.3 points. This was improved by 55% and 54% with unilateral stimulation at short-term and long-term follow-up, respectively(p≤0.00001). Contralateral tremor of the hand (item 5/6) was improved by 94% with stimulation at short-term and by 83% at long-term follow-up(p≤0.00001).

The mean head tremor score was reduced from 1.7 at baseline to 0.2 with stimulation at both short- and long-term follow-up (88%, p≤0.0001).

The mean coordinates of contacts used for stimulation was 11.7 mm lateral to the AC-PC-line, 6.8mm posterior to the mid-commissural point (MCP) and 2.1 mm inferior to the MCP. The mean coordinates did not change over time. 

Conclusion: Unilateral stimulation in the cZi was effective in alleviating essential head tremor and the effect did not diminish over time.


Patric BLOMSTEDT, Rasmus STENMARK P. (Umeå, Sweden)
15:12 - 15:24 #10407 - OP17 Comparison of 1.5, 3.0 and 7.0-Tesla MRI for STN targeting in DBS.
Comparison of 1.5, 3.0 and 7.0-Tesla MRI for STN targeting in DBS.

Background: High field MRI is expected to increase visibility of STN contour representation and considered an advantage for direct planning in STN DBS. Whether this results in significant alterations of target coordinates in comparison to lower field strengths is currently unknown.     

Objective: Evaluating possible influence of different field strength T2-weighted MRI on STN target planning.

Design/methods: STN target planning was performed by three DBS surgeons on 1.5, 3.0 and 7.0-Tesla MRI in order to evaluate if higher field strength leads to significant alterations of STN target coordinates. For all sequences X, Y and Z coordinates were compared.

Results: Direct planning of the target point based on STN representation on 1.5 Tesla, 3.0 Tesla and 7.0 Tesla showed high correspondence for X, Y and Z coordinates between the three field strengths (intra-rater) and between surgeons (inter-rater).

Conclusion: STN targeted coordinates were comparable on 1.5, 3.0 and 7.0-Tesla T2-weighted MRI. This could be explained by the fact that visibility of anatomical references used for target planning as red nucleus and medial STN border were comparable on the different sequences. 

figure: Axial midbrain section showing STN at maximal diameter of RN on three different MRI sequences. The horziontal red dotted line coincides with the Bejjani line, the cross section of the lines coincides with the medial STN border, identification of both references is readily done on all field strenghts.


Maarten BOT (Amsterdam, The Netherlands), Okker VERHAGEN, Rick SCHUURMAN, Pepijn VAN DEN MUNCKHOF
15:24 - 15:36 #10403 - OP18 Defining the dorsolateral STN using 7-Tesla MRI.
Defining the dorsolateral STN using 7-Tesla MRI.

Background: 7-Tesla T2-weighted Magnetic Resonance Imaging (MRI) offers improved visibility of the dorsolateral subthalamic nucleus (STN), which is considered the optimal location for deep brain stimulation (DBS) in Parkinson’s Disease (PD). However, it is unknown whether the dorsolateral STN on 7-Tesla T2 corresponds to the neurophysiological location.

Objective: To compare dorsolateral STN border identified on 7.0-Tesla T2-weighted MRI with the border obtained during microelectrode recordings (MER) in patients undergoing DBS for PD.

Design/methods: Dorsolateral border identification was done using axial and coronal orientated 7.0-Tesla T2-weigthed MRI. This was compared to dorsolateral border identified by MER.

Results: A total of 108 microelectrode tracks were evaluated in 19 patients. For the central and anterior microelectrode channel, the dorsolateral STN border on MRI was located more superior in 74% of trajectories compared to MER. Average distance from MRI to MER border was 1.0 millimeter.

Conclusion: 7-Tesla T2 MRI offers the possibility of dorsolateral STN identification. In the vast majority of cases this border was located more superior compared to MER. For STN DBS, the optimal location on 7-Tesla MRI is located just below the dorsolateral border. 

figure: Axial and coronal midbrain sections showing optimal DBS location within the STN on three different MRI field-strenghts. The cross section of the two dotted red lines coincides with the defined optimal DBS location.


Maarten BOT (Amsterdam, The Netherlands), Okker VERHAGEN, Vincent ODEKERKEN, Rob DE BIE, Rick SCHUURMAN, Pepijn VAN DEN MUNCKHOF
15:36 - 15:48 #10816 - OP19 Frequency and Characterization of Lead Revision and Removal Rates following DBS from the Product Surveillance Registry.
Frequency and Characterization of Lead Revision and Removal Rates following DBS from the Product Surveillance Registry.

Background:  Previous retrospective studies of DBS lead revision and removal rates conducted at single sites have reported a percentage between 4.7-12.4%.  However, patient follow-up time in these analyses had wide variation.  A recent retrospective report evaluating United States Medicare data, as well as from a smaller patient cohort where data was collected at two sites, reported a revision and removal rate of 15.2% and 34.0%, respectively.  In order to characterize the rates and types of events that result in lead revisions or removals in a prospective study, information was analyzed from the Product Surveillance Registry (PSR). The PSR tracks data across a large practice population beyond Medicare or single payor systems. It provides insights in how the therapy is utilized at DBS implanting and managing centers while collecting product and safety information on DBS systems and patients. 

Methods: Data was analyzed on 2109 DBS patients registered from July 2009-2016 from 36 centers located in three continents.  Lead survival was the primary endpoint, and analyses were performed to quantify the duration of time until a lead revision or removal occurs while adjusting for varying lengths of post-implant follow-up time. 

Results: Of the 2109 DBS patients, 67.1% were implanted for Parkinson’s disease (n=1416), 21.3% for Essential Tremor (n=449), 7.1% for Dystonia (n=150), and 4.5% for other indications (n=94).  Based upon survival analyses for all indications, lead revision and removal rates were 2.7% at 6 months and 7.9% at 57 months.  There were no observed differences by indication; however the study was not powered for that endpoint. The technical reasons for lead revision and removal were unacceptable lead impedance issues (6/16), lead fracture (5/16), and lead migration (5/16). Whereas, the reasons for lead revision and removal due to non-technical reasons were device-related infections (39/57), other infections (6/57), implant site erosion (4/57), wound dehiscence (4/57), subdural hygroma (2/57), and other reasons (2/57).

Conclusions: Results from this large, prospective global registry demonstrated lead revision and removal rates of 7.9% at approximately five years post-implant.  Lead revision and removals were predominately due to non-technical issues such as infection versus technical issues.  Further analyses of this registry over time will enable comparison across anatomical lead locations or other variables of interest.


Steven FALOWSKI, Peter KONRAD (Nashville, USA), Mya SCHIESS, Stephane PALFI, Gayle JOHNSON, Todd WEAVER, Joachim K. KRAUSS
15:48 - 16:00 #10099 - OP20 Impact of segmented leads in deep brain stimulation.
Impact of segmented leads in deep brain stimulation.

Introduction: Deep Brain Stimulation is an established treatment modality in various movement disorders. Targets are
usually located within the basal ganglia. Due to the proximity of the target points to critical functional structures as the
internal capsule, therapeutic yield might be limited by side effects. Furthermore energy consumption is potentially
higher in conventional monopolar stimulation. Recently, segmented DBS leads have been made available. This
technique comes with the promise of increased efficacy and side effect reduction. We therefore compared our
preliminary data with segmented leads with the data from the Libra study conducted 4 years ago.
Materials/Methods: The purpose of the Libra study was to evaluate the effects of a new Deep Brain Stimulation
System for reducing symptoms of advanced, Parkinson’s disease Also the Activities of Daily Living, UPDRS scores,
Quality of life of subject, device parameters including active contact in relation to efficacy, frequency, type and severity
of therapy related AE’s events were evaluated. 3 months data from patients with segmented leads (Infinity) 6 patients
will be compared to the Libra data (6 patients).
Results: DBS Targeting was guided by three micro electrode recording tracts and a directional lead system (Infinity
DBS, SJM) was implanted in an all-in-one GA setting in 6 patients. The segmented contacts were intensively tested at
90μs and 130 Hz in the postoperative course. Distinct effect/side-effect patterns for each contact were observed.
Comparison of Parkinson’s symptoms as demonstrated by the UPDRS motor scores in the medication “off” state at
Baseline compared to the medication “off” with stimulation “on” 3 months after device implantation. No differences in
efficacy where seen between Libra and Infinity data among those 6 patients. However compared to the Libra data, no
stimulation dependent side effects occurred in the Infinity group. Amplitude and frequency did not differ, however
lower pulse width was used in 2 patients.
Discussion: Segmented leads allowing current steering offer new perspectives for DBS and will likely result in
increased treatment efficacy while reducing side effect at the same time. 
Conclusions: Since the threshold for side effects is higher in segmented leads, they are more adaptable to the
individual patients’ needs and potentially resulting in a longer battery life


Jan VESPER (Duesseldorf, Germany), Jarek MACIACZYK, Philipp SLOTTY

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OPS03
OPS03 PARALLEL SESSIONS: ORAL PRESENTATIONS

OPS03 PARALLEL SESSIONS: ORAL PRESENTATIONS

Moderators: Alex GREEN (Consultant Neurosurgeon) (Oxford, United Kingdom), Ali SAVAS (NA) (ANKARA, Turkey)
15:00 - 15:12 #10526 - OP11 Crucial white matter tracts involved in successful slMFB DBS in major depression.
Crucial white matter tracts involved in successful slMFB DBS in major depression.

Introduction:The superolateral branch of the medial forebrain bundle (slMFB) is currently investigated as a putative DBS target for the treatment of major depression (MD) and OCD.  DTI FT- assisted targeting is necessary. A total of 24 patients have been bilaterally implanted and stimulated for MD at our institutions in two IITs. We present a first analysis focusing on the effectively stimulated fiber tracts and their connections using probabilistic DTI FT.

Methods: n=24, 9f, 47.3+/-10.5 years.  Imaging data consisted of high-resolution anatomical T1W and T2W MRI sequences (3T, Philips Intera, Best, Netherlands) and 32-direction diffusion tensor imaging. Postoperative (after DTI assisted DBS (1)) helical CT scans were used to delineate electrode positions. A complex pipeline of Probabilistic streamline tractography was performed with MRtrix 3 (http://www.mrtrix.org/).

Results: A total of 21 data sets had sufficient quality for further evaluation. In all cases only the slMFB and not the inferomedial branch of the medial forebrain bundle (imMFB) where included in the VAT, as expected. On the group level (not normalized), fibers that were affected by DBS connected bilaterally to the nucleus accumbens, the corpus callosum and the medial prefronal cortex (BA 24 and 32). The strongest connection was seen with the rostral prefrontal cortex (BA10) and BA46 (but only before normalizing data).

 

Conclusion: The presented data supports the modulation of a widespread network containing the rostral prefrontal cortex and parts of the forceps minor and the medial prefrontal cortex in slMFB DBS together with subcortical structures of the reward system. BA10 is a unique part of the human brain. Involvement of this region has also been described before with cg25 as target regions (2). BA10 might represent a common denominator for antidepressant efficacy. A combined modulation of cortical and subcortical structures might explain the short and long-term clinical effects (2).

References:

(1)  Schlaepfer, T. E., Bewernick, B., Kayser, S., Maedler, B., & Coenen, V. A. (2013). Rapid Effects of Deep Brain Stimulation for Treatment-Resistant Major Depression. Biological Psychiatry.

(2)  Riva-Posse, P., Choi, K. S., Holtzheimer, P. E., McIntyre, C. C., Gross, R. E., Chaturvedi, A., et al. (2014). Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression. Biological Psychiatry, 76(12), 963–969.


Volker Arnd COENEN (Freiburg, Germany), Thomas Eduard SCHLAEPFER, Bettina H BEWERNICK, Jan BOSTROEM, Elke HATTINGEN, Horst URBACH, Meng LI
15:12 - 15:24 #10470 - OP12 Six-month outcomes of tractography targeted subgenual cingulate DBS for treatment resistant depresion.
Six-month outcomes of tractography targeted subgenual cingulate DBS for treatment resistant depresion.

BACKGROUND: The subgenual cingulate (SGC) is an investigational target for DBS in treatment-resistant depresion (TRD). Case series have reported 40-60% response rates, however a large industry sponsored randomized sham controlled trial failed futility analysis and closed accrual prematurely. In 2013, we developed an open label study to examine the safety and efficacy of SGC DBS using two types of stimulation (long pulse width or high amplitude) and targeted the confluence of uncinate, frontothalamic, cingulate and forceps minor using 3T MR tractography.

METHODS: In this pilot study of bilateral SGC-DBS we enrolled 23 patients with TRD (12M: 11F, mean age 47, range 23-69) into two different DBS protocols: ‘short pw’, where we increased amplitude (from 4-8 V, keeping pulse width at 90 μs, 130 Hz); ‘long pw’, where we increased pulse width (from 210-450 μs, keeping 3 V, 130 Hz) monthly based on response. Non-responders at 6 months were crossed over to the other stimulation protocol for another 6 months. Study psychiatrist and patients were blinded to stimulation type. Primary outcome was the Hamilton Depression Rating Scale (HDRS-17) and 50% reduction from baseline was considered response. Several other scales, imaging (PET, MRI), electrophysiological (EEG), and chemical biomarkers were also obtained.

RESULTS: Among the 23 patients enrolled one did not receive an implant and another committed suicide shortly after surgery. Six month outcomes are available in 18 patients, at present. HDRS-17 scores improved from a baseline of 23.2±3.9 (mean±SD) to 12.7±6.0 at 6 months (paired t-test, t=5.9, p<0.001), with 9 of 18 patients fulfilling response criteria. Responders were younger than non-responders (37.6±11.9 vs. 54.0±13.2, p=0.014). Four responders were on long pulse duration DBS. Aside from the 1 suicide and 3 intra-op seizures, no complications were encountered at the 6 month time point.

CONCLUSIONS: Our preliminary results support ≈50% efficacy of SGC DBS for TRD. The surgery is overall safe and phenytoin prophylaxis has eliminated the seizure complications. There is no obvious advantage of one type of stimulation over the other, which may suggest that optimization of stimulation over time is more important than type of stimulation. We are examining possible predictive biomarkers of response, however these data suggest that younger patients do better.

FUNDING: Alberta Innovates Health Solutions


Zelma Ht KISS (Calgary, Canada), Sandra GOLDING, Darren CLARK, Aaron MACKIE, Ramasubbu RAJ
15:24 - 15:36 #10575 - OP13 Characterizing capsulotomy targets for OCD based on frontal structural connectivity.
Characterizing capsulotomy targets for OCD based on frontal structural connectivity.

Introduction

Although most patients with obsessive-compulsive disorder (OCD) are well controlled with pharmacological and cognitive behavioral therapy, 10-20% remain severe and refractory. Stereotactic lesions in the anterior limb of the internal capsule (ALIC) have been used for decades to treat these patients. However, there is controversy about optimal sites for lesions within the ALIC as different locations appear to have variable efficacy in alleviating symptoms. Using diffusion tensor imaging (DTI), we segmented the ALIC based on frontal connectivity and used the resulting segmentation to evaluate capsulotomy targeting in OCD.

 

Methods

A segmentation of the ALIC based on frontal structural connectivity was generated using connectivity-based seed classification on 40 control subjects from the Human Connectome Project (HCP) (Figure 1a). Literature review revealed five differentially defined stereotactic radiosurgical (SRS) and radiofrequency (RF) targets for capsulotomy for OCD performed between 2003 and 2014. Capsulotomy lesions were modeled as 5mm-spheres centered on these targets (Figure 1b) and were evaluated for overlap with the created ALIC segmentation and with surrounding gray matter structures (Figure 1c). Modeled lesions were used as seed regions for deterministic tractography on an 842-subject diffusion data template from HCP in order to identify involved connectomic networks.

 

Results

Across the five targets, a mean of 25.4% of modeled lesions overlapped with the ALIC by volume. Means of 16.2%, 12.7%, and 36.8% of modeled lesions coincided with nucleus accumbens, caudate, and putamen, respectively. According to the ALIC segmentation, a mean of 63.9% of the volume of modeled lesions within the ALIC intersected with the subregion connecting primarily to Brodmann area 11 (orbitofrontal cortex, OFC). All five modeled lesions exhibited connectivity to OFC as per the 842-subject HCP template (Figure 2).

 

Conclusion

These results indicate that anterior capsulotomies for OCD have generated lesions extending outside of the ALIC. The overlap between lesions and gray matter structures surrounding the ALIC could represent incidental effects of capsulotomy or it could possibly represent alternate therapeutic mechanisms. These findings also suggest that capsulotomy for OCD may involve the modulation of frontal-subcortical tracts connecting to the OFC, which bears relevance to the cortico-striato-thalamo-cortical (CSTC) model of OCD pathophysiology.


Pranav NANDA (New York, USA), Justin OH, Garrett BANKS, Yagna PATHAK, Sameer SHETH
15:36 - 15:48 #10454 - OP14 Graphical analysis of lead position in regard to outcome for nucleus accumbens/anterior limb of internal capsule (Nacc/ALIC) deep brain stimulation (DBS) in obsessive compulsive disorder (OCD).
Graphical analysis of lead position in regard to outcome for nucleus accumbens/anterior limb of internal capsule (Nacc/ALIC) deep brain stimulation (DBS) in obsessive compulsive disorder (OCD).

Objective: OCD is a sometimes debilitating psychiatric disease with a 2% lifetime prevalence. Up to 10% of patients do not respond to conservative treatment. For severe cases, DBS targeting the Nacc/ALIC is a viable option, receiving CE-mark in 2009. However, because of variable success rates and side effects, 8 different targets have been proposed for OCD in the last 18 years - the search for a hotspot continues.

In this study, using a novel visualization software, we correlated lead position and resulting volume of tissue activated (VTA) with clinical outcome and side effects in order to narrow down the optimal target area.

 Methods: We analyzed data for 16 consecutive patients treated at our center over a period of 3 years with DBS of the Nacc/ALIC, following a routine targeting procedure. Based on improvement on the Yale-Brown obsessive compulsive scale (YBOCS) and clinical profit at 12 months follow up, four outcome groups were defined. Subgroups were also designated for unexpected side effects.

Individual ROIs from all patient hemispheres were stacked to create a median intensity image, and then registered to the resulting intermediate to create a common anatomical space (Patient average MRI, PAM). Using the Suretune Expert Tuning Tool software (Medtronic), the location of the individual contacts used and the resulting VTA were aggregated into the PAM and probabilistic stimulation maps (PSM) were calculated. The adapting Yelnik-Bardinet atlas was aligned to the PAM as an anatomical reference.

 Results: The graphical analysis indicates anatomical localization to be correlating with both clinical outcome as well as side-effects. PSM of non- and fair responders were revealed to be distinct from - but nearby to - the PSM of good and excellent responders. All patients reporting unwanted weight-gain had their active contacts clustered in a circumscript area, independent of their improvement in OCD. These patients are followed up with a multidisciplinary approach to further elucidate the underlying mechanism.

 Conclusion: While data and analysis is preliminary, this novel tool shows promise for correlation of lead location and clinical effect in the way that PSM suggest an area of best profit. The results also open the way for further research into the insufficiently understood side effect of weight gain through DBS in OCD.

 


Martin KLEHR (Cologne/Köln, Germany), Daniel HUYS, Maxim RYZHKOV, Rutger NIJLUNSING, Veerle VISSER-VANDEWALLE
15:48 - 16:00 #10609 - OP15 Identifying brain regions implicated in OCD using simultaneous EEG-fMRI.
Identifying brain regions implicated in OCD using simultaneous EEG-fMRI.

Obsessive-compulsive disorder (OCD) affects 2-3% of the American population. Patients suffering from severe, refractory OCD have limited therapeutic options. Neurosurgical interventions (e.g. deep brain stimulation (DBS) and stereotactic lesions (cingulotomy, capsulotomy)) are currently employed in treating OCD, but are limited in their applications owing to the complexity of potential targets and involved circuitry. Therefore, it is essential to delineate imaging correlates of pathological circuits in OCD. The objective of this study is to use multimodal imaging (simultaneous EEG-fMRI) to identify specific brain regions that are implicated in OCD.

 

We used multimodal imaging to identify correlates of cognitive control impairment that correspond to OCD by comparing results from healthy controls (n=6) and patients with severe, refractory OCD preparing to undergo neurosurgical intervention (n=5). We simultaneously acquired fMRI and EEG data while subjects engaged in the Multi-Source Interference Task (MSIT), a Stroop-like cognitive interference task that is known to engage the dorsal anterior cingulate cortex (dACC). Cue-locked midline frontal theta power (4-8Hz) from EEG was used in the general linear model as a modulator of fMRI regressors. Implicated regions were determined by thresholding the images at a corrected cluster significance of p = 0.05.

 

Results from the EEG analyses confirm that midline frontal theta power, as measured at electrode Fz, is modulated during the MSIT. Additionally, we observed increased task-relevant BOLD activations in the dorsolateral prefrontal cortex (dlPFC) in the control group and in the dlPFC, supplementary motor area (SMA) and the insula for the OCD group. Compared to controls, OCD subjects exhibited increased BOLD activations in the OFC, insula, and the dlPFC in high conflict versus low conflict trials (Figure 1). These results are specific to the cue-locked analysis using an EEG-informed fMRI model and were not observed in the fMRI-only model.

 

We used simultaneous EEG and fMRI in this study to overcome their respective limitations in spatial and temporal resolution. The fMRI model incorporated behavioral task (trial type and reaction times) and EEG data, thereby optimizing the information obtained from the neural signals. The results of this study are a step towards precisely understanding the dysfunction of cognitive control in OCD and delineating specific regions in the brain that are implicated in OCD. 


Yagna PATHAK (New York, USA), Noam SCHNECK, Pranav NANDA, Marina GERSHKOVICH, Helen SIMPSON, Paul SAJDA, Sameer SHETH

15:00-16:00
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OPS05
OPS05 PARALLEL SESSIONS: ORAL PRESENTATIONS

OPS05 PARALLEL SESSIONS: ORAL PRESENTATIONS

Moderators: Jocelyne BLOCH (Médecin Cadre) (Lausanne, Switzerland), Alon MOGILNER (New York, USA)
15:00 - 15:12 #10402 - OP21 How does vagal nerve stimulation modify functional connectivity? A study based on intracerebral EEG recordings and comparison between ‘on’ and ‘off’ stimulation periods.
How does vagal nerve stimulation modify functional connectivity? A study based on intracerebral EEG recordings and comparison between ‘on’ and ‘off’ stimulation periods.

Introduction: The mechanisms of the anti-epileptic action of vagal nerve stimulation (VNS) are still poorly understood.In this study, we investigated the impact of VNS on functional connectivity (Fc) using direct intracerebral recordings of several cortical areas (SEEG) by comparing the “on” versus “off’ stimulation periods.

Material & Methods:Six patients with drug resistant epilepsy who underwent SEEG recordings during ongoing VNS therapy were investigated. Five patients were regarded as non responders to VNS whereas one was deemed responder (> 50% seizure-frequency decrease). SEEG signal was acquired during resting periods without sleep at a distance from seizures. The functional connectivity was computed from co-occurrence of signal estimated by nonlinear regression analysis based of h2 coefficient between pairs of selected bipolar SEEG channels from all sampled cortical areas of the patients. Comparisons were performed during ‘on’ and ‘off’ periods of stimulation. The parameters were similar to those chronically used for the patients. For four patients, different stimulation amplitude were also tested and in one patient different stimulation frequencies and pulse widths.Levels for significance were adjusted according to Bonferroni’s method.

Results: In comparison with ‘off’ periods, the ‘on’ periods disclosed significantly higher values (increased Fc) for five patients (P1, P3, P4, P5, P6) and lower values for one patient (P2). In P6, we observed a significant but nonlinear effect of stimulation parameters on Fc (Fc increased by setting the frequency from 20 to 25 Hz, the amplitude from 1 to 1.25 mA or the pulse-width from 250 to 500μs but without additional effect of setting the parameters to higher values (plateau effect).Finally, the only decreased Fc occurring during VNS corresponded to the responder patient suggesting that the therapeutic benefit might be related to this mechanism.

Conclusion: Our study suggests that VNS alters brain functional connectivity but in a complex and variable way according to the brain areas and parameters settings. The only patient in whom the functional connectivity was decreased was the only patient deriving a true benefit from VNS. The study is too preliminary to draw any solid conclusion but the mechanisms of action may involve a decrease in Fc. These results are consistent with the existing literature (decreased Fc of interictal activity during VNS in responders).


Romain CARRON (MARSEILLE), Stanislas LAGARDE, Elsa VIDAL, Francesca BONINI, Jean RÉGIS, Fabrice BARTOLOMEI
15:12 - 15:24 #10262 - OP22 Comparative Analysis of pre- and post-operative Magnetoencephalography for Patients with Medically Intractable Epilepsy.
Comparative Analysis of pre- and post-operative Magnetoencephalography for Patients with Medically Intractable Epilepsy.

Objective: Magnetoencephalography (MEG) is a functional neuroimaging technique for mapping brain activity by recording magnetic fields produced by electrical currents occurring naturally in the brain. The clinical uses of MEG are in detecting and localizing pathological activity in patients with epilepsy. Single dipole method is an established procedure for analyzing single or spatially and temporally limited activities such as interictal epileptiform activities; however, it has limitations for analyzing spatially propagated and temporally prolonged rhythmic magnetological activity including ictal data during the secondary generalization. Thus, a reliable confirmatory method for analyzing ictal MEG is needed. We analyzed MEG using time-frequency method. It estimated the time frequency component of the signal and it could show the spectral distribution of signal. In such spectral distributions, the gamma oscillation (GOs) is known as useful indicator of epileptogenic focus. In the present study, we investigated GOs of pre-and post-operative MEG to define it had value of prognostic factor.

Methods: From July 2012 to July 2016, a total of 31 patients received the pre- and post-operative MEG test. Among them, we selected ten patients which composed of 5 patients with seizure free and 5 with symptoms after surgery. We find to the epileptic spike on pre-operative electroencephalography (EEG), and then we estimate epileptogenic zone on the brain. Then, based on the EEG, we designate a region of interest location (ROI). Then, we did time frequency analysis of MEG for ROI.

Results: In seizure free group, all patients showed spike wave and GOs on pre-operative EEG and MEG. However, despite the absence of symptoms, spike wave and GOs were seen in one patient on post-operative tests. In the group with seizure after surgery, all patients showed spike wave and GOs on pre-operative tests. However, on post-operative tests, while three patients showed spike wave on EEG, a total of five patients showed GOs still on MEG. We evaluated the relationship between surgical outcome and epileptogenic sign. There was statistical significance between GOs and surgical outcome (p=0.048).

Conclusion: MEG could provide valuable information for post-surgical evaluations to define epileptic focus for patients with persistent symptom after surgery and GOs on MEG is correlated with epileptic focus. Ascertaining the presence of GOs on MEG after epilepsy surgery could predict the prognosis of seizures.


Chang Kyu PARK (Seoul, Korea), Na Young JUNG, Si Woo LEE, Won Seok CHANG, Hyun Ho JUNG, Jin Woo CHANG
15:24 - 15:36 #10102 - OP23 Clinical Outcome and Location of Active Contacts in the Centromedian Thalamic Nucleus Deep Brain Stimulation in Refractory Epilepsy.
Clinical Outcome and Location of Active Contacts in the Centromedian Thalamic Nucleus Deep Brain Stimulation in Refractory Epilepsy.

Objectives: To investigate the clinical outcome and location of active contacts in chronic centromedian nucleus (CM) deep brain stimulation (DBS) for refractory epilepsy.

Methods: The outcome of CM stimulation was evaluated with percent (%) seizure reduction compared to the baseline three months. To determine the location of active contacts, 27 leads in 14 patients with refractory epilepsy were studied. An analysis was conducted to determine whether any coordinates of the center of the active contacts predicted percent seizure reduction. (Fig. 1)

Results: With an average follow-up of 18.2 ± 5.6 months, the mean percent seizure reduction (n=14) was 68 ± 22.4% (25-100%). Eleven of 14 patients (78.6%) could achieve >50% improvement in the frequency of seizure. Specifically, all four patients (100%) with generalized epilepsy (Lennox-Gastaut syndrome) and seven out of 10 patients (70%) with multilobar epilepsy showed >50% reduction in seizure frequency. (Fig. 2)

The mean coordinates of center of the active contact were located in the superior part of anterior ventrolateral CM. The calculated coordinates of laterality from midline (x), anterior-posterior (y) and height (z) from posterior commissure (PC) did not correlate with seizure outcome measured by percent seizure reduction. However, the locations of active contacts used during chronic CM stimulation in multilobar epilepsy were identified more dorsal to those used in generalized epilepsy. (Fig. 3).

Conclusions: Chronic CM stimulation is a safe and effective means in the treatment of refractory epilepsy. 


Son BYUNG-CHUL (Seoul, Korea), Shon YOUNG-MIN, Choi JIN-GYU, Ha SANG-WOO, Ko HAK-CHOEL
15:36 - 15:48 #10743 - OP24 Magnetic resonance-guided stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy is not inferior to anterior temporal lobectomy.
Magnetic resonance-guided stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy is not inferior to anterior temporal lobectomy.

OBJECTIVES: Stereotactic laser amygdalohippocampotomy (SLAH) is a less invasive alternative to anterior temporal lobectomy (ATL) for medically intractable mesial temporal lobe epilepsy (MTLE). To properly compare SLAH to ATL, a large series with 12-month seizure outcomes is required. Here we present 12-month outcomes on 50 SLAH MTLE patients, the largest single center series. We hypothesized that ATL was superior to SLAH.

METHODS: Outcomes 12-months following SLAH were retrospectively analyzed and the proportion of patients who were seizure free was compared to that following ATL, as demonstrated by the Wiebe et al. 2001 randomized controlled trial (64%). The outcome of patients who had recurrent seizures and underwent repeat SLAH (N=9) was re-categorized only if they were seizure free at 12-months. A performance goal of 43% seizure free was also set, the threshold at which SLAH is predicted to achieve higher quality adjusted life years than ATL (Attiah et al. 2015). A select subgroup of MTLE patients with mesial temporal sclerosis (MTS) and without evidence of dual pathology or previous epilepsy surgery was similarly analyzed as an “ideal MTS” subgroup (N=29).

RESULTS: 56.0% (95% CI ±14.3%) of all patients, and 65.5% (95% CI ±18.4%) of the ideal MTS subgroup were seizure free for ≥12 months following all SLAH procedures. These outcomes were not significantly different from the ATL historical comparator group (all: p=0.24; ideal: p=0.87). Further, the ideal MTS subgroup’s seizure free rate was superior to the 43% performance goal. Four of the 9 patients who underwent repeat SLAH became seizure free for ≥12 months, which was included in the above analysis. Four patients not seizure free following SLAH underwent ATL, only 1 of whom became seizure free. Complications were minimal, including 4 postoperative visual field deficits (1 transient; 1 disabling), 2 hemorrhages without persistent deficit and 3 transient cranial nerve palsies.

CONCLUSION: These results fail to reject the null hypothesis that there is no statistically significant difference between ATL and SLAH with respect to 12-month seizure freedom, supporting SLAH as a minimally invasive alternative to open resection for patients with MTLE. Additionally, consistent with ATL outcomes, a higher seizure free rate was achieved in the ideal MTS subgroup. Furthermore, in the minority of patients where seizure freedom remains elusive following SLAH, this procedure does not preclude subsequent open resection.


Matthew STERN (Atlanta, USA), Jon WILLIE, Daniel DRANE, Rebecca FASANO, Amit SAINDANE, Bruno SOARES, Nigel PEDERSEN, Robert GROSS
15:48 - 16:00 #10720 - OP25 Relevant behavioral events may be signaled by the Centromedian-Parafascicular Complex.
Relevant behavioral events may be signaled by the Centromedian-Parafascicular Complex.

Relevant behavioral events may be signaled by the Centromedian-Parafascicular Complex

 

Anne-Kathrin Beck1, Kerstin Schwabe1, Mahmoud Abdallat1, Pascale Sandmann2, Joachim K. Krauss1


1 Department of Neurosurgery, Hannover Medical School, Hanover, Germany

2 Department of Otorhinolaryngology, University of Cologne, Cologne, Germany

 

Objective: The centromedian-parafascicular complex (CM-Pf) of the intralaminar thalamus was shown to be activated during attentional orienting and processing of behaviorally relevant stimuli. Therefore, the CM-Pf was suggested to be a part of a subcortical cognitive control loop. Here, we investigated the human CM-Pf and its involvement in processing of task relevant information during an auditory three-class oddball paradigm with simultaneous cortical recordings.

Methods: Simultaneous intracranial local field potentials (LFPs) and scalp electroencephalographic (EEG) recordings were obtained in 6 patients (2 woman; mean age=48±12 years) who received deep brain stimulation (DBS) electrodes in the CM-Pf for the treatment of their pain syndromes. Within 2 days after surgery, they performed an auditory three-class oddball paradigm with externalized DBS electrodes. Subcortical and cortical event-related potentials (ERPs) were analyzed upon presentation of one frequent standard stimulus (900Hz; 72%) and two infrequent stimuli (600Hz and 1200Hz; 14%), either being a relevant or a distractor stimulus.

Results: Analysis revealed high accuracy (>70%) for all participants. As expected, the rare relevant stimuli elicited a P3 response over parietal regions in the EEG. The P3 component of an ERP is known to reflect attentional processes in tasks requiring stimulus detection and discrimination. Recordings in the CM-Pf revealed highest amplitudes to the relevant stimuli as well. Interestingly, peak latencies of the CM-Pf precede the cortical P3 response.   

Conclusion: The CM-Pf seems to be involved in goal-oriented action selection and attentional mechanisms. Importantly, subcortical responses in the CM-Pf precede cortical responses, suggesting that auditory information is labelled as behavioral relevant from subcortical circuits and is then distributed to cortical areas; possibly via thalamo-striatal loop mechanisms.


Anne-Kathrin BECK (HANNOVER, Germany), Kerstin SCHWABE, Mahmoud ABDALLAT, Pascale SANDMANN, Joachim K. KRAUSS

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FP2 - PARALLEL SESSIONS: FLASH PRESENTATIONS

FP2 - PARALLEL SESSIONS: FLASH PRESENTATIONS

Moderators: Jung-Il LEE (Seoul, Korea), Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Lausanne, Switzerland)
16:15 - 17:15 #10718 - OF11 Effects of 5 weeks fornix deep brain stimulation in a transgenic Alzheimer rat model.
Effects of 5 weeks fornix deep brain stimulation in a transgenic Alzheimer rat model.

Background: Deep brain stimulation (DBS) is promising therapy in patients with Alzheimer’s disease (AD). Few studies have suggested that stimulation of the forniceal area might slow down the cognitive decline of AD patients, but its biological effects on memory circuits remain unclear.

Objective: To study the behavioral and histological effects of continuous chronic DBS of the fornix in a transgenic Alzheimer murine model and wild type (WT) rats.

Methods:  We used a transgenic Alzheimer rat model TgF344-AD that manifests age-dependent cerebral amyloidosis, taupathy, gliosis and apoptotic loss of neurons in the cerebral cortex and hippocampus, as well as cognitive disturbance. All the 18 month-old rats were surgically implanted in stereotactic conditions, using a DBS system specially adapted for rats, allowing a chronic continuous stimulation for 5 weeks. Cognitive tests (open field and Novel Object recognition test) were performed before surgery, and after 2 and 5 weeks. At 5 weeks the animals were sacrificed for immunohistochemical study. Implanted but non stimulated rats were used as controls.

Results: We confirmed the above described differences between transgenic AD rats and WT rats. Moreover we found that DBS led to a significantly reduce in Aβ deposition and in neuroinflammation markers (Iba1 and GFAP); DBS prevented neuronal (NeuN staining) and synaptic (Synaptophysin stainig) loss.  Cognitive tests suggested an improvement of memory in the DBS transgenic rat model but did not differ significantly between groups.

Conclusion: In the Tg-F344-AD rat model, 5 weeks of forniceal DBS decreased amyloidosis and inflammatory responses, prevented neuronal and synaptic loss in the cortex and hippocampus. These findings show a neuro protective effect of forniceal DBS.


Aurélie LEPLUS (NICE), Denys FONTAINE, Frederic CHECLER, Lydia KERKERIAN LE GOFF
16:15 - 17:15 #10495 - OF12 Lateral Cerebellar Nucleus Stimulation Promotes Motor Recovery In A Rodent Model Of Traumatic Brain Injury.
Lateral Cerebellar Nucleus Stimulation Promotes Motor Recovery In A Rodent Model Of Traumatic Brain Injury.

Objective: To evaluate the effect of deep brain stimulation of the lateral cerebellar nucleus (LCN) on motor recovery in a rodent model of traumatic brain injury. 

Background: We have previously shown that chronic electrical stimulation of the LCN enhances motor rehabilitation in different rodent models of ischemic stroke.  Those improvements were further associated with enhanced synaptogenesis and expression of markers of long-term potentiation in the perilesional cortex, suggesting that stimulation induced significant, functional plasticity even in chronic, post-ischemic animals. Based on these findings, we speculated that LCN stimulation may similarly enhance motor rehabilitation following traumatic brain injury (TBI).

 Methods: Ten male Long Evans rats were trained on the pasta matrix retrieval task, followed by induction of TBI using the fluid percussion injury (FPI) model (1.3-1.5 atms) and implantation of an electrode in the contralesional LCN. Electrical stimulation was initiated at four weeks after FPI induction and sustained for an additional four weeks during which rats were evaluated continually on the pasta matrix task. Motor recovery was also evaluated using the cylinder test. After sacrifice, 30µm cryosections of the motor cortex and thalamus were collected onto polysine slides for histology and immunohistochemistry. The FPI induced primary lesion was visualized by Nissl staining and quantified, while the FPI-mediated perilesional area was visualized by Fluoro-Jade C staining. Neuroinflammation markers, including CD68 and IBA1, were analyzed by immunohistochemistry.  

 Result: The FPI injury model yielded a focal lesion centered over the primary and secondary motor as well as the primary sensory cortical regions with penetration to the corpus callosum. Animals that received stimulation showed enhanced motor recovery relative to sham controls, with retrieval rates 34.8%, 70.7%, 58.0%, and 36.3% higher in treated animals over weeks 1, 2, 3, and 4 following stimulation onset. Notably, stimulation was associated with a significant reduction in lesion volume in the treated rats compared to sham controls.

 Conclusion: DBS of the dentatothalamocortical pathway, targeting the LCN, was found to promote motor rehabilitation in a TBI rat model. These findings are consistent with our previous work in the ischemic rodent model and have strong implications for the potential use of DBS to promote recovery after traumatic brain lesions.


Hugh CHAN, Connor WATHEN, Nicole MATHEWS, Jessica COOPERRIDER, Hyun-Joo PARK, Kenneth BAKER, Andre MACHADO (Cleveland, USA)
16:15 - 17:15 #10504 - OF13 DBS of the STN causes Impulsive Responses to Bursts of Evidence.
DBS of the STN causes Impulsive Responses to Bursts of Evidence.

In addition to its motor functions, the subthalamic nucleus (STN) has a cognitive role in inhibiting impulsivity. Previous studies have suggested that the STN raises the evidence threshold for making decisions. We tested this theory in 8 patients receiving bilateral DBS of the STN using an auditory task (n=5085 trials) in which subjects listen to bilaterally presented “clicks” and decide which side has more. Subjects’ decision-making could be interrupted prior to reaching their evidence threshold. The statistics of stimulus presentation and trial ending were designed so that subjects could not predict when these events would occur resulting in evidence accumulation to a bound. We expected performance to decline in the DBS ON compared to the OFF condition on trials where subjects hit their decision bound (i.e. responded before stimulus-offset). However, DBS caused a performance decrease in only leftward trials (p=1.82 * 10-4, Fisher’s exact test, Figure A-C). Drift-diffusion modeling showed that DBS caused 6/8 subjects to increase the value of clicks that occur temporally close to other clicks. There was no clear effect on decision bound. Using model-free analysis, we found that subjects responded impulsively to bursts of evidence that were associated with high levels of conflicting evidence, as shown in Figure D-G. While DBS of the STN may lower the decision bound, our data suggests that it may also prevent premature responses to bursts of evidence that portend conflict.

 


Dennis LONDON, Michael POURFAR, Alon MOGILNER (New York, USA)
16:15 - 17:15 #10370 - OF14 Clinical Trial on Deep Brain Stimulation in subiculum for mesial temporal lobe epilepsy, an 18 months of follow-up.
Clinical Trial on Deep Brain Stimulation in subiculum for mesial temporal lobe epilepsy, an 18 months of follow-up.

Objective: Recent studies have proposed that the subiculum (SC) plays an important role in the genesis and propagation of epileptic seizures, and another group report correlated improvement of seizures by DBS to the proximity of active contacts to the SC. Since in most cases of hippocampal sclerosis (HCS) the SC is well preserved, the aim of this study was to test SC-DBS in cases of mesial temporal lobe epilepsy with HCS.  We had already presented a preleminary report, in this case we present an 18 months follow-up.                                                                                                             

Material and Methods: Seven patients with mesial temporal lobe seizures and HCS were implanted in the interface between hippocampus and parahippocampus for DBS. All had previously intracranial recordings to identify the side and precise location of seizure onset. Patients entered a randomized, double blind (DB) protocol in which, after a 4 months baseline (BL) period and one month post-implantation period OFF stimulation, 3 cases had the DBS turned ON, while 4 patients continued OFF DBS for a period of 3 months. Thereafter DBS was turned ON in all and followed for a period of 14 months. DBS parameters were cycling mode 1min ON/4 min OFF, 3.0 V, 450microsec and 130HZ. AED’s were maintained unchanged along the study. The outcome for this series was compared with a similar number of cases with HCS treated by DBS in the sclerotic tissue and reported before.                                                                                                                                             

Results: In BL mean total number of seizure per month for the group was 8.29 with 7.26 ending in Generalized Tonic-Clonic (GTC) seizures. Seizure number decrease during the 1st month after implantation and returned to BL levels by the 2nd month. Thereafter, there was not a significant difference between patients ON/OFF stimulation during DB period. When all patients were turned ON, there was a reduction of 56.94% in total number of seizures (p=0.027) and 78.25% for GTC (p<0.017), which was no different to what has been reported for DBS in HCS.    

Conclusion: Electrode placement in the SC induced a transient decrease in seizures. Thereafter decrease in number of seizures was more prominent for GTC than for partial complex seizures. Therefore subiculum seems related to seizure propagation more than seizure onset. 


Gustavo AGUADO CARRILLO (Mexico City, Mexico), Manola CUELLAR HERRERA, Daruni VÁZQUEZ BARRÓN, Francisco VELASCO CAMPOS, Ana Luisa VELASCO MONROY
16:15 - 17:15 #10625 - OF15 Altered somtatosensory cortex neuronal activity in a rat model of Parkinson`s disease and levodopa-induced dyskinesias.
Altered somtatosensory cortex neuronal activity in a rat model of Parkinson`s disease and levodopa-induced dyskinesias.

Objective

Several findings support the concept that sensorimotor integration is disturbed in Parkinson`s disease (PD) and in levodopa-induced dyskinesias. In this study, we explored the neuronal firing activity of excitatory pyramidal cells and inhibitory interneurons in the forelimb region of the primary somatosensory cortex (S1FL-Ctx), along with its interaction with oscillatory activity of the primary motor cortex (MCtx) in 6-hydroxydopamine lesioned hemiparkinsonian (HP) and levodopa-primed dyskinetic (HP-LID) rats as compared to controls. Further, gene expression patterns of distinct markers for inhibitory GABAergic neurons were analyzed in both cortical regions.

 

Methods

Single unit activity and local field potential were recorded under urethane (1.4 g/kg, i.p) anesthesia by using quartz coated micro-electrode. Additionally, an electrocorticogram (ECoG) was acquired via a 1 mm diameter jeweller’s screw, positioned on the dura mater above the MCtx ipsilateral to the 6-OHDA lesioned hemisphere.

 

Results

While firing frequency and burst activity of S1FL-Ctx inhibitory interneurons were reduced in HP and HP-LID rats, measures of irregularity were enhanced in pyramidal cells. Further, enhanced coherence of distinct frequency bands of the theta/alpha, high-beta, and gamma frequency, together with enhanced synchronization of pyramidal cells and interneurons with MCtx oscillatory activity were observed. While GABA level was similar, gene expression levels of interneuron and GABAergic markers in S1FL-Ctx and MCtx of HP-LID rats differed to some extent.

Conclusion

Our study shows both electrophysiological alterations and changes in gene expression in the sensorimotor cortices in a rat model of PD, which differ depending on the functional state after dopamine depletion and treatment indicating maladaptive neuroplasticity.


Mesbah ALAM (Hannover, Germany), Regina RUMPEL, Xingxing JIN, Christof VON WRANGEL, Sarah TSCHIRNER, Joachim K KRAUSS, Claudia GROTHE, Andreas RATZKA, Kerstin SCHWABE
16:15 - 17:15 #10158 - OF16 Characteristic features of cortical and pallidal alpha and beta oscillations during ipsilateral and contralateral movements in Parkinson’s disease.
Characteristic features of cortical and pallidal alpha and beta oscillations during ipsilateral and contralateral movements in Parkinson’s disease.

Introduction.  The precise functional roles of alpha (8-12 Hz), low beta (12-20 Hz), and high beta (21-35 Hz) oscillations within cortical and subcortical sensorimotor circuits remain unclear. Studies on subjects with Parkinson’s disease (PD) demonstrated alpha and beta modulation within bilateral subthalamic nuclei (STN) during unilateral movement.  Is bihemispheric movement-modulation of alpha and beta oscillations a consequence of direct cortical-STN pathways or intrinsic features of the cortical-basal ganglia motor network?  In this study, we investigated both alpha and beta oscillations within the globus pallidus interna (GPi) and sensorimotor cortices during ipsilateral and contralateral movement.

Methods.  Local field potentials (LFP) within the right GPi and sensorimotor cortices were recorded intraoperatively during contralateral self-paced hand grasping and rest in 18 PD subjects.  In a subeset of 5 subjects, recordings were also carried out during ipsilateral movement.  Hand activity was captured concurrently with a sensor-embedded glove. 

Results.  Attenuation of alpha, low beta, and high beta oscillations were observed with both contralateral and ipsilateral movement within the GPi and sensorimotor cortices. In general, movement attenuation of low beta was greater than alpha or high Beta.  Low beta attenuation was greater during contralateral movement than ipsilateral movement (65 %  versus 45 % respectively). Resting sensorimotor cortical alpha power was found to be 39 % higher on average during ipsilateral as compared to contralateral movement states.  Coherence results demonstrated two main features; 1) High Beta cortico-pallidal coherence persists during movement and rest with both contralateral and ipsilateral movements and 2) Resting cortico-pallidal alpha coherence was greater during ipsilateral as compared to contralateral movements states.

Conclusion.  While movement-related modulation of alpha and beta oscillations occurs irrespective of movement side, distinguishing features of ipsilateral movement states include a higher resting sensorimotor cortical alpha power, increased resting cortico-pallidal alpha coherence, and a reduced low beta attenuation during movement.  Our findings support the proposed concepts of; 1) the inhibitory function of alpha oscillations on unneeded cortical circuits, 2) ‘akinetic’ role of low beta oscillations and 3) a pathological high beta coupling in Parkinson’s disease.


Nicholas AUYONG (Los Angeles, USA), Mahsa MALEKMOHAMMADI, Andrew HUDSON, Nader POURATIAN
16:15 - 17:15 #10529 - OF17 Response to Deep Brain Stimulation is Associated with Increased Resting State Connectivity in the Associative Basal Ganglia Circuit.
Response to Deep Brain Stimulation is Associated with Increased Resting State Connectivity in the Associative Basal Ganglia Circuit.

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus pars interna (GPi) is indicated in patients with refractory Parkinson's disease (PD) with significant motor fluctuations. While clinical characteristics facilitate patient selection, no objective tool to predict response to DBS exists. We examined resting state functional magnetic resonance imaging (rsfMRI) to determine the feasibility of this modality to serve as such a predictive tool. 

Methods: Eight patients (3 female) with advanced PD underwent a preoperative MRI under anesthesia in preparation for DBS surgery. Motor scores (UPDRS-III) were collected before and after DBS (mean follow-up of 5.9 months). Scans were performed in a 3T Achieva Philips MR scanner, including rsfMRI (TR=2000ms, TE=25ms, FOV=68×68mm, flip angle=90o, spatial resolution=1.87×1.87×3.5mm, matrix size=128×128). Images were preprocessed to correct for spatial and temporal artifacts. Regions of interest (ROIs) were defined using the Harvard-Oxford atlas and the ATAG-MNI04 basal ganglia atlas. Functional connectivity (FC) was calculated using the MatLab-based CONN toolbox via two-tailed bivariate correlations. Significant FC differences between patients who had improved UPDRS-III scores following DBS versus those who had worse UPDRS-III scores following DBS were evaluated with both a ROI-to-voxel and ROI-to-ROI analysis (FDR-corrected p<0.05).

Results: Patients were 66.5±8.9 years old with disease duration of 7.3±1.8 years. Preoperative UPDRS-III was 29.3±10.6 and postoperative UPDRS-III was 21.9±9.0. Patients who responded more favorably to DBS had increased resting state connectivity within the basal ganglia (STN, pallidum, thalamus, striatum) and increased connectivity between the striatum and the frontal operculum (p=0.001).

Conclusions: Three major basal ganglia networks consisting of motor, associative, and limbic circuits have been described. While much focus has been on motor circuits in PD, our findings suggest that the associative circuit may play a role in response to DBS. Our findings echo a related study, which demonstrated a similar increase in associative circuit connectivity in patients who had a greater response to L-DOPA. Together, these results show promise in the ability for rsfMRI to provide better pre-surgical consultation and guidance to patients regarding prognosis from DBS.


Anup BHATTACHARYA, John PEARCE, Mahdi ALIZADEH, Jennifer MULLER, Daniel KREMENS, Tsao-Wei LIANG, Ashwini SHARAN, Feroze MOHAMED, Chengyuan WU (Philadelphia, PA, USA, USA)
16:15 - 17:15 #10530 - OF18 Identification of a Resting State Biomarker for Prediction of Disease Severity in Parkinson’s Disease.
Identification of a Resting State Biomarker for Prediction of Disease Severity in Parkinson’s Disease.

Introduction: Parkinson’s disease (PD) is a neurodegenerative disorder that primarily affects the motor system. Prominent motor symptoms in the disease include unilateral tremor, rigidity, and bradykinesia. For the clinical standardization of disease severity, the motor scores from the Unified Parkinson’s Disease Rating Scale (UPDRS-III) have long been used but recent evidence suggests there can be significant inter-rater variability in these scores that can be influenced by experience level. Our project therefore aims to identify a resting state functional magnetic resonance imaging (rsfMRI) biomarker that provides a more objective determination of disease severity.

Methods: Seven patients (3 female) with advanced PD underwent a preoperative MRI under anesthesia in preparation for DBS surgery. Motor scores (UPDRS-III) were collected before and after DBS (mean follow-up of 5.9 months). Scans were performed in a 3T Achieva Philips MR scanner, including rsfMRI (TR=2000ms, TE=25ms, FOV=68×68mm, flip angle=90o, spatial resolution=1.87×1.87×3.5mm, matrix size=128×128). Images were preprocessed to correct for spatial and temporal artifacts. Regions of interest (ROIs) were defined using the Harvard-Oxford atlas and the ATAG-MNI04 basal ganglia atlas. Functional connectivity was calculated using the MatLab-based CONN toolbox via two-tailed bivariate correlations. Significant connectivity differences were evaluated in a linear fashion based on UPDRS-III scores with both a ROI-to-voxel and ROI-to-ROI analysis (FDR-corrected p<0.05).

Results: Patients were 66.1±8.9 years old with disease duration of 7.2±1.8 years. Preoperative UPDRS-III was 26.6±8.5 and postoperative UPDRS-III was 22.3±9.5. Individuals with higher UPDRS-III scores demonstrated increased resting state connectivity within the basal ganglia (STN, pallidum, thalamus, striatum) (p=0.006).

Conclusions: Our findings demonstrate that Parkinson’s disease severity is associated with increased resting state connectivity between the various nuclei of the basal ganglia, which have long been hypothesized to be key players in disease progression. In the future, rsfMRI may be beneficial in offering a more objective measurement of disease severity in PD.


Anup BHATTACHARYA, John PEARCE, Mahdi ALIZADEH, Jennifer MULLER, Daniel KREMENS, Tsao-Wei LIANG, Ashwini SHARAN, Feroze MOHAMED, Chengyuan WU (Philadelphia, PA, USA, USA)
16:15 - 17:15 #10541 - OF19 Spikes and Field Potential Oscillations in the Nucleus Accumbens during Impulsivity: Evidence from Mice and Man.
Spikes and Field Potential Oscillations in the Nucleus Accumbens during Impulsivity: Evidence from Mice and Man.

Introduction:
Impulsivity is one of the most pervasive and disabling features common to many neurological disorders. Heightened responsivity in the nucleus accumbens (NAc) during anticipation of rewarding stimuli predisposes to impulsivity. Electrophysiological correlates have been reported during brief windows of anticipation. This period represents a critical opportunity for intervention, but no available therapy is capable of sensing and therapeutically responding to this vulnerable moment. The objectives of our research are: to identify biomarkers of anticipation of highly-reinforcing food reward in mouse NAc, to use these biomarkers to guide responsive neurostimulation (RNS) to suppress binge-like behavior, and to examine the translatability of these biomarkers in a human subject anticipating monetary rewards.
Methods:
Multielectrode arrays were implanted into the mouse NAc, and were put on a limited high-fat (HF) exposure protocol known to induce binge-like behavior. Power spectral density analysis of NAc local field potentials (LFPs) and spike analysis before HF intake were performed to identify electrophysiological biomarkers. Identical analyses were performed before house chow intake. RNS was triggered whenever potential biomarkers appeared, and reduction in HF intake induced by RNS was examined. RNS was applied during juvenile interaction test to assess behavioral specificity. In parallel, NAc spikes and LFPs from a human subject performing Monetary Incentive Delay Task were recorded and analyzed.
Results:
Unique spike patterns and increased delta oscillations were observed immediately prior to HF intake after mice developed binge-like behavior, which was not detected immediately prior to chow intake. RNS utilizing delta power as biomarker significantly reduced HF intake. Unique spike patterns and prominent delta oscillations during anticipation of monetary reward were also revealed in human NAc.
Conclusion:
We demonstrate that anticipation of rewards is correlated with certain spike patterns and increased delta oscillations in NAc in both mice and a human subject. NAc electrophysiological signals carry critical information relevant to reward anticipation, and have the potential to be used as a biomarker to guide RNS treatment for neuropsychiatric disorders exhibiting impulsivity.


Hemmings WU (Stanford, USA), Kai MILLER, Zack BLUMENFELD, Williams NOLAN, Vinod RAVIKUMAR, Karen LEE, Bina KAKUSA, Mathhew SACCHET, Max WINTERMARK, Daniel CHRISTOFFEL, Brian RUTT, Helen BRONTE-STEWART, Brian KNUTSON, Robert MALENKA, Casey HALPERN
16:15 - 17:15 #10569 - OF20 Assessing the impact on bradykinesia and dyskinesia in patients with Parkinson’s disease undergoing deep brain stimulation using a novel and objective automated assessment tool.
Assessing the impact on bradykinesia and dyskinesia in patients with Parkinson’s disease undergoing deep brain stimulation using a novel and objective automated assessment tool.

Introduction

The Parkinson’s KinetiGraphTM (PKG) is a wrist-worn device for patients with Parkinson’s disease (PD). Inbuilt accelerometers capture real-time movement data and utilise frequency and spectral analysis to generate dyskinesia (DKS) and bradykinesia scores (BKS), which correlate to clinical severity, quantified against scores such as the Unified Parkinson’s Disease Rating Scale (UPDRS-III/IV) and modified Abnormal Involuntary Movement Scale (mAIMS)1. The fluctuation and dyskinesia score (FDS) summarises the interquartile range of bradykinesia and dyskinesia into a single score and represents symptom variability. Deep brain stimulation (DBS) is used to alleviate the motor symptoms of PD and its impact was assessed in depth with this continuous automated monitoring tool.

Methods

16 PD patients (10M, 6F) wore the device on their most symptomatic arm and continuous recordings over a 6-day period were obtained and analysed. In 6 patients (4M, 2F), 6 months after DBS, postoperative PKG was obtained to determine changes in BKS, DKS and FDS. This was compared against validated control data derived from the PKG database1. Wilcoxon signed-rank test was used for paired analysis.

Results

PKG data analysis generates BKS and DKS across 25-50-75 percentiles and a single FDS score. Pre-operatively, median BKS in all 16 PD patients (PKG control data) was 13.8 (12.7), 20.2 (18.6), 28.6 (26.1) with DKS, 1.3 (0.9), 7.2 (4.3), 22.1 (16.5) indicating PD patients with symptomatic motor dysfunction. In the DBS-subset, there was a statistically significant difference in DKS postoperatively (p = 0.03) and FDS (p = 0.03) with a non-significant difference in BKS. Mean FDS improved 25.2% from 14.8 (high fluctuations) preoperatively to 10.6 (controlled and stable fluctuations) postoperatively (reference range 7.7-12.8). Median DKS improved 31.8% from 7.55 preoperatively to 5.15 postoperatively.

Conclusions

Scores generated following the use of a PKG can objectively demonstrate dyskinesia and bradykinesia variability and correlate changes following an intervention. PKG can complement existing clinical tools to assess motor symptoms in PD patients objectively and automatically. Larger numbers are needed to determine the effect of disease progression and therapeutic intervention.

References

1          Griffiths et al. J Parkinsons Dis. 2012; 2(1): 47-55.


Bobby SACHDEV (Cambridge, United Kingdom), Philip BUTTERY, Robert MORRIS

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FP1 - PARALLEL SESSIONS: FLASH PRESENTATIONS

FP1 - PARALLEL SESSIONS: FLASH PRESENTATIONS

Moderators: Alireza GHARABAGHI (Medical Director) (Tuebingen, Germany), Jan MEHRKENS (Head of Functional Neurosurgery) (München, Germany)
16:15 - 17:15 #10807 - OF01 Improvement of consciousness after severe traumatic brain injury with deep cerebellar stimulation.
Improvement of consciousness after severe traumatic brain injury with deep cerebellar stimulation.

Introduction

The failure of the brain mechanisms following severe traumatic brain injury is mostly assumed to be the result of widespread loss of cerebral connectivity. Extensive plastic potential of brain can be limited by chronic underactivation of the large–scale networks. There are indications that properly selected  DBS techniques could effectively modulate brain activity and promote recovery.

 

Methods

The deep cerebellar stimulation has been applied for symptomatic treatment of spasticity and dyskinesias in 49 patients. Four quadruparetic spastic patients were 6, 7 12, 18 month after severe brain injury, three in vegetative state, one in minimally conscious state. Two electrodes were bilaterally implanted into medial vermal lobar white matter region of the anterior cerebellar lobe, superiorly to the brachia conjunctiva, position verified by intraoperative stimulation tests. Chronic high frequency stimulation (250 Hz, 2-4mA, 20min ON, 3 hours OFF) were applied. Patients were followed up during 14, 16, 40, 69 months respectively.

 

 

Results

All three patients emerged from vegetative state, however two became able to obey verbal commands, remained in bedridden state, but third one was able to speak, feed himself, move on wheelchair. Forth patient emerged from MCS, walks with support, speaks, oriented, feed himself.

 

Conclusion

The role of the cerebellum in sensorimotor regulation is well known. Its widespread reciprocal connections with the areas of the brain involved in processes of emotion, consciousness and cognitive functions is especially documented in recent fMRI studies. According to our observations specific augmentation of cerebellar modulation on the brain network could be taken account.


Miroslav GALANDA (Kosice, Slovakia), Tomas GALANDA, Jana MISTINOVA, Peter JOMBIK, Maria KLUZOVA
16:15 - 17:15 #10547 - OF02 The importance of somatotopy to achieve clinical benefit in motor cortex stimulation for pain relief.
The importance of somatotopy to achieve clinical benefit in motor cortex stimulation for pain relief.

Introduction: 

The aim of this study was to search the relationship between the anatomical location and the eventual analgesic effect of each contact. 

Materials and Methods: 

22 patients (14 men and 8 women) suffering from central and / or peripheral neuropathic pain were implanted with stimulation of the precentral cortex.

The implantation of the electrodes was performed using intraoperative: 1) Anatomical identification by Neuronavigation with 3D MRI, 2) Somesthetic evoqued potentials monitoring to check the potential reverse over the central sulcus, 3) Electrical stimulations through the dura to identify the motor responses and its somatotopy.

In order to locate postoperatively the electrodes, a 3D-CT was performed in each case and fused with the preoperative MRI. The clinical analgesic effects of cortical stimulation were collected on a regular basis (VAS reduction > 50%, drugs consumption). Data were analyzed to search a correlation between the anatomical position of contacts and analgesic effects.

Results: 

Post implantation analgesic effects were obtained in 18 (81.81 %) patients out of 22. The analgesic effect was companied with reduction of the drugs consumption in 15 patients (68.18 %). The post-operative 3D CT analysis shows a correspondence between the effective contacts localization and the motor cerebral cortex somatotopy in the patients with post-operative good analgesic effects. No correspondence was found between the contacts localization and the motor cerebral cortex somatotopy in the 4 patients with no analgesic effects. In three out of these four patients, analgesic effects were obtained after a new surgery allowing a replacement of the electrode position over the motor cortex somatotopy corresponding to the painful area. 

Conclusion: This study shows the correlation between position of the contact over the precentral cortex and the analgesia obtained when the somatotopy of the stimulated cortex correspond to the painful area.


Afif AFIF (Lyon), Luis GARCIA-LARREA, Patrick MERTENS
16:15 - 17:15 #10598 - OF03 High-density spinal cord stimulation for chronic neuropathic pain: a prospective observational study.
High-density spinal cord stimulation for chronic neuropathic pain: a prospective observational study.

Introduction:

High-density spinal cord stimulation (HD-SCS) is an emerging treatment modality for chronic neuropathic pain, based on the concept that the amount of electric charge is the key determinant of SCS efficacy. HD-SCS is paraesthesia-free and may represent a treatment option for patients who do not derive benefit from conventional SCS. This study sought to determine the effect of HD-SCS on pain intensity and quality of life, when initiated either primarily during the test phase following SCS lead implantation or as a salvage treatment following unsuccessful treatment with conventional SCS.

Methods:

This prospective, IRB-approved observational study enrolled consecutive patients with chronic neuropathic pain who began receiving high-density SCS in July-December 2015.  We examined medical history, procedural information, programming parameters, and clinical outcomes including pain reduction, activities of daily living, and change in pain medications.

Results:

The median age of the 16 study participants was 60 years (SD 10, range 45-79) and 9/16 were female. The indications for initial SCS included failed back surgery syndrome (11 patients), syringomyelia, pudendal neuralgia, post-thoracotomy syndrome, peripheral neuropathy and phantom upper limb pain (each 1 patient). 5/16 cases represented primary HD-SCS therapy, while 11/16 cases involved conversion from standard SCS after a mean period of 33 months (SD 3). The most common reason for such conversion was refractory or residual pain (8 patients) despite SCS, followed by undesired side-effects of SCS including intolerable paraesthesia (2 patients). The median duration of follow-up after HD-SCS initiation was 7 months (SD 4.5). The mean pulse density utilised was 15% (SD 7.2, median 15). 15/16 subjects reported improved pain with HD-SCS. Overall, a mean VAS pain reduction of 2.9 points (SD 1.8, p<0.001, paired t-test) from 7.1 (baseline, SD 1.5, IQR 6-8) to 4.2 (SD 1.8, IQR 3-5.5) in overall pain at last follow-up was observed. Patients receiving HD-SCS as a salvage therapy were, however, more likely to have VAS improvement (p<0.05, Fischer’s exact test). Improvement in activities of daily living and reduction in pain medication usage were also reported.

Conclusion:

HD-SCS represents a safe, well-tolerated and efficacious alternative to conventional SCS, offering particular promise in patients with pain refractory to conventional SCS therapy.


Aaron LAWSON MCLEAN (Jena, Germany), Susanne FRANK, Denise FEIERABEND, Rolf KALFF, Jan WALTER, Rupert REICHART
16:15 - 17:15 #10817 - OF04 Limbic Leucotomy for Self-Injurious Behavior: Long term follow-up of two cases.
Limbic Leucotomy for Self-Injurious Behavior: Long term follow-up of two cases.

Self-injurious behavior (SIB) is amongst the most severe and treatment refractory of all psychiatric conditions. SIB is associated with a variety of psychiatric disorders and can manifest in various ways and is potentially life threatening. Limbic leucotomy, which combines the lesions of the anterior cingulotomy and subcaudate tractotomy, has been shown to be beneficial in a small cohort of patients with severe, intractable SIB. However, to date there have been no long-term follow-up reports. We describe the long term effects of limbic leucotomy in two adult female patients with severe repetitive SIB that was unresponsive to an exhaustive treatment regimen. Both patients had been chronically institutionalized with 24 hour 1:1 or 2:1 care. Both patients underwent MRI guided stereotactic limbic leucotomy after comprehensive review and careful ethical deliberation. Throughout >18 years of follow-up, both patients have demonstrated slow, steady improvement without significant cognitive or behavioral side effects. Both experienced eventual cessation of SIB and are now working and living independently. The favorable outcomes of these two cases demonstrate the safety and sustained therapeutic benefit of ablative limbic leucotomy in the treatment of severe, intractable SIB.


Rees COSGROVE (Boston, USA), Erdong CHEN, Bruce PRICE, Darin DOUGHERTY
16:15 - 17:15 #10458 - OF05 Intraoperative neurophysiological monitoring in Dorsal Rhizotomy for Spasticity. Usefulness in a prospective series of 10 spastic diplegic patients.
Intraoperative neurophysiological monitoring in Dorsal Rhizotomy for Spasticity. Usefulness in a prospective series of 10 spastic diplegic patients.

Introduction: Intraoperative explorations, especially muscular responses to radicular stimulation, remain controversial. A few teams deny interest of any monitoring and base their surgeries on anatomical identification of roots. Others favor studying not only responses to ventral root (VR) stimulation to identify radicular levels, but also to stimulation of dorsal roots (DR) - or even of each of their constituting rootlets. Most teams use variable intermediate modalities. We carried out a prospective study associating VR stimulation to map anatomical levels and DR stimulation as physiological testing for metameric reflex excitability to assess the usefulness of monitoring.

Material and methods: Ten children with spastic diplegia were operated on with the following protocol: bilateral intradural approach of L2-S2 roots at exit/entry of/to their respective dural sheaths, through multi-level inter-laminar enlarged openings; stimulation of VR (2Hz) for checking topography, i.e., radicular myotome distribution, then of DR (50Hz) as excitability test of root circuitry; identification of the muscle responses by the physical therapist and EMG recordings. The study consists of comparing the amount and levels of root sectioning after monitoring-guidance, with those determined by the multidisciplinary team written in the pre-surgical chart.

Results: Intra-operative observations and EMG-recordings resulted in changes in the pre-operative program in 9 of the 10 patients. Changes in L2-S1 on both sides in the 9 patients were 13.5% compared to Chart guidelines, with SD ± 10.2%. These changes were either a decrease (3.7%) or an increase (7.1%) in the amount of section. In the 9 patients the chart indicated a symmetrical section, which was modified in one patient, at four levels. Changes also affected the sectioning amount/level. Thus, in the 9 patients (18 dorsal root levels) the changes were as follows: at L2 and L3 roots: sectioning was decreased in 6 and 5 roots and increased in 0 and 2 roots, respectively; at L4 and L5 roots: sectioning was decreased in 0 and 2 roots and increased in 5 and 6 roots, respectively; at S1 root: sectioning was decreased in 2 and increased in 4 roots.  

Conclusion: Changes in the targets and quantity of the sections according to the intraoperative information helped to adjust surgery. Use of IONM allowed to better tailor the Dorsal Rhizotomy according to clinical presentation and therefore reach therapeutic goals.


George GEORGOULIS, Andrei BRINZEU, Marc SINDOU (Lyon)
16:15 - 17:15 #9914 - OF06 The "iron sights" method to determine the orientation of directional deep brain stimulation electrodes using 3D rotational fluoroscopy.
The "iron sights" method to determine the orientation of directional deep brain stimulation electrodes using 3D rotational fluoroscopy.

Background and Purpose: New Deep Brain Stimulation leads with electrode contacts that are split along their circumference allow steering the electrical field in a pre-defined direction. However, imaging-assisted directional stimulation requires detailed knowledge of the exact orientation of the electrode array. The purpose of this study was to evaluate if this information can be obtained by rotational 3D fluoroscopy.

Materials and Methods: Two directional leads were inserted into a 3D printed plaster skull filled with gelatin. Torsion of the lead tip versus the lead at burr hole level was investigated. Then, three blinded raters evaluated twelve 3D fluoroscopies with random lead orientations. They determined the lead orientation considering the x-ray marker only and considering the overlap of the gaps between the contact segments (like iron sights). Intraclass Correlation Coefficients (ICC) and an extended version of the Bland-Altman plot were used to determine inter-rater-reliability and agreement of the measurements of different raters.

Results: Electrode torsion of up to 35° could be demonstrated. Evaluation of the lead rotation considering the x-ray marker only revealed limits of agreement of ± 9.37° and an ICC of 0.9975. Additionally, taking into account the lines resulting from overlapping of the gaps between the electrode segments, the limits of agreement to the mean were ± 2.44° and an ICC of 0,9998.

Conclusion: In directional DBS systems, intraoperative correction of the lead orientation is limited by torsion of the electrode. Rotational 3D fluoroscopy in combination with the described evaluation method allows determining the exact orientation (± 2.44°) of the leads after surgery, enabling the full potential of imaging-assisted personalized programming. 


Peter C. REINACHER (Freiburg, Germany), Marie T. KRÜGER, Mukesch SHAH, Roland ROELZ, Carolin JENCKNER, Karl EGGER, Volker Arnd COENEN
16:15 - 17:15 #8993 - OF07 Two Birds with One Stone: Single electrode Deep Brain Stimulation for dual targeting at dual frequency for the treatment of chronic pain.
Two Birds with One Stone: Single electrode Deep Brain Stimulation for dual targeting at dual frequency for the treatment of chronic pain.

Deep brain stimulation (DBS) has been used to treat chronic pain for many years. Research has led to the discovery of many potential deep brain targets amenable to stimulation but with variable results which are sometimes short-lived or subject to tolerance. The Periaqueductal Grey and Periventricular Grey (PAG/PVG) has been demonstrated to be an effective target for the treatment of nociceptive pain. However, not all patients with chronic pain benefit from PAG/PVG stimulation particularly those with neuropathic pain arising from central and peripheral causes. The centromedian intra-laminar parafascicular complex (CMPf) is a thalamic target with promising results following DBS for neuropathic pain modulating medial pain pathways and potentially addressing the affective aspects of pain perception. Stimulation of multiple deep brain targets may offer a strategy to optimise management of patients with complex pain symptomatology. However, such an approach presents several challenges. A pre-requisite of stimulating multiple targets is the ability to use different stimulation parameters simultaneously. Indeed, multiple targeting using multiple trajectories has additional safety implications and costs. We describe a novel technique in 3 patients with chronic pain syndromes beyond the technological capabilities of spinal cord stimulation using a single electrode technique to stimulate PVG/PAG and CMPf at dual frequencies. 


Milo HOLLINGWORTH (Bristol, United Kingdom), Hugh SIMMS-WILLIAMS, Anthony PICKERING, Neil BARUA, Nikunj PATEL
16:15 - 17:15 #10595 - OF08 New imaging insights in the technique of Motor Cortex Stimulation.
New imaging insights in the technique of Motor Cortex Stimulation.

Introduction
In the 1990's, Motor cortex stimulation (MCS) was introduced as a last-resort treatment for chronic neuropathic pain syndromes such as central post-stroke pain, neuropathic orofacial pain, phantom limb pain, and pain due to brachial plexus avulsion. It has recently been estimated that over 700 patients have been treated with MCS worldwide, using a variety of surgical and stimulation protocols. This heterogeneity makes comparison of results difficult, which resulted in skepticism. The discrepancies in the field of MCS concern, apart from the  inclusion and exclusion criteria and definition of effect,  most importantly, surgical issues like targeting and methods of stimulation.

Objective
To address the aforementioned issue, the authors developed a technique that allows direct peroperative visualization of the lead in relation to the cortical surface. With this method we are able to confirm the correct position of the lead as well as to determine the exact location of each contact to the cortical surface. The latter has great advantages for the postoperative screening and programming. This method provides the opportunity to optimally define positive and negative electrodes necessary to create stimulation of the desired area.

Method
A pre-operative functional MRI (fMRI) was fused with a volumetric T1 weighted MRI scan. The target location was determined and the craniotomy planned to accommodate the intended lead placement. The target was redefined intraoperatively with the help of intraoperative neurophysiology. To verify the targeting, we developed a new technique introducing  intra-operative imaging in a hybrid operating room (MITeC®, Radboudumc, Nijmegen, the Netherlands), using the Siemens Artis Zeego® robotic C-arm system, that generates 3D CT scan. The images are immediately fused with the preoperative imaging and lead contacts are plotted on the cortical surface and reviewed.

Discussion
In our experience, MCS shows to be effective at long-term follow-up (> 3 yrs, during 2005-2012, N=18) in patients suffering from neuropathic facial pain, especially caused by a central lesion. We expect that results will improve with this new approach as the exact position of the lead can be visualized. Further research is indicated to show a probable beneficial effect of programming based on visualization of each individual contact on the cortical surface.


Erkan KURT (Nijmegen, The Netherlands), Dylan HENSSEN, Maroeska ROVERS, Robert VAN DONGEN, Ruben Saman VINKE
16:15 - 17:15 #10156 - OF09 Delineation of cerebellar-thalamic fibers for deep brain stimulation.
Delineation of cerebellar-thalamic fibers for deep brain stimulation.

This study compared tractography approaches for identifying cerebellar-thalamic fiber bundles relevant for planning target sites for deep brain stimulation (DBS). In particular, probabilistic and deterministic tracking of the dentate-rubro-thalamic tract (DRTT) and differences between the spatial courses of the DRTT and the cerebello-thalamo-cortical (CTC) tract were compared.

Six patients with movement disorders were examined by magnetic resonance imaging (MRI) including two sets of diffusion-weighted images (12 and 64 directions). Probabilistic and deterministic tractography was applied on each diffusion-weighted dataset to delineate the DRTT. Results were compared with regard to their sensitivity in revealing the DRTT and additional fiber tracts and processing time. Two sets of regions-of-interests (ROIs) guided deterministic tractography of the DRTT or the CTC, respectively. Tract distance to an atlas-based reference target were compared.

Probabilistic fiber tracking with 64 orientations detected the DRTT in all twelve hemispheres. Deterministic tracking detected the DRTT in nine (12 directions) and in only two (64 directions) hemispheres. Probabilistic tracking was more sensitive in detecting additional fibers (e.g., ansa lenticularis and medial forebrain bundle) than deterministic tracking. Probabilistic tracking lasted substantially longer than deterministic. Deterministic tracking was more sensitive in detecting the CTC than the DRTT. CTC tracts were located adjacent but consistently more posterior to DRTT tracts. 

These results suggest that probabilistic tracking is more sensitive and robust in detecting the DRTT but harder to implement than deterministic approaches. Although sensitivity of deterministic tracking is higher for the CTC than the DRTT, targets for DBS based on these tracts likely differ.


Juergen SCHLAIER (Regensburg, Germany), Anton BEER, Max LANGE, Claudia FELLNER, Nils Ole SCHMIDT, Judith ANTHOFER
16:15 - 17:15 #10241 - OF10 Threats to DBS patients posed by the ethical debate about personal identity changes.
Threats to DBS patients posed by the ethical debate about personal identity changes.

Many neuroethicists and some legal theorists are worried that patients are no longer the same persons after deep brain stimulation (DBS). These concerns are fueled by reports about patients whose personality or behavior had changed or who had feelings of self-estrangement after DBS. These reports are often interpreted that deep brain stimulation threats the “personal identity”. Suchlike metaphysical interpretations of psychological alterations following DBS have gained currency in neuroethics.

However, it is questionable whether metaphysical interpretations of ambiguous statements of patients are useful for deriving ethical and legal conclusions.

First, patients describe quite different and even contradictory experiences. Some patients lose their “self”, others find their “true self”. Some patients who feel as different persons enjoy it; others feel estranged from themselves. The neuroethicists who debate about “personal identity changes” take the patients’ metaphorical, vague and colloquial reports at face value. In light of empirical science, particularly psychological test theory and psychometrics, it is inacceptable to ground far-reaching ethical and legal claims on such weak evidence.

Second, these metaphysical interpretations imply highly questionable ethical and legal revisions, namely the denial of psychiatric advance directives (Ulysses contracts). Patients can use Ulysses contracts for stipulating that in case of stimulation-induced mania the stimulation has to be switched off, if necessary against the present, mania-determined will.If legal theorists would really regard patients, who have certain personality changes after DBS, as new persons, then Ulysses contracts written before DBS would have to be regarded as inapplicable. The denial of advance directives would significantly affect the patients’ self-determination and possibly their (mental) health, freedom, social status, and relationships.

For ethically evaluating the risk of personality changes following DBS, metaphysical concepts are superfluous and harmful. Rather empirical research work is necessary that is based on standardized psychometric assessments, clinical trials with sufficient sample size and power, and continued psychiatric follow-up assessment.


Sabine MÜLLER (Berlin, Germany)

16:15-17:15
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FP3
FP3 - PARALLEL SESSIONS: FLASH PRESENTATIONS

FP3 - PARALLEL SESSIONS: FLASH PRESENTATIONS

Moderators: Mohammad MAAROUF (Borhneim, Germany), Alexandre RAINHA-CAMPOS (Neurosurgeon - Consultant) (Lisbon, Portugal)
16:15 - 17:15 #10219 - OF21 LRRK2+ R1441G and G2019S-related Parkinson’s disease: are these mutations a distinctive inclusion criteria for DBS surgery?
LRRK2+ R1441G and G2019S-related Parkinson’s disease: are these mutations a distinctive inclusion criteria for DBS surgery?

Introduction

Mutations in LRRK2+ gene in chromosome 12 (also called dardarin, from the Basque word dardara, meaning tremor) have been related to the appearance of Parkinson’s disease in several families. One particular mutation on this gene (R1441G) is specific to subjects of a Basque inheritance, whereas others have been described in families around the world, being G2019S the most frequent one. A previous study in our unit with a small sample size suggested that R1441G carriers had a worse outcome after DBS compared to an idiopatic PD group.

Objective

To determine if DBS is equally valuable and has the same outcome to patients with PD with G2019S or R1441G mutation in LRRK2+ gene as is to idiopatic PD patients.

Patients and methods

Patients with LRRK2+ anomalies who have had surgery in Cruces University Hospital (Barakaldo, Basque Country) have been included in this analysis with a minimum of one year after procedure follow-up. As a control, patients matched 2:1 have been selected being similar in age at surgery and time of evolution of disease. Clinical data included variation of UPDRS and Schwab-England at onset and one year postoperatively, as well as variation of levodopa equivalent daily dose (LEDD).

Results

Seventeen patients have been found in our cohort with LRRK2+ mutations, 12 of these with the R1441G mutation and 5 with G2019S one. Mean age at surgery  in the case group was 60.05 (61.8 in the control group) and patients had a mean of 12.5 years of evolution of disease in the case group (12.3 in the control group). Implementing a linear mixed model, no differences were found related to UPDRS-III reduction after one year of surgery (31.05% in the genetic group and 30.29% in the control group) (p=0.857). No differences were found in the reduction of the Schwab-England scale (18.82 point reduction in the genetic group versus 17.71 point reduction in the control group) (p=0.886). LEDD was reduced in mean 572.53 mg in the genetic group versus 530.44 mg in the control group, which also was non-significant (p=0.734). Comparing between both mutated groups, no differences have been found in any parameter.

Conclusion

There is no evidence in our study that DBS outcomes may be different  in the LRRK2+ mutated group including G2019S or R1441G mutations PD than in the idiopatic PD group. Therefore, contrary to our previous report, LRRK2+ mutation carrier status should not be relevant criteria to select patients to surgery.


Edurne RUIZ DE GOPEGUI (Spain, Spain), Gaizka BILBAO, Juan Carlos GÓMEZ, Imanol LAMBARRI, Koldo BERGANZO, Beatriz TIJERO, Ainara DOLADO, Josu MENDIOLA, Olivia RODRIGUEZ, Rafael VILLORIA, Jose I PIJOÁN, Julene ESCUDERO, Iñigo POMPOSO
16:15 - 17:15 #10324 - OF22 The potential need for deep brain stimulation in depression.
The potential need for deep brain stimulation in depression.

Background: Deep brain stimulation (DBS) is currently under investigation for therapy resistant major depressive disorder (MDD). It has been suggested that 12-30% of patients with MDD will present with a therapy resistant form. The question remains how many of these patients would qualify for treatment with DBS. Therefore, the aim of this study was to derive an estimate of a naturalistic clinical sample of MDD patients, on how many would fulfill common DBS trial criteria and common causes for exclusion.

Methods: Data from 393 patients diagnosed with MDD were analyzed based on our ongoing controlled trial of DBS for MDD. The data was analyzed in regards to age, sex, comorbid psychiatric disorders, duration of current depressive episode, numbers of hospitalizations, history of suicide-attempts and history of treatment with psychopharmacology, psychotherapy and electroconvulsive therapy. 

Results: After application of available criterion 79 of the 393 patients met avialiable screening criteria for DBS. Figure 1 shows the process of remaining subjects after application of each criterion that was available from the database extraction. The most common cause for exclusion was psychatric comorbidity (aproximately 50% of the sample). The most common psychiatric comorbidities were attention deficit hyperactivity disorder, bipolar disorder, personality disorder, post-traumatic stress disorder, generalized anxiety disorder, obsessive compulsive disorder and psychotic disorder.

Conclusions: MDD is a highly heterogenous disorder with many interacting risk factors that contributes to its etiology (biological, psychological, genetic, enviromental and social). This is also reflected in treatment heterogeneity and varying nonresponse rates. Consequently, given the limited number of MDD patients who receive DBS, it is too premature to put forth specific recommendations for improving identification of optimal DBS candidates. It has been difficult to characterize this heterogeneous group and even more difficult to begin to identify characteristics of those candidates most likely to benefit from DBS. Therefore, future DBS trials for MDD should seek to identify subgroups of patients who may respond differentially to the treatment and to different brain targets. This would serve to further refine candidate selection and optimize patient outcomes for this diverse group of patients.


Matilda NAESSTRÖM (Umeå, Sweden), Patric BLOMSTEDT, Owe BODLUND
16:15 - 17:15 #10408 - OF23 The Re-emergence of Psychiatric Neurosurgery: A Cross-National Comparison of Media Coverage.
The Re-emergence of Psychiatric Neurosurgery: A Cross-National Comparison of Media Coverage.

In light of the dark history of many surgical approaches to treat psychiatric disorders, understanding contemporary trends around the re-emergence of different methods to which patients and the public are exposed is essential to understanding their views and receptivity to them, both for healthcare and society.

To achieve this goal, we conducted an in-depth content analysis of media articles reporting on psychiatric neurosurgery between 1960 and 2015. We characterized and compared the themes and trends of media coverage of different interventions with a focus on North America (Canada and the USA), Germany and Spain–collaborating countries in an international research consortium on this subject. We used Factiva and the media websites to generate the samples for the study from full-length articles published in major national newspapers and magazines of the target countries. After curating for duplicates and irrelevant articles, the samples comprised 167 Spanish articles, 160 German articles, and 217 articles from North America. Articles were analyzed for content inductively and coded for the phenomena of interest.

Overall, coverage increased steadily beginning in 2005. Deep brain stimulation received the most coverage from all the different psychiatric neurosurgery interventions (Spain=49%, Germany=53%, and North America 63%). Depression was the most frequently mentioned condition. The tone across articles was generally positive across psychiatric neurosurgical interventions, although the German press tended to be more critical than the others. Risk was the disadvantage most commonly cited, and particularly so in German media. Identity and privacy and mind control were the most frequently cited ethical and philosophical issues among the few noted, and again found mostly in the German press.

The findings suggest that media in these three countries has focused predominantly on one method and condition. They also reveal few differences across the countries except Germany, which seems to be more cautious than the others. Empirically studied views from affected people and health care providers will further inform the future application of older techniques and translation of new ones for the benefit of people with intractable mental illness, and the influence that popular news is having on their values, perceptions of risk and hope for benefits.


Laura Y CABRERA (East Lansing, USA), Merlin BITTLINGER, Hayami LOU, Sabine MÜLLER, Judy ILLES
16:15 - 17:15 #10581 - OF24 Clinical outcome in 14 severe refractory aggressivity cases with deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH).
Clinical outcome in 14 severe refractory aggressivity cases with deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH).

Background:  Deep Brain Stimulation (DBS) of the posteromedial Hypothalamus (PMH) has shown significant improvement in aggressive patients with a long and complex history of ineffective therapies.  We have previously observed beneficial outcomes in the first 8 of these refractory patients undergoing DBS for aggressivity. 

Objective:  To report the clinical follow-up in 14 patients who underwent DBS of the PMH for severe and refractory aggressivity.

Methods:  14 patients between 10 and 40 years old, 6 women and 8 men, with moderate and severe cognitive impairment, were evaluated by a multidisciplinary group, and after multiple failed treatments and with the approval of the ethics committee were implanted bilaterally with electrodes Medtronic 3387.  The Leksell frame was applied under general anesthesia and most cases,  and a 3T MRI was taken. Target planning (Surgiplan) was carried out with coordinates of 2mm lateral to the wall of the third ventricle, 0-3 mm posterior, and 2-5 mm inferior with respect to the AC PC line.  Microrecording (FHC system) was performed in all 14 cases using 1mm above the dorsal border of Red Nucleus as the final target to tip of the electrode.  Responses to macrostimulation such as temperature, blood pressure and heart rate were monitored.  A second 3T MRI was done to confirm the position of the electrodes before battery internalization in most cases, and another 1.5T MRI was also performed within the first post operative week. Parameters ranged, between 180-200Hz, 80-140 usec, and 1.5-5 volts, with contacts 0 and 8 both negative and case positive.  

Results:  For this medium term follow-up of 1-48 months, quality of life(EQ-5D-5L) improved between 70-85%, MOAS(Modified Over Aggressivity Score) improved between 58-90%, and Health Status improved between 60-90% with stable outcome over time.  Some cognitive improvements were developed in some of the patients, and were correlated to findings in cerebraL PET(Positron Emission Tomography).  Minor complications:  one device was removed as a result of skin erosion, one infection in antibiotic treatment, and one case of central fever which improved with decreased pulse width. We also performed one repositioning due to lead migration. 

Conclusions:  DBS of th PMH is safe with manageable complications and an option for severe refractory aggressivity patients.  Improvements were long-standing and some cognitive benefits were observed, but more cases and longer follow-up should be carried out.  


Adriana Lucia LOPEZ RIOS (TORONTO, Canada), Alejandro ARISTIZABAL GAVIRIA, Catalina GIL RESTREPO, Luisa Fernanda AHUNCA VELASQUEZ, Katherine Johanna NARANJO PEREZ, Yeison Esteban MONTOYA MUÑOZ, William Duncan HUTCHISON
16:15 - 17:15 #10646 - OF25 Stereotactic electroencephalography guided laser ablation for neocortical epilepsy.
Stereotactic electroencephalography guided laser ablation for neocortical epilepsy.

Stereotactic electroencephalography (sEEG) is a standard minimally invasive approach to identifying seizure networks. Magnetic resonance thermometry-guided stereotactic laser ablation (SLA) is a minimally invasive surgical approach to treating epilepsy. While SLA for mesial temporal lobe epilepsy (MTLE) has been studied, less is known about its combined use in neocortical epilepsy.

We reviewed all patients that underwent SLA after sEEG localization (intracranial depth electrodes with occasional subdural strips), excluding patients with MTLE. Under general anesthesia SLA was performed by stereotactic twist-drill craniostomy, or by placing the laser assembly down an existing sEEG bolt. The assembly consisted of a saline-cooled cannula through which was passed an optical fiber to deliver laser energy (Visualase, Medtronic). Anatomic MRI provided confirmation of accuracy and MR thermometry provided real-time feedback on extent of thermocoagulation during the procedure.  Postoperative clinical status was recorded at 3, 6, and 12mo.

Thirteen patients were treated (7 male, 6 female, median age 26, interquartile range [iqr] 22). Inciting pathologies included tuberous sclerosis (3), prior tumor resection (2), trauma (2), cavernous malformation (1), cortical dysplasia (2), and unidentified (3).  Seven patients had already failed one or more prior epilepsy operations (resection, transection, radiofrequency ablation, laser ablation). Median symptom duration was 13yrs (iqr 15). Median antiepileptic drugs trialed was 6 (iqr 1.25). Median number of depth arrays was 15 (iqr 10) and median number of strip arrays was 2 (iqr 6).  Seizure localizations were frontal (7), parietal (2), temporal (1 inferior, 1 lateral), occipital (1), and specifically insula (2) and cingulate (3).  There were no procedural complications and no unanticipated neurologic deficits (ablating supplemental motor area caused temporary expected deficit in one subject). Median length of postoperative stay was one day (iqr 1, max 4).  Median follow-up was 500 days (iqr 578) of which 10 (77%) had >12mo follow-up.  At 12mo, outcomes were n=5 Engel-1, 1 Engel-2, 1 Engel-2/3 (unclear), 2 Engel-3, 1 Engel-4.  The remaining three cases with <12mo follow-up were seizure free at 3-6mo follow up. All cases with Engel 2-4 outcomes had failed prior epilepsy operations.

Minimally invasive sEEG and MR-guided ablation is a safe and effective alternative to open resection. Additional experience and longer follow-up needed.


James MALCOLM, Matthew STERN, Rebecca FASANO, Robert GROSS, Jon WILLIE (Atlanta, USA)
16:15 - 17:15 #10438 - OF26 Modulation of subthalamic nucleus (STN) neuronal firing by macrostimulation at sites dorsal to the STN during surgery for Parkinson’s disease (PD).
Modulation of subthalamic nucleus (STN) neuronal firing by macrostimulation at sites dorsal to the STN during surgery for Parkinson’s disease (PD).

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is standard therapy for Parkinson’s disease (PD) symptoms including tremor, but effective sites can also be produced dorsal to STN in the subthalamic area.  This subthalamic area has been targeted for the treatment of tremor by interruption of pallidofugal and dentatothalamic pathways (Struppler, Stereotact Func Neurosurg 52: 205, 1989. However significant pallidosubthalamic afferents impinge on central STN from GPe (Shink et al Neurosci 73: 335 1996 ) and therefore activation of  this pathway may be involved in the therapeutic effects of the subthalamic area on PD symptoms, particularly for tremor relief.

Objective: To perform macrostimulation at different intensities in the subthalamic area dorsal to STN and observe the effects on neuronal activity within STN itself.  

Methods: Two concentric bipolar microelectrodes were used with macrostimulaton contacts at 3 or 5 mm distant to the tip (LP+ FHC, Bowdoin, MA). One microelectrode was used to record the spikes and the other was used to macrostimulate (1 – 3 mA, 130 Hz. 0.5Hz) in the subthalamic area. Stimulation was repeated up to 3 times and the amount of inhibition was measured up to the first spike and termed “silent period”.

Results: A total of 139 STN neurons was tested in 12 PD for effects of stimulation in the subthalamic area. The average depth of all tested cells was -0.56 +/- 2.83 (SD, with n= 139), consistent with a broad sampling across the entire 5-6 mm dorsoventral extent of the nucleus.  Of these well isolated spikes, 20 (14.3%) were found with modulatory effects from macrostimulation dorsal to STN. The average depth of these responsive  neurons tended to cluster more dorsal in STN at 0.80 +/- 1.67 (SD).  A majority of neurons showed inhibition following the train (18 neurons or 90 %) with an average silent period of 1.1 +/- 1.2 s (SD) and only a minority were excited (2 neurons or 10 %). Rebound burst was seen in 13 neurons (65 %) and oscillatory bursts following stimulation were seen in 3 neurons. Focal microstimulation near the cell soma produced the same inhibitory effect as distal macrostimulation on the few STN neurons tested.

Conclusions: Inhibition of STN activity produced by stimulation of the subthalamic area dorsal to the nucleus is mediated by the pallidosubthalamic afferents. It may be a clinically useful indicator of the optimal target for DBS electrode implantation in somatosensory part of STN.


William Duncan HUTCHISON (Toronto, Canada), Kimberly SY, Luka MILOSEVIC, Botero Posada LUIS FERNANDO, Ricardo PLATA AGUILAR, Adriana Lucia LOPEZ-RIOS
16:15 - 17:15 #10627 - OF27 Spend well to spend less: making sense of the Oxford directional DBS for tremor study.
Spend well to spend less: making sense of the Oxford directional DBS for tremor study.

Introduction: We previously presented our clinical experience with the use of the InfinityTM Directional Deep Brain Stimulation (D-DBS) system in treating symptoms associated with tremor1.  In addition to the therapeutic benefits of D-DBS in treating tremor symptoms, we also showed that utilization of D-DBS resulted in significantly larger therapeutic windows (TW), and fewer side-effects at significantly lower therapeutic amplitudes (TA)1. Here, we present VTA differences between N-DBS and D-DBS at their most effective TA in the same cohort of tremor patients.

Methods: A two-stage computational model (Sim4Life v3.2) was used to compare the VTA resulting from the most-effective N-DBS and D-DBS monophasic cathodic stimulation configurations (N=8 Tremor patients; 15 implanted leads). The first stage involved using a finite element analysis (FEA) model to calculate electrical potentials using the Infinity (Abbott, Plano, TX) lead. The second stage used biophysical cellular models of 5.7 µm diameter myelinated axons2. Each axon had 21 nodes of Ranvier and 0.5 mm node-to-node spacing. A total of 6888 axons were distributed around the lead by creating a 21×41 grid centered at contact 2, with the axons oriented perpendicular to the lead axis, and then replicating and rotating this grid.  The electrical potentials from the FEA model were interpolated along each axon, and delivered as extracellular stimulation to determine the VTA for each configuration.3

Results:  The mean difference in average VTA size between D-DBS (52.0mm3) and N-DBS (60.7mm3) for the patient cohort was minimal (14%), despite the mean most-effective D-DBS TA (1.51 mA) being 31% lower than mean most-effective N-DBS TA (2.19 mA). Moreover, there was a greater extent of directionality for the D-DBS configuration (78% of VTA volume was on the side with contact 2A) than the N-DBS configuration (49.3%).  

Conclusions: D-DBS leads enable spatial directionality of neural activation, and achieve VTA sizes similar to N-DBS leads at lower stimulation amplitudes. This may explain the significantly better TW and TA observed clinically for directional DBS leads compared to conventional DBS leads.

References:

1. Rebelo et al. NANS DOI: 10.13140/RG.2.2.22595.60962/1 

2. McIntyre CC et al.  J Neurophysiol 2002 Feb;87(2):995–1006.

3. Butson CC and McIntyre CC. Brain Stimul 2008 Jan;1(1):7-15.


Alex KENT, Binith CHEERAN (Austin, USA), Pedro REBELO, Alexander GREEN, Tipu AZIZ, Lalit VENKATESAN
16:15 - 17:15 #10214 - OF28 PaCER - Precise and Convenient Electrode Reconstruction for Deep Brain Stimulation: Preliminary Results.
PaCER - Precise and Convenient Electrode Reconstruction for Deep Brain Stimulation: Preliminary Results.

Background: There are various drawbacks to existing approaches to the reconstruction of DBS electrode trajectories from post-operative imaging, including restricted straight-line trajectory models or a need for subjective manual interaction for contact localization.
Methods: We present PaCER, a novel algorithm for fully-automatic high-accuracy DBS electrode trajectory and contact reconstruction from post-operative imaging.
Unlike most existing approaches, our algorithm accurately preserves curved electrode trajectories, thus enabling additional analysis of electrode behavior (e.g. to assess influence of brain shift). Furthermore PaCER features a fully automatic contact localization.
Results: PaCER was evaluated using clinical CT data of DBS patients as well as CT scans of an individually-fabricated high-accuracy phantom. The phantom experiments enabled precise measurements of the algorithm’s accuracy with a known ground-truth. For a Medtronic 3387 electrode, the average trajectory reconstruction error was 0.049±0.029mm (< 4% of the electrode diameter of 1.27mm).
Conclusion: In phantom experiments, PaCER yielded excellent trajectory reconstruction accuracy, with errors below 100 micron. This holds true for curved trajectories and along the whole trajectory path. Accordingly, to the best of our knowledge, PaCER has higher accuracy than any other published method. PaCER is fully automatic and enables a convenient adoption for both clinical and research use.


Andreas HUSCH (Luxembourg, Luxembourg), Peter GEMMAR, Frank HERTEL
16:15 - 17:15 #10741 - OF29 White matter edema associated with implanted deep brain stimulation electrodes.
White matter edema associated with implanted deep brain stimulation electrodes.

Objective

Retrospective studies have been published documenting the appearance of white matter edema surrounding implanted deep brain stimulation (DBS) electrodes. This is usually asymptomatic but often prompts workup for possible hardware infection.  While the incidence and evolution over time of this phenomenon is presumed to be rare, no systematic examination of this has been published.  The goal of this study is to determine the prevalence and time course of this edema following DBS implantation by obtaining a series of postoperative MRI scans from patients who undergo DBS surgery.

 

Methods

Postoperative MRIs were obtained following DBS surgery.  Patients underwent either unilateral (N=11, 3 were the second hemisphere[M1] ) or bilateral (N=2) DBS electrode implants (Medtronic models 3387 or 3389) in a single implant session.   MRIs occurred one day, two weeks (+/- two days), four weeks (+/- two days), six weeks (+/- two days) and ten weeks (+/- two days) postoperatively.  Edema volume was quantified in cubic centimeters (cc) by measuring the length of the peri-electrode T2 signal change in the white matter in perpendicular maximal planes.

 

Results

Data was collected on thirteen patients.  Eleven patients exhibited white matter edema in at least one MRI, with the largest volume being 29.76cc.  Eight patients had maximal edema volume at two weeks postoperatively, while in three patients the maximal edema volume was at  at ten weeks.  The first incidence of edema was observed at day one in five patients, two weeks in five patients and ten weeks in one patient.  Edema completely resolved in two patients.  In both patients, edema was first observed at two weeks, resolving at four weeks for one patient and six weeks for the second.  The edema observed in the other nine patients did not fully resolve by ten weeks.All patients in the study were asymptomatic. 

Conclusions

This small case series shows that edema following DBS surgery is not a rare occurrence.  It often presents without symptoms, and is therefore likely missed in patients that do not return for a postoperative MRI.  This edema can first appear at up to ten weeks postoperatively and may persist for many weeks, but may improve without removal of the electrode.  This study demonstrates the need for a much larger study examining the incidence, time course, and cause of this edema following DBS surgery.


Mark NOLT (Winfield, USA), Rajeev POLASANI, Allison MONETTE, Taras MASNYK, Michael REZAK, Joshua ROSENOW
16:15 - 17:15 #9900 - OF30 Complications in impulse generator exchange surgery for Deep Brain Stimulation: A single center, retrospective study.
Complications in impulse generator exchange surgery for Deep Brain Stimulation: A single center, retrospective study.

Question Low or empty battery status of non-rechargeable deep brain stimulation impulse generators (IG) requires a surgical IG exchange several years after initial implantation. Complications in patients undergoing DBS surgery are reported in the range between 7,6 % up to 25,3 %. The aim of this study was to investigate the rate of complications after IG exchanges and to identify risk factors for complications.

 

Methods We retrospectively analyzed the complications in IG exchange surgery from 2008 to 2015 in a single center university hospital setting. Medical reports from all patients, who had undergone IG exchange surgery were systematically reviewed. The shortest follow-up was 11 months.

 

Results From 2008 to 2015, 438 generators were exchanged in 319 patients. Overall complication rate and revision rate was 8,9 % of cases. 13 patients (2,96%) developed an infection of the IG with a secondary removal of the IG. Five patients (1,14 %) suffered from local wound erosions surrounding the IG; for this particular complication in one patient the IG had to be removed while in the other 4 patients a local wound revision was sufficient. We found hardware malfunctions in 11 patients (2,51 %) and local hemorrhage surrounding the IG in three cases (0,68 %)requiring surgical revision. In two patients (0,46 %) the IG needed to be refixated. In two patients (0,46 %) tension of the connecting cables triggered a surgical revision because of patient’s discomfort. One 80 years patient (0,23%) suffered from worsened severe heart failure and died 4 days after IG exchange in local anesthesia. In two cases (0,46 %) the IG was placed abdominally or exchanged to a smaller device due to patient discomfort from initial positioning.

Infection rate after the first exchange was 1,92 %, after the second exchange 7,78 % and after three or more exchanges 8,70 %.

 

Conclusion IG exchange surgery, although often considered a” minor surgery”, is associated with a complication rate of roughly 9% in our center. Infection is the most relevant complication as it causes removal of the IG. The implantation of smaller IGs might reduce complications such as wound erosions or local hemorrhages. Patients and physicians should know the rate of complication in IG exchange surgery since this information might facilitate a decision in favor of a rechargeable IG.


Ann-Kristin HELMERS (Kiel, Germany), Isabell LÜBBING, Karsten WITT, Michael SYNOWITZ, Hubertus Maximilian MEHDORN, Daniela FALK

17:15
17:15-17:45
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WU1
PLENARY SESSION: WRAP UP SESSION-3 presenters

PLENARY SESSION: WRAP UP SESSION-3 presenters

Moderators: Harith AKRAM (Associate Professor) (London, United Kingdom), Vibhor KRISHNA (Neurosurgeon / Associate Professor, Clinical) (Chapel Hill, USA), Hemmings WU (Stanford, USA)

17:15-17:45
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CT1
CLINICAL TRIALS SESSION 1

CLINICAL TRIALS SESSION 1

Moderators: Nir LIPSMAN (Toronto, Canada), Adriana Lucía LÓPEZ RÍOS (Neurocirujana Funcional y Estereotáctica) (TORONTO, Canada)
17:15 - 17:45 #12028 - CT01 Phase I Trial of MR-guided Focused Ultrasound Blood Brain Barrier Opening in Early-to- Moderate Alzheimer’s Disease.
Phase I Trial of MR-guided Focused Ultrasound Blood Brain Barrier Opening in Early-to- Moderate Alzheimer’s Disease.

Despite decades of advances in the pathology, genetics and imaging of Alzheimer's disease (AD), there remain no effective treatments that significantly alter its natural history. Several late phase clinical trials, focused largely on amyloid beta metabolism and clearance, have unfortunately demonstrated no significant benefit in early AD patients. Recent work investigating blood-brain barrier opening using MR-guided focused ultrasound (MRgFUS) in transgenic animal models has shown that repeated ultrasound administration coupled with microbubble-containing contrast can reduce plaque burden and reverse memory deficits. While the mechanisms underlying plaque clearance are under investigation, this image-guided, noninvasive technique appears promising. We have designed a phase I, pilot trial to investigate the safety and technical feasibility of temporary and reversible MRgFUS-mediated BBB opening in patients with early to moderate AD. Patients will have confirmed amyloid deposits based on PET imaging, and undergo two sessions of BBB opening in a staged fashion. Follow-up investigations will focus on safety, tolerability, technical feasibility, as well as structural and functional imaging. This trial represents the first attempt at focal, image-guided BBB opening in AD, with results used to design further studies to determine whether this technology, either alone or in conjunction with targeted therapies, can be of potential benefit for patients.


Nir LIPSMAN (Toronto, Canada), Sandra BLACK, Kullervo HYNYNEN
17:15 - 17:45 #12029 - CT02 Long-term results of posteromedial hypothalamic deep brain stimulation for patients with resistant aggressiveness.
Long-term results of posteromedial hypothalamic deep brain stimulation for patients with resistant aggressiveness.

Object. Erethism describes severe cases of unprovoked aggressive behavior, usually associated with mental impairment and gross brain damage. Erethism is often refractory to medication, and patients need to be managed with major restraining measures. Deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH) has been proposed as a treatment for resistant erethism, although experience with this treatment around the world is scarce. The objective of this study was to examine the long-term outcome of PMH DBS in 6 patients with severe erethism treated at the authors’ institution.

Methods. Medical records of 6 patients treated with PMH DBS for intractable aggressiveness were reviewed. The therapeutic effect on behavior was assessed by the Inventory for Client and Agency Planning (ICAP) preoperatively and at the last follow-up visit.

Results. Two patients died during the follow-up period due to causes unrelated to the neurosurgical treatment. Five of 6 patients experienced significant reduction in aggressiveness (the mean ICAP general aggressiveness score was -47 at baseline and -25 at the last follow-up; mean follow-up 3.5 years). One patient experienced a marked sympathetic response with highfrequency stimulation during the first stimulation trial, but this subsided when stimulation was set at low frequency. A worsening of a previous headache was noted by 1 patient.

Conclusions. In this case series, 5 of 6 patients with pathological aggressiveness had a reduction of their outbursts of violence after PMH DBS, without significant adverse effects. Prospective controlled studies with a larger number of patients are needed to confirm these results. 


Cristina TORRES (Madrid, Spain), Jesus PASTOR, Manuel PEDROSA, Marta NAVAS, Eduardo GARCÍA-NAVARRETE, Elena EZQUIAGA, Rafael G. SOLA
17:15 - 17:45 #9757 - CT03 Clinical cognitive improvement and Positron Emission Tomography changes in patients who underwent deep brain stimulation in the hypothalamus for severe aggressivity behaviour but also with previous cognitive impairment.
Clinical cognitive improvement and Positron Emission Tomography changes in patients who underwent deep brain stimulation in the hypothalamus for severe aggressivity behaviour but also with previous cognitive impairment.

Background:  Deep Brain Stimulation (DBS) of the hypothalamus has shown significant lmprovement in agressive patients with a long and complex history of ineffective therapies.  Some groups described case reports about it but we did not find described association between some learning skills and improvement in adaptive skills scale related with changes in Cerebral Positron Emission Tomography(PET).

Objective:To report the clinical follow-up in 14 patients who underwent DBS of the hypothalamus for severe and refractory aggressivity and improvement in adaptive skills scale related with changes in cerebral PET.  

Methods:14 patients between 10-14 years old, 6 women and 8 men,with moderate and severe cognitive impairment,were evaluated by a multidisciplinary group,and after multiple failed treatments,and with the approval of the ethics commitee were taken to surgery.12 of them had the Cerebral PET within one year before the surgery and so far 5 also have done that test within 18 months after the procedure.All of them have been evaluated by neuropsychology and psychology before and after surgery.Diagnostic Adaptive Behaviour Scale (DABS),Quality of Life(EQ-5D-5L),Modified Over Aggressivity Score(MOAS),were applied. 

Results:The 14 patients have improved their adaptive skills scale by at least 60%,which has helped them to improve the functions in the activity of daily living according to the quality fo life scales(EQ-5D-5L) which has improved between 70-85% and(MOAS) improvement between 58-90%.5 patients underwent Cerebral PET showing homogeneity and diffuse increase in the metabolic activity for the cerebral cortex practically in all of the lobes, ganglia of the base, thalamus and subthalamic area.   Same areas prior to surgery showed complete heterogeneity and decreased metabolism. Most common clinical skills that patients have been learned were going to the bathroom to do their needs such as urinating and defecating,eating by themselves,dressing alone, waiting, and those with greater cognitive impairment allow their caregivers to feed, clean and dress them without opposing.One of the patient is learning to read and write and another learned how to choose music and play it.

Conclusions:There is a relation between adaptative behaviour and Cerebral PET findings in relation with adaptative skills scale in patients who underwent DBS for extreme and refractory aggressivity. Further studies with increase number of patients and longer term follow-up should be carried out.


Adriana Lucia LOPEZ RIOS (TORONTO, Canada), Catalina GIL RESTREPO, Alejandro ARISTIZABAL GAVIRIA, Nora Patricia CEBALLOS, Juan Felipe VANEGAS, Yesion Felipe GUTIERREZ VELEZ, Luisa Fernanda AHUNCA VELASQUEZ, Laura Victoria ZAPATA, William Duncan HUTCHISON
17:15 - 17:45 #10542 - CT04 The Neurosurgical Treatment of Spasmodic Dysphonia: Interim Results of DEBUSSY.
The Neurosurgical Treatment of Spasmodic Dysphonia: Interim Results of DEBUSSY.

Objectives: Spasmodic dysphonia (SD) is a neurological speech disorder characterized by sudden, involuntary contractions in the laryngeal musculature during speech production. Since the 1980s, SD has been treated with Botox (BTX) injections into the throat, a therapy with several well-known limitations to the functional neurosurgery community. After extensive preliminary experiments, we launched a Prospective, Randomized, Double-Blinded, Cross-Over, Phase 1 Left Vim Thalamic DBS trial (DEBUSSY- DEep Brain stimUlation for SpaSmodic dYsphonia).

Methods: Instiutional ethics (H15-02535) and clinicaltrials.gov (NCT02558634) registration were completed. Through our institution’s laryngology clinic, n=6 isolated adductor SD patients with inadequate response to BTX were identified. Patients were excluded if they presented with dystonia in other body parts. The medial left Vim was targeted on pre-operative T1 imaging with intraoperative electrophysiological confirmation. Six weeks after surgery, patients were programmed over a 14-day a period in a variety of acoustic, stressful, and pragmatic conditions. A randomized, double-blind, three month cross-over trial was then conducted with patients receiving active treatment followed by sham or vice versa. The primary endpoints were the Unified Spasmodic Dysphonia Rating Scale (USDRS) and the Voice-Related Quality of Life (Vr-QoL), assessed in a double-blinded fashion at the 3 and 6-month mark.

Results: Interim results of our trial will be presented at the WSSFN meeting with details on target justification, kinetics of benefit/washout, programming strategy, and side effect profiles for DBS in SD. Interim imaging results of VTA, DTI, PET, and laryngoscopy will also be presented. Finally, the analysis of each unique component of SD (dystonic spasm, dystonic tremor, and muscle tension dysphonia) and its response to DBS will be presented.

Conclusions: Interim results of DEBUSSY suggest the left Vim is a promising target for SD despite its classification as a dystonia and speech disorder. Dystonia relating to jaw, eyes, tongue are clearly best treated with pallidal neuromodulation or ablation. However, to our initial surprise, dystonia of the larynx appears to require treatment of the cerebello-thalamic circuitry, likely related to the evolution of the speech motor neural networks. We provide a neurophysiological explanation of this phenomenon and highlight our future work in the emerging field of neuro-laryngology. 


Anujan POOLOGAINDRAN (Vancouver/Cambridge, Canada), Adi SULISTYANTO, Zurab IVANISHVILI, Murray MORRISON, Linda RAMMAGE, Silke CRESSWELL, Vesna SOSSI, Tejas SANKAR, Mini SANDHU, Nancy POLYHRONOPOULOS, Christopher HONEY
17:15 - 17:45 #10557 - CT05 Predicting pain relief: The role of diffusion tensor imaging metrics as a pre-surgical tool for individualized prediction of response to trigeminal neuralgia surgery.
Predicting pain relief: The role of diffusion tensor imaging metrics as a pre-surgical tool for individualized prediction of response to trigeminal neuralgia surgery.

Introduction: Trigeminal neuralgia (TN) is a chronic neuropathic facial pain disorder with commonly excellent surgical response. A proportion of patients do not respond well and require frequent re-treatments. No imaging tools can currently predict treatment response, yet this would be of crucial value when considering further surgeries. We used diffusion tensor imaging (DTI) as a tool to determine whether pre-surgical trigeminal nerve microstructural diffusivities can predict clinical response to TN surgery.

Methods: 31 TN patients and 16 healthy controls were recruited for this study retrospectively. Multi-tensor DTI tractography allowed microstructural DTI metrics—axial, radial, mean diffusivity (AD, RD, MD), and fractional anisotropy (FA)—to be extracted from the trigeminal nerve cisternal segment, root entry zone and pontine segments bilaterally. TN patients were subdivided into responders and non-responders based on the presence of pain 1-year following TN surgical treatment (microvascular decompression or Gamma Knife radiosurgery). Differences in diffusivities between nerves and across response groups were assessed with false discovery rate-corrected Student’s t-tests. Group-level diffusivity thresholds of long-term response were obtained through bootstrap resampling of ipsilateral diffusivities (n=2000). Individual-level prognosticator of treatment response was obtained via discriminant function analysis (DFA) of ipsilateral/contralateral ratios and ipsilateral measurements of AD and RD across all trigeminal nerve regions of interest.

Results: Non-responders were highlighted by abnormal pontine diffusivities. Three ipsilateral diffusivity thresholds of response separated 85% of non-responders from responders, two of which were thresholds based on pontine diffusivities. The DFA prognosticator of response was 83.9% accurate at separating responders from non-responders, discriminating equally well for both groups.

Conclusion: A highly predictive, individualized prognostication tool for clinical response to surgical interventions for TN can be constructed from pre-surgical trigeminal nerve DTI metrics. Diffusivity abnormalities within pontine segment of the trigeminal nerve are key features of non-responders to surgical interventions for TN, suggesting a more central role of pain in non-responders. Our study represents an important step towards a more objective, imaging-based personalized treatment of TN and prediction of pain outcome after surgery.


Peter Shih-Ping HUNG, David Qixiang CHEN, Karen D. DAVIS, Jidan ZHONG, Mojgan HODAIE (Toronto, Canada, Canada)

18:00
18:00-18:45
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SST
Sunset industry-sponsored symposium

Sunset industry-sponsored symposium

18:00-19:00
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MEET3
SFN EDITORIAL BOARD MEETING

SFN EDITORIAL BOARD MEETING