Monday 26 June
Time Potsdam I-III Bellevue Glienicke Tegel Lincke I-II Schinkel I-II Kaminzimmer
09:00
09:00-12:00
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PMW1
PRE-MEETING WORKSHOPS
ELECTROPHYSIOLOGY

PRE-MEETING WORKSHOPS
ELECTROPHYSIOLOGY

Moderators: Hagai BERGMAN (Prof) (Jerusalem, ISRAEL), Erich RICHTER (Marrero, USA)
Coordinator: William D HUTCHISON (neurophysiology) (Toronto, CANADA)
09:00 - 12:00 Techniques in microelectrode recording. William D HUTCHISON (neurophysiology) (Toronto, CANADA)
09:00 - 12:00 Physiology of the thalamus and basal ganglia in movement disorder surgery. Zvi ISRAEL (Jerusalem, ISRAEL)
09:00 - 12:00 Current models of basal ganglia circuitry. Hagai BERGMAN (Prof) (Jerusalem, ISRAEL)
09:00 - 12:00 Basal ganglia physiology in animal models. Mesbah ALAM (Scientist) (Hannover, GERMANY)
09:00 - 12:00 Selected cases - recordings and interpretation. Brigitte PIALLAT (Grenoble, FRANCE)
09:00 - 12:00 Effect of sedation and anesthesia on recordings. Alexandre EUSEBIO (Marseille, FRANCE)
09:00 - 12:00 Neural rhythms in MD surgery. Sameer SHETH (Associate Professor of Neurosurgery) (Houston, USA)

09:00-12:00
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PMW2
PRE-MEETING WORKSHOPS
EPILEPSY

PRE-MEETING WORKSHOPS
EPILEPSY

Moderators: Claudio POLLO (Deputy Chief Doctor) (Bern, SWITZERLAND), Igor TRIFONOF (Moscou, RUSSIA)
Coordinator: Faisal AL OTAIBI (Riyadh, SAUDI ARABIA)
09:00 - 12:00 Assessment of surgical patients. Youssef COMAIR (Chair Department) (Beirut, LEBANON)
09:00 - 12:00 The role of adjunct testing in epilepsy. Faisal AL OTAIBI (Riyadh, SAUDI ARABIA)
09:00 - 12:00 Electrocorticography. Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (LISBON, PORTUGAL)
09:00 - 12:00 StereoEEG recordings. Nitin TANDON (Houston, USA)
09:00 - 12:00 Temporal lobectomy. Claudio POLLO (Deputy Chief Doctor) (Bern, SWITZERLAND)
09:00 - 12:00 Functional imaging. Dario ENGLOT (Fellow/Trainee) (Nashville, USA)
09:00 - 12:00 Laser ablation in epilepsy. Chengyuan WU (Assistant Professor/Attending) (Philadelphia, USA)
09:00 - 12:00 How epilepsy helps us understand cognition and memory. Itzhak FRIED (Los Angeles, USA)
09:00 - 12:00 MEG. Masaki IWASAKI (Kodaira, Tokyo, JAPAN)

09:00-12:00
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PMW4
PRE-MEETING WORKSHOPS
PAIN SURGERY

PRE-MEETING WORKSHOPS
PAIN SURGERY

Moderators: Wolfgang HAMEL (Hamburg, GERMANY), Chris HONEY (Vancouver, CANADA)
Coordinator: Marc SINDOU (Professor of Neurosurgery) (Lyon, FRANCE)
09:00 - 12:00 Trigeminal neuralgia and facial pain. Marc SINDOU (Professor of Neurosurgery) (Lyon, FRANCE)
09:00 - 12:00 Spinal cord stimulation. Josh ROSENOW (Director, Functional Neurosurgery) (Chicago, USA)
09:00 - 12:00 DREZ lesioning. Peter KONRAD (Nashville, USA)
09:00 - 12:00 DBS for pain. Alex GREEN (Consultant Neurosurgeon) (Oxford, UK)
09:00 - 12:00 Surgical treatment of headache syndromes. Denys FONTAINE (Neurosurgeon) (NICE, FRANCE)
09:00 - 12:00 Motor cortex stimulation. Gaston SCHECHTMANN (Doctor) (Stockholm, SWEDEN)
09:00 - 12:00 Sphenopalatine ganglion stimulation. Jocelyne BLOCH (Médecin Cadre) (Lausanne, SWITZERLAND)
09:00 - 12:00 DRG stimulation. Jan VESPER (DUSSELDORF, GERMANY)

09:00-12:00
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PMW3
PRE-MEETING WORKSHOPS
RADIOSURGERY

PRE-MEETING WORKSHOPS
RADIOSURGERY

Moderators: Motohiro HAYASHI (Associate professor) (Tokyo, JAPAN), Roberto SPIEGELMANN (Ramat Gan, ISRAEL)
Coordinator: Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
09:00 - 12:00 Fundamentals of radiosurgery-from frames to physics. Antonio DE SALLES (Professor - Chief) (Sao Paulo, BRAZIL)
09:00 - 12:00 Radiosurgery for benign tumors. Marc LEVIVIER (Chef de Service) (Lausanne, SWITZERLAND)
09:00 - 12:00 Radiosurgery for acoustic neuromas. Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
09:00 - 12:00 Radiosurgery for metastatic disease. David MATHIEU (Professor) (Sherbrooke, CANADA)
09:00 - 12:00 Functional radiosurgery. Roberto MARTINEZ-ALVAREZ (Neurosurgeon) (Madrid, SPAIN)
09:00 - 12:00 Radiosurgery for treatment of arteriovenous malformations. Roman LISCAK (head) (PRAGUE, CZECH REPUBLIC)

09:00-12:00
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PMW5
PRE-MEETING WORKSHOPS
TREATMENT OF TOURETTE’S SYNDROME

PRE-MEETING WORKSHOPS
TREATMENT OF TOURETTE’S SYNDROME

Moderators: Rees COSGROVE (Director, Epilepsy and Functional Neurosurgery) (Boston, USA), Mansour PARVARESH (Associate Professor) (Tehran, IRAN, ISLAMIC REPUBLIC)
Coordinator: Yasin TEMEL (Maastricht, THE NETHERLANDS)
09:00 - 12:00 Overview ofTourette’s syndrome. Ludvic ZRINZO (London, UK)
09:00 - 12:00 Psychiatric issues inTourette’s. Kirsten MUELLER-VAHL (GERMANY)
09:00 - 12:00 Surgical patient selection. Yasin TEMEL (Maastricht, THE NETHERLANDS)
09:00 - 12:00 Treatment ofTourette with GPi stimulation. Veerle VISSER-VANDEWALLE (Köln, GERMANY)
09:00 - 12:00 Treatment ofTourette with GPe stimulation. Osvaldo VILELA FILHO (GOIANIA, BRAZIL)
09:00 - 12:00 Treatment ofTourette with thalamic stimulation. Terry COYNE (Neurosurgeon) (Brisbane, AUSTRALIA)

09:00-12:00
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OFFM
OFFICER’S MEETING

OFFICER’S MEETING

12:00
12:00-14:00
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SSW1
SATELLITE SYMPOSIUM SPONSORED BY WSSFN
NEUROMODULATION ZUR BEHANDLUNG PSYCHIATRISCHER ERKRANKUNGEN

SATELLITE SYMPOSIUM SPONSORED BY WSSFN
NEUROMODULATION ZUR BEHANDLUNG PSYCHIATRISCHER ERKRANKUNGEN

Coordinator: Juergen VOGES (Head of the Department) (Magdeburg, GERMANY)
12:00 - 14:00
Speakers: Prof. Dr. med.Th. Schläper, Univ.-Freiburg; Prof. Dr. med. Dr. phil. A. Heinz, Univ.-Hospital, Charitè Berlin, Prof. Dr. med. V. Coenen, Univ.- Freiburg, Prof. Dr. med. J. Voges, Univ.-Magdeburg

12:00-14:00
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SSW2
SATELLITE SYMPOSIUM SPONSORED BY WSSFN
GLOBAL BRAIN INITIATIVES - IMPLICATIONS FOR FUNCTIONAL NEUROSURGERY

SATELLITE SYMPOSIUM SPONSORED BY WSSFN
GLOBAL BRAIN INITIATIVES - IMPLICATIONS FOR FUNCTIONAL NEUROSURGERY

Coordinators: Joseph NEIMAT (Chairman) (NASHVILLE, USA), Mark RICHARDSON (Neurosurgeon) (Pittsburgh, USA)
Keynote Speakers: James GNADT (Rockville, USA), Ferath KHERIF (SWITZERLAND), Philippe RYVLIN (SWITZERLAND)

14:00
14:00-18:00
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PMW8
PRE-MEETING WORKSHOPS
LESIONING

PRE-MEETING WORKSHOPS
LESIONING

Moderators: Jin Woo CHANG (Seoul, KOREA), Emil ISAGULYAN (Neurosurgeon (Pain Management)) (Moscow, RUSSIA)
Coordinator: Jin Woo CHANG (Seoul, KOREA)
14:00 - 18:00 Historical aspects of lesioning -from Cooper’s cryolesioning to HiFU. Takaomi TAIRA (faculty, speaker) (Tokyo, JAPAN)
14:00 - 18:00 Lesioning using invasive methods. Tipu AZIZ (Professor) (Oxford, UK)
14:00 - 18:00 Radiosurgical lesioning. Sun-Ha PAEK (Professor) (Seoul, KOREA)
14:00 - 18:00 Stereotactic laser ablation surgery. Robert GROSS (Neurosurgeon, MD/PhD Dir, eNTICE Chair, SOM Faculty) (Atlanta, USA)
14:00 - 18:00 Lesioning using HiFU. Nir LIPSMAN (Toronto, CANADA)
14:00 - 18:00 Lesioning for unusual movement disorders. Takaomi TAIRA (faculty, speaker) (Tokyo, JAPAN)
14:00 - 18:00 Increasing the accuracy of lesioning procedures. Mojgan HODAIE (Attending Neurosurgeon) (Toronto, Canada, CANADA)

14:00-18:00
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PMW10
PRE-MEETING WORKSHOPS
SURGERY FOR PSYCHIATRIC DISORDERS

PRE-MEETING WORKSHOPS
SURGERY FOR PSYCHIATRIC DISORDERS

Coordinators: Marwan HARIZ (London, UK), Keith MATTHEWS (Professor) (Dundee, UK), Bart NUTTIN (Professor) (Rotselaar, BELGIUM)
14:00 - 18:00 Introduction: Is surgery for psychiatric disorders really needed? Marwan HARIZ (London, UK)
14:00 - 18:00 DBS for OCD: Why it is not flying like DBS for PD? Bart NUTTIN (Professor) (Rotselaar, BELGIUM)
14:00 - 18:00 Two failed trials of DBS for depression; what went wrong? Andres LOZANO (Chairman of Neurosurgery, University of Toronto) (Toronto, CANADA)
14:00 - 18:00 What happened to STN DBS for OCD? Anne-Helene CLAIR (PARIS, FRANCE)
14:00 - 18:00 When is a patient with OCD treatment refractory? David CHRISTMAS (Consultant Psychiatrist) (Dundee, Scotland, UK)
14:00 - 18:00 When is a patient with major depression treatment refractory? Raphaëlle RICHIERI (marseille, FRANCE)
14:00 - 18:00 Long-term outcome of DBS for OCD with emphasis on side-effects. Rick SCHUURMAN (neurosurgeon) (Amsterdam, THE NETHERLANDS)
14:00 - 18:00 DBS for addiction. Juergen VOGES (Head of the Department) (Magdeburg, GERMANY)
14:00 - 18:00 DBS for post-traumatic stress disorder (PTSD). Ali R. REZAI (Ohio, USA)
14:00 - 18:00 Ablative surgery for aggressiveness. Osvaldo VILELA FILHO (GOIANIA, BRAZIL)
14:00 - 18:00 DBS for obesity. Antonio DE SALLES (Professor - Chief) (Sao Paulo, BRAZIL)
14:00 - 18:00 Surgery for anorexia nervosa. Bomin SUN (director) (shanghai, CHINA)
14:00 - 18:00 DBS for Gilles de la Tourette syndrome. Veerle VISSER-VANDEWALLE (Köln, GERMANY)
14:00 - 18:00 Imaging of psychiatric brain circuitries. Sameer SHETH (Associate Professor of Neurosurgery) (Houston, USA)
14:00 - 18:00 Animal models for psychiatric disorders. Christelle BAUNEZ (Director of Research) (Marseille, FRANCE)
14:00 - 18:00 How to proceed? Why is the field stagnating? Are psychiatrists aversive to psychiatric surgery? Why is it still experimental?
Panel Discussion
14:00 - 18:00 Closing talk: Ideal requirements for neurosurgery to become accepted credible treatment of refractory patients. Keith MATTHEWS (Professor) (Dundee, UK)

14:00-18:00
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PMW7
PRE-MEETING WORKSHOPS
STEREOTACTIC AND FUNCTIONAL NEUROSURGERY WORKSHOP FOR INDUSTRY

PRE-MEETING WORKSHOPS
STEREOTACTIC AND FUNCTIONAL NEUROSURGERY WORKSHOP FOR INDUSTRY

Moderators: Paresh DOSHI (Neurosurgeon) (Mumbai, INDIA), Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)
Coordinator: Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)
14:00 - 18:00 A primer of Neurodegenerative disorders. Suneil KALIA (Assistant Professor) (Toronto, CANADA)
14:00 - 18:00 Introduction to movement disorder surgery-targets, techniques and indications. Paresh DOSHI (Neurosurgeon) (Mumbai, INDIA)
14:00 - 18:00 Preoperative patient assessment-how do we select surgical candidates? Jens VOLKMANN (Chairman) (Würzburg, GERMANY)
14:00 - 18:00 Novel indications for treatment. Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)
14:00 - 18:00 The delicate art of programming - What are the key issues? Joerg MUELLER (Berlin, GERMANY)
14:00 - 18:00 Movement disorders - the patient’s perspective and impact on quality of life. Gun-Marie HARIZ (ergotherapist) (Umeå, SWEDEN)
14:00 - 18:00 What I always wanted to know about Functional Neurosurgery-(but was afraid to ask...).
Panel discussion

14:00-18:00
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PMW6
PRE-MEETING WORKSHOPS
DBS

PRE-MEETING WORKSHOPS
DBS

Moderators: Jorge GURIDI (Neurosurgery) (Pamplona, SPAIN), Angelo FRANZINI (MILANO, ITALY)
Coordinator: Erlick PEREIRA (Consultant Neurosurgeon) (London, UK)
14:00 - 18:00 Methods of stereotaxy, cartesian coordinates, frame application. Romain CARRON (MEDECIN) (MARSEILLE, FRANCE)
14:00 - 18:00 Targets, frames and maximizing trageting accuracy. Patric BLOMSTEDT (Neurosurgeon) (Umeå, SWEDEN)
14:00 - 18:00 Nexframe and Starfix systems. Joseph NEIMAT (Chairman) (NASHVILLE, USA)
14:00 - 18:00 Neuromodulation for movement disorders-technique, indications and current outcomes. Stephan CHABARDÈS (head of the unit) (GRENOBLE, FRANCE)
14:00 - 18:00 Neuromodulation for epilepsy. Dirk VAN ROOST (Head of Department) (Ghent, BELGIUM)
14:00 - 18:00 Neuromodulation for novel indications: Depression, Alzheimers, Anorexia. Clement HAMANI (Toronto, CANADA)
14:00 - 18:00 DBS complications. Maria Fiorella CONTARINO (Den Haag, THE NETHERLANDS)
14:00 - 18:00 Neuromodulation for pain. Erlick PEREIRA (Consultant Neurosurgeon) (London, UK)

14:00-18:00
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PMW9
PRE-MEETING WORKSHOPS
EDUCATION AND TRAINING in collaboration with ESSFN and WSSFN Education Committees

PRE-MEETING WORKSHOPS
EDUCATION AND TRAINING in collaboration with ESSFN and WSSFN Education Committees

Moderators: Joachim K. KRAUSS (HANNOVER, GERMANY), Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
Coordinators: Joachim K. KRAUSS (HANNOVER, GERMANY), Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
14:00 - 18:00 Stereotactic and Functional Neurosurgery across the globe-The diverse aspects of treatment. Jairo ESPINOSA (CEO) (Bogotà, COLOMBIA)
14:00 - 18:00 A comprehensive fellowship in SFN - What should it include? Zelma KISS (Associate Professor) (Calgary, CANADA)
14:00 - 18:00 Stereotactic and Functional Neurosurgery inTaiwan. Jung-Tung LIU (Taipei, TAIWAN)
14:00 - 18:00 Setting up a DBS in Indonesia. Achmad FAHMI (Surabaya, INDONESIA)
14:00 - 18:00 Starting a functional neurosurgery group. Akmal HUSSAIN (Punjab, PAKISTAN)
14:00 - 18:00 Setting up an epilepsy center. Andy PARRENT (Ontario, CANADA)
14:00 - 18:00 Stereotactic and Functional Neurosurgery in Africa. Graham FIEGGEN (Head of Department) (Cape Town, SOUTH AFRICA)
14:00 - 18:00 Stereotactic and Functional Neurosurgery in South America. Fabian PIEDIMONTE (Buenos Aires, ARGENTINA)
14:00 - 18:00 Stereotactic and Functional Neurosrugery in Algeria. Guenane LAKHDAR (Pr neurosurgen) (Algeria, ALGERIA), Benaissa ABDENNEBI (Alger, ALGERIA)

Tuesday 27 June
Time Potsdam I-III Bellevue Glienicke Tegel Lincke I-II Schinkel I-II Kaminzimmer
07:30
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) (MADRID, SPAIN), Volker COENEN (Head of Department) (Freiburg, GERMANY), Dario ENGLOT (Fellow/Trainee) (Nashville, USA), Nader POURATIAN (Los Angeles, USA)

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) (Brisbane, AUSTRALIA), Paresh DOSHI (Neurosurgeon) (Mumbai, INDIA), Shiro HORISAWA (TOKYO, JAPAN)

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, UK), Philippe CORNU (PROFESSEUR) (PARIS, FRANCE)
Keynote Speakers: Tipu AZIZ (Professor) (Oxford, UK), Stephan CHABARDÈS (head of the unit) (GRENOBLE, FRANCE), David ROBERTS (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 (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 (London, UK)

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), 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) (NASHVILLE, 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, UK), 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) (NASHVILLE, USA)
11:45 - 12:30 Spiegel and Wycis Award. Yves LAZORTHES (Toulouse, FRANCE)
Introduced by Joachim K. Krauss
11:45 - 12:30 Spiegel and Wycis Award. Francisco VELASCO CAMPOS (SENIOR INVESTIGATOR) (Mexico, MEXICO)
Introduced by Michael Schulder
11:45 - 12:30 Tasker Award. David ROBERTS (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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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, UK), Ali SAVAS (NA) (ANKARA, TURKEY)
Plenary Speaker: Lara RZESNITZEK (psychiatrist) (Berlin, GERMANY)

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 (Seoul, KOREA)

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 (Berlin, GERMANY)

15:00
15:00-16:00
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OPS03
OPS03 PARALLEL SESSIONS: ORAL PRESENTATIONS

OPS03 PARALLEL SESSIONS: ORAL PRESENTATIONS

Moderators: Alex GREEN (Consultant Neurosurgeon) (Oxford, UK), 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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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 (DUSSELDORF, GERMANY), Jarek MACIACZYK, Philipp SLOTTY

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 Cedex 5), 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

16:15
16:15-17:15
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FP1 - PARALLEL SESSIONS: FLASH PRESENTATIONS

FP1 - PARALLEL SESSIONS: FLASH PRESENTATIONS

Moderators: Alireza GHARABAGHI (Tuebingen, GERMANY), Jan MEHRKENS (Munich, 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, UK), 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, Alexander BRAWANSKI, 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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FP2 - PARALLEL SESSIONS: FLASH PRESENTATIONS

FP2 - PARALLEL SESSIONS: FLASH PRESENTATIONS

Moderators: Jung-Il LEE (Seoul, KOREA), Constantin TULEASCA (Resident) (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.

Aurelie LEPLUS WUERTZER (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 (Ciudad de México, 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, 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, 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, UK), Philip BUTTERY, Robert MORRIS

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

FP3 - PARALLEL SESSIONS: FLASH PRESENTATIONS

Moderators: Mohammad MAAROUF (Bornheim, GERMANY), Alexandre RAINHA CAMPOS (Neurosurgeon) (Lisboa, 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 (Baracaldo, 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 (London, UK), 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 (London, UK), Vibhor KRISHNA (Neurosurgeon / Assistant Professor, Clinical) (Columbus, 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, 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)

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

Wednesday 28 June
Time Potsdam I-III Bellevue Glienicke Tegel Lincke I-II Schinkel I-II Kaminzimmer
07:30
07:30-08:15
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BS5
PARALLEL SESSIONS: BREAKFAST SESSIONS
CHALLENGING CASES IN EPILEPSY

PARALLEL SESSIONS: BREAKFAST SESSIONS
CHALLENGING CASES IN EPILEPSY

Moderators: Shabbar DANISH (Surgeon) (New Brunswick, USA), Nitin TANDON (Houston, USA)
Keynote Speakers: Robert GROSS (Neurosurgeon, MD/PhD Dir, eNTICE Chair, SOM Faculty) (Atlanta, USA), Kai LEHTIMÄKI (Associate Professor in Neurosurgery) (Tampere, FINLAND), Dirk VAN ROOST (Head of Department) (Ghent, BELGIUM)

07:30-08:15
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BS4
PARALLEL SESSIONS: BREAKFAST SESSIONS
RADIOSURGERY FOR PSYCHIATRIC DISEASE, EPILEPSY, PAIN

PARALLEL SESSIONS: BREAKFAST SESSIONS
RADIOSURGERY FOR PSYCHIATRIC DISEASE, EPILEPSY, PAIN

Moderators: Antonio DE SALLES (Professor - Chief) (Sao Paulo, BRAZIL), Marc LEVIVIER (Chef de Service) (Lausanne, SWITZERLAND)
Keynote Speakers: Rees COSGROVE (Director, Epilepsy and Functional Neurosurgery) (Boston, USA), Antonio DE SALLES (Professor - Chief) (Sao Paulo, BRAZIL), Motohiro HAYASHI (Associate professor) (Tokyo, JAPAN)

07:30-08:15
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BS6
PARALLEL SESSIONS: BREAKFAST SESSIONS
SPASTICITY/INTRATHECAL BACLOFEN TREATMENT INDICATIONS, PEARLS AND CHALLENGES

PARALLEL SESSIONS: BREAKFAST SESSIONS
SPASTICITY/INTRATHECAL BACLOFEN TREATMENT INDICATIONS, PEARLS AND CHALLENGES

Moderators: Johannes ENSLIN (Specialist) (Cape town, SOUTH AFRICA), Patrick MERTENS (Head of the department) (LYON, FRANCE)
Keynote Speakers: Johannes ENSLIN (Specialist) (Cape town, SOUTH AFRICA), Patrick MERTENS (Head of the department) (LYON, FRANCE), Marc SINDOU (Professor of Neurosurgery) (Lyon, FRANCE)

08:30
08:30-09:00
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KL6
PLENARY SESSION: KEYNOTE LECTURE
EMERGING INDICATIONS: DISORDERS OF MEMORY, BEHAVIOUR, MOOD AND METABOLISM

PLENARY SESSION: KEYNOTE LECTURE
EMERGING INDICATIONS: DISORDERS OF MEMORY, BEHAVIOUR, MOOD AND METABOLISM

Moderators: Hidehiro HIRABAYASHI (Tokyo, JAPAN), Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)
Plenary Speaker: Andres LOZANO (Chairman of Neurosurgery, University of Toronto) (Toronto, CANADA)

09:00
09:00-10:00
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OPS06a
OPS06a PLENARY SESSION: ORAL PRESENTATIONS

OPS06a PLENARY SESSION: ORAL PRESENTATIONS

Moderators: Hidehiro HIRABAYASHI (Tokyo, JAPAN), Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)
09:00 - 09:12 #10287 - OP26 Image-guided and image-verified DBS in a surgical theatre equipped with an MRI scanner: A 5-year experience.
Image-guided and image-verified DBS in a surgical theatre equipped with an MRI scanner: A 5-year experience.

Introduction

Deep brain stimulation (DBS) is a commonly used treatment for movement disorders with additional indications including epilepsy and neuropsychiatric diseases. Although DBS has proven to be effective and safe, success highly depends on the accuracy of stereotactic targeting and the prevention of surgery related complications, such as haemorrhage, infection and suboptimal lead placement. Our centre employs an image-guided image-verified approach with direct targeting on tailored MRI sequences that allow direct visualisation of the anatomical target followed by routine immediate postoperative stereotactic imaging. We report safety and accuracy data from a large consecutive series of image-guided and image-verified DBS within an intraoperative MRI suite.

 

Methods

The records of all patients who underwent DBS surgery in the period from August 2011 to August 2016 at The National Hospital for Neurology and Neurosurgery, Queen Square, London were reviewed. Data collected included the accuracy of targeting and the need for immediate relocation of DBS leads, as well as the occurrence of surgical complications.

 

Results

A total of 399 patients underwent 725 electrode implantations on a total of 13 targets. All patients were operated under general anaesthesia except when targeting the ventral intermediate nucleus of the thalamus for tremor. It was often possible for two patients to undergo DBS in one day. The indications for surgery were: Parkinson’s disease (PD) 208 (52.1%), dystonia 77 (19.3%), tremor 34 (8.5%), Tourette’s syndrome 17 (4.3%), PD dementia or Lewy body dementia 12 (3.0%), obsessive-compulsive disorder (OCD) 6 (1.5%), trigeminal autonomic cephalalgia 42 (10.6%), chronic post-stroke pain 2 (0.5%) and progressive supranuclear palsy (PSP) 1 (0.3%).Based on stereotactic accuracy and anatomical location, 21 (2.9%) leads were relocated immediately by 1.5 to 3.0mm. Final placement of all leads was within 2mm of the intended target with a maximum of two brain passes. The overall infection rate was 2.8%. Postoperative imaging revealed a small haemorrhage in 2 patients (0.5%), one asymptomatic subcortical and one peduncular, the latter associated with permanent cognitive, behavioural and gait difficulties.

 

Conclusion

MRI-guided and MRI-verified DBS is a safe and accurate technique. A surgical theatre equipped with an MRI scanner allows immediate verification of targeting accuracy and is time-saving, allowing to implant more than one patient in one day.

R. Saman VINKE (Nijmegen, THE NETHERLANDS), Jonathan A. HYAM, Tsinsue CHEN, Thomas FOLTYNIE, Patricia LIMOUSIN, Marwan HARIZ, Ludvic ZRINZO
09:12 - 09:24 #10437 - OP27 Different stimulus response properties and short-term plasticity in subthalamic and nigral neurons in patients with Parkinson's disease.
Different stimulus response properties and short-term plasticity in subthalamic and nigral neurons in patients with Parkinson's disease.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective procedure for the treatment of Parkinson’s disease (PD) symptoms. The therapeutic benefits of DBS are frequency-dependent, but the underlying physiological mechanisms remain unclear. We previously reported short-term plasticity changes in substantia nigra pars reticulata (SNr) with short trains of high frequency stimulation (HFS), but long-trains have not been investigated.

Objectives:  (i) Compare frequency-dependent effects on cell firing in STN and SNr neurons, (ii) quantify frequency-dependent dynamics of short-term plasticity in SNr, and (iii) compare effects of continuous long-train HFS on short-term plasticity to our previous study.

Methods: In PD patients undergoing stereotactic DBS surgery, two microelectrodes (600um spacing) were advanced into the STN and SNr. One microelectrode recorded single units and evoked field potentials (fEPs) during stimulation trains of different frequencies (1Hz, 10s - 100Hz, 0.5s) from the adjacent microelectrode.

Results: STN neuronal firing showed significant attenuation with 20Hz (p<0.01) stimulation and greater (silenced at 100Hz), while SNr decreased with 3Hz (p<0.05) and greater (silenced at 50Hz). The average peak amplitude of the fEP in SNr neurons was attenuated above 30Hz (p<0.05). However, the first-fEP within the train was potentiated above 30Hz (p<0.01). This is suggestive of synaptic facilitation, followed by rapid synaptic depression. Furthermore, the fEP amplitude during 1Hz pulses showed significant inhibitory synaptic potentiation after continuous HFS (100Hz, 10s). The fEP amplitude increased by a factor of 1.72 (p<0.001), while the time delay between stimulation pulses and the first spike increased by 1.88 (p<0.01).

Conclusions: STN neurons exhibited a higher frequency threshold to stimulation either due to a differing ratio of GABA:glutamate terminals on the soma compared to SNr, and/or the nature of their GABAergic inputs (pallidal vs striatal). Nevertheless, this supports the hypothesis that HFS produces predominantly GABA release, resulting in a reduction of neuronal firing through excitation of pre-synaptic axon fibers. We also showed enhancement of inhibitory synaptic plasticity in SNr by continuous HFS, and the frequency-dependent dynamics of short-term synaptic plasticity (believed to be modulated by neurotransmitter release properties) and consider these to be additional putative mechanisms of DBS.

Luka MILOSEVIC (Toronto, CANADA), Suneil KALIA, Mojgan HODAIE, Andres LOZANO, Milos POPOVIC, William Duncan HUTCHISON
09:24 - 09:36 #10201 - OP28 Outcomes of a prospective, multicenter international registry of Deep Brain Stimulation for Parkinson's disease.
Outcomes of a prospective, multicenter international registry of Deep Brain Stimulation for Parkinson's disease.

Objective:

The effectiveness and safety of the use of DBS to reduce motor complications of PD patients has been substantiated by several randomized controlled trials (Schuepbach et al., 2013). Motor improvement following DBS is sustained for up to 10 years as reported by Deuschl et al. 2013. An in-depth evaluation of real world outcomes following DBS will add to the existing database of knowledge and be a useful tool for physicians.  As part of an on-going, large scale registry study, we investigated the effectiveness and safety-related real-world outcomes of a multiple independent current source control (MICC) Deep Brain Stimulation (DBS) System for use in the management of motor symptoms of levodopa-responsive Parkinson’s disease (PD). 

Materials/Methods:

The is a prospective, on-label, multi-center, international registry sponsored by Boston Scientific Corporation. Patients were implanted with a CE-marked, MICC-based DBS system (Vercise, Boston Scientific). Subjects will be followed up at 6 and 12 months and up to 3 years post-implantation where their overall improvement in quality of life and PD motor symptoms will be evaluated. Clinical endpoints will be evaluated at baseline and during study follow up that include Unified Parkinson's disease Rating Scale (UPDRS), MDS-UPDRS, Parkinson's disease Questionnaire (PDQ-39), and Global Impression of Change. Adverse events are also collected.

Results:

Preliminary data suggests an overall improvement in Quality of life at 6 months post implant as compared with Baseline as measured by a 17.6% (n = 89) improvement in PDQ-39 Summary Index. Over 90% of patients, caregivers and clinicians reported improvement as compared with Baseline. This report will provide the safety and effectiveness outcomes of the first cohort of subjects analyzed at 6 (N=150) and 12 months (N=100) post-implantation as compared with baseline.

Conclusions:

Deep Brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment option for patients with advanced Parkinson’s disease (PD). A device that enables fractionalization of current using a multiple source mode of delivery (MICC) can permit the application of a well-defined, shaped electrical field. This registry represents the first comprehensive, large scale collection of real-world outcomes and includes evaluation of the safety and effectiveness of the Vercise DBS System up to 12 months post lead placement.

Jan VESPER (DUSSELDORF, GERMANY), Karsten WITT, H. Maximilian MEHDORN, Andrea KÜHN, Michael T. BARBE, Veerle VISSER-VANDEWALLE, Monika PÖTTER-NERGER, Wolfgang HAMEL, Carsten BUHMANN, Paul ELDRIDGE , Roshini JAIN, Heleen SCHOLTES, Alex WANG, Guenther DEUSCHL
09:36 - 09:48 #10236 - OP29 The evolution of automatic microelectrode guided navigation for deep brain stimulation surgery.
The evolution of automatic microelectrode guided navigation for deep brain stimulation surgery.

Objective

Microelectrode recording (MER) is a widely-used tool to confirm and define deep brain targets during deep brain stimulation (DBS) surgery. However, MER has been considered a time-consuming technique necessitating expertise. Our objective was to design an automatic recording and display algorithm to both simplify and reduce the time necessary for MER during surgery.

Methods

Previous work has utilized techniques exploiting cellular firing patterns to accurately help define the borders and sub territories of the subthalamic nucleus (STN) and the substantia nigra. These methods were combined within an automatic “push-button” algorithm and tested on 40 patients.

Results

Automatic MER guided navigation successfully extracted and displayed all the necessary and important features of an STN trajectory in real time. MER time was reduced on average by 49% (from 37 minutes to 19 minutes per trajectory).

Conclusion

Automatic navigation is safe and has a high level of reliability. Results of an MER track can easily be displayed in an inbuilt, user friendly, graphical form providing all the information necessary to help make a decision concerning the most appropriate place to position the permanent DBS electrode contact(s). Furthermore, automatic navigation is associated with very significant surgical time savings. Additional electrophysiological data may be added in the future to further refine this tool for navigation in the STN and to other deep brain targets.

Zvi ISRAEL (Jerusalem, ISRAEL), Dan VALSKY, Hagai BERGMAN
09:48 - 10:00 #10195 - OP30 Nucleus accumbens projections: validity and reliability of fiber reconstructions based on high-resolution diffusion-weighted MRI.
Nucleus accumbens projections: validity and reliability of fiber reconstructions based on high-resolution diffusion-weighted MRI.

Objective: The N. accumbens (NAc) is a key relay in the mesolimbic dopaminergic reward system, also connected to the amygdala, dorsomedial thalamus and hippocampus. As such, it is a promising target for deep brain stimulation (DBS) in patients with psychiatric diseases. In the present study, we aimed to reconstruct the neural projections connecting the NAc with the ventral tegmental area (VTA) and the medial prefrontal cortex (mPFC) using probabilistic fiber tractography based on diffusion-weighted MR imaging (DWI).

Methods: MR data (T1-MPRAGE; FLAIR; DWI: 1.6 mm isotropic resolution, 60 gradient directions) for 11 healthy subjects were acquired in two sessions on a Siemens Magnetom Prisma 3T MRI scanner. For each subject, the bilateral NAc, mPFC, and VTA were manually segmented based on the T1 and FLAIR data and transformed to the session-specific DWI space for probabilistic fiber tractography. The results were subject to detailed visual inspection to assess their validity in terms of anatomical plausibility by comparing them with the relevant literature. To quantitatively assess the reliability of the reconstructions, the fiber density maps corresponding to the individual tracts (NAc ↔ VTA and NAc ↔ mPFC) were transformed to a study template constructed from the T1 data before correlation analysis.

Results: Using MRI data from 11 healthy subjects, we were able to reconstruct neural projections connecting the NAc with the mPFC and the VTA. The connectivity patterns formed by the obtained fibers were in good concordance with the literature (anatomical tracer studies). The reliability assessment yielded moderate to high correlations, which were higher for projections between NAc and mPFC (r = 0.85) than for those between NAc and VTA (r = 0.696).

Conclusion: In the present work, we assessed the feasibility and reliability of the in vivo reconstruction of neural fibers connecting the human NAc with the mPFC and the VTA from high-resolution DWI data using probabilistic fiber tractography. In clinical practice, the presented procedure may guide selective electrical stimulation of the mesolimbic fibers using directional lead technology. Compared to undirected neuromodulation of the entire NAc, this could improve the efficacy of DBS for the treatment of mental disorders, such as addiction and obesity compulsive disorder.

Thilo RUSCHE (Magdeburg, GERMANY), Jörn KAUFMANN, Kristian LOEWE, Jürgen VOGES

10:30
10:30-11:30
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OPS06b
OPS06b PLENARY SESSION: ORAL PRESENTATIONS

OPS06b PLENARY SESSION: ORAL PRESENTATIONS

Moderators: Arthur CUKIERT (São Paulo, BRAZIL), Veerle VISSER-VANDEWALLE (Köln, GERMANY)
10:30 - 10:42 #10525 - OP31 Surgical approach to the superolateral branch of the medial forebrain bundle (slMFB) for DBS in depression.
Surgical approach to the superolateral branch of the medial forebrain bundle (slMFB) for DBS in depression.

Background: Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) emerges as an interesting alternative  - yet experimental - treatment for therapy refractory psychiatric diseases. First experiences have been reported from a pilot trial in major depression (1) and an uncontrolled case series for obsessive compulsive disorder (OCD) (2).

Objective: To describe the surgical technique for deep brain stimulation (DBS) of the supero-lateral branch of the medial forebrain bundle (slMFB). To report our experience with the successful bilateral implantation in a larger patient group.

Methods: Surgical experience from bilateral implantation procedures in n=27 patients is reported. The detailed procedure of diffusion tensor imaging magnetic resonance imaging fiber tracking (DTI FT) assisted targeting together with detailed descriptive electrophysiology in 144 trajectories of the target region (recording and stimulation) and intraoperative testing are addressed.

Results: Bilateral slMFB DBS requires DTI FT assisted targeting combined with in depth intraoperative electrophysiological investigation of the target region.

Conclusion: The slMFB is a promising target for the treatment of depression and possibly OCD (1,2). DTI FT assisted DBS of the slMFB is based on an imaging technology that is readily addressed in other indications (3). To the authors’ knowledge the slMFB is the only target region for psychiatric disorders that allows for intra-operative testing with clear therapeutic effects and side effects to guide implantation. In our eyes, this makes surgery of the slMFB is in many features comparable to typical movement disorder surgery.

 

1)    Schlaepfer, T. E., Bewernick, B. H., Kayser, S., dler, B. M. X., & Coenen, V. A. (2013). Rapid Effects of Deep Brain Stimulation for Treatment-Resistant Major Depression. Biological Psychiatry, 1–9. http://doi.org/10.1016/j.biopsych.2013.01.034

2)    Coenen, V. A., Schlaepfer, T. E., Goll, P., Reinacher, P. C., Voderholzer, U., Tebartz van Elst, L., et al. (2016). The medial forebrain bundle as a target for deep brain stimulation for obsessive-compulsive disorder. CNS Spectrums, 1–8. http://doi.org/10.1017/S1092852916000286

3)    Coenen, V. A., Allert, N., Paus, S., Kronenbürger, M., Urbach, H., & Mädler, B. (2014). Modulation of the Cerebello-Thalamo-Cortical Network in Thalamic Deep Brain Stimulation for Tremor. Neurosurgery, 75(6), 657–670. http://doi.org/10.1227/NEU.0000000000000540

 

Volker Arnd COENEN (Freiburg, GERMANY), Peter Christoph REINACHER, Jan BOSTROEM, Bettina H BEWERNICK, Susanne GRESCHUS, Burkhard MAEDLER, Horst URBACH, Thomas Eduard SCHLAEPFER
10:42 - 10:54 #9876 - OP32 Functional connectivity alterations of brainstem arousal centers in temporal lobe epilepsy.
Functional connectivity alterations of brainstem arousal centers in temporal lobe epilepsy.

Introduction: Seizures in temporal lobe epilepsy (TLE) disturb brain network physiology and lead to brain connectivity disturbances. We have previously hypothesized that recurrent seizures in TLE may lead to abnormal connections involving subcortical activating structures including the ascending reticular activating system (ARAS), contributing to neocortical dysfunction and neurocognitive impairments. However, no prior studies of ARAS connectivity have been previously reported in epilepsy patients.

Methods: We used resting-state functional MRI (fMRI) recordings in 27 TLE patients (67% right-sided) and 27 matched controls to examine functional connectivity (partial correlation) between eight brainstem ARAS structures and 105 cortical/subcortical regions. ARAS nuclei included: cuneiform/subcuneiform, dorsal raphe, locus coeruleus, median raphe, parabrachial complex, pontine oralis, pendunculopontine, and ventral tegmental area. Connectivity patterns were related to factors of interest.

Results: In control subjects, regions showing the most positive connectivity to ARAS structures included limbic structures, thalamus, and certain neocortical areas, consistent with prior studies of ARAS projections. Overall ARAS connectivity was significantly lower in TLE patients than controls (p < 0.05, paired t-test), particularly to neocortical regions including insular, lateral frontal, posterior temporal, and opercular cortex. Diminished ARAS connectivity to these regions was related to increased frequency of consciousness-impairing seizures (p < 0.01, Pearson correlation), suggesting an association with severity of illness. Furthermore, reductions in ARAS connectivity were associated with impairments in verbal IQ, attention, executive function, language, and visuospatial memory on formal neuropsychological evaluation (p < 0.05, Spearman’s rho or Kendell’s tau-b).

Conclusions: Recurrent seizures in TLE may lead to disturbances in ARAS functional connectivity, contributing to more widespread network dysfunction which may help explain neurocognitive problems suffered in this devastating disorder. 

Dario ENGLOT (Nashville, USA), Pierre-Francois D’HAESE, Peter KONRAD, Monica JACOBS, John GORE, Bassel ABOU-KHALIL, , Victoria MORGAN
10:54 - 11:06 #10570 - OP33 Double-blind Randomized Trial of V1 Trigeminal Stimulation for Refractory Major Depression.
Double-blind Randomized Trial of V1 Trigeminal Stimulation for Refractory Major Depression.

Double-blind Randomized Trial of V1 Trigeminal Stimulation for Refractory Major Depression

Alessandra Gorgulho, Fernando Fernandes, Camila Lasagno, Priscila Bueno, Lucas Damian, Otávio Berwanger, Ricardo A. Moreno, Antonio De Salles

HCor Neurosciences, Sao Paulo, Brazil and Mood Disorders Unit, Institute and Department of Psychiatry, Clinical Hospital, University of Sao Paulo, Brazil. 

 

Introduction: One-third of patients with Major Depression are refractory to combined medication trials and psychotherapy. We conducted a double-blind, one-way crossover randomized surgical trial of trigeminal stimulation (TNS) in unipolar treatment resistant depression patients.

 

Materials and Methods: Twenty patients, mean age: (50.3; SD+7.23 years), 16-females, enrolled after IRB approval. Bilateral electrodes under the eyebrow aiming the V1 branch of the trigeminal nerve were implanted and connected to a generator subcutaneously below the right clavicle. Ten participants were randomized to active stimulation (AS) at 2-weeks after surgery. The other half was turned-on for 1 minute and then remained turned-off, sham stimulation (SS) for 12 weeks. At 3- month the SS non-responders were turned-on. Placebo responders were rescued during the additional 12 weeks of blinded stimulation. The double-blind stimulation period lasted 6-months. Medications were unchanged throughout the study, unless prompted modification by the Psychiatrist. Depression was evaluated with Hamilton -Depression-Scale-17-items(HDS17), Beck-Depression-Inventory(BDI), Inventory of Depression-Symptomatology(IDS) and Ugvlag for Kiniske Undersgelsen(UKU).

 

Results: Stimulation was well tolerated. Three patients asked for a slight surgical retraction of the electrode because it was bothersome at the eyebrow area. There were no infections or erosions. Baseline-HDRS17 fell in the AS and SS groups by placebo effect. However, the fall in the AS was more robust and statistically significant at 12 weeks (p<0.023) as compared to the SS (20.4+2.9 to 16.9+5.3 versus 22.3+4.0 to 10.2+2.5), confirmed with the crossover. BDI and IDS decreased in both groups without reaching statistical significance at 12-weeks. UKU demonstrated safety and tolerability of the procedure.

 

Conclusion: Patients tolerated well the V1 stimulation electrodes, as well as the continuous stimulation. It was well tolerated cosmetically. The treatment was robust with a significant decrease in HDS17 and a great adherence to the treatment.

Alessandra GORGULHO (Sao Paulo, BRAZIL), Fernando FERNANDES, Camila LASAGNO, Priscila BUENO, Lucas DAMIAN, Otavio BERWANGER, Ricardo A. MORENO, Antonio DE SALLES
11:06 - 11:18 #10800 - OP34 Deploying autologous peripheral nerve grafts in patients with Parkinson's disease at the time of deep brain stimulation surgery.
Deploying autologous peripheral nerve grafts in patients with Parkinson's disease at the time of deep brain stimulation surgery.

Introduction: We are investigating a strategy that couples the delivery of a cell therapy at the time of DBS surgery in an attempt to restore areas of the brain affected in Parkinson’s disease (PD). We deployed nerve grafts containing Schwann cells from the sural nerve; Schwann cells, after injury, transdifferentiate to become “repair cells” and release a host of factors including GDNF, NGF, BDNF, and NT-3. We have ongoing clinical trials (NCT01833364) and (NCT02369003) examining the safety and feasibility of implanting single or multiple autologous peripheral nerve grafts to one more target locations in patients with PD undergoing DBS surgery. Methods: DBS surgery targeting the subthalamic nucleus or internal globus pallidus was performed using standard procedures. A 5mm section of sural nerve was excised, stripped of the epineurium, cut into 1mm pieces, and unilaterally delivered into the area of the substantia nigra (SN) and/or nucleus basalis of Meynert (NBM). Adverse events were continuously monitored. The primary endpoint was safety. Secondary endpoints include neurocognitive performance, quality of life, gait, (123I-ioflupane) SPECT imaging, and Unified Parkinson’s Disease Rating Scale (UPDRS) scores. Results: To date, 41 participants have received grafts with an adverse event profile comparable to standard DBS surgery and with no serious adverse events related to the delivery of the graft. So far, 17 participants who received a graft to the SN have reached the 1 year time point and have had a decrease of 7.3 ± 10.6 points (considered a moderate clinically important difference, mean ± SD) in the mean UPDRS motor score off medication and off stimulation compared to before surgery.  Meanwhile, a review of 16 patients in our clinic who received only DBS showed an increase of 0.3 ± 15.0 points in their mean UPDRS motor score compared to before surgery. We recently began a dose escalation to either deploy grafts to the SN and NBM (one participant) or dual deployments to the SN (six participants) unilaterally.  Immediate post op adverse event profiles were comparable to standard DBS surgery. Conclusion: We are finding that combining the delivery of cell therapy at the time of DBS surgery appears to be safe and feasible.  While more time is needed to fully assess the efficacy of this therapy, preliminary clinical evidence is showing baseline improvements in motor function at one year.

Craig VAN HORNE (Lexington, USA), Jorge QUINTERO, Julie GURWELL, Amelia ANDERSON-MOONEY, Andrew WELLEFORD, John LAMM, John SLEVIN, Greg GERHARDT
11:18 - 11:30 #10680 - OP35 Direct Electrical Stimulation of the Amygdala Enhances Event-Specific Declarative Memory in Humans.
Direct Electrical Stimulation of the Amygdala Enhances Event-Specific Declarative Memory in Humans.

Introduction

Significant events are often prioritized to become lasting memories. A common example is that emotional events are often remembered better than neutral events. This prioritization is mediated by the amygdala, which modulates memory consolidation processes in the hippocampus and related medial temporal cortices, including the perirhinal cortex. Further, rodent studies have demonstrated that direct activation of the amygdala enhances memory consolidation even during non-emotional events. Here we show that brief electrical stimulation to the amygdala in humans can enhance declarative memory without eliciting an emotional response.

Methods

Fourteen epilepsy patients undergoing monitoring of seizures via intracranial depth electrodes viewed a series of neutral object images, half of which were immediately followed by brief low amplitude electrical stimulation to the amygdala (8 trains of 50-Hz pulses for 1-second at 0.5 mA; no epileptiform activity was elicited by the stimulation). Recognition memory for different subsets of objects was tested immediately and one day after the study phase.

Results

When recognition memory was tested the next day, the specific images previously followed by amygdala stimulation were consistently better remembered than images previously presented without such stimulation. Analysis of oscillatory activity from the amygdala, hippocampus, and perirhinal cortex during this next-day memory test showed increased synchrony in theta and gamma frequency bands at presentation of the remembered object images previously paired with amygdala stimulation on the previous day compared to objects not paired with stimulation. In addition, the objects in the stimulation condition during the one-day test appeared to elicit patterns of oscillations in the memory network that were similar to those used for amygdala stimulation the previous day. In a separate test, patients, blinded to experimental conditions, were unable to detect the stimulation.

Conclusion

These results demonstrate that amygdala stimulation in humans can lead to a prioritization of specific memories in long-term storage, and suggest that the memory enhancement involves an interaction between the amygdala and medial temporal lobe structures essential for declarative memory. This study extends prior rodent studies on the role of the amygdala in influencing synaptic plasticity in the medial temporal lobe and suggests a novel target of therapeutic intervention for memory disorders.

Cory INMAN (Decatur, USA), Joseph MANNS, Kelly BIJANKI, David BASS, Stephan HAMANN, Daniel DRANE, Rebecca FASANO, Christopher KOVACH, Robert GROSS, Jon WILLIE

11:30
11:30-12:00
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KL7
PLENARY SESSION: KEYNOTE LECTURE
WHY HAVE WE HAD SO MANY FAILED TRIALS?

PLENARY SESSION: KEYNOTE LECTURE
WHY HAVE WE HAD SO MANY FAILED TRIALS?

Moderators: Arthur CUKIERT (São Paulo, BRAZIL), Veerle VISSER-VANDEWALLE (Köln, GERMANY)
Plenary Speaker: Bart NUTTIN (Professor) (Rotselaar, BELGIUM)

12:00
12:00-14:00
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LUNCH SYMPOSIUM - INDUSTRY SPONSORED

LUNCH SYMPOSIUM - INDUSTRY SPONSORED

12:00-14:00
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LUNCH SYMPOSIUM - INDUSTRY SPONSORED

LUNCH SYMPOSIUM - INDUSTRY SPONSORED

12:30-13:00
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MEET6
WSSFN INDUSTRY COMMITTEE MEETING

WSSFN INDUSTRY COMMITTEE MEETING

12:00-14:00
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MEET4
WSSFN PSYCHIATRIC COMMITTEE MEETING

WSSFN PSYCHIATRIC COMMITTEE MEETING

12:00-12:30
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MEET5
WSSFN SCIENCE COMMITTEE MEETING

WSSFN SCIENCE COMMITTEE MEETING

12:30-13:00
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MEET7
WSSFN EDUCATION COMMITTEE MEETING

WSSFN EDUCATION COMMITTEE MEETING

14:15
14:15-14:45
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KL8
PARALLEL SESSIONS: KEYNOTE LECTURES
NEURAL TRANSPLANTATION

PARALLEL SESSIONS: KEYNOTE LECTURES
NEURAL TRANSPLANTATION

Moderators: Ethan TAUB (Head of Functional Neurosurgery) (Basel, SWITZERLAND), Hiroki TODA (Director) (Osaka, JAPAN)
Plenary Speaker: Stéphane PALFI (HEAD) (Créteil, FRANCE)

14:15-14:45
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KL9
PARALLEL SESSIONS: KEYNOTE LECTURES
IMAGING THE BRAINSTEM-7T AND BEYOND

PARALLEL SESSIONS: KEYNOTE LECTURES
IMAGING THE BRAINSTEM-7T AND BEYOND

Moderators: Volker COENEN (Head of Department) (Freiburg, GERMANY), Mooseong KIM (Chairman) (Busan, KOREA)
Plenary Speaker: Aviva ABOSCH (Denver, USA)

14:15-14:45
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KL10
PARALLEL SESSIONS: KEYNOTE LECTURES
NON-INVASIVE STIMULATION FOR COGNITIVE ENHANCEMENT

PARALLEL SESSIONS: KEYNOTE LECTURES
NON-INVASIVE STIMULATION FOR COGNITIVE ENHANCEMENT

Moderator: Cristina TORRES (Madrid, SPAIN)
Plenary Speaker: Bahram MOHAMMADI (Hannovre, GERMANY)

14:45
14:45-15:45
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OPS07
OPS07 PARALLEL SESSIONS: ORAL PRESENTATIONS

OPS07 PARALLEL SESSIONS: ORAL PRESENTATIONS

Moderators: Ethan TAUB (Head of Functional Neurosurgery) (Basel, SWITZERLAND), Hiroki TODA (Director) (Osaka, JAPAN)
14:45 - 14:57 #10413 - OP36 Sonication conditions influencing the efficacy and safety of blood-brain barrier modulation by low-intensity focused ultrasound.
Sonication conditions influencing the efficacy and safety of blood-brain barrier modulation by low-intensity focused ultrasound.

Background: The application of pharmacological therapeutics in neurological disorders is limited by
the ability of these agents to penetrate the blood-brain barrier (BBB). We examined
several FUS conditions in order to optimize FUS sonication for BBB opening in small animals.


Methods: Changes in BBB permeability were observed during transcranial sonication with contrast
agent microbubbles (MB) using low-intensity focused ultrasound (FUS) in rats (N = 20). We examined the
effects of FUS sonication with different sonication parameters, varying acoustic pressure, center
frequency, burst duration, MB type, MB dose, pulse repetition frequency (PRF), and total exposure time.
The focal region of BBB opening was identified Evans blue dye extravasation. Additionally,
hematoxylin and eosin staining was used to identify tissue damage in the sonicated region.


Results: Acoustic pressure amplitude, burst duration, and total exposure time were associated with
increased damage in the sonicated region of the brain when parameter values were increased. In contrast,
variations in MB type, MB dose, and PRF had little effect on the degree of tissue damage after FUS
sonication. 


Conclusions: The clinical application of FUS sonication for drug delivery across the BBB requires the
guarantee of both safety and efficacy and thus the careful optimization of relevant sonication conditions.
Our study aimed to identify these influential conditions and provide optimized values for further studies.

Shin JAEWOO, Chang WON SEOK (Seoul, KOREA), Cho JAE SUNG, Lee JIHYUN, Na YOUNG CHUL, Jin Woo CHANG
14:57 - 15:09 #10784 - OP37 DIFFUSION METRICS AND FIBER TRACTS CHANGES AFTER MRI-GUIDED HIGH INTENSITY FOCUSED ULTRASOUND SURGERY IN A SWINE MODEL.
DIFFUSION METRICS AND FIBER TRACTS CHANGES AFTER MRI-GUIDED HIGH INTENSITY FOCUSED ULTRASOUND SURGERY IN A SWINE MODEL.

Objective: MR-guided focused ultrasound (MRgFUS) is increasingly used as a lesioning tool in functional neurosurgery. While the generated lesion can be visualized using traditional MR imaging, these do not provide detailed information about tissue microstructure or direct visualization of affected tracts. To study this, we used a neonatal swine model to investigate in-vivo acute changes in water diffusion and fiber tracts after MRgFUS treatment of the fornix.

Methods: Four piglets (5-6.7kg) were treated with MRgFUS system (Sonalleve, Philips Medical Systems, Finland). Treatment cells were positioned along the anterior body of the fornix with a cross-sectional diameter of 4mm and a length of 10mm (volume= 83.78mm3). 3-4 sonications from 40W to 80W, frequency 1.2MHz were performed to generate the ablation with a peak temperature above 60°C. Between each sonication, there was a 5-minute cool-down interval. Pre- and post-treatment T1, Diffusion weighted images (DWI), and histological data were collected. DWI metrics (FA, AD, RD, MD, and ADC) were calculated for the lesion core, inner and outer boundaries of the lesion determined on the hyper-intensity signal in the mean DWI image. Paired t-test was performed for DWI metrics from each region of interest. One-way ANOVA followed by post-hoc Tukey’s HSD was applied for each DWI metric across the three regions of interest for pre- and post-treatment separately. Fornix fiber tracts were generated before and after the treatment for qualitative assessment.

Results: In all treatments, final peak temperature reached a range between 60.8°C and 68.8°C. The volume of treatment was comparable (correlation= 0.88) between values measured through mean DWI (347.5±58.12 mm3) and histological data (342.35±44.69mm3), however this was significantly larger than the treatment cell volume. MRgFUS resulted in a significant decrease in diffusion metrics in the treatment region (Ps<0.05 FDR-corrected). The fiber disruption was most pronounced as the lesion core was approached.

Conclusions: Diffusion metrics and tractography can accurately assess treatment location, volume and necrotic core after MRgFUS treatment. DWI can successfully advance MRgFUS targeting. In our case, ablated tissue volume was much larger than the planned cell likely due to the set peak temperature. Further comparative tract alterations based on peak temperature should help determine the relationship between temperature and final lesion volume more accurately. 

Jidan ZHONG, Matthew WALKER, Adam WASPE, Looi THOMAS, Karolina PIORKOWSKA, James DRAKE, Mojgan HODAIE (Toronto, CANADA)
15:09 - 15:21 #10574 - OP38 Segmenting the anterior limb of the internal capsule by structural connectivity: a potential tool for neuromodulatory targeting.
Segmenting the anterior limb of the internal capsule by structural connectivity: a potential tool for neuromodulatory targeting.

Introduction

The anterior limb of internal capsule (ALIC) is a promising target for neuromodulatory interventions for severe, treatment refractory psychiatric disorders, including deep brain stimulation (DBS) and capsulotomy, for obsessive-compulsive disorder (OCD) and depression. These disorders are heterogeneous phenomena and there is controversy about optimal targets within the ALIC. Using diffusion tensor imaging (DTI), we parcellated the ALIC based on structural connectivity. We then compared the ALIC segmentations between individuals to evaluate regional patterns of consistency.

 

Methods

ALIC segmentations were generated for 40 subjects from the Human Connectome Project (HCP) using connectivity-based seed classification in FSL v5.0. Voxels within the ALIC were treated as seed regions and frontal Brodmann areas (BAs) as independent targets. We combined patient-specific segmentations by assigning each ALIC voxel to the most frequently associated frontal BA in the 40 individual segmentations. We compared this combined individual-based parcellation to one similarly created using a template from HCP that averaged diffusion data from 842 subjects. Segmentations were compared to one another using the Sørensen-Dice Index of similarity (SDI).

 

Results

All 40 segmentations exhibited a posterior-superior to anterior-inferior axis of organization (Figure 1). On average, the frontal BA assignments of voxels in the group analysis were consistent with 66.2% of individuals’ segmentations. In this analysis, the region assigned to BA11 (orbitofrontal cortex, OFC), exhibited the highest degree of consistency across individuals, with 12.1% of this region being assigned to BA11 in all 40 subjects. The mean SDI between the individual-based combined segmentation and the template-based segmentation regions was 0.283. The mean SDI between individual segmentation regions was 0.455. Regions assigned to BA11 were the most similar across individual segmentations, with a mean SDI of 0.714.

 

Conclusion

These results clarify the organization of the ALIC in humans. They also demonstrate the high variability in ALIC organization between individuals, albeit with some loci of focal consistency. This variability suggests that patients may benefit from tractography prior to neuromodulation in order to facilitate patient-specific targeting. Interestingly, the most consistent regions of the ALIC, those connecting to OFC, are the regions most frequently targeted by neuromodulatory procedures.

Pranav NANDA (New York, USA), Garrett BANKS, Yagna PATHAK, Justin OH, Sameer SHETH
15:21 - 15:33 #10799 - OP39 Localizing Ventral Intermediate nucleus of the thalamus using primary fiber direction.
Localizing Ventral Intermediate nucleus of the thalamus using primary fiber direction.

Intro:

While pharmacological therapy for essential tremor is the first line of treatment, some patients may only experience partial benefits.  For these patients, surgical lesion or deep brain stimulation (DBS) of the ventral intermediate (VIM) nucleus of the thalamus has been shown to ameliorate tremor symptoms. Precise targeting of the VIM has been correlated with superior outcomes, but targeting of this structure based on MRI may be challenging.  Diffusion tensor imaging (DTI) has been used to approximate the VIM indirectly by calculating the pyramidal tracts (PT) and medial lemniscus (ML) trajectories as anatomical reference.  Here we show that the primary diffusion vector map can be used to directly delineate VIM without the need for post processing tractography calculation.

Methods:

DTI from 40 subjects in the Human Connectome Project was used to compare methodologies.  Free surfer library’s FDT toolkit was used to calculate the primary diffusion vector map, PT, and ML. Using the vector map we identified the VIM internal capsule boundary and sensory boundary, and compared the location to the indirect DTI localization (Fig1).  The average Euclidian distance between both methods was compared.

Results:

By comparing methods, the Euclidian distance in the VIM internal capsule boundary in the ACPC plane was found to differ by 0.53mm(+/- 0.70mm), and the VIM sensory boundary was found to differ by 0.96mm(+/- 0.99mm).

Conclusion:

Our localization method allows delineation of VIM thalamus utilizing a primary vector map. The method is able to produce a direct VIM delineation similar to tractography calculated methods within a millimeter on average.  This map can be produced using most current surgical navigation software packages, making this technique easy to use and readily accessible.  Future directions include comparing the localized area to both efficacy and side effects resulting from DBS implantation and radio surgery lesions.

Garrett BANKS (New York, USA), Nora VANEGAS-ARROYAVE, Sameer SHETH
15:33 - 15:45 #10787 - OP40 Caudate is involved in human associative learning.
Caudate is involved in human associative learning.

Caudate Is Involved in Human Associative Learning

 

Introduction

Disorders of learning and memory account for an increasing disease burden in our aging population with significant social and financial consequences. Unfortunately, existing treatments have limited utility. Research in humans and primates supports an important role for the caudate in learning. Our objective was to further characterize the role of the caudate in human learning and to determine whether caudate stimulation could alter performance on a learning task.

Methods

Five subjects who underwent depth electrode placement for seizure localization for medically refractory epilepsy participated in our study. Local field potentials were recorded from intracranial electrodes while subjects participated in study tasks. A learning task required subjects to learn an association between a series of presented images and a button press. A gambling task required subjects to place a wager on the outcome of a simulated card game. We computed power in caudate electrodes and compared power during the feedback epoch of the task between correct and incorrect trials for the learning task and between winning and losing trials for the gambling task. Three subjects additionally played a stimulated block of the learning task during which half of the images received bilateral caudate stimulation at 200Hz and 2mA for 1 second during the feedback epoch after correct responses.

Results

There was a significant increase in caudate beta (15-30Hz) power during the feedback period of the learning task. There was a significant difference between beta power following correct versus incorrect trials. There was no difference in beta power following winning versus losing trials in the gambling task. Of the three subjects who underwent caudate stimulation during the feedback epoch of the learning task, 2 had a significant improvement in learning for stimulated versus unstimulated images.

Conclusion

Changes in caudate beta power during feedback differed between correct and incorrect trials in the learning task. Stimulation during feedback following correct trials enhanced learning. These findings suggest that the caudate plays an important role in updating response associations in human associative learning, 

Sarah BICK (Boston, USA), Emad ESKANDAR

14:45-15:45
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OPS08
OPS08 PARALLEL SESSIONS: ORAL PRESENTATIONS

OPS08 PARALLEL SESSIONS: ORAL PRESENTATIONS

Moderators: Volker COENEN (Head of Department) (Freiburg, GERMANY), Mooseong KIM (Chairman) (Busan, KOREA)
14:45 - 14:57 #10204 - OP41 Four year outcomes of a prospective, multicenter study evaluating Deep Brain Stimulation with a new multiple-source, constant-current rechargeable system in Parkinson's disease.
Four year outcomes of a prospective, multicenter study evaluating Deep Brain Stimulation with a new multiple-source, constant-current rechargeable system in Parkinson's disease.

Objective

A DBS device that enables current fractionalization using a multiple-source mode of delivery can permit the application of a well-defined, shaped electrical field. Thus, we postulated that a multiple-source, constant-current device that permits a well-defined distribution of current would lead to motor improvement in patients with Parkinson’s disease (PD). Previously, results from the VANTAGE clinical study demonstrated highly significant improved motor function (p < 0.0001) as assessed by UPDRS III "meds off" at 6 months post-first lead implant as compared with Baseline "meds off," thereby successfully achieving the study primary endpoint. Here we present the four year, long-term follow up results of patients in the VANTAGE clinical study that employed multiple independent current control (MICC) Deep Brain Stimulation (DBS) in the management of motor symptoms of Parkinson's disease.

Methods

VANTAGE is a prospective, multi-center, non-randomized, open-label study sponsored by Boston Scientific Corporation. Forty subjects with idiopathic PD were implanted bilaterally with a DBS system (Vercise, Boston Scientific) targeting the subthalamic nucleus and followed up to three years post-lead placement. Assessments measured up to 3 years post-lead placement included the following: Levodopa Equivalent Dose (LED), Parkinson's Disease Questionnaire (PDQ-39), Global Impression of Change (GIC), and Modified Schwab and England (SE) scores.

Results

Data from three years post-lead placement has been collected and analyzed.  Anti-parkinsonian medications were found to have remained stable (average of 1399 mg at baseline versus average of 699 mg at 3 years follow up). PDQ-39 summary index scores demonstrate continued improvement (versus baseline values) in quality of life based on assessments of bodily discomfort, activity of daily living, mobility, emotional well-being, and stability of cognition.  Further, a high proportion of GIC responses were characterized as "improved" (Clinician: 88.2% ; Subject: 82.4%), and modified Schwab and England scores remained stable. Results from 4 years post-lead placement to be presented.

Conclusion

The collected outcomes from the VANTAGE clinical study will inform clinicians on the use of this system, and its flexibility to manage the motor symptoms of idiopathic PD.

Lars TIMMERMANN (Cologne, GERMANY), Roshini JAIN, Nic VAN DYCK, Lilly CHEN, Thomas BRÜCKE, Fernando SEIJO, Esther SUAREZ SAN MARTIN, Veerle VISSER-VANDEWALLE, Michael T. BARBE, Steven GILL, Alan WHONE, Mauro PORTA, Domenico SERVELLO, François ALESCH
14:57 - 15:09 #10169 - OP42 Deep brain stimulation of subthalamic nucleus increases dopamine transporter binding in the ventral striatum in patients with Parkinson’s disease.
Deep brain stimulation of subthalamic nucleus increases dopamine transporter binding in the ventral striatum in patients with Parkinson’s disease.

Purpose.

It is well known that deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms of Parkinson’s disease (PD). However, the effects of STN-DBS on presynaptic dopaminergic systems are still unclear. The nigrostriatal neuronal degeneration usually continues to progress in PD patients without DBS. Positron emission tomography (PET) with 11C-Labeled 2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane ([11C]CFT) is a marker for loss of presynaptic dopamine transporters in the striatum in PD. Here we used  [11C]CFT PET in order to evaluate binding to the dopamine transporter in PD patients before and after neurosurgical treatment with STN-DBS.

 

Methods.

10 patients with PD were examined with [11C]CFT-PET pre-operatively (within one month before surgery), and 12 months after surgery. [11C]CFT  binding was evaluated using the region-of interest (ROI) method. ROIs were set bilaterally over the head of the caudate (divided into ventral and dorsal segments at its midpoint), nucleus accumbens, and putamen (divided into anterior-ventral, anterior-dorsal, posterior-ventral, and posterior-dorsal segments at its midpoint).

Results.

There was a significant reduction in postoperative [11C]CFT uptake in the posterior-dorsal putamen contralateral to the clinically more affected side (to 7.4% of the preoperative mean, p<0.05). However, there was significant increase in [11C]CFT uptake in the contralateral anterior-ventral putamen and ipsilateral ventral caudate (to 4.9% and 10.1% of the preoperative mean, respectively, p<0.05). [11C]CFT uptake was also increased in the bilateral nucleus accumbens although it did not reach statistical significance.

 

Conclusions.

Our result showed that STN-DBS increases dopamine transporters in the ventral striatum, which is different from natural course of PD. This result may indicate the compensative and neuroprotective effect of STN-DBS on the presynaptic dopaminergic systems of PD.

 

Takao NOZAKI (Hamamatsu, JAPAN), Kenji SUGIYAKA, Tetsuya ASAKAWA, Hiroki NAMBA, Masamichi YOKOKURA, Tatsuhiro TERADA, Yasuomi OUCHI
15:09 - 15:21 #10297 - OP43 Long-term outcome and post-mortem studies of bilateral pallidotomy performed by Roeder and Orthner from Göttingen in the 1960's.
Long-term outcome and post-mortem studies of bilateral pallidotomy performed by Roeder and Orthner from Göttingen in the 1960's.

Before the advent of levodopa, pallidotomy was the most effective treatment for Parkinson's disease but was soon superseded by thalamotomy. It is widely unknown that, apart from Lars Leksell in Sweden, two neurologists from Göttingen, Hans Orthner and Fritz Roeder, held on to pallidotomy. Using a unique and sophisticated stereotactic technique lesions were individually tailored, and lesion volume was reduced over time. Post-mortem studies demonstrated that eventually true posterior and ventral pallidoansotomy sparing the overwhelming mass of the pallidum was accomplished. During surgery complete alleviation of rigidity was observed as well as associated pain. In 1962, the long-term effects (3 years follow-up on average) of the first 18 out of 36 patients (largest published cohort) with staged bilateral pallidotomies were reported in great detail. In detailed descriptions of each case, long-term improvements of parkinsonian posture, gait, and akinesia (e.g. improved repetitive movements and arm swinging) were reported. Alleviation of tremor was found to require larger lesions than needed for suppression of rigidity. No improvement of speech, drooling or seborrhea was observed. By 1962 the team had operated 13 patients with postencephalitic oculogyric crises with remarkable results (mean follow-up 5 years). They also described alleviation of hyperkinetic disorders (e.g. hemiballism, chorea) with pallidotomy. Surgical mortality and complications (e.g. hemorrhages; inadvertant lesioning of the corticospinal or optic tract; cognitive and behavioural abnormalities) had been remarkably low. In the mid-1980ies, unilateral posteroventral pallidotomy was re-introduced by Laitinen after that long-term complications of levodopa treatment had become evident, but none of the contemporary approaches did reach the same technical sophistication as the Göttingen technique. The intricate history of pallidotomy is incomplete without the appreciation of the achievements of these pioneers who perpetuated pallidotomy against the mainstream of that time, and mastered bilateral and safe pallidal lesioning in an era long before modern imaging was available.

Wolfgang HAMEL (Hamburg, GERMANY), Johannes A KOEPPEN, Dieter MÜLLER, Marwan HARIZ, Christian Ke MOLL, Paul KRACK
15:21 - 15:33 #10092 - OP44 Clinical Outcomes of Asleep versus Awake Deep Brain Stimulation for Parkinson’s Disease.
Clinical Outcomes of Asleep versus Awake Deep Brain Stimulation for Parkinson’s Disease.

Background:  DBS for Parkinson’s Disease, has traditionally been performed awake using microelectrode recording to confirm accurate placement of electrodes.  Newer technologies have allowed DBS to be performed asleep, using intraoperative image guidance to confirm electrode placement without the need of multiple passes into the brain.  

Methods:  DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS using image guidance.  Patients underwent awake DBS by the same surgeon at the same center. Assessments at preoperative baseline and 6-month follow-up included an OFF-levodopa motor UPDRS part II, the PD Questionnaire quality of life scale, motor diaries, the dementia rating scale and speech fluency with the controlled oral word association category fluency and F-A-S  phonemic fluency tests. 

Results:  62 subjects underwent asleep DBS using iCT and 39 subjects underwent awake DBS using MER guidance.  No significant difference was observed in the change of motor UPDRS (14.5±9.9 point improvement in asleep DBS, 17.6±12.3 point improvement in awake DBS, t=1.24, p=0.222) or UPDRS II score (9.3±2.7 point improvement in asleep DBS, 7.4±5.8 point improvement in awake DBS, t=1.75).  Improvement in ON time without dyskinesia was superior in the asleep DBS group (+6.4 hours/day versus +1.7 hours/day, p=0.04).  Quality of life scores significantly improved in both the asleep and awake groups (17.7±15.7 and 8.9 ±11.5 points respectively), with improvement in the total score (p=0.004) and subscores for cognition (p=0.002), communication (p<0.001) and emotional well-being (p=0.03) being superior in asleep DBS.  Speech fluency outcomes were superior in asleep DBS  (category fluency 3.66±11.9 point improvement versus 6.31±9.7 point decline, p<0.001; phonemic fluency 0.18 ±10.6 point improvement versus 5.5 ±9.6 point decline, p=0.023).  The dementia rating scale remained stable without significant change in both the asleep and awake cohorts (p=0.44).  One subject in the awake DBS cohort and two subjects in the asleep DBS cohort had treatment-related adverse events.  

Conclusions:  Asleep DBS for PD with intraoperative imaging guidance improved motor outcomes over 6 months that were on par with or better than awake DBS at our center, and superior with regard to speech fluency and quality of life.   Serious adverse events were uncommon in both groups.  

Kim BURCHIEL (Portland, Oregon, USA), Matthew BRODSKY, Shannon ANDERSON, Chad MURCHISON, Mara SEIER , Jennifer WILHELM, Kitty LEELAAMORNVICHET, Aaron VEDERMAN
15:33 - 15:45 #10361 - OP45 Surgical Revision Rescues Suboptimal Outcomes in Subthalamic Deep Brain Stimulation for Parkinson’s Disease.
Surgical Revision Rescues Suboptimal Outcomes in Subthalamic Deep Brain Stimulation for Parkinson’s Disease.

STN-DBS is a well-established treatment for motor complications in PD. However, there is a significant individual outcome variability. This includes patient/disease related factors and differences in lead placement/DBS programming. It’s important to identify patients with suboptimal outcome after DBS for an intensified reevaluation of programming or lead revision. The levodopa response correlates significantly with the DBS stimulation response and is therefore used as a DBS eligibility criterion. Here we propose to use a ratio between best levodopa and DBS response as a benchmark for individual DBS outcome quality and show that surgical revision can rescue suboptimal outcome, when re-programming is inefficient.

Methods

We investigated 9 PD patients with STN DBS (Øage 63,7 years, ØUPDRS III(off): 54) 6-60 months after implantation. Motor symptoms control (in UPDRS III) by STN-DBS (after median reprogramming time of 60 hours) and Levodopa challenge were assessed after an overnight medication (+1h stim off) washout. The DBS response ratio (DBSrr) was defined as stimulation effect / levodopa response. Surgical revision was considered if the primary electrodes were placed outside the dorsolateral part of the STN (>2mm) in MRI-CT fusion analysis and the DBSrr was <0,7. Surgical techniques included explantation and reimplantation in two or one sessions.

 Results

15 electrodes were revised (6 bilateral, 3 unilateral), six were initially located in the anterio-medial part of STN, one lateral to the STN and four slightly medial (red cylinders, Figure 1). Median vector distance between active contact pre/postrevision was 4.08mm (range 1.6mm–8.42mm). Mean UPDRS III under DBS was significantly improved after revision (38.2±6.6 to 15.5±7.9 points, p<0.001), being even superior to the levodopa effect (15.5±7.9 vs. 27.1±9.7 points, p=0.014). Therefore, the DBSrr was significantly increased from 57% to 132% after revision.

Conclusions

STN-DBS has proved to be a very effective treatment for PD on a group level, but there is an increasing concern about DBS “failures”, in whom postoperative outcomes do not match the preoperative expectations. Our study suggests this patients, can be rescued with surgical replacement to a response similar to the levodopa-induced one, even years after surgery. The computation of the ratio of STN-DBS and levodopa motor improvement might support clinicians managing DBS “failure” cases, anticipating the benchmark of possible improvement after revision.

Robert NICKL (Würzburg, GERMANY), Martin REICH, Nicolo POZZI, Patrick FRICKE, Frank STEIGERWALD, Jonas ROOTHANS, Mattias ÅSTRÖM, Ioannis ISAIAS, Ralf-Ingo ERNESTUS, Jens VOLKMANN, Cordula MATTHIES

14:45-15:45
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OPS09
OPS09 PARALLEL SESSIONS: ORAL PRESENTATIONS

OPS09 PARALLEL SESSIONS: ORAL PRESENTATIONS

Moderator: Cristina TORRES (Madrid, SPAIN)
14:45 - 14:57 #10085 - OP46 Interaction patterns of brain activity across space and frequency in obsessive-compulsive disorder.
Interaction patterns of brain activity across space and frequency in obsessive-compulsive disorder.

Objectives:

    Despite available pharmacological and psychotherapeutic treatments about 10% of obsessive-compulsive disorder (OCD) patients remain severe, treatment-refractory. For some of these patients deep brain stimulation (DBS) offers an appropriate treatment method. In hopes of identifying better treatment options such as DBS, many attempts have been made to clarify pathological brain mechanisms, but neurophysiological measures have not been systematically examined yet. To address this question, the aim of the present study was to search for specific functional correlates cross brain region/frequency interactions in OCD patients.

Methods:

    Routine scalp-EEG (19 electrodes) was recorded in ten OCD patients and ten healthy controls matched for age, while they were at rest with eyes closed. The investigation compares current source density measures of patients with OCD to the control group by using the techniques of low-resolution brain electromagnetic tomography (LORETA; Pascual-Marqui, et al, 1994). We also used the functional independent component analysis (fICA) to examine the interaction patterns of brain activity across region and frequency in the resting state networks by comparing between OCD patients and control subjects (Pascual-Marqui, et al, 2011).

Results:

    The findings of the current source density measure indicated that OCD patients were characterized by significantly higher activities in the following three regions, compared to control subjects. 1) In the delta, theta and alpha bands in the fronto-temporal region, 2) in the alpha and beta bands in the cingulate and 3) in the theta, alpha and beta bands in the nucleus accumbens and the bed nucleus of the stria terminalis (BNST).

    Although both groups of brain utilized the common resting networks, the fICA study showed how the OCD brain used following two resting state networks differently from the healthy control brain. OCD patients have 1) excess left prefrontal (PFC) delta and reduced right PFC delta, and 2) excess left frontal alpha and reduced parieto-occipital alpha.   

Conclusions:

    The nucleus accumbens as well as adjacent nucleus BNST are suggested as feasible targets for DBS in OCD from LORETA current density measures. Although most resting state networks were common to both groups of subjects, two resting state networks (between PFC hemispheres for delta activity, between left frontal and parieto-occipital area for alpha activity) differently used in OCD brain.

Katsushige WATANABE (Tokyo, JAPAN), Yasushi OKAMURA, Hiromi KAMO, Ayako ISOO, Sumito SATO, Makoto TANIGUCHI
14:57 - 15:09 #10565 - OP47 Deep brain stimulation of bed nucleus of stria terminalis in obsessive-compulsive disorder.
Deep brain stimulation of bed nucleus of stria terminalis in obsessive-compulsive disorder.

Background: Deep brain stimulation (DBS) is under investigation for severe obsessive-compulsive disorder (OCD) resistant to other therapies. OCD is a chronic disorder affecting approximately 2 % of the population. The disorder is characterized by persistent obsessive, intrusive thoughts generating anxiety, and related compulsions (tasks or "rituals") with the aim of neutralizing the distress. Up to 10 % of patients with OCD continue to demonstrate severe therapy-refractory symptoms despite trying multiple available treatments. We present here the 12-month follow-up data from 6 patient with severe therapy resistant OCD treated with DBS in the bed nucleus of the stria terminalis (BNST).

Methods: 6 patients with severe OCD who had tried psychotherapy and several different pharmacological treatments with little effect were included in an ongoing study of DBS for OCD. The patients underwent bilateral electrode implantation in the BNST and the stimulation was started immediately after surgery. The patients were evaluated at baseline and at 6 and 12 months after surgery with the Yale-Brown Obsessive-Compulsive Scale (YBOCS) as the primary outcome measure.

Results: Twelve months after surgery the mean YBOCS had improved from 33 to 18 points (46%). Thus, the severity of the OCD had decreased from severe to moderate on average. Similar effects were seen in secondary outcome measures for depression and anxiety. Minor signs of hypomania, reversed with a change of stimulation parameters, were seen in one patient. No serious adverse events occurred. 

Conclusions: The preliminary results from this study of BNST DBS in severe therapy-refractory OCD are promising and in line with previous publications. Nevertheless, DBS for OCD is still an investigational therapy and should therefore be performed in clinical studies driven by multidisciplinary teams.

Matilda NAESSTRÖM (Umeå, SWEDEN), Patric BLOMSTEDT, Marwan HARIZ, Owe BODLUND
15:09 - 15:21 #10234 - OP48 Tau Accumulation and Neurodegeneration in Lobotomized Schizophrenic brains: Neuropathological Study coupled with Diffusion Tensor Imaging.
Tau Accumulation and Neurodegeneration in Lobotomized Schizophrenic brains: Neuropathological Study coupled with Diffusion Tensor Imaging.

【objectives】 Neuropsychiatric disorders can be caused by dysfunction in specific brain circuits. Accordingly, the stereotactic neurosurgical techniques for intractable mental disorders, such as deep brain stimulation, might have effect through modulation of the aberrant circuit and the interest of this field has been rapidly increasing. Although prefrontal lobotomy was performed to treat psychiatric disorders such as severe schizophrenia in the past, such procedure became an obsolete remedy in 1970s. Therefore, the neuroimaging and neuropathological studies in the lobotomized brains have not been systematically made until now. 【methods】 We identified fiber connectivities in the lobotomiized brains using diffusion tensor imaging (DTI). Voxelwise statistical analysis of the fractional anisotropy (FA) data in white matter tracts were carried out to compare between non lobotomized schizophrenic group (n=4), lobotomized schizophrenic group (n=4) and healthy control subject group (n=4). Furthermore, in two lobotomized schizophrenic brains, the sections were stained with hematoxylin-eosin and Kluver-Barrera stains. Immunohistochemistry was performed with the antibodies specific to tau protein. This study was approved by the local ethical committee and ethical aspects have been fully considered. 【results】 In the DTI study, lobotomized schizophrenia group had lower FA in the bilateral white matter of ventromedial prefrontal lobe, forceps minor, forceps major, corpus callosum, nucleus accumbens, cingulate bundle, the medial nucleus of thalamus, the anterior and a part of posterior limb of internal capsule and brainstem. As for histological study, gliosis and neural cell loss were found not only in prefrontal ablated lesion but also in the medial nucleus of thalamus, cingulate gyrus and nucleus accumbens, all of which connect to prefrontal related areas. Tau accumulation was detected in lobotomized prefrontal area and in thalamus or striatum which connect to prefrontal areas, similar to the pattern found in the DTI study. These findings may support the idea that abnormal tau aggregation reflects the afflicted pathways with the secondary degeneration by the surgical impact. 【conclusion】 This study demonstrated that the connectivity sacrificed by lobotomy is largely divergent, which was confirmed by the secondary neurodegeneration in the pathological study. Abnormal tau aggregation may propagate along the pathways with the secondary degeneration in lobotomized brains.

Yasushi OKAMURA (Tokyo, JAPAN), Ito KAWAKAMI, Katsushige WATANABE, Kazuhiro NIIZATO, Kenichi OSHIMA, Kenji IKEDA, Makoto TANIGUCHI, Yoshio HIRAYASU, Masahiko SAITO, Masaaki MATSUSHITA
15:21 - 15:33 #10148 - OP49 Deep Brain Stimulation (DBS) of the Accumbens Nucleus (NA), Ventral Striatum (VE) and Internal Capsule (IC) for medication resistant Obsessive Compulsive Disorder, multicentric prospective study on eight patients.
Deep Brain Stimulation (DBS) of the Accumbens Nucleus (NA), Ventral Striatum (VE) and Internal Capsule (IC) for medication resistant Obsessive Compulsive Disorder, multicentric prospective study on eight patients.

Objective:

Deep brain stimulation (DBS) of the accumbens nucleus (AN), ventral striatum and ventral capsule (VC/VS) region has shown a 50% response in adults with severe treatment-refractory obsessive-compulsive disorder (OCD), no matter which target is used. We sought to improve the effectiveness of DBS, by inserting the electrode along the three targets, so we might change the stimulation site depending on the patient's response.

Materials and Methods: A multicentric prospective study was conducted on eight patients, four from the University Hospital La Princesa,  two from the University Hospital Central de Asturias, and two from University Hospital Fundación Jiménez Díaz. All patients were operated on under the same protocol. Qualitative and quantitative data were collected.

Results:  Out of the 8 patients (mean age 42±9), 7 had a reduction in OCD symptoms, as objectified in an improvement in their YBOCS rates (preoperatory and 6 months follow-up means were 31±7 y 13±9, respectively). Six of them responded with stimulation at the AN (the first area we set for stimulation), while in one patient, stimulation needed to be switched to the ventral capsule to be effective.

Discussion:  These data indicate that DBS was safe and conferred a benefit in reduction in Y-BOCS scores in our series of patients with obsessive-compulsive symptoms. The insertion of the electrode through the three stimulation sites might improve effectiveness to the therapy, although this results need to be confirmed with further studies.

Cristina TORRES (Madrid, SPAIN), Maia Angeles GARCIA PALLERO, Fernando SEIJO, Jesus MUÑIZ, Marta NAVAS, Elena EZQUIAGA, Elisa SEIJO, Juncal SEVILLA, Jesus PASTOR, Pedro GARCIA, Muñiz ISABEL, Vega-Zelaya LORENA, Beatriz LOZANO, Rafael G. SOLA
15:33 - 15:45 #10659 - OP50 Deep brain stimulation for the early treatment of the minimally conscious state and vegetative state.
Deep brain stimulation for the early treatment of the minimally conscious state and vegetative state.

Introduction: An effective treatment of patients in a minimally conscious state (MCS) or vegetative state (VS), caused by hypoxic encephalopathy (HE) or traumatic brain injury (TBI), is not yet available. Deep brain stimulation (DBS) of the thalamic reticular nuclei, as a therapeutic procedure, has been attempted mainly in patients with TBI. 
Methods: Fourteen out of 49 patients were included in this study (4 patients had TBI and 10 patients had HE, 4 being in MCS and 10 patients in VS). The selection criteria for DBS, evaluating status of cerebral cortex and thalamocortical reticular formation, included: neurological evaluation, electrophysiological evaluation and the use of imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI). The target for DBS was the centromedian-parafascicular nucleus (CM-pf) complex. Patient follow-up was between 38 and 60 months. 
Results: Two MCS patients regained consciousness and regained their ability to walk, to speak fluently and live independently. One MCS patient reached the level of consciousness, but currently is still in a wheelchair. One VS patient (after cerebral ischemic lesion) improved to the level of consciousness and currently responds to simple commands. Three VS patients died from respiratory infection, sepsis or cerebrovascular insult, respectively. Other patients remained without substantial improvement of consciousness. 
Conclusion: The spontaneous recovery of MCS/ VS to the level of consciousness with no or minimal need for assistance in everyday life is very rare, therefore if a patient is a candidate according to the above mentioned criteria, DBS could be a treatment option.

Darko CHUDY (Zagreb, CROATIA)

16:15
16:15-17:15
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FP4
FP4 - PARALLEL SESSIONS: FLASH PRESENTATIONS

FP4 - PARALLEL SESSIONS: FLASH PRESENTATIONS

Moderators: Ahmed ALKHANI (Professor and Consultant) (RIYADH, SAUDI ARABIA), Ryoong HUH (PROFESSOR) (Incheon, KOREA)
16:15 - 17:15 #10760 - OF31 Fibre based optical techniques for guidance during stereotactic neurosurgery – a review.
Fibre based optical techniques for guidance during stereotactic neurosurgery – a review.

Introduction

During the last decade the interest for using optical-based techniques for guidance during brain surgery has increased [1]. A review of fibre optical methods applicable in stereotactic neurosurgery is presented.

Methods

Measurement probes and systems have been designed, constructed and evaluated during DBS implantations, stereotactic biopsies and open tumour surgery. The optical fibres along the probe can be connected to laser Doppler flowmetry (LDF) for measurements of microcirculation and tissue greyness [2] to diffuse reflectance spectroscopy (DRS) for estimation of the tissues SO2 [3] and to a fluorescence spectroscopy system for real-time tumour detection after administration of 5-ALA [4].

Results and Conclusions

The LDF-DRS probe acts as a guide during DBS implantations and no other instruments are necessary for creation of the trajectory. It’s forward looking feature make detection of increased blood flow and grey-white matter borders along a trajectory possible during DBS implantations. The fluorescence spectroscopy makes direct indications of tumour tissue possible during the intervention, i.e open surgery and stereotactic biopsies. By combining the various features added values are gained within the same measurement session. The LDF-DRS probe has been used in more than 120 DBS implantations and the fluorescence probes during more than 50 surgeries, about 25 of them together with blue light microscopy and five during stereotactic biopsies. As a next step the LDF-optical guidance method will be combined with microelectrode recording.

References

1.   Wårdell, K., Optical Monitoring Techniques for Navigation during Stereotactic Neurosurgery. Sensors and Materials, 2016. 28(10): p. 1105-1116.

2.   Wårdell, K., S. Hemm-Ode, P. Rejmstad and P. Zsigmond, High-Resolution Laser Doppler Measurements of Microcirculation in the Deep Brain Structures: A Method for Potential Vessel Tracking.    Stereotact Funct Neurosurg, 2016. 94(1): p. 1-9.

3.   Rejmstad, P., P. Zsigmond and K. Wårdell, Oxygen Saturation Estimation in Brain Tissue using Diffuse Reflectance Spectroscopy along Stereotactic Trajectories. Optics Express, 2017. 25, No. 7(7, 8192): p. 1-10.

4.   Richter, J., N. Haj-Hosseini, M. Hallbeck and K. Wårdell, Combination of Hand-Held Probe and Microscopy for Fluorescence Guided Surgery in the Brain Tumor Marginal Zone. Photodiagnosis Photodyn Ther, 2017 (In Press).

Karin WÅRDELL (Linköping, SWEDEN)
16:15 - 17:15 #10768 - OF32 Tractography-based VIM identification for deep brain stimulation: Initial results.
Tractography-based VIM identification for deep brain stimulation: Initial results.

Introduction:

            Stereotactic targeting of ventral intermediate nucleus (VIM) relies on formulaic methods due to the limitations of current imaging sequences. Tractography-based VIM (T-VIM) targeting may address these limitations. We prospectively targeted T-VIM in consecutive patients undergoing deep brain stimulation (DBS) for essential tremor (ET) and tremor-dominant Parkinson’s disease (PD). Here we report the short-term clinical outcomes using this technique.

 

Methodology:

            All patients underwent imaging with structural (3D T1) and diffusion weighted sequences (60 diffusion directions, 2 mm isovoxel). The images were processed using streamline tractography (Stealth Viz, Medtronic Inc.) with a methodology described previously. Besides visualizing T-VIM, this method also localizes the pyramidal tract and medial lemniscus for avoiding off-target side effects. A T-VIM object was overlaid on the DICOM images for stereotactic targeting (Framelink, Medtronic Inc.). The composite tremor scores (for ET - rest, posture, action, handwriting & Archimides spiral and for PD - tremor scores from UPDRS-III, rated on a 5-points scale each) were compared before and after surgery. The T-VIM coordinates, stimulation parameters were also analyzed.

 

Results:

Eight patients (7ET and 1 PD) succesfully underwent T-VIM targeting (n=9 hemispheres). We performed DBS implantations both in awake patients with MER guidance (n=5) and in asleep patients with intraoperative MRI guidance (n=4). T-VIM was more medial (12.5±1.5 vs. 14.3±0.6) and anterior (7.7±1.5 vs. 6.6±0.4 in relation to PC) than the standard coordinates. During a mean follow-up of 5 months (range 2-12 months) tremor improved significantly (treated side: 80.1±17.7%, overall: 58.1±12.8%). Monopolar stimulation was most commonly used at contact 1 with a mean voltage of 2.8±0.9 Volts. Tremor medications were decreased in 4 patients and maintained at baseline in 2 others (2 patients were not on medications at baseline).

 

Conclusion:

            The short-term clinical results are satisfactory in both awake and asleep T-VIM DBS implantatons. Long-term tremor outcomes are being assessed to determine the usefulness of this technique.

Vibhor KRISHNA (Columbus, USA), Aboubakr AMER, Francesco SAMMARTINO, Nicole YOUNG, Punit AGRAWAL, Barbara CHANGIZI, Ali REZAI
16:15 - 17:15 #10655 - OF33 Tailored Deep Brain Stimulation with directional leads for movement disorders: 12 months follow-up of a multicenter series.
Tailored Deep Brain Stimulation with directional leads for movement disorders: 12 months follow-up of a multicenter series.

 

The efficacy of DBS in basal ganglia depends upon the effective stimulation of target nuclei: altogether, it results from a careful anatomical reperage, a refined intraoperative neurophysiology and a scrupulous postoperative reglage. Light errors in surgical positioning, individual anatomy and possible variables in local electrical fields, due to different tissue impedances or fibers versus nuclei stimulation, may impinge upon the efficacy of DBS. Tailoring at best the electric field may overcome some of these constrains. This goal may be reached nowadays, after the developing of segmented directional electrodes, able to configure anisotropic electric fields, as to cover variable tissue volumes, according to clinical clues.

The aim of this investigation is to verify the efficacy of directional leads in patients undergoing DBS for movement disorders of different origin on a 12 months follow-up time.

12 patients (7M-5F, mean age 53 – mean disease duration 9 yrs) suffering from movement disorders (10 PD, 1 Generalized dystonia, 1 cerebellar tremor), underwent DBS (8 Stn, 3 Gpi, 1 RaPl) with stereotactic approach, anatomical reperage in volumetric Mri normalized over S&W atlas and intraoperative multitraces MERs. Intraoperative confirmation of electrode positioning and orientation of the segmented contacts were obtained by means of plain fluoroscopy. Patients were selected after the usual London BB criteria; pre and postoperative clinical evaluation followed validated scores (UPDRS – BFMDRS - TRS). Mean FU is 12 months: for each patient were considered stimulus parameters, electrode configurations and possible adverse events.

11 patients are actually on FU; 1 drop out for infection of the IPG. Active leads are 22; 18 in directional configuration and 4 in “ring” configuration; in all the cases with monopolar stimulation, with two directional contacts, current splitting 25% and 75%, PW 60 microsec, Fr 130 Hz, mean current 2.3 mA, mean voltage 2.2 V. Last FU reported mean decrease of UPDRS III 50%, UPDRS II 70%, BFMDRS 60%, TRS 85%. Mean LEDD decrease 50%. No surgical complications were observed. Collateral effects of stimulation were better managed with directional stimulation; the overall time of the postoperative reglage was non consistently longer than in conventional stimulation mode.

Directional leads allowed us to obtain tailored electric fields in 18 sides out of 22, obtaining clinical effects more consistent than in “ring” mode, particularly for the decrease of stimulation collateral effects. No troubles were observed for the higher impedances typical of these configurations. The follow-up at 12 months confirmed the efficacy of the DBS and only minor modifications to the electrode configurations were required.

Andrea LANDI (Milano, ITALY), David PIRILLO, Massimo PIACENTINO, Giusy GUZZI, Angelo PADOAN, Clarissa CAVANDOLI, Andrea TREZZA, Angelo ANTONINI, Manuela PILLERI, Lorenzo VOLPIN, Erik SGANZERLA, Angelo LAVANO, Domenico D'AVELLA
16:15 - 17:15 #10611 - OF34 DIRECT DBS: A prospective, multi-center clinical study with blinding for a directional Deep Brain Stimulation (DBS) lead.
DIRECT DBS: A prospective, multi-center clinical study with blinding for a directional Deep Brain Stimulation (DBS) lead.

Objective:

Historically, DBS systems have delivered stimulation using leads with cylindrical electrodes, which may stimulate neurons around the entire circumference of the lead. In this study, we test a directional DBS system with leads that include radially segmented electrodes designed for selective stimulation in directions orthogonal to the lead trajectory, in addition to standard cylindrical electrodes. This directional system is also capable of current steering to shape stimulation in the plane orthogonal to the long axis of the lead (directional stimulation), as well as providing Ring Mode (omnidirectional) stimulation equivalent to historical leads. We aim to characterize the effects of directional stimulation in subjects implanted with this system.

Materials:

DIRECT-DBS is a prospective, randomized, multi-center, double-blind study employing a crossover design. Up to a total of 12 subjects will be enrolled and implanted per standard of care with bilateral directional DBS leads (Vercise Cartesia, Boston Scientific) connected to a pulse generator providing an independent current source for each of the 16 contacts. Visits occur in 3 major periods: implant visit, 3-5 months visits, and a 1 year visit. Programming is restricted during the first 3 months post-implant to Ring Mode. At 3 months, multiple single-day programming visits will be undertaken to optimize directional programming. Patients are then randomized to one of two arms (4 weeks per arm) for a double-blind crossover comparison between Ring Mode and unrestricted (e.g. directional) programming. After the crossover phase, subjects enter an open-label phase of the study, with follow-up at 1 year.

Results:

This evaluation has no prospective statistical hypothesis, but collects data such as therapeutic thresholds, side effect thresholds, therapeutic window, UPDRS-III, PDQ-39, and quantitative accelerometer-based measures of bradykinesia and tremor. The preliminary data obtained so far will be reported.

Conclusions:

Preliminary results so far show differences in the clinical responses related to different directional stimulation. Results will inform future studies.

Frank STEIGERWALD (Würzburg, GERMANY), Jens VOLKMANN, Cordula MATTHIES , David BLUM, Leon JUAREZ PAZ, Kenny WYNANTS, Ljubomir MANOLA
16:15 - 17:15 #10563 - OF35 Therapy impedance reflects active contact location and associates with outcome after ANT-DBS in patients with refractoryy epilepsy.
Therapy impedance reflects active contact location and associates with outcome after ANT-DBS in patients with refractoryy epilepsy.

Background: Deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) is an emerging form of adjunctive therapy in focal refractory epilepsy. ANT is encapsulated by incomplete white matter layers and located immediately adjacent to cerebrospinal fluid space which may be reflected to impedance values of implanted DBS leads. Objective: In the present study we asked whether therapeutic impedance values correlate with the location of a given contact and/or patient outcomes. Patients and methods: A total of 16 patients with chronic ANT-DBS for refractory epilepsy comprising 57 contacts and 604 impedance measurements recorded on regular outpatient clinic visits were studied. Contact locations were analyzed in detail using postoperative CT - 3T MRI STIR fusion images previously shown to demonstrate anatomical boundaries of ANT. Results: The contacts in leads implanted using transventricular trajectory (n=21) which were located immediately below the CSF surface showed overall lower and slightly decreasing impedances over time compared to higher and more stable impedances in contacts with deeper parenchymal location implanted either transventricularly (n=3) or extraventricularly (n=6). Impedance values in contacts in ANT (n=35) were significantly lower compared to the outside-ANT (n=19) location (821 ± 170 Ω vs. 1070 ± 146 Ω; p<0,001) or location at the inferior, lateral and posterior border of ANT (998 ± 102 Ω; p<0,001, figure 1A). We found a significant correlation between therapeutic impedance and the distance of contact from CSF surface in leads implanted using transventricular trajectory (r=0.75; R2=0.56, figure 1B). We also found that therapy impedance values were significantly lower (mean 748 ± 176 Ω) in contacts with favorable therapy response (n=25) compared to non-responding contacts (n=29) (mean 988 ± 200 Ω; p<0,001; independent samples t-test, Figure 1C). Finally, we observed a significant correlation between impedance (left and right side averaged) and the reduction of total number of seizures (r=0.60; R2=0.36, Figure 1D). Conclusion: Therapeutic impedance values may be used to select active contact with most optimal location at ANT (between CSF and deeper thalamic structures) with most probable therapeutic effect.

Kai LEHTIMÄKI (Tampere, FINLAND), Timo MÖTTÖNEN, Soila JÄRVENPÄÄ, Joonas HAAPASALO, Timo TÄHTINEN, Hannu ESKOLA, Juha ÖHMAN, Jukka PELTOLA
16:15 - 17:15 #10383 - OF36 Influence of Disease Lateralization in Movement Disorders on Fiber Tracking and Deep Brain Stimulation.
OF36 Influence of Disease Lateralization in Movement Disorders on Fiber Tracking and Deep Brain Stimulation.

Influence of Disease Lateralization in Movement Disorders on Fiber Tracking and Deep Brain Stimulation

Background:

Lateralization is commonly encountered in movement disorders, especially Parkinson’s disease. Besides being an important diagnostic criterion the side of the onset may have implications on the prognosis of the disease. Recent studies have looked at the integration of tractography in Deep Brain Stimulation (DBS) in general and in Parkinson’s disease in particular. Therefore, exploring the lateralization aspects of tractography in movement disorders is an important step for a better understanding of the heterogeneity of tractography results. So far, no study looked at the implications lateralization has on fiber tracking (figure 1). This study focused on the influence of disease and hand dominance on fibers, fractional anisotropy and seed points.

Methods:

Diffusion tensor imaging (DTI) was acquired in 10 DBS candidates with movement disorders. Tractography was carried out in a standardized setting using standard regions of interest and a 75% FA threshold. The number of fibers, seed points and the number of voxels were measured. Statistical analysis was performed using students t-test and for categorical data a fisher’s exact test. A p<= 0.05 was considered significant.

Results:

DTI Datasets of 10 patients (Parkinson’s 7, Dystonia 3). Disease dominance was left in 3 and right in 7 cases. The left disease group had a mean of 7723 (SD 10935) for the left and 784 (SD 524) for the right hemisphere. The right disease group had a mean of 7723 1087 (SD 1012) left and 1858 (SD 1443) right hemisphere. A trend indicates that disease dominance is reflected by the lack of fibers and seed points of the corresponding contralateral hemisphere. Hemisphere dominance of fibers and seeds and their association to disease dominance where statistically significant (fisher’s exact test p= 0.008).

Conclusion:

There is an important correlation of disease dominance and the density of fibers and seed points in movement disorders and especially in Parkinson’s disease. This might be an expression of the degeneration of the striatum and cortical neurons in the more affected hemisphere and corroborates with prior investigations of the motor cortex. The implications of these findings on Deep Brain Stimulation might be multifold, such as optimal positioning of the electrode, side effect thresholds and prediction of outcome.

Lutz WEISE (Halifax, CANADA), Ron HILL, Johanna QUICK, Andrea HEBB, Matthias SCHMIDT
16:15 - 17:15 #10582 - OF37 IDENTIFYING POSTOPERATIVE STRUCTURAL MRI BIOMARKERS OF SEIZURE FREEDOM AFTER TEMPORAL LOBE EPILEPSY SURGERY.
IDENTIFYING POSTOPERATIVE STRUCTURAL MRI BIOMARKERS OF SEIZURE FREEDOM AFTER TEMPORAL LOBE EPILEPSY SURGERY.

Objectives: It is difficult to reliably predict durable treatment response following surgery for temporal lobe epilepsy (TLE). We hypothesized that limbic structural change after surgery could be a potential biomarker of seizure control and neuropsychological outcomes in TLE. Consequently, we characterized limbic structural change in the days, weeks, months and years after TLE surgery using anatomical and diffusion tensor imaging (DTI) MRI.

Methods: Pre- and post-operative (mean 4.3 ± 3 years post-surgery) 1.5-T T1-weighted and DTI MRI were obtained in 26 surgical TLE patients. Ten patients were also scanned on post-operative days 1, 2, 3, 6, 60, 120 & > 360. Blinded, manual volumetry of the contralateral hippocampus (cHC), fornix (FO) and mammillary bodies (MB) was performed. cHC mean diffusivity (MD) and fractional anisotropy (FA) were also measured. Imaging metrics were correlated with seizure outcome (at 5 ± 4 years) and neuropsychology (at 2 ± 2 years).

Results: There was significant postoperative bilateral atrophy of the FO (38% ipsilateral, p < 0.0001; 13% contralateral, p < 0.001), MB (38%; p < 0.001) and cHC (12%, p < 0.001)(Fig 1A-C). cHC volume loss was significant within the first week after surgery while atrophy of the FO and MB was not evident until 1 year. There was significant postoperative recovery of cHC MD (preop: 960 ± 50, postop: 990 ± 70 µmm2/s; p=0.008) and decline in FA (preop: 0.18 ± 0.02, postop: 0.16 ± 0.02; p < 0.001; Fig 1E-F) in contrast to age-matched healthy controls. cHC volume loss was significantly more pronounced in patients with ongoing disabling seizures (Engel > 1, n = 6; p = 0.048; Fig 1D). Postoperative neuropsychological testing revealed significant improvement in figural memory performance in dominant hemisphere resections (p = 0.02) with no observed correlation to limbic structural measures.

Conclusion: Significant postoperative, contralateral limbic macro- and micro-structural changes occur after TLE surgery. Taken together, these findings suggest deafferentation resulting in a removal of tonic subclinical transsynaptic forniceal commissural excitatory input from the circuit. Postoperative recovery of cHC diffusivity may be due to resolution of preoperative cytotoxic edema. cHC atrophy may represent an early biomarker of TLE surgery failure, requiring prospective evaluation in future work. 

Cameron ELLIOTT (Edmonton, CANADA), Donald GROSS, B Matt WHEATLEY, Christian BEAULIEU, Tejas SANKAR
16:15 - 17:15 #10579 - OF38 Focal MRI findings as a positive predictor factor for good outcome in a large series of resective epilepsy surgery procedures.
Focal MRI findings as a positive predictor factor for good outcome in a large series of resective epilepsy surgery procedures.

Rationale: The introduction of MRI in clinical practice 25 years ago changed the epilepsy surgery landscape considerably. Scalp and invasive neurophysiology are still part of a comprehensive workup of refractory epilepsy patients, but the relevance of standalone MRI anatomical findings in defining outcome related to seizures has been evaluated over the years. We compared the outcome of MRI positive or negative refractory epilepsy patients submitted to resective procedures in a large single-center series.

 

Methods: One thousand five hundred and eighty-six patients were studied. One thousand and sixteen patients (160 with normal MRI; 16%) had temporal lobe epilepsy, 233 (46 with normal MRI; 20%) had frontal lobe epilepsy, 77 (40 with normal MRI; 52%) had Rolandic epilepsy, 120 (no patient with normal MRI) had hemispheric pathology, 79 (11 with normal MRI; 14%) had posterior quadrant epilepsy, 31 (11 with normal MRI; 35%) had parietal epilepsy, 21 (4 with normal MRI; 19%) had occipital epilepsy, and 9 (2 with normal MRI; 12%) had insular epilepsy. Eighty-six percent of the patients with normal MRI were submitted to invasive recordings.

 

Results: Outcome regarding seizures could be summarized as follows (type of resection: seizure freedom in positive MRI patients %/seizure freedom in negative MRI patients %):

Temporal resections: 86-67; frontal resections: 92-66; Rolandic resections: 94-60; posterior quadrant resections: 91-77; parietal resections: 89-80; occipital resections: 85-81 and insular resections: 85-50. Patients who received temporal, frontal, Rolandic, posterior quadrant and parietal and were MRI positive had a significantly better outcome. There was no significant difference in patients submitted to occipital lobe resection or insular (small number) resection.

 

Discussion: MRI was a good positive outcome predictor in a large  epilepsy surgery, irrespective to any other clinical findings. Patients submitted to hemispherectomy always had a positive MRI; patients with Rolandic epilepsy were more prone to disclose no lesion on MRI. Results in normal MRI patients were systematically poorer compared to those obtained in MRI positive patients, but consistently efficacious compared to medical therapy in this carefully selected series of refractory epilepsy patients. Invasive recordings are likely to be part of the work-up of patients with refractory epilepsy and normal MRI. Conversely, invasive neurophysiology is unlikely to be needed in positive MRI patients.

Arthur CUKIERT, Cristine CUKIERT (São Paulo, BRAZIL), Jose BURATTINI, Pedro MARIANI
16:15 - 17:15 #10416 - OF39 Behavior of post-radiosurgery tumor progression and treatment with magnetic resonance guided laser induced thermal therapy.
OF39 Behavior of post-radiosurgery tumor progression and treatment with magnetic resonance guided laser induced thermal therapy.

Objective: Recurrence or progression after maximal radiation therapy for brain metastasis is a well-known problem. At our institution, magnetic resonance-guided laser induced thermal therapy (MRgLITT) is used for the treatment of progressive in-field recurrences, regardless of the underlying physiology. We analyze the volumetric trends from the time of radiosurgery to laser ablation to understand the behavior of progression prior to laser therapy.  

 

Methods: A retrospective review of patients who underwent MRgLITT for treatment of post GammaKnife (GKS) recurrent metastatic tumors between November 2010 and October 2016 was performed. Lesion volumes were calculated using OsiriX Software. Volumetric trends were obtained by plotting individual lesion volumes from the nadir volume after radiosurgery to volume at laser ablation. The majority of tumors followed an exponential growth pattern (n=23), while a smaller number followed a linear trend (n=11). Here, we examine the major exponential growth pattern by inverting a three-parameter exponential decay curve fit and applying it to the recurrence data. Parameters derived from the exponential decay function, f=y0+abx, were used to identify the asymptote or nadir volume and to calculate a doubling factor for the rate of tumor growth.

 

Results: A total of 23 post-radiation recurrent lesions in 20 patients followed a non-linear exponential growth after GKS and were treated using MRgLITT. At an average of 299 days before laser ablation, the average nadir volume was 0.28 cm3 (SEM=0.07) with average absolute difference from the nadir regression estimate being 0.08 cm3 (SEM= 0.02). The mean volume at ablation was 2.83 cm3 (SEM= 0.45) with a mean absolute difference of 0.14 cm3 (SEM= 0.06) from the end volume regression estimate. The average adjusted coefficient of determination, adj. r2, was 0.93 (SEM= 0.014). The mean value for the half-life or doubling factor for tumor growth was 75.46 days (SEM= 14.87).

 

Conclusions: The three- parameter exponential decay regression is an accurate representation of tumor progression behavior following radiation. The regression estimates may predict tumor volume at a given time from nadir volume to pre-ablation end volume. These preliminary results, most importantly the doubling factor, can be valuable in future cases to predict tumor growth and determine an optimal time window when MRgLITT can be used to ablate progressive in-field recurrences following prior GKS treatment.

Purvee PATEL, Eric HARGREAVES, Shabbar DANISH (New Brunswick, USA)
16:15 - 17:15 #9883 - OF41 Is complete tumor ablation required for optimal tumor control? The effect of the extent of ablation on the rate of recurrence in MgLITT in the treatment of recurrent cerebral metastatic disease.
Is complete tumor ablation required for optimal tumor control? The effect of the extent of ablation on the rate of recurrence in MgLITT in the treatment of recurrent cerebral metastatic disease.

Introduction:

Targeting ablation to superficial or deep seated tumors, Magnetic resonance guided laser induced thermal therapy (MgLITT) provides a safe and minimally invasive alternative to open surgery and radiosurgery in the management of recurrent cerebral metastatic disease. It still remains to be determined what proportion of recurrent tumor must be ablated to provide optimal local control. In our series, we evaluated the effect of percentage of ablation and residual tumor volume on the rate of recurrence in MgLITT treated recurrent cerebral metastatic disease.

Methods:

46 tumors in 38 patients were treated with the Visualase Thermal Therapy System. One patient had three tumors treated at once and two patients had two tumors treated at once. Five patients were treated again for the same or different tumor at a later date. Volumetric analysis was performed, and the effect of percentage volume ablated (PVA) and residual tumor volume (RTV) on the rate of local recurrence was determined using a two tailed t-test with unequal variance.  

Results:

There were eight total recurrences in 46 tumors. The average PVA was 96.36 +/- 7.59% in the non-recurrent and 81.89 +/- 18.10% in the recurrent groups . The average RTV was 0.21 +/- 0.51 cm3 in the non-recurrent and 0.92 +/- 1.17 cm3 in the recurrent groups. The volume of residual tumor did not have an effect on recurrence (p=0.136). The PVA did approach significance (p=0.059).

Conclusions:

Through using RTV and PVA, we determined that it is not critical to ablate the entire tumor volume of a recurrent metastatic tumor to provide optimal local control. Furthermore, leaving residual tumor may be a safer and yet, still effective treatment strategy for tumors located near eloquent or critical structures. Subtotal ablation from MgLITT may have a role in the management of recurrent cerebral metastatic disease.

Mohammed IQBAL, Shabbar DANISH (New Brunswick, USA)

16:15-17:15
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FP5
FP5 - PARALLEL SESSIONS: FLASH PRESENTATIONS

FP5 - PARALLEL SESSIONS: FLASH PRESENTATIONS

Moderators: Jairo ESPINOSA (CEO) (Bogotà, COLOMBIA), Sameer SHETH (Associate Professor of Neurosurgery) (Houston, USA)
16:15 - 17:15 #10740 - OF40 Evolution of Stereotactic Targeting in Anterior Capsulotomy and Deep Brain Stimulation for Treatment Refractory Obsessive-Compulsive Disorder: A Systematic Review.
Evolution of Stereotactic Targeting in Anterior Capsulotomy and Deep Brain Stimulation for Treatment Refractory Obsessive-Compulsive Disorder: A Systematic Review.

Objective: The anterior limb of the internal capsule (ALIC) is an established target for anterior capsulotomy and deep brain stimulation (DBS) for the treatment of refractory obsessive-compulsive disorder (OCD). Although the DBS target was initially based on the capsulotomy experience, both targets have diverged over time. We performed a systematic review to evaluate the evolution of stereotactic targeting for capsulotomy and DBS in OCD, with the goal of better understanding the underlying neuro-circuitry of OCD.

Methods: We identified studies reporting stereotactic coordinates for anterior capsulotomy (stereotactic radiosurgery [SRS] or radiofrequency [RF]) or DBS for OCD. Stereotactic coordinates were plotted onto a standard Montreal Neurologic Institute (MNI) brain to trend target evolution over time.

Results: There were 7 anterior capsulotomy studies (3 RF, 3 SRS, 1 RF+SRS) and 10 DBS studies. We found that both the capsulotomy and DBS targets have moved more ventrally, medially, and posteriorly from their earliest coordinates, but to different degrees (Figure). The average capsulotomy target in recent years was 14 mm lateral to midline, 10 mm anterior to the posterior border of the anterior commissure (AC), and 3 mm above the intercommissural line. The average DBS electrode tip target in recent years was 9 mm lateral to midline, 5 mm anterior to the posterior border of the AC, and 3 mm inferior to the intercommissural line. 

Conclusions: These results show that both targets have moved ventral, medial, and posterior to the original lesion target, but to different degrees, with greater excursion for the DBS target. Further work using connectivity analyses will shed light on the physiological significance of this difference. A better understanding of this difference and its effect on patient outcomes will advance our knowledge of the underlying circuit-level pathophysiology of OCD.

Justin OH (New York, USA), Yagna PATHAK, Pranav NANDA, Garrett BANKS, Sameer SHETH
16:15 - 17:15 #10811 - OF42 Frequency and Characterization of Speech Problems following DBS from the Product Surveillance Registry.
Frequency and Characterization of Speech Problems following DBS from the Product Surveillance Registry.

Background:  There has been a relatively high frequency of dysarthria and speech disorders reported to occur after DBS, and often attributed to current spread to adjacent internal capsule/corticobulbar fibers. In order to address the reversible nature of these speech disorders, we characterized the rate of speech problems across DBS indications, unilateral or bilateral placement, lead location and time to resolution as documented in the Product Surveillance Registry (PSR). The PSR tracks data in real-world clinical environments to provide insights in how the therapy is utilized while collecting product and safety information on DBS systems. 

Methods: Data was analyzed on 2109 patients registered from July 2009-2016 from 36 centers located in three continents. Speech problems were defined as dysarthria, speech disorder, or device stimulation issue (adverse event related to speech).

Results: A total of 41 events in 37 patients have been reported to date, resulting in a patient occurrence rate of 1.8% (37/2109). In the PSR, speech-related events which quickly resolved through reprogramming, especially during the initial optimization period may not be reported and may account for the relatively low rate.  Thirty-one of the 37 patients with speech events had complete lead location information available.    Of these patients, based on the anatomical lead location, the rate of speech disorder events in GPI, STN, and VIM were 1.2% (3/243), 2.0% (18/910), and 2.6% (10/391), respectively (table 1).  For bilateral VIM the rate was 3.3% (10/304) and 0% (0/87) in unilateral VIM. Importantly, the majority of speech related events (n=28) resolved over an average of 3.3 months, and unresolved or ongoing speech disorders (n=13) lasted a mean of 19.9 months to date (table 2).

Conclusions: Results from the PSR suggest that dysarthria and speech disorder events are an infrequent event, and are more common with bilateral implants of the VIM but most of them resolve within three months post implant. Further studies may be warranted to further elucidate and characterize these types of events.

Mya SCHIESS (Houston, USA), Steven FALOWSKI, George PLOTKIN, Stephane PALFI, Thomas WITT, Emmanuel CUNY, Tom THEYS, Kenneth MARTINEZ, Robert PLUNKETT, Yesin TEMEL, Gayle JOHNSON, Todd WEAVER, Joachim K. KRAUSS, Peter KONRAD
16:15 - 17:15 #10096 - OF43 Cervical and high-thoracic dorsal root ganglion stimulation (DRG) in chronic pain.
Cervical and high-thoracic dorsal root ganglion stimulation (DRG) in chronic pain.

Introduction

Dorsal root ganglion stimulation is a promising new technique in chronic pain states of different origin. Commonly used in the lumbar region, DRG can be used in the upper thoracic and cervical region with slight alterations of the surgical approach. Data on outcome and complications rates of DRG in this region are limited.

Methods

We report on a consecutive series of 11 patients treated with DRG stimulation (Spinal Modulation®) in the upper thoracic and cervical region. All patients suffered from chronic pain due to peripheral nerve or brachial plexus injuries, spinal cord surgery, post-herpetic neuralgia or CRPS II. All patients were trialed with externalized electrodes for 3-7 days; a successful trial was defined as at least 50% pain reduction. 

Results 

Out of all 11 patients trialed, 9 were successfully trialed and implanted with a permanent stimulation system. All but one patient (suffering from post-herpetic neuralgia) reported permanent clinical significant pain reduction (VAS reduction from mean 8.1 to 2.3). Loss of treatment effect requiring reprogramming was commonly observed during the first few month of treatment. In one patient a transient paresis of the arm and hand was observed immediately following electrode implantation. 

Conclusion

Cervical and upper thoracic DRG stimulation is feasible and resulted in good overall response rates to trialing and excellent long-term pain relief in primary responders. A modified approach has to be used when compared with lumbar DRG electrode placement. Surgery itself in this region is more complication prone and challenging. Best results were seen in patients with brachial plexus and peripheral nerve injuries.

Philipp SLOTTY (Düsseldorf, GERMANY), Stefan SCHU, Jarek MACIACZYK, Jan VESPER
16:15 - 17:15 #10449 - OF44 Stereotactic thalamotomy and contralateral pallidotomy for Parkinson’s disease.
Stereotactic thalamotomy and contralateral pallidotomy for Parkinson’s disease.

OBJECTIVES. Parkinson’s disease (PD) is one of the most widespread progressive neurodegenerative diseases, which in most cases has bilateral clinical signs. The application of ablative surgical procedures remains important in the treatment of movement disorders in view of economical, geographical and some other reasons. The purpose of the study is to evaluate the effectiveness of bilateral stereotactic lesion procedures for PD.

 

METHODS. From 2011 to 2017 in Romodanov Neurosurgery Institute 473 patients with PD underwent ablative stereotactic interventions, among them 26 patients (15 males and 11 females) underwent stereotactic thalamotomy and contralateral pallidotomy. At the time of the first surgery patient’s age ranged from 42 to 71 years (mean 56.6 years). Surgery performed on CRW stereotactic system. Intraoperative macrostimulation was used to delineate the optimal target location. Postoperative follow-up was from 6 months to 5,5 years (mean 2.6 years).

 

RESULTS. The mean duration of disease before first surgery was 7.3 years. Term between two interventions ranged from 1.1 to 7.5 years (mean 2.7 years). Before first treatment 19 from 26 pts (73.1%) used L-dopa therapy from 3 to 21 years (mean 4.7 years) and 10 (38.5%) of them had motor fluctuations and or levodopa-induced dyskinesia.

In 1 year after the second intervention UPDRS score improved by 48% in ON period and by 44% in OFF period. Regression of tremor observed in 21 (80.8%) patients, rigidity - in 24 (92.3%), bradikinesia - in 16 (61.5%) patients. Levodopa-induced dyskinesia stopped in all five patients who had it before treatment. The dose of levodopa decreased in average on 32% - from 756.8±204.6 mg/day to 514.8 mg/day. After treatment Schwab and England score increased from to 54% to 71%. Complications after treatment observed in 4 (15.4%) cases among them in 3 (12%) cases neurological deficit was temporal and in 1 (4%) case was permanent.

 

CONCLUSION. Our results demonstrate that bilateral ablative surgery is effective and safe method of treatment for PD. Such treatment improves overall motor function, increased patient’s mobility, daily living activities and improves quality of life. Bilateral lesion interventions allow to reduce levodopa dose, providing them with increased freedom from a complex medication regimen. Careful identification and selection of patients for ablative surgery allows to achieve optimal results in the treatment of PD.

Kostiantyn KOSTIUK (Kyiv, UKRAINE), Yuri MEDVEDEV, Andriy POPOV, Maxim SHEVELOV, Varelii CHEBURAKHIN, Nazar VASYLIV, Victor LOMADZE, Sergii DICHKO
16:15 - 17:15 #10442 - OF45 Visualization and computer-assisted classification of the microelectrode recording data in real time during STN DBS surgery.
Visualization and computer-assisted classification of the microelectrode recording data in real time during STN DBS surgery.

Introduction

Intraoperative microelectrode recording (MER) helps to define the limits of the subthalamic nucleus (STN) and is a standard procedure for deep brain stimulation (DBS) in patients with Parkinson’s. The MER evaluation of the STN is usually done by acoustic and visual analysis of the curves (raw data). In this study we use computer-learning and spectral analysis of multiunit activity (MUA) to find the electrophysiological borders of STN and to visualize the obtained 3D data in individual MRI space, in real-time during DBS surgery.

Patients and methods

The STN DBS surgery with real-time automatic STN Mapping and visualization was performed as awake-surgery in 3 Parkinson’s patients. The stereotactic MRT and CT data with the stereotactic plan calculated in Surgiplan Software (Elekta, Sweden) were coregistered and displayed three-dimensionally in a newly developed Brainviz visualization software. Intraoperatively, the MER data were recorded via microelectrodes and MER device (FA Inomed, Emmendingen). Recordings were made from 3 parallel trajectories per implantation side in 1 mm steps. The raw data were passed in real time to the high performance visualization station via a network connection, where the data were spectrally analyzed and classified using a neural network algorithm (perceptron). The results of the spectral analysis and classification were color coded and visualized on the planned implantation trajectories according to recording depths immediately after each recording step. The results were compared with conventional MER analysis.

Results

Results of data analysis and visualization provided a realistic representation of the target area, which was consistent with clinical stimulation effects and the assessment of the surgical team. The definition of STN / SNR transition was not clear in spectral MUA analysis in 2 of 3 cases, but computer learning classification provided plausible results. The application of the procedure did not lead to an extension of the operating time.

Conclusion

The use of spectral analysis, computer learning and multimodal visualization in real time is able to support the intraoperative determination of the STN target area. Whether this will increase the safety in DBS surgery and save decision time required for traditional MER analysis will be examined in further studies.

Yaroslav PARPALEY (Dortmund, GERMANY), Manuel MACHADO LEMOS RODRIGUES, Sabine SKODDA, Andre WASCHK, Jens KRÜGER
16:15 - 17:15 #10296 - OF46 Early results of DBS Vs Lesioning in Parkinsons disease in Nepal.
Early results of DBS Vs Lesioning in Parkinsons disease in Nepal.

Introduction

Surgical treatment of Parkinsons disease (PD) is already an established mode of treatment. Both Deep brain stimulation and Lesioning (pallidotomy) surgeries may be used in PD.

Methods

All the patients who underwent either DBS or lesioning for idiopathic Parkinsons disease in Annapurna Neurological institute and Allied Sciences from 2014 to till date were included in this study. The demographics and their clinical status were measured in terms of Unified Parkinsons Disease Rating Score(UPDRS). The preoperative and postoperative UPDRS score was compared and analysed. All surgeries were done in awake state except for IPG(implantable pulse generator) implantation which was done under general anesthesia. The standard functional coordinates for STN and GPi was used. We used ZD Fisher Frame with its software and rechecked the targets with inbuilt Shaltenbrant Atlas. Intraoperative MER recording(inmito) was also done in these cases. For DBS we used Brio rechargeable system with 10 years battery life. For lesioning we either used Cosman RF generator with 1mm diameter nad 2 mm exposed tips. The decision for DBS and lesioning was based on patients preference and affordability. In cases of Pallidotomy we used staged lesioning with at least three months gap in most of the cases.

Results

There were total of fourteen cases out of which 7 cases were DBS and 7 cases were that of lesioning. There were total of 9 male and 5 female patients. The mean age of patients in DBS was 54 years and in Lesioning was 53 years(p value>0.05). The mean preoperative UPDRS in DBS was 61 and in lesioning was 63 . Mean postoperative UPDRS was 22 in DBS group and 16 in lesioning group(p value<0.05). Mean change in UPDRS in DBS 65% and was 71% in lesioning was   (p value = 0.47).One patients of DBS developed postoperative hematoma which had to evacuated but eventually recovered. One patient of pallidotomy developed Parkinsons crisis and and it took us almost one month for his recovery. Otherwise there were no other procedure related complications

Conclusion

Though DBS is more popular than lesioning nowadays, our results show that there is no significant difference in improvements in terms of UPDRS score. We still believe that lesioning has a definite place in PD and it is cheaper and does not require time consuming battery adjustment. We believe that in context of developing country like Nepal lesioning may surpass DBS in long term.

Basant PANT (Kathmandu, NEPAL)
16:15 - 17:15 #10226 - OF47 Improved atypical tremor control after DBS directly targeting the dentatorubrothalamic tract.
Improved atypical tremor control after DBS directly targeting the dentatorubrothalamic tract.

Background: Atypical tremors secondary to a subcortical insult are ataxic and characterized as irregular, coarse, high amplitude movements affecting the proximal and distal limb present at rest, posture and/or with intention.  Direct targeting of the dentato-rubro-thalamic tract (DRTt) has been suggested to be efficacious in deep brain stimulation (DBS) for tremor suppression (Coenen et al., 2011; Fenoy et al., 2017); we analyzed outcomes after such use in atypical tremor patients.

Methods: 6 consecutively enrolled atypical tremor patients obtained pre-operative MRI with diffusion tensor (dTi) sequences. Mean baseline tremor amplitude based on The Essential Tremor Rating Assessment Scale (TETRAS) was recorded. The DRTt was drawn for each individual on StealthViz software (Medtronic) using the dentate nucleus as the seed region and the ipsilateral pre-central gyrus as the end region and then directly targeted during surgery. Intraoperative testing confirmed improved tremor control. Post-operative analysis of electrode position relative to the DRTt was performed, as was assessment of tremor improvement.

Results: Patient demographics are shown in Table 1. Mean voltage used was 3.5 V. Mean distance from the center of the active electrode contact to the DRTt was 0.5 mm. Improvement in arm tremor amplitude from baseline after DBS was significant (p<0.005).

Conclusion: Direct targeting of the DRTt in DBS is an effective strategy for tremor improvement in patients with atypical tremor.  

Albert FENOY (Houston, USA), Mya SCHIESS
16:15 - 17:15 #10329 - OF48 Target-specific deep brain stimulation of the ventral capsule/ventral striatum for the treatment of intractable obsessive-compulsive disorder.
Target-specific deep brain stimulation of the ventral capsule/ventral striatum for the treatment of intractable obsessive-compulsive disorder.

Deep brain stimulation (DBS) is a procedure that is widely used for the treatment of movement disorders. The United States Food and Drug Administration has granted limited approval, i.e., Humanitarian Device Exemption, for the use of DBS in adults with treatment-resistant obsessive-compulsive disorder (OCD). Although DBS is approved in the U.S. and Europe, and this technology has demonstrated effectiveness in patients with difficult-to-treat OCD, the application of DBS in OCD has not yet been reported in China. Here, we report target-specific use of DBS, using a SceneRay 1242 electrode, on the ventral capsule/ventral striatum (VC/VS) in a case of refractory OCD. The SceneRay 1242 (SceneRay, SuZhou, China) electrode with a diameter of 1.27 mm containing 4 contacts was used (Figure 1). This novel electrode shares common technology with the Medtronic device, but allows for simultaneous and independently programmed stimulation of the nucleus accumbens and the anterior limb of the internal capsule. The contact length is 3.0 mm and the spacings between the ventral and dorsal contacts are 2 mm, 4 mm, and 4 mm, respectively, covering a total length of 22.5 mm (3 + 2 + 3 + 4 + 3 + 4 + 3 mm, with 0.5 mm projecting from the electrode tip). These electrodes were designed to enable simultaneous implantation in the nucleus accumbens (NAc) and the anterior limb of the internal capsule (ALIC), with 2 ventral contacts located in the ventral NAc and 2 dorsal contacts located in the ALIC. The 2 ventral and 2 dorsal contacts can be programmed with different stimulation parameters, i.e., voltage, pulse width, and frequency. Our experience suggests that such target-specific DBS in VC/VS is effective for refractory OCD, which is concurrent with its approved indication. Increased impulsivity could be redressed in this patient by reducing the amplitude of the stimulation. Further studies are required to determine whether this treatment is superior to the use of traditional electrodes and to determine the exact mechanisms by which these changes occurred.

Keywords: anxiety, compulsion, electrode, obsession, psychosurgery, neuromodulation 

Chencheng ZHANG (Shanghai, CHINA)
16:15 - 17:15 #10217 - OF49 INTREPID trial: a prospective, double blinded, multi-center randomized controlled trial evaluating Deep Brain Stimulation with a new multiple-source, constant-current rechargeable system in Parkinson’s disease.
INTREPID trial: a prospective, double blinded, multi-center randomized controlled trial evaluating Deep Brain Stimulation with a new multiple-source, constant-current rechargeable system in Parkinson’s disease.

 Objective

The objective of the INTREPID clinical trial is to assess the improvement in motor function and quality of life in patients with advanced, levodopa-responsive Parkinson's disease (PD) following bilateral subthalamic nucleus Deep Brain Stimulation (DBS) using a new device capable of multiple current sources that provides selective activation of individual contacts on the DBS lead. DBS is a surgical therapy used for treatment of the motor signs and fluctuations associated with Parkinson’s disease (PD). Its efficacy has been substantiated by several randomized controlled trials. Moreover, motor improvement following DBS may be sustained for up to 10 years (Castrioto et al. 2011).

Methods

INTREPID is a multi-center, prospective, double blinded, randomized controlled trial (RCT) sponsored by Boston Scientific Corporation. Subjects with advanced PD were implanted bilaterally in the subthalamic nucleus (STN) with a multiple-source constant current DBS System (Vercise, Boston Scientific). Subjects were randomized to either receive active vs. control settings for a 12 week blinded period. Subjects were blinded to their treatment assignment and study assessments were administered by a clinician blinded to the treatment condition; thus maintaining the double blind in the study. Following completion of a 12-week blinded period, all subjects were programmed to receive best therapeutic settings in the open label period. Motor improvement was evaluated using several assessments including subject motor diaries, UPDRS scores, etc. Assessments for quality of life such as the PDQ-39, SF-36, and functional independence, Schwab and England, were also administered. Adverse events were recorded.

Results

The INTREPID trial is currently ongoing at over 20 centers in the US. The accompanying report provides the study design, demographics, and other preliminary data.

Conclusions

INTREPID is the first US double-blinded RCT of a multiple-source, constant-current rechargeable system in PD.

Jerrold VITEK (Minneapolis, USA), Philip A. STARR, Roshini JAIN
16:15 - 17:15 #10527 - OF50 The cerebello-thalamo-cortical network as the putative target in diffusion tensor imaging tractography - assisted DBS for tremor: an observational case series.
The cerebello-thalamo-cortical network as the putative target in diffusion tensor imaging tractography - assisted DBS for tremor: an observational case series.

Introduction: Deep brain stimulation (DBS) alleviates tremor of various origin. We report the results of an uncontrolled case series of patients with refractory tremor who underwent Diffusion Tensor Imaging fiber tractography (DTI FT) - assisted DBS of the dentato-rubro-thalamic tract (DRT).

Methods: 36 patients (64 +/- 13.6 years, 17 female) were enrolled (Essential Tremor (17), Parkinson’s tremor (8), Encephalitis disseminate (7), dystonic head tremor (3), tardive dystonia (1)) and received 60 DBS electrodes. Preoperatively, diffusion tensor magnetic resonance imaging sequences were acquired together with high-resolution anatomical T1W and T2W sequences. The DRT was individually tracked with deterministic tractography (StealthViz DTI, MEdtronic USA) and used as a direct target. Stereotactic surgery was performed with a Leksell G-Frame (Elekta, Sweden) with the patients awake. Electrodes were lowered into the target region via Microdrive (FHC, USA) in 2mm steps typically starting 10 mm above target. Intraoperative tremor reduction was graded on a 4-point scale (0=no tremor reduction, 3=full tremor control) and recorded together with the current amplitude, respectively (0.5-4 mA, 150Hz, 100us, lesion generator, Cosman, USA). 241 stimulation points were analyzed in this cohort in the planning system (MCP coordinates of stimulation points, closest distances to DRT border and center were recorded). The relation of the current amplitude needed to reduce tremor was expressed as TiCR (tremor improvement to current ratio = Ti /I [1/mA]).

Results: TiCR values increase significantly in proximity to the DRT (* p<0.001). The TiCR is a new efficiency measure for tremor control and appears to be interesting in the definition of optimal stimulation points. A total of 51 out of 60 finally implanted DBS electrodes were positioned on the planned trajectory (85%) and 68 trajectories were tested in 60 electrode placements (1.13 trajectories tested per implanted DBS electrode).

Discussion: The DRT is a fiber bundle that shows tremor-reducing effects when modulated with the DBS technology. Tremor signals can sufficiently be perturbed at different points in the system (above and below the MCP plane). Tractography techniques can be used to directly visualize the DRT and therefore optimize target definition in individual patients. The TiCR is a newly introduced measure to define the efficiency of stimulation and by that to identify an optimal stimulation point.

Volker Arnd COENEN (Freiburg, GERMANY), Thomas PROKOP, Bastian SAJONZ, Niels ALLERT, Burkhard MAEDLER, Horst URBACH, Peter Christoph REINACHER

16:15-17:15
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FP6
FP6 - PARALLEL SESSIONS: FLASH PRESENTATIONS

FP6 - PARALLEL SESSIONS: FLASH PRESENTATIONS

Moderators: Jung-Tung LIU (Taipei, TAIWAN), Andre MACHADO (Chairman) (Cleveland, USA)
16:15 - 17:15 #10621 - OF51 Microsurgical re-decompression for recurrent trigeminal neuralgia after microvascular decompression.
Microsurgical re-decompression for recurrent trigeminal neuralgia after microvascular decompression.

Objective: Microvascular decompression (MVD) is a well-accepted treatment option for trigeminus neuralgia (TN). The initial success rate is high, however,in a subset of patients TN might recur in the longterm. Recurrent TN after MVD might be due to several reasons and treatment algorithms remain unclear. Here, we present the surgical findings and clinical outcome of patients with recurrent TN after MVD who underwent another microsurgical decompression procedure.

Methods: Twenty-four patients with recurrent TN underwent microsurgical re-decompression over a period of 10 years. Patients with multiple sclerosis were excluded. All patients had magnetic resonance imaging before surgery.  Microsurgical re-decompression included meticulous preparation of the previously inserted Teflon and scar tissue avoiding any damage to the trigeminal nerve. In no case the trigeminal nerve was lesioned or “combed” or dissected. New Teflon felts were placed in case a nearby artery was found. There was no operative morbidity or mortality. All patients were available for postoperative follow-up. The outcome of the repeat intervention was graded according to the Barrow Neurological Institute (BNI) pain score. Mean follow-up was 32 months.

Results: Recurrent TN was thought to be caused by the following findings identified intraoperatively: scar tissue at the trigeminal entry zone (21/24), deformation of the trigeminal nerve/ tefloma (16/24), new nerve/ vein contact (8/24), artery/ Teflon contact with marked pulsation (12/24), and compression of the trigeminal nerve by a cavum Meckeli electrode for treatment neuropathic pain (1/24). Early postoperative pain relief was achieved in all patients. On longterm follow-up 20 patients had complete pain relief (BNI I), 3 patients had pain relief under medication (BNI III) and one patient had a BNI pain score of IV. Hypaesthesia secondary to the microsurgical re-decompression occurred in only 2/24 patients.

Conclusion: In the present study microsurgical re-decompression was highly successful for recurrent TN. There were no serious side effects and the frequency of postoperative hypaesthesia was low. We conclude that microsurgical re-decompression avoiding any damage to the trigeminal nerve is a very useful treatment option in this context. Any manoeuvres such as dissecting or “combing” the trigeminal nerve are unnecessary and should be avoided.

Gökce HATIPOGLU MAJERNIK (Hannover, GERMANY), Shadi AL-AFIF, Joachim K. KRAUSS
16:15 - 17:15 #10083 - OF52 Changes in Intracortical Inhibition and Clinical Symptoms After STN-DBS in Parkinson’s Disease.
Changes in Intracortical Inhibition and Clinical Symptoms After STN-DBS in Parkinson’s Disease.

Objectives: To examine the effects of subthalamic nucleus deep brain stimulation (STN-DBS) on intracortical inhibition in Parkinson’s disease (PD) and the correlation between intracortical inhibition and clinical symptoms after alteration of STN-DBS status.

Methods: Nine PD patients treated by STN-DBS were compared with eight age-matched controls. Antiparkinsonian medication was withdrawn 12 hours before the study. Short-interval intracortical inhibition (SICI) with a 3-ms interval and silent period (SP) were examined using transcranial magnetic stimulation. The SP, SICI and motor symptoms (rigidity and tremor) were evaluated sequentially before and after withdrawal of STN-DBS. 

Results: Even during STN-DBS, PD patients showed a shortened SP and reduced SICI relative to the normal controls. SICI was decreased significantly 10 min after STN-DBS withdrawal resulting in facilitation rather than inhibition, whereas SP was shortened 120 min later. Both rigidity and tremor were significantly worsened at 10 min after STN-DBS withdrawal.

Conclusion: Even during STN-DBS, both SICI and SP in PD patients remain impaired without medication. The changes in SICI, but not SP, show a time course similar to those of motor symptoms.

Significance: The dissimilarity of SICI and SP changes suggests differences in how inhibitory mechanisms are mediated and/or superimposition of exaggerated intracortical facilitation on SICI.

Masahito KOBAYASHI (Saitama, JAPAN), Takayuki OHIRA, Ban MIHARA, Takamitsu FUJIMAKI
16:15 - 17:15 #10366 - OF53 deep brain stimulation in routine clinical practice: monocentric study of the battery lifetime of different generations of neurostimulators.
deep brain stimulation in routine clinical practice: monocentric study of the battery lifetime of different generations of neurostimulators.

Routine clinical practice of Deep Brain Stimulation (DBS) enters a new era where battery-related events are challenging. The important number of primary implantations and replacements pushed industrials to develop new generations of devices. We aimed to analyze the battery lifetime of different kinds of non-rechargeable devices, manufactured by a single company (Medtronic, USA): the first generation of 4-contact neurostimulator for one DBS-lead (1 channel; Soletra®) and 8-contact neurostimulator for two DBS-leads (two channels of 4 contacts; Kinetra®); the second generation of advanced programming neurostimulator (Activa® PC, two channels of 8 contacts, and SC, 1 channel of 8 contacts).  
We retrospectively reviewed 281 consecutive patients operated on in a single institution (from 1995 to 2016): 584 surgeries for primary implantation or replacement of neurostimulator (infection and traumatic etiologies of battery replacement were excluded). The battery lifetime was defined as the period between the surgical implantation and the removal at battery depletion. Two hundred and eighty eight battery-lifetimes were analyzed in 157 patients suffering of Parkinson disease (n=129), essential tremor (n=19), dystonia (n=9). Exclusion criteria were: battery related, still operational (n=217); patient related, died before battery depletion (n=50); missing follow-up (n=3); and other diseases treated by DBS (n=2). Battery lifetime was analyzed using survival methods (univariate, Log-Rank test; multivariate, marginal cox model; two-sided tests) accounting for the following parameters: gender, neurological disease, age at the primary implantation, the UPDRS-score before DBS surgery, the deep brain target, battery model, mean voltage (low < 2V; usual from 2V to 4V; high v> 4V), location of battery (abdominal or sub clavicular) and presence of an adapter for replacement of first generation (Kinetra or Soletra) by second generation model (Activa).Results: The battery lifetime was shorter in male (p=0.03) and young (p<0.001) patients suffering of essential tremor (p<0.001) and dystonia (p<0.001). High voltage reduced battery lifetime (p<0.001). The second generation device, Activa models, had shorter lifetime than first generation, Soletra and Kinetra (p<0.001). Replacement of battery decreased lifetime independently of models (p<0.001).
Patient and disease characteristics, high voltage, second generation devices and replacement seem to shorten lifetime of battery.

Emmanuel DE SCHLICHTING (Clermont-Ferrand), Ana-Raquel MARQUES, Aurélien MULLIEZ, Francois GAMPOUROU, Philippe DEROST, Bérangère DEBILLY, Jérôme COSTE, Guillaume COLL, Franck DURIF, Jean-Jacques LEMAIRE
16:15 - 17:15 #10120 - OF54 GPi DBS rescue for severe dyskinesia or dystonia following STN DBS in Parkinson's Disease - dual or replacement therapy.
GPi DBS rescue for severe dyskinesia or dystonia following STN DBS in Parkinson's Disease - dual or replacement therapy.

It is well known that either STN DBS or GPi DBS can improve the cardinal symptoms of Parkinson's Disease (PD).Studies have demonstrated similar overall efficacy on

"motor parkinsonism" symptoms although the two targets have differential effects on individual parkinsonian symptoms and a varying side effect profile.

A significant clinical problem arises when a DBS target is selected which long term does not effectively control a disabling symptom- in this case dyskinesia/dystonia.

The surgical team is then faced with the dilema of switching from one stimulation site to another either as replacement therapy or perhaps adding another system

to provide dual  stimulation of both STN and GPi. 

Over the past 16 years ,Sydney DBS has operated on more than 400 patients with PD performing >800 STN implants and 30 posteroventral GPi implants.3 of the 400

patients,<1% have required GPi DBS due to the development of refractory dyskinesia and or dystonia.These 3 patients(cases1,2&3) are now treated with dual STN and

GPi DBS. A fourth patient (case 4), treated with STN DBS at another Australian centre has undergone GPi DBS in our surgical unit with STN DBS removal.

All four patients sufferd both diphasic and peak dose dyskinesia and "off" dystonia.In case 2, dyskinesia emerged one month after STN DBS. Tremor was the principal

initial indication for surgery in this instance and despite one year of stimulation and medication trials,control of tremor could not be consistently achieved without

troublesome dyskinesia. In the other 3 cases, good control of parkinsonism was initially achieved with STN DBS but with the requirement over the years to re-introduce

incresed doses of anti-Parkinsonian medication, troublesome dyskinesia re-emerged.

Empirically, we have found optimal control to be achieved with simultaneous use of both STN and GPi DBS in the patients with dual systems. Either system in isolation

was not as effective as combining the effect of dual stimulation.  Parkinsonian control also was significantly improved in the patient switched from STN DBS to GPi DBS.

The predominance of dyskinesia and dystonia and the absence of tremor in this patient likely underscores the greater efficacy of pallidal DBS in this instance.

Conclusion

All four patients had successful surgical rescue treatment with dramatic control of dystonia/dyskinesia with GPi DBS.In our experience ,simultaneous use of STN DBS and

GPi DBS provided better symptomatic control than either system alone in the cases treated.

Raymond COOK (Sydney, AUSTRALIA), Paul SILBERSTEIN, Linton MEAGHER, George FRACCHIA
16:15 - 17:15 #10325 - OF55 Differential approach to surgical management of facial pain.
Differential approach to surgical management of facial pain.

Introduction: In addition to classic trigeminal neuralgia (TN), multiple other facial pain (FP) conditions may be successfully addressed with surgery.

Purpose: To evaluate usefulness of published FP treatment algorithm on the base of clinical experience analysis in a large multi-center group of FP patients.

Materials / methods: We analyzed 378 FP patients surgically treated in 4 neurosurgical centers (Novosibirsk, Irkutsk, St.-Petersburg and Chicago); they were chosen for analysis based on diagnostic and follow-up data availability. FP treatment algorithm (Slavin, 2007) was used to facilitate decision making. Patients not expected to benefit from surgery were excluded during screening and referred to other specialists. 56.7% were diagnosed with TN type 1; 18.7% - TN 2; 7.5% - trigeminal neuropathic pain;  3.6% - symptomatic TN (multiple sclerosis (MS)); 1.6% - postherpetic neuralgia; 1.7% - deafferentation facial pain; 0.3% - geniculate neuralgia; 8.4% - secondary TN (other than MS); 1.1% - glossopharyngeal neuralgia. Severity of clinical symptoms was assessed with Visual Analog Scale (VAS), Barrow Neurological Institute Pain Scale (BNIPS), DN4 and BPI-Facial.

Results: A total of 426 surgeries were undertaken: 40.2% - MVD; 15.7% - radiofrequency gangliolysis; 9.5% - balloon compression; 9.2% - glycerol gangliolysis; 7.3% - peripheral nerve stimulation; 0.2% - percutaneous trigeminal tractotomy; 0.2% - open trigeminal nucleotractotomy; 0.2% - neurectomy; 8.9% - stereotactic radiosurgery; 6.9% - posterior fossa tumor resection; 1.7% - motor cortex stimulation.

According to Miller scale surgical results were classified as excellent (75-100% pain reduction), good (25-74%) and poor (0-25%). Open surgery results were excellent in 91% cases, good – 4%, poor – 5%. Percutaneous treatment had excellent results in 58% cases, good – 19%, poor – 23%. Neuromodulation options showed excellent results in 42% cases, good – 18%, poor – 39%. Success of stereotactic radiosurgery was evaluated as excellent in 53% cases, good – 14%, poor – 33%.

Conclusion: Differentiation of FP type is essential for effective choice of surgical treatment. The existent algorithm allowed us to clearly classify large volume of FP patients and establish optimal surgical treatment based on diagnosis and individual patient characteristics.

Jamil RZAEV (Novosibirsk, RUSSIA), Galina MOISAK, Elena KULIKOVA, Natalia DENISOVA, Amelin MIKHAIL, Eugenia AMELINA, Aleksandr SEMENOV, Pavel IVANOV, Konstantin SLAVIN
16:15 - 17:15 #10546 - OF56 Tractography-guided Stereotactic Anterior Capsulotomy for Depression or OCD: Teaching an Old Procedure New Tricks.
Tractography-guided Stereotactic Anterior Capsulotomy for Depression or OCD: Teaching an Old Procedure New Tricks.

Objectives: Bilateral Anterior Capsulotomy (BAC) has been traditionally performed by placing lesions in the anterior limb of the internal capsule (ALIC) based on standard MR-imaging. This ‘anti-sadness’ surgery is a powerful operation designed to eliminate ‘psychic pain’ and destroy the circuit that mediates separation-distress (PANIC system).  In this study, for the first time ever, we demonstrate a tractography-guided approach in performing BAC for treatment-refractory depression (TR-D) or obsessive-compulsive disorder (TR-OCD). 

Methods: After acquiring a 3T 64-direction DTI scan, we mapped the Medial Forebrain Bundle (MFB) and the Anterior Thalamic Radiations (ATR) with DTI tractography on StealthViz in n=6 subjects: three who became medication-free following BAC, one who became chronically fatigued following BAC, one healthy control, and one surgical candidate for BAC. Figure 1 illustrates a sample of this pre-operative limbic white matter mapping step. We then prospectively targeted the ATR white matter tracts in BAC surgery in the last subject.

Results: Details of tractography- and functional-mapping will be presented at the WSSFN meeting. We will provide neuroimaging and behavioral confirmation that: 1) a distinct topography in the ALIC can guide BAC surgery, 2) partial destruction of the supero-lateral branch of the MFB leads to sustained apathy/fatigue, and 3) selective destruction of ATR fibers leads to rapid resolution of suicidality and then gradual neuro-rehabilitation to cessation of psychiatric medications. Functional neuroimaging analysis revealed that the Anterior Nucleus of the Thalamus could be subdivided to serve as a pre-operative seed region.

Conclusions: We provide a new and refined version of BAC surgery for TR-D or TR-OCD using fiber tractography and functional mapping. In our 20-year experience, BAC has been demonstrated to have powerful and reproducible results for mood disorders. Unlike DBS, this surgery can be effective in low-resource countries, requires no post-operative programming, and infections are non-existent. We argue the merits of BAC over cingulotomy. We hope that functional neurosurgeons continue using ablative surgical procedures until more robust and reproducible DBS research emerges for psychiatric disorders. We hope this work stimulates the application and development of circuit-, rather than disorder-, based, therapeutics for psychiatric illnesses and advance the NIH’s RDoC and Precision Medicine initiatives. 

Anujan POOLOGAINDRAN (Vancouver, CANADA), Adi SULISTYANTO , Trevor HURWITZ, Andrew HOWARD, Christopher HONEY
16:15 - 17:15 #10189 - OF57 Long term results of the selective dorsal rhizotomy.
Long term results of the selective dorsal rhizotomy.

Object: Long-term results of the selective dorsal rhizotomy are estimated insufficiently neatly and controversial.  The aim of  investigation is to estimate the  long-term results of  SDR in  different  groups of patients with cerebral palsy and to compare these results with the control group. 

Methods: 33 patients with  spastic CP  have  been operated. In all cases  SDR  of L1-S1 roots have been  performed  under   EMG  control. In all cases we have use laminoplasty. The  control  group  includes  19  patients  with CP. All patients received conservative therapy only (rehabilitation treatment + oral drug treatment + botulinum toxin injections). The  results of  treatment  have been estimated  by the Ashworth scale and  GMFM 88 scale. The data have been exposed statistically  analysis.   The duration  of follow-up was  3  years.       

Results:  Significantly decreasing of spasticity  have been  revealed in  most cases:  from  4,24±0,54 points before  the  operation till  1,53±0,37   points  after the operation  (p ‹ 0,05). In the control group  we also  observed  the dynamic of spasticity:  from  3,57±0,6   before  till  3,11±0,55  after (p ‹ 0,05). But  we have seen  the   relapse and increasing  of  spasticity in the follow-up  in 3 cases.  The  dynamic of  motor  function  after SDR was  maximal in  the  3-th  GMFM class: from   49%±3% points  before the  operation  till  54%±5%  points  36  month after the operation   (p‹ 0,05).   In 4-th  GMFM class the dynamic of motor function  was  less – only 2%   and  in  5-th  it was  minimal.  In the control group the maximal  dynamic  of  locomotion status  was  in  patients concerning to  3 GMFM class - 6% (from 49%±7% till 55%±9%). ).   In 4-th  and 5-th  GMFM class the dynamic of motor function  was  minimal. We have  not  revealed  any correlation  between  the   volume of  cutting rootlets  and  the dynamic  of motor  function.   We  have not  observe  any  spinal cord deformities  in  follow-up.   

Conclusion:  Decrease of spasticity is most significant after SDR   in comparison with the conservative therapy.   The  functional result of SDR  depends on not  only  decreasing of  spasticity  but also   initial  motor status  and age of patients. SDR is optimal  procedure  in  patients  belonged to  3-th GMFM class  and high  spasticity.   In all cases  laminoplasty  should be  performed  to  prevent  the spinal  cord  deformities.   

Andrey DEKOPOV, Aleksey TOMSKY (Moscow, RUSSIA)
16:15 - 17:15 #10555 - OF58 Relationship between body mass index and efforts for optimal conditioning of STN-DBS.
Relationship between body mass index and efforts for optimal conditioning of STN-DBS.

Anti-Parkinson drugs can be decreased after subthalamic nucleus-deep brain stimulation (STN-DBS) in many cases, however, the dose should be carefully reduced especially in low body weight patients.  Because Parkinson disease (PD) often causes body weight loss, slight dose changes might influence their symptoms prominently. We studied an impact of low body weights for conditioning of DBS and medication after surgery, analyzing relationships between body weight or body mass index (BMI) and frequency of outpatient follow-up for conditioning of STN-DBS after discharge.

Materials and Methods: Clinical data were obtained from 12 patients with Parkinson disease (average age 62.3, 8 females) who underwent STN-DBS from 2010 to 2013. Body weight, BMI, age, dose of anti-Parkinson drugs before and after DBS surgery, UPDRS and disease duration were estimated. We studied correlations between these parameters and frequency of outpatient visits for conditioning DBS parameters and medication within 3 months after surgery.

Results: After STN-DBS, L-DOPA was reduced to 60-80% (300-350mg/day) of preoperative dose in each patient. There was no significant correlation between numbers of their outpatient visits in 3 months after surgery and preoperative L-DOPA dose while there were significant negative correlations between the outpatient visit and both body weight and BMI, and also a strong correlation with L-DOPA dose per body weight or BMI were observed. The mean number of the outpatient visits within 3 months was 3.6 times in the patients with BMI > 20, and 7.0 times in those with BMI <20. A multiple regression analysis revealed that BMI was an only significant factor that affects outpatient visit frequency. There was no patient with depression before STN-DBS.

Discussion: Conditioning of medication and stimulation after STN-DBS could be difficult especially for patients with low body weight or BMI, and thus should be carefully managed, considering possible psychiatric symptoms of PD.

Ryosuke TOMIO (Tokyo, JAPAN), Masahito KOBAYASHI, Ban MIHARA, Takayuki OHIRA, Takamitsu FUJIMAKI
16:15 - 17:15 #10534 - OF59 Safe approach to the subthalamic nucleus.
Safe approach to the subthalamic nucleus.

Objective: To evaluate the accuracy, effectiveness and safety of STN targeting using a non-standard method for image-guided surgical approach. Special attention was focused on the impact of ventricular dilatation and brain atrophy over the electrode trajectory and targeting accuracy.
Methods: A prospective study of targeting data collected during 36 stereotactic planning for ablation of the STN in 36 patients with PD was performed. The targeting method was based on stereotactic computed tomographic imaging, deep brain activity recording with semi-microelectrode and electrical stimulation. Parasagittal recommended trajectory for this type of procedure is between 0 and 15 degrees, this was modified to values over 20 degrees in the first recording track in order to avoid the lateral ventricle. The trajectories of the electrodes relative to the lateral ventricles were analyzed in postoperative CT or MR images. The efficacy of the targeting procedure for STN localization and ablation was statistically evaluated.
Results: The average number of recorded trajectories per procedure was 5, and the average number of tracts necessary to lesion the STN was two. Average parasagittal approach angle in the first recording track was 21.6 degrees, with minimum of 20 and maximum of 25.5 degrees. STN´s electrical activity was identified in the first pass of deep brain neuronal activity recording in the 86.7% of the procedures. No complications were reported related to the surgical procedure.   
Conclusions: The proposed method for anatomical and neurophysiological targeting of the STN using a parasagittal approach angle over 20 degrees, was found to be effective and surgically safe in patients with PD with ventricular dilatation and brain atrophy.

Nelson E. QUINTANAL CORDERO (La Habana, CUBA), Rafael RODRÍGUEZ ROJAS
16:15 - 17:15 #10213 - OF60 Sacral Nerve Neuromodulation for the Management of Intractable Bowel Incontinence.
Sacral Nerve Neuromodulation for the Management of Intractable Bowel Incontinence.

Background : In the treatment of urinary incontinence, spinal or supra-spinal neuromodulation has been reported. Fecal incontinence (FI) result in significant secondary disability in bowel incontinence. In 1995, sacral nerve root stimulation was reported that the effective management against FI. The aim of current presentation was to discuss our clinical outcome of sacral nerve stimulation and to review previous reports. METHODS: We retrospectively reviewed fecal incontinence, occurred 5-year ago. He experienced hemorrhoidectomy, Discectomy L4-5 and liver lobectomy for hepatocellular cancer with bilateral L5-S1 radiculopathy and complained of incontinence. Motor power of the legs were intact, Anorectal physiology testing and electromyographic recruitment done for the motor unit potential of the puborectalis muscle. Endo-anal ultrasound was investigated. Test stimulation period was 3 to 7 days, up to 14 days at Stage 1.  We choose the test based on frequency of FI. Long-term therapy was applied to the patient with implantation of lead and extension. Finally implantation of neurostimulator (INS) was done. Review of literatures were discussed with the three of patients. RESULTS: All of the three patients underwent test stimulation with good successful responses, of whom two of males and one female with a mean age of 71.5 years and a mean duration of fecal incontinence of 5 years received chronic implantation. Mean duration of follow-up was 1.3 (range, 0.5-2.1) years. Two patients completed about 2-year follow-up for assessment and one patient for 5 months. All of patients reported more than 50% reduction of FI episodes compared with baseline. Cleveland clinic Incontinence Score (CCIS) were checked and the number of incontinent episodes per week improved from the average of 12.3 at baseline to 4.7. The fecal incontinence severity (FIS) index showed 18 to 14 with improvement of episodes. Sacral nerve stimulation had a positive impact on daily living. The adverse events through the mean two years of follow-up included local pain on implant site, and the unusual tingling sensation of stimulation. There were no significant adverse effects associated with sacral neuro-modulation in this study. CONCLUSION: Sacral nerve neuromodulation is a safe and effective management for patients with FI. These data support short-term safety and effectiveness to 21 months. Literatures support our presentation.

Joon CHO, Moo Kyung SEONG, Joon CHO (Seoul, KOREA)

17:15
17:15-17:45
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WU2
PLENARY SESSION: WRAP UP SESSION-3 presenters

PLENARY SESSION: WRAP UP SESSION-3 presenters

Moderators: Keyoumars ASHKAN (London, UK), Adrian LAXTON (Winston Salem, USA), Ido STRAUSS (Neurosurgeon) (Tel Aviv, ISRAEL)

17:45
17:45-18:15
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CT2
CLINICAL TRIALS SESSION 2

CLINICAL TRIALS SESSION 2

Moderators: Albert FENOY (Houston, USA), Craig VAN HORNE (clinician) (Lexington, USA)
17:45 - 18:15 #10798 - CT06 Enabling volitional motor control using spinal cord neuromodulation in a human patient with paraplegia.
Enabling volitional motor control using spinal cord neuromodulation in a human patient with paraplegia.

WSSFN

 

Enabling volitional motor control using spinal cord neuromodulation in a human patient with paraplegia

 

 

Peter J. Grahn, Ph.D. Igor A. Lavrov, M.D., Ph.D. Dimitry G. Sayenko, Ph.D. Meegan G. Van Straaten, P.T. Megan L. Gill, D.P.T. Jeffrey A. Strommen, M.D. Jonathan S. Calvert, B.S. Dina I. Drubach, D.Sc.P.T. Lisa A. Beck, M.S. Margaux B. Linde, B.S. Andrew R. Thoreson, M.S. Cesar Lopez, M.S. Aldo A. Mendez, M.D. Parag N. Gad, Ph.D. Yury P. Gerasimenko, Ph.D., Kevin E. Bennet, Ph.D.,  V. Reggie Edgerton, Ph.D. Kristin D. Zhao, Ph.D. Kendall H. Lee, M.D., Ph.D.

 

 

Severe spinal cord injury (SCI) leads to functional disconnection of ascending and descending spinal pathways, impairing neural circuitry through and below the SCI. An emerging therapy for enabling motor function following SCI is epidural electrical stimulation (EES). In SCI subjects diagnosed with ASIA-A or B, EES of the lumbosacral spinal cord was initially shown to drive non-volitional rhythmic motor circuitry. In a recent study, EES facilitated volitional control of joint-specific muscles and independent standing after months of training with EES. Although these findings were powerful, they have yet to be reported by other research teams. Therefore, the initial goal of this study was to replicate the findings from work performed at the University of Louisville that reported: 1) EES enabled volitional control of motor activity; 2) and EES enabled independent standing. In addition to the initial goal of replication, we set out to determine if EES could enable volitional control over rhythmic locomotor activity.  We report a case of chronic traumatic paraplegia in which epidural electrical stimulation (EES) of the lumbosacral spinal cord enabled: 1) volitional control of task-specific muscle activity; 2) independent standing; 3) and voluntary control of step-like movements and rhythmic muscle activity. This is the first time the application of EES enabled all of these tasks in the same subject within the first eight sessions of EES.

Peter GRAHN, Dimitry SAYENKO, Meegan VAN STRAATEN, Megan GILL, Jeffrey STROMMEN, Igor LAVROV, Lisa BECK, Margaux LINDE, Jonathan CALVERT, Dina DRUBACH, Andrew THORESON, Cesar LOPEZ, Parag GAD, Aldo MENDEZ, Yury GERASIMENKO, V. Reggie EDGERTON, Kristin ZHAO, Kendall LEE (Rochester, USA), Kevin BENNET
17:45 - 18:15 #12030 - CT07 A phase 1B trial evaluating the safety and feasibility of autologous peripheral nerve grafts in patients with Parkinson's disease.
A phase 1B trial evaluating the safety and feasibility of autologous peripheral nerve grafts in patients with Parkinson's disease.

We present an open-label, Phase Ib trial examining the safety and feasibility of grafting autologous peripheral nerve tissue to target brain areas in patients with Parkinson’s disease (PD). Grafts are harvested from sural nerve and deployed during routine DBS surgery. Peripheral nerve tissue was chosen because it contains Schwann cells, which transdifferentiate after nerve injury or transection to become “repair cells” for neural tissue. Immediately following DBS surgery (targeting STN or GPi) a 5mm section of sural nerve was excised, stripped of the epineurium, cut into 1 mm pieces, and unilaterally delivered into the substantia nigra (SN). Our primary endpoint is safety. Secondary endpoints include Unified Parkinson’s Disease Rating Scale (UPDRS) scores and changes in DaTscan quantification. To date, 25 participants have received a single implantation to the SN, and 8 with two separate implants to the SN unilaterally. The overall adverse event profile is comparable to standard DBS surgery, with no serious adverse events related to the delivery of the graft. Seventeen participants who received a single graft to the SN have reached the 1 year time point and have demonstrated a decrease of 7.3 ± 10.6 points (considered a moderate clinically important difference, mean ± SD) in the UPDRS motor scores off medication and off stimulation compared to before surgery. Combining the delivery of cell therapy at the time of DBS surgery is beginning to show a good safety profile and positive preliminary clinical data that warrants further investigation. 

Craig G VAN HORNE (Lexington, USA), Jorge E. QUINTERO, Julie A. GURWELL, Amelia J. ANDERSON-MOONEY, Andrew WELLEFORD, John R. LAMM, John T. SLEVIN, Greg A. GERHARDT
17:45 - 18:15 #12174 - CT08 Real-time MRI-guided intraputaminal AADC gene therapy for advanced Parkinson's disease.
Real-time MRI-guided intraputaminal AADC gene therapy for advanced Parkinson's disease.

In PD, loss of aromatic L-amino acid decarboxylase (AADC), which converts levodopa into dopamine, is associated with loss of oral levodopa effectiveness. We are evaluating the safety of AADC gene therapy in an ongoing Phase 1b clinical trial. To improve upon limited coverage of the anatomic target in prior studies, intraputaminal gene expression is achieved by intraoperative-MRI-guided co-infusion of AAV2-hAADC and gadoteridol. Fifteen subjects (N=5/cohort) with advanced PD received bilateral infusions of either a lower concentration (0.83x1012vg/ml), ≤ 450 μl/putamen (cohort 1), ≤ 900 μl/putamen (cohort 2), or higher concentration (2.7x1012vg/ml) ≤ 900 μl/putamen (cohort 3). The infusion strategy evolved to maximize coverage of the putamen by modifying cannula design, altering the position of infusion sites along cannula trajectories, and increasing infusion volumes. These steps resulted in an increase in average infusate coverage of the putamen from 21% to 34% and 42% (cohorts 1,2 and 3, respectively). Infusions were well tolerated. Enzyme activity on 18F-dopa PET increased from 13% (cohort 1) to 56% (cohort 2). Imaging and clinical data are pending for cohort 3. We observed coverage-dependent reductions in dopaminergic medications and improvements in motor function in subjects who have reached 12-month follow-up, including: 10% (cohort 1) and 35% (cohort 2) reductions in dopaminergic medications; 1.8-point (cohort 1) and 9.3-point (cohort 2) improvements in UPDRS III on medications; 1.6-hour (cohort 1) and 4.1-hour (cohort 2) increases in on-time without troublesome dyskinesia. Real-time-MRI-guided delivery allows modification of infusions that maximize target coverage and potential coverage-related clinical benefits. 

Mark RICHARSON (Pittsburgh, USA), Christine CHADWICK W. , Krystof S. BANKIEWICZ, Amber VAN LAAR, Bernard RAVINA, Adrian KELLS, Brendon BOOT, Paul S. LARSON
17:45 - 18:15 #12031 - CT09 Deep Brain Stimulation for Treatment Resistant Depression Clinical Trial.
Deep Brain Stimulation for Treatment Resistant Depression Clinical Trial.

Currently, we have open an FDA-approved clinical trial for patients with treatment resistant depression to undergo deep brain stimulation (DBS) of the medial forebrain bundle (MFB); our interim analysis of this study shows encouraging results (Fenoy et al., 2016).

Patients are considered candidates if they meet Inclusion Criteria: (a) Major depression, severe, unipolar, diagnosed by Structured Clinical Interview for DSM-IV, judged to be of disabling severity; (b) Hamilton Depression Rating Scale (HDRS) score > 21; (c) Montgomery- Asburg Depression Rating Scale (MADRS) score > 21; (d) Global Assessment of Function (GAF) score of < 45; (e) a recurrent (>4 episodes) or chronic (episode duration >2 y) course and a minimum of 5 y since the onset of the first depressive episode; (f) age 22-65 y; (g) refractory to > 6 weeks of multiple medication regimens; (h) refractory to > 20 sessions psychotherapy; (i) refractory to a trial of ECT.

Exclusion criteria are as follows: (a) current or past non-affective psychotic disorder, schizophrenia, or schizo-affective disorder; (b) severe personality disorder; (c) significant neurological disorder; (d) previous surgery to destroy the target region of the brain; (e) surgical contraindications to DBS.

Candidates who meet such criteria will then undergo placement of DBS electrodes into the bilateral MFB. Participants and clinicians performing behavioral assessments will be blinded to onset of stimulation, which will occur four weeks after implantation. Behavioral assessments will occur weekly for 52 weeks. MADRS is the primary outcome measure.

For more information, visit ClinicalTrials.gov (identifier: NCT02046330).

Albert FENOY (Houston, USA)
17:45 - 18:15 #12032 - CT10 Combined Anterior and Posterior Lumbar Rhizotomy for Treatment of Mixed Dystonia and Spasticity in Children with Cerebral Palsy.
Combined Anterior and Posterior Lumbar Rhizotomy for Treatment of Mixed Dystonia and Spasticity in Children with Cerebral Palsy.

BACKGROUND:
Children with cerebral palsy (CP) can present with severe secondary dystonia with or without associated spasticity of their extremities.

OBJECTIVE:
To assess the outcomes of combined anterior and posterior lumbar rhizotomy for the treatment of mixed hypertonia in the lower extremities of children with CP.

METHODS:
Fifty children with CP were subjected to combined anterior and posterior lumbar rhizotomies in a prospective study. Clinical outcome measurements were recorded preoperatively and were evaluated at 2, 6, and 12 months postoperatively. The operative techniques were performed by laminotomy from L1- S1, and intraoperative monitoring was used in all cases. All patients underwent intensive postoperative physiotherapy programs.

RESULTS:
Changes in muscle tone, joint range of motion, and dystonia were significant (P = .000) at postoperative assessment visits.

CONCLUSION:
This study demonstrated the potential of combined anterior and posterior lumbar rhizotomies to improve activities of daily living in children with CP and with mixed spasticity and dystonia.

Neurosurgery. 2016 Sep;79(3):336-44. doi: 10.1227/NEU.0000000000001271. 

Walid ABDEL GHANY (CAIRO, EGYPT), M. NADA, Ma. MAHRAN, Ma. NASEF, M. GABER, T. SABRY, Mh IBRAHIM, Mh TAHA

18:00-19:00
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MEET8
WFNS STEREOTACTIC AND FUNCTIONAL NEUROSURGERY COMMITTEE

WFNS STEREOTACTIC AND FUNCTIONAL NEUROSURGERY COMMITTEE

Thursday 29 June
Time Potsdam I-III Bellevue Glienicke Tegel Lincke I-II Schinkel I-II Kaminzimmer
07:30
07:30-08:15
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BS8
PARALLEL SESSIONS: BREAKFAST SESSIONS
SURGICAL TREATMENT AND TARGETS FOR OBSESSIVE COMPULSIVE DISORDER

PARALLEL SESSIONS: BREAKFAST SESSIONS
SURGICAL TREATMENT AND TARGETS FOR OBSESSIVE COMPULSIVE DISORDER

Moderators: Clement HAMANI (Toronto, CANADA), Jian-Guo ZHANG (Beijing, CHINA)
Keynote Speakers: Keith MATTHEWS (Professor) (Dundee, UK), Bomin SUN (director) (shanghai, CHINA), Rick SCHUURMAN (neurosurgeon) (Amsterdam, THE NETHERLANDS)

07:30-08:15
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BS7
PARALLEL SESSIONS: BREAKFAST SESSIONS
LESIONING SURGERY FOR MOVEMENT DISORDERS AND EPILEPSY - PEARLS AND PITFALLS

PARALLEL SESSIONS: BREAKFAST SESSIONS
LESIONING SURGERY FOR MOVEMENT DISORDERS AND EPILEPSY - PEARLS AND PITFALLS

Moderators: Benaissa ABDENNEBI (Alger, ALGERIA), Kostiantyn KOSTIUK (Neurosurgeon) (KYIV, UKRAINE)
Keynote Speakers: Erich FONOFF (Associate Professor) (São Paulo, BRAZIL), Chris HONEY (Vancouver, CANADA), Andrei SITNIKOV (Neurosurgeon) (Moscow, RUSSIA)

07:30-08:15
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BS9
PARALLEL SESSIONS: BREAKFAST SESSIONS
CHALLENGING CASES IN THE TREATMENT OF PAIN

PARALLEL SESSIONS: BREAKFAST SESSIONS
CHALLENGING CASES IN THE TREATMENT OF PAIN

Moderators: Zeiad Yossry FAYED (Associate professor of neurosurgery) (Cairo, EGYPT), Jamil RZAEV (Physician-in-chief) (Novosibirsk, RUSSIA)
Keynote Speakers: Konstantin V. SLAVIN (Chicago, USA), Byung-Chul SON (Professor) (Seoul, KOREA), Andreas WLOCH (HANNOVER, GERMANY)

08:30
08:30-09:00
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KL11
PLENARY SESSION: KEYNOTE LECTURE State of the art of SFN
THIRTY YEARS OF DEEP BRAIN STIMULATION FOR MOVEMENT DISORDERS - WHERE ARE WE NOW?

PLENARY SESSION: KEYNOTE LECTURE State of the art of SFN
THIRTY YEARS OF DEEP BRAIN STIMULATION FOR MOVEMENT DISORDERS - WHERE ARE WE NOW?

Moderators: Young Hwan AHN (Suwon, KOREA), Konstantin V. SLAVIN (Chicago, USA)
Plenary Speaker: Alim Louis BENABID (Grenoble, FRANCE)

09:00
09:00-10:00
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OPS10
OPS10 PLENARY SESSION: ORAL PRESENTATIONS

OPS10 PLENARY SESSION: ORAL PRESENTATIONS

Moderators: Young Hwan AHN (Suwon, KOREA), Konstantin V. SLAVIN (Chicago, USA)
09:00 - 09:12 #10543 - OP51 Hemispheric Analysis of Cerebellar Thalamic Deep Brain Stimulation on Voice Tremor: Is it Left, Right, or Both?
Hemispheric Analysis of Cerebellar Thalamic Deep Brain Stimulation on Voice Tremor: Is it Left, Right, or Both?

Objectives: Essential Voice Tremor (EVT) is the phonatory manifestation of Essential Tremor (ET). Several publications cite the prevalence of EVT in ET patients to be 10-25%. EVT is associated with significant social embarrassment, discontinuation of employment and hobbies, and an overall decrease in quality of life. In this study, we investigated whether unilateral (left / right) or bilateral thalamic Vim stimulation is necessary to treat EVT in a prospective, randomized, double-blinded fashion. Our goal was to determine hemispheric dominance in voice tremor as this may provide insight into speech motor neural control and treating medically-refractory isolated EVT.

Methods: All ET patients who were implanted at the Surgical Center for Movement Disorder, Vancouver, BC were screened for a pre-operative EVT. We identified n=8 right-handed patients. These patients underwent bilateral Vim DBS surgery. After several sessions of optimizing DBS parameters for limb tremor, patients were randomized to receive: none, left-only, right-only, or bilateral Vim stimulation for 15 minutes each to assess voice tremor. A five-minute washout period was used in between settings. With their limbs at rest, subjects read the ‘Rainbow Passage’, sustained vowels ‘a’ and ‘e’, and produced one minute of spontaneous speech. A speech-language pathologist blinded to these settings then evaluated voice recordings using the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) scale, a standard scale used in speech-language pathology and otolaryngology.

Results: CAPE-V results were examined in relation to hemispheric Vim DBS stimulation. Preliminary findings indicate that the left thalamic Vim plays a critical role in laryngeal speech motor control. This has not been reported before. This suggests that there is hemispheric dominance in speech production similar to language. A detailed analysis will be presented at the WSSFN meeting along with DBS kinetics of voice and limb tremor benefit/washout. 

Conclusions: This study adds to our knowledge of the effects of high-frequency left, right, and bilateral Vim thalamic stimulation on voice tremor in a prospective, randomized, double blinded, controlled manner. The results from this study should be taken into consideration for future endeavours using DBS for treatment of voice-related disorders and provides further information on the neurophysiology of speech motor control.

Adi SULISTYANTO (Vancouver, CANADA), Anujan POOLOGAINDRAN, Olivia CHORNY, Murray MORRISON, Linda RAMMAGE, Zurab IVANISHVILI, Mini SANDHU, Nancy POLYHRONOPOULOS, Natasha SARAI, Christopher HONEY
09:12 - 09:24 #10080 - OP52 Simultaneous electrical stimulation of DBS electrodes and fMRI in movement disorders.
Simultaneous electrical stimulation of DBS electrodes and fMRI in movement disorders.

Background:  We present a new intra-operative MRI technique for evaluating placement of DBS electrodes in patients with movement disorders, using simultaneous electrical stimulation and fMRI, which elicits a strong BOLD effect whose pattern can reflect underlying networks. The strong spatial sensitivity of these maps suggests clinical utility in predicting clinical response and unwanted side-effects. DBS for patients with movement disorders is now FDA approved. While motor symptoms can improve, a drawback is non-motor side effects that overwhelm benefits. Implantation typically requires the patient awake, which deters many patients. This motivates this work to permitting functional implantation with patients under anesthesia. To address this we obtain functional information about DBS location in patients under GA, by using intra-operative fMRI while the DBS electrodes are electrically stimulated.

Method: Patients were scanned in a 1.5T intra-operative MRI, during DBS implantation while under GA. After anatomically guided implantation, a BOLD sensitive EPI sequence was acquired during stimulation of the electrodes in a block design of 30 seconds on/off. Stimulation parameters were 2,5,8 volts across bipolar contacts, at 130 Hz. A total of up to 4 DBS-fMRI sequences were obtained during the imaging session, each with variations of stimulation parameters such as voltages, contacts, and duration. Analysis was performed using AFNI.

Results: A total of 7 patients have been studied and there have been no adverse reactions. Various stimulation parameters explored parameter space, generally showing robust BOLD activation with voltages greater than 5 volts. BOLD activation was both proximal & distal to leads, with patterns reflecting motor circuits. Patterns were very sensitive to lead location. 

Conclusion: We present initial results from simultaneous stimulation of DBS electrodes and fMRI, performed in patients with movement disorders at 1.5T while under GA. Robust BOLD activation can be easily elicited at voltages greater than 4V, whose patterns are both proximal and distal, with high spatial sensitivity, and whose patterns reflect clinical efficacy. This technique offers a possible alternative for patients wishing DBS implantation while under GA, in which the functional location of electrodes is desired to maximize clinical response and minimize side effects. This technique could easily be generalized to any functional localization electrodes during implantation.

Stephen JONES (Cleveland Heights, USA), Hyun-Joo PARK, Kenneth BAKER, Pallab BHATTACHARYYA, Mark LOWE, Andre MACHADO
09:00 - 10:00 Late Breaking News: First Bilateral Implantation of wireless 64 electrode ECoG recorders controlling a Four Limb Exoskeleton to improve mobility in a Quadriplegic Patient. Alim Louis BENABID (Grenoble, FRANCE)
09:36 - 09:48 #10622 - OP54 Bilateral VIM Radiosurgery for severe Essential Tremor: preliminary results of a prospective trial.
Bilateral VIM Radiosurgery for severe Essential Tremor: preliminary results of a prospective trial.

Objective: To assess the feasibility and tolerance of bilateral Gamma Knife thalamotomy (GKT) in Essential Tremor (ET).

Background: Unilateral GKT is an established treatment for severe tremors. However, essential tremor is usually bilateral. The persistence of contralateral tremor may induce an impairment in activities of daily living (ADL). Bilateral procedures with thermocoagulation were contraindicated because of the risk of balance, cognitive or speech problems. As the lesion induced by radiosurgery within the VIM is progressive and limited, we proposed a study on bilateral GKT. Here are the preliminary results.

Methods: 15 patients (8 women) with severe ET who had benefit from a first GKT and who had a severe permanent contralateral tremor were included. Patients were included if there was no impairment in their balance or speech and if the neuropsychological assessment was stable. The 2nd GKT was performed at least 18 months after the first GKT. Patients were assessed before and quarterly for at least 12 months after GKT2, with tremor rating scale, neuropsychological and gait/balance assessments and MRI. VIM lesioning was performed with Leksell Gamma unit with a single exposure through a 4mm collimator. Radiosurgical dose was 130Grays.

Results:  here are the preliminary results for 9 patients who completed the study at 1 year. Tremor score on the treated hand was improved by 57%. The improvement of ADL was 95%. Cognitive score and gait assessment were stable. No patient had hypophonia or dysarthria. Two patients were not significantly improved. One patient had a side effect related to GKT2. She developed hemiataxia and dysarthria induced by a hyperresponse pattern 11months after GKT.

Conclusions: These preliminary results on bilateral GKT for severe ET in a selected cohort of patients shows that the procedure is feasible without a major risk of cognitive or balance problems. However, a longer follow-up is needed.

Jean REGIS (Marseille), Romain CARRON, Tatiana WITJAS
09:48 - 10:00 #10819 - OP55 Spinal cord stimulation improves antecipatory postural adjustment and freezing of gait in Parkinson disease in chronic implanted stn-dbs patients: Preliminary Data.
Spinal cord stimulation improves antecipatory postural adjustment and freezing of gait in Parkinson disease in chronic implanted stn-dbs patients: Preliminary Data.

Background: Gait disturbances and freezing of gait (FoG) are common in late Parkinson’s disease (PD), often leading to loss of independence and increasing morbidity. A recent pilot study suggested positive effects of spinal cord stimulation (SCS) in PD patients previously treated with DBS. Despite the encouraging clinical results, no mechanistic approach was investigated at the initial trial. Anticipatory postural adjustment (APA) is an essential aspect of postural control required for starting any successful voluntary movement. APA combines motor and cognitive components of movement preparation involving the supplementary motor area (SMA) and prefrontal cortex. Aim: To evaluate the effects of SCS over the APA measurements in PD patients and its correlation to gait improvement.Methods: 4 PD patients with gait disorder and FoG, previously treated with STN DBS underwent evaluations in 3 conditions: SCS at 300 Hz, SCS at 60 Hz and SCS turned off. DBS was kept always on. We evaluated the SCS effects on APA and FoG. The assessment comprised: 1) Force plate analysis during step initiation (3 trials) measuring the amplitude and time of APA (time between onset of APA and the step); 2) Accelerometry spectral analysis during 10m-walk test (3 trials) providing the percentage of FoG occurrence and trunk acceleration. For each patient was calculated the average of 3 trials, so in each one the following calculations were made: 60-OFF/OFF*100 or 300-OFF/OFF*100, which is the gain of the condition (60Hz or 300Hz) in relation to OFF condition. For the group (N=4)a t-test was applied  and a simple t-test contrasting 60 and 300hz. Results:FoG index was reduced in SCS 300Hz in relation to SCS Off and 60Hz stimulation (p0.042), so patients had significantly less in freezing time while under SCS at 300Hz. APA time decreased in 300Hz condition comparing with OFF and 60 Hz conditions (p0,041), suggesting better coupling  between preparation and movement during step initiation. Conclusion: 300 Hz SCS seems to improve gait by decreasing FoG and increasing the efficiency of the preparation and movement coupling during step initiation.

Figure 1 (A) shows the position of the accelerometer in lumbar region; (B) represents vertical curve acceleration; The dotted square shows a window to frequency analysis domain; (C) Spectral analysis of acceleration: band representing the locomotor period (0-3Hz) and the FoG band (3-8Hz). (D) FoG index showing the clinical threshold (>2=FoG).

Carolina PINTO DE SOUZA, Carolina DE OLIVEIRA SOUZA, Andrea Cristina PARDINI, Daniel Boari COELHO, Luis Augusto TEIXEIRA, Erich FONOFF (Sao Paulo, BRAZIL)

10:30
10:30-11:30
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OPS11
OPS11 PLENARY SESSION: ORAL PRESENTATIONS

OPS11 PLENARY SESSION: ORAL PRESENTATIONS

Moderators: István VALÁLIK (head of department) (Budapest, HUNGARY), Angelo FRANZINI (MILANO, ITALY)
10:30 - 10:42 #10290 - OP56 Functional imaging of Essential Tremor treated with Deep Brain Stimulation In the caudal Zona incerta.
Functional imaging of Essential Tremor treated with Deep Brain Stimulation In the caudal Zona incerta.

Background: Essential tremor (ET), characterised by postural and/or action tremor, is the most common movement disorder. Several brain regions along the cerebello-thalamo-cortical network have been hypothesised to be involved in the generation of tremor oscillations, but the pathophysiology of ET is poorly understood.

ET can be disabling to the grade of necessitating invasive Deep Brain Stimulation (DBS). DBS in the caudal zona incerta (cZi) has shown a considerable reduction in tremor for patients with otherwise medically intractable tremor. However, the mechanisms underlying the effects of DBS remain unclear.

Objective: Investigating, by using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), whether regions within the cerebello-thalamo-cortical network are influenced by therapeutic DBS.

Method: Sixteen patients with cZi-DBS for ET underwent 1.5 T fMRI. During fMRI, the patients executed right-arm tremor-inducing postural holding movements as well as a baseline resting task. Tremor and hand movements were recorded by an MR-compatible single-axis accelerometer attached to the hand. The tasks were performed with the DBS turned on and off, with the initial stimulation setting (on/off) counterbalanced across patients. fMRI data were pre-processed and analysed using a general linear model implemented in SPM12.

Results: Clear therapeutic effects of cZi-DBS, in terms of tremor intensity reduction, were measured by the accelerometer. fMRI analysis showed effects of DBS in brain regions related to right-arm movement control: the contralateral motor cortex and ipsilateral cerebellum. However, different parts of this network showed different effects of the DBS depending on the motor task. Specifically, two circuits within these areas demonstrating different responses to DBS. Neural activity, expressed as BOLD, in the primary sensorimotor cortex and lobule VIII in the cerebellum decreased when performing postural holding while DBS was turned on. In contrast, neural activity in the supplementary motor area and lobule VI in the cerebellum increased during the resting condition when DBS was turned on.

Conclusions: Our results support the notion of DBS acting upon modulation of the cerebello-thalamo-cortical loop in ET. Furthermore, the study illustrates the complexity of DBS mechanisms by demonstrating different DBS actions depending on the motor state of the patient and in brain areas distant to the stimulated target.

Amar AWAD (Umeå, SWEDEN), Patric BLOMSTEDT, Göran WESTLING, Johan ERIKSSON
10:42 - 10:54 #10434 - OP57 Patient-specific model of subthalamic local field potentials recorded from deep brain stimulation electrodes.
Patient-specific model of subthalamic local field potentials recorded from deep brain stimulation electrodes.

Emerging innovations in deep brain stimulation (DBS) therapy are attempting to use local field potentials (LFPs) as biomarkers in the control of closed-loop algorithms. However, understanding of the biophysical origin of LFP signals remains elusive, and little is known about how the patient’s unique brain anatomy and electrode placement impact the recording of such signals. Therefore, we developed a computational framework to theoretically analyze LFP recordings from clinical DBS electrodes that can be customized to individual patients. To demonstrate our model system, we selected a subject with Parkinson’s disease implanted with a Medtronic Activa PC+S DBS system. First, we virtually reconstructed the subthalamic nucleus (STN) using MRI data. This virtual STN was then populated with ~250,000 realistic STN neuron models, each receiving time varying synaptic input. Finally, a finite element volume conductor model was used to represent the DBS electrode and tissue medium. We studied the role of subpopulations of highly synchronous neurons within the STN on the LFP recorded by DBS electrodes. We used three bipolar combinations of experimental LFP recordings to combinatorially determine the best fit model parameters. The results show that incorporating patient-specific STN anatomy impacted the LFP signal and varying the synchrony of spatially discrete subpopulations of neurons near the electrode had a strong effect on the LFP.  

Nicholas MAILING, Scott LEMPKA, Cameron MCINTYRE (Cleveland, USA)
10:54 - 11:06 #10494 - OP58 Deep Brain Stimulation Of The Ventral-Striatum And Ventral-Capsular Area For Post-Stroke Pain Syndrome.
Deep Brain Stimulation Of The Ventral-Striatum And Ventral-Capsular Area For Post-Stroke Pain Syndrome.

OBJECTIVE: To test our hypothesis that targeting neural pathways underlying emotion and affective behavior could alleviate the suffering and disability associated with chronic pain, we conducted a first-in-humans study of deep brain stimulation (DBS) targeting the ventral striatum (VS) / anterior limb of the internal capsule (ALIC) in 10 patients with post-stroke pain syndrome.

METHOD: Patients presenting with persistent and medically-refractory post-stroke hemibody pain and anesthesia dolorosa due to contralateral lesion(s) of thalamic areas and somatosensory pathways were enrolled in a prospective, double-blind, randomized, placebo-controlled, double-arm crossover trial over 24 months. The figure summarizes the trial design. Patients had had severe pain for more than six months and had failed treatment with at least one antidepressant, one anticonvulsant and one opioid. A quadripolar lead was implanted along the ALIC into the VS bilaterally, with the tip ~3-5 mm ventral to the junction between the ALIC and the anterior commissure.

RESULTS: A total of 10 patients were enrolled in the trial and primary and secondary clinical outcome measures were prospectively acquired in each study phase. Active DBS versus sham stimulation was associated with an increased probability of response (i.e. ≥ 50% improvement) in the Montgomery-Åsberg Depression Rating Scale (44% DBS ON v. 19% DBS OFF, p=0.02), Beck's Depression Inventory (45% DBS ON v. 27% DBS OFF, p=0.004), and the Affective Pain Rating Index (39% DBS ON v. 18% DBS OFF, p=0.002) and Present Pain Intensity (10% DBS ON v. 3% DBS OFF, p=0.002) in the Short-form McGill Pain Questionnaire. Individual patients showed changes in the following measures but we did not observe significant group effects: Visual Analog Scale, Pain Disability Index and the Sensory Pain Rating Index in the Short-form McGill Pain Questionnaire.

CONCLUSION: Our results suggest that DBS of the ventral capsule and ventral striatal area is safe and can effectively modulate the affective sphere of chronic pain, benefiting select patients. 

Scott LEMPKA, Donald MALONE, Hu BO, Kenneth BAKER, Alexandria WYANT, Ela PLOW, Paul FORD, Andre MACHADO (Cleveland, USA)
11:06 - 11:18 #9968 - OP59 Radiofrequency stereotactic lesions versus chronic stimulation of anterior thalamic nuclei for treatment of epilepsy.
Radiofrequency stereotactic lesions versus chronic stimulation of anterior thalamic nuclei for treatment of epilepsy.

The aim of this study was to compare the results of chronic stimulation and bilateral radiofrequency lesions of anterior thalamic nuclei in patients with pharmacoresistant epilepsy. The selection of the anterior nucleus of thalamus (ANT) as a potential target for treatment of pharmacoresistant epilepsy was based on data suggesting its crucial role in seizure propagation. This article describes the results of bilateral ANT lesions and chronic stimulation in 31 patients with refractory epilepsy. 19 patients underwent the stereotactic radiofrequency lesions of ANT (I group) and 12 have the ANT-DBS (II group).  Targeting was based on stereotactic atlas information with correction of the final coordinates according to location of clearly visible structures and microelectrode recording. Both groups were quite similar in age, gender, seizures frequency and duration of disease. The median x, y, and z coordinates of ANT were found to be 2.9, 5, and 11 mm anterior, lateral, and superior to the midcommissural point, respectively. Mean seizures reduction reached 80,3% in I group with 2 non-responders and 91,2% in II group. 3 patients form I group and 4 patients from II group are seizure-free now. The morbidity rate was low in both groups. The stereotactic lesion and chronic stimulation of ANT both effective for seizure control in epilepsy originated from frontal and temporal lobes. Secondary generalized seizures more demonstrated more sensitivity to ANT lesions and stimulation comparatively to simple partial seizures. Microelectrode recording allows to identify the physiological borders of ANT and improves the surgical outcomes. 

Andrey SITNIKOV (Moscow, RUSSIA), Yuri GRIGORYAN
11:18 - 11:30 #10316 - OP60 Feasibility and consistency of chronic visual cortex stimulation for vision restoration using an implanted neurostimulator.
Feasibility and consistency of chronic visual cortex stimulation for vision restoration using an implanted neurostimulator.

Introduction: Chronic stimulation of visual cortices could potentially be used to restore some vision in individuals with blindness. However, the feasibility, utility, and consistency of response to chronic epicortical stimulation of the medial occipital lobe remains uncharacterized. Our goal was to evaluate the nature, stimulation thresholds, retinotopic localization, and reproducibility over time, of cortical stimulation-evoked phosphenes in a blind volunteer over 6 months. 

Methods: A 30 year old with an 8 year history of bare light perception blindness due to Voght-Koaynagi-Harada Syndrome underwent implantation of a Neuropace responsive neurostimulation device with 2 parallel 4-contact leads implanted over the right medial occipital lobe via a posterior interhemispheric approach. Postoperatively, the subject’s perception of cortically-stimulated phosphenes was assessed with systematic manipulations of stimulation intensity, pulse width, frequency, and site of stimulation over a period of 6 months.

Results: Phosphenes were elicited with stimulation of every contact; percepts elicited at each electrode varied in brightness, shape, color, and spatial location. Phosphene characteristics were related to charge density and could be elicited with as little as a single stimulation pulse. The perceived quality and spatial localization of elicited phosphenes varied with eye position but was stable over time. The perception of simultaneous stimulation of two contacts as distinct phosphenes varied depending on distance between contacts. Percepts did not change over 6 months. There were no significant adverse events.

Conclusion: This is the first demonstration of chronic epicortical stimulation of visual cortices (primary and secondary) demonstrating feasibility and safety of chronic stimulation in providing reproducible phosphenes. Based on these results, further studies exploring using epicortical visual cortex stimulation, including biobehavioral studies, are warranted to evaluate the utility of this approach to restore some form of useful vision to blind individuals who were previously sighted. 

Nader POURATIAN (Los Angeles, USA), Abirami MURALIDHARAN, Soroush NIKETEGHAD, Uday PATEL, Jessy DORN, Robert GREENBERG

11:30
11:30-12:00
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KL12
PLENARY SESSION: KEYNOTE LECTURE
TREATMENT OF DYSTONIA

PLENARY SESSION: KEYNOTE LECTURE
TREATMENT OF DYSTONIA

Moderators: István VALÁLIK (head of department) (Budapest, HUNGARY), Angelo FRANZINI (MILANO, ITALY)
Plenary Speaker: Joachim K. KRAUSS (HANNOVER, GERMANY)

12:00
12:00-13:00
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DEB1
PLENARY SESSION: DEBATES

PLENARY SESSION: DEBATES

Moderators: Stephan CHABARDÈS (head of the unit) (GRENOBLE, FRANCE), Michael KAPLITT (New York, USA)
12:00 - 13:00 Target localization in functional neurosurgery - Microelectrode recordings is no longer necessary. Marwan HARIZ (London, UK), Emad ESKANDAR (Boston, USA)
12:00 - 13:00 THE CONTROVERSIAL HISTORY OF PSYCHOSURGERY: WHAT IMPACT DOES OUR PAST HAVE ON OUR FUTURE? Takaomi TAIRA (faculty, speaker) (Tokyo, JAPAN), Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)

14:15
14:15-15:15
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MEET9
GENERAL ASSEMBLY

GENERAL ASSEMBLY

15:15
15:15-15:45
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KL13
PARALLEL SESSIONS: KEYNOTE LECTURES
FACIAL PAIN

PARALLEL SESSIONS: KEYNOTE LECTURES
FACIAL PAIN

Moderators: Mojgan HODAIE (Attending Neurosurgeon) (Toronto, Canada, CANADA), Ludvic ZRINZO (London, UK)
Plenary Speaker: Kim BURCHIEL (Portland, Oregon, USA)

15:15-15:45
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KL15
PARALLEL SESSIONS: KEYNOTE LECTURES
NEW DBS ELECTRODES

PARALLEL SESSIONS: KEYNOTE LECTURES
NEW DBS ELECTRODES

Moderators: Faisal AL OTAIBI (Riyadh, SAUDI ARABIA), Constantin TULEASCA (Resident) (Lausanne, SWITZERLAND)
Plenary Speaker: François ALESCH (Vienna, AUSTRIA)

15:15-15:45
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KL14
PARALLEL SESSIONS: KEYNOTE LECTURES
CONTROVERSIES IN MD TREATMENT HIFU VS. RADIOSURGERY

PARALLEL SESSIONS: KEYNOTE LECTURES
CONTROVERSIES IN MD TREATMENT HIFU VS. RADIOSURGERY

Moderators: Jean CIUREA (head of the dept) (Bucharest, ROMANIA), Andrey GOLANOV (Head of the Department) (Moscow, RUSSIA)
Keynote Speaker: Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)

15:45
15:45-16:45
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OPS12
OPS12 PARALLEL SESSIONS: ORAL PRESENTATIONS

OPS12 PARALLEL SESSIONS: ORAL PRESENTATIONS

Moderators: Mojgan HODAIE (Attending Neurosurgeon) (Toronto, Canada, CANADA), Ludvic ZRINZO (London, UK)
15:45 - 15:57 #10336 - OP61 Thalamic Deep Brain Stimulation for neuropathic pain: efficacy at 3 years' follow-up.
Thalamic Deep Brain Stimulation for neuropathic pain: efficacy at 3 years' follow-up.

Object. Chronic neuropathic pain is estimated to affect 3%-4,5% of the worldwide population. Deep Brain Stimulation (DBS) is established for movement disorders but, for the treatment of chronic, drug refractory, neuropathic pain, DBS has shown variable outcomes, in the few studies performed in the past. Thus, this procedure has consensus approval in parts of Europe but not in the USA. This study prospectively evaluated the efficacy at 3 years of DBS for neuropathic pain.

 

Methods. Sixteen consecutive patients received 36 months post-surgical follow-up in a single-center. Five had phantom limb pain after amputation and eleven deafferentation pain after brachial plexus avulsion (BPA), all due to trauma. To evaluate the efficacy of DBS, patient-reported outcome measures were collated before and after surgery, using a visual analogue scale (VAS) score, University of Washington Neuropathic Pain Score (UWNPS), Brief Pain Inventory (BPI), and 36-Item Short-Form Health Survey (SF-36).

 

Results. Contralateral ventroposterolateral sensory thalamic DBS was performed in sixteen patients with chronic neuropathic pain over 29 months. A postoperative trial of externalized DBS failed in one patient with BPA. Fifteen patients proceeded to implantation. One patient with phantom limb pain after amputation was lost for follow-up after 12 months. No surgical complications or stimulation side effects were noted. After 36 months, mean pain relief was sustained, and the median (and interquartile range) of the improvement of VAS score was 52.8% (45.4%) (p=0,00021), UWNPS was 30.7% (49.2%) (p=0,0590), BPI was 55.0 % (32.0%) (p=0,00737) and SF-36 was 16.3% (30.3%) (p=0,4754). Among the BPA patients, VAS score improved by 40% (31,9%) (p=0.01298), UWNPS by 22.7% (37.1%) (p=0.4632), BPI by 47.8% (62.8%) (p=0.189) and SF-36 by 16.0% (42.7%) (p=0.9953). In the amputation group, after 36 months median VAS score improved by 66.7% (51.7%) (p=0.0494), UWNPS by 50.8% (62.9%) (p=0.3225), BPI by 65.2% (31.6%) (p=0.1623) and SF-36 by 16.7% (140,2%) (p=0.2406). Initial mean parameters were 2.1V, 23Hz and 187 µs and after 36 months both amplitude and pulse width were increased with parameters of 4.1V, 15 Hz and 196 µs.

 

Conclusions. DBS demonstrated efficacy at 3 years for chronic neuropathic pain after traumatic amputation and BPA, with benefits sustained across all pain outcome measures and slightly greater improvement in phantom limb pain.

Pedro MONTEIRO (PORTO, PORTUGAL), Vasco ABREU, Rui VAZ, Pedro ABREU, Virginia REBELO, Maria José ROSAS, Paulo LINHARES, Martin GILLIES, Tipu AZIZ, Erlick PEREIRA
15:57 - 16:09 #10489 - OP62 Bifocal thalamic deep brain stimulation for treatment of chronic neuropathic pain.
Bifocal thalamic deep brain stimulation for treatment of chronic neuropathic pain.

Objective: To assess long-term efficacy of deep brain stimulation (DBS) for chronic neuropathic pain in consecutive patient.

Methods: Patients with chronic neuropathic pain which were refractory to medication underwent bifocal thalamic implantation of DBS electrodes. Targets were the centromedian parafascicular nucleus (CM-Pf) and somatosensory thalamus (either nucleus ventralis postereolateralis, VPL, or ventralis postereomedialis, VPM) Elektrodes were implanted by CT-stereotactic surgery and externalized for 4-14 days to assess the effect of the two targets and to decide whether chronic stimulation could be administrated. Therefore DBS electrodes were either removed or a pulse generator was implanted. Assesment of pain included VAS scores and patient self rating. Patients were follow-up regularly at annual visits on longterm.

 

RESULTS :Over a period of 16 years, a total of forty patients (20 women, 20 men; mean age of surgery 53.8 years, range 24-73 years) underwent bifocal implantation of thalamic DBS electrodes. Etiologies included central pain after stroke or hemorrhage (11 patients), complex regional pain syndrome (10 patients), a typical facial pain (5 patients), post Zoster pain (4 patients), post-amputation pain (2 patients), myelon injury (2 patients), and others. There were no surgical complications. Impulse generator were implanted in 33/40 patients for chronic stimulation, while 7 patients did not a chieve adequate benefit during test stimulation. Three patients were lost to follow-up in longterm followup, and in five patients the neurostimulation system was explanted due to infection. On longterm 20/33 had chronic CM-Pf stimulation and 13/33 had VPL/VPM stimulation. The properties of marked/ excellent vs moderate/ minor vs no improvement was similar with both targets in longterm follow-up according to patient self-rating.

 

Conclusion: Thalamic DBS is a useful treatment option in selected patients with severe and medically refractory neuropathic pain. While some patients achieve greater benefit with CM-Pf stimulation (which is thought to represent the paleospinothalamic projection associated with the sensation of unpleasant of pain), others prefer somatosensory thalamic stimulation (which relates to the neospinothalamic pathway transferring the most immediate pain experience. Bifocal implantation is helpful to select the optimal stimulation target in the individual patient.

Mahmoud ABDALLAT (Amman, JORDAN), Andreas WLOCH, Joachim K. KRAUSS
16:09 - 16:21 #10243 - OP63 Stereotactic anterior cingulotomy for intractable oncological pain.
Stereotactic anterior cingulotomy for intractable oncological pain.

Background

Stereotactic anterior cingulotomy has been reported to be effective in the treatment of patients suffering from refractory oncological pain by influencing pain perception. However, the optimal target as well as suitable candidates have not been well defined. We have established a specialized palliative service consisting of palliative care specialists, pain specialists and a neurosurgeon to aid in the patients’ selection process and outcome assessment. We report our initial experience in the ablation of two cingulotomies targets on each side and the use of brief pain inventory (BPI) as a perioperative assessment tool. 

Methods

This is a retrospective review of all patients who underwent stereotactic anterior cingulotomy in our department between November 2015 and February 2017. All patients had advanced metastatic cancer with limited prognosis and suffered from intractable oncological pain.

Results

Thirteen patients (10 females) underwent 14 cingulotomy procedures. Mean age was 56±13.5, and median KPS was 50. Median pain duration was 12 months (range 1-48). All patients reported significant pain relief immediately after the operation and out of the 6 pre-operatively bedridden patients, 3 started ambulating shortly after. Eight patients were discharged home, 3 were referred for rehabilitation and 2 for hospice care. Median pre-operative and post-operative VAS scores were 9/10 (range 8-10) and 3/10 (range 0-5), respectively. Mean pre-operative BPI pain severity and interference scores were 30±12 and 59±11, respectively, as compared with post-operative values of 14±9 and 32± 13, respectively. During the 1-month and 3-months follow-up visits, 10/11 patients (90%) and 5/7 patients (71%) available for follow-up, reported significant pain relief. No patient reported worsening of the pain.

Adverse events included transient confusion or mild apathy in 5 patients (38%) lasting 1-4 weeks. Two of these patients developed transient urinary incontinence that resolved after 1 week.

Neuropsychological analyses of 5 patients showed mild deficits in focused attention and visual memory, while the rest of cognitive functions were relatively stable. There was a significant improvement in depression symptoms.

Conclusions

Two-target stereotactic cingulotomy is safe and effective in alleviating refractory pain of cancer patients. BPI score may add to VAS for the evaluation of response to cingulotomy. No substantial cognitive changes were detected.

Ido STRAUSS (Tel Aviv, ISRAEL), Assaf BERGER, Shlomit BEN MOSHE, Tal GONEN, Rotem TELLEM
16:21 - 16:33 #10093 - OP64 Extended dorsal root entry zone-lesioning for alleviating intractable arm pain following brachial plexus avulsion injury.
Extended dorsal root entry zone-lesioning for alleviating intractable arm pain following brachial plexus avulsion injury.

Introduction

Arm pain following brachial plexus avulsion injury is known to be refractory to any conventional method for pain relief. Dorsal root entry zone (DREZ)-lesioning has been the most effective surgical treatment for the relief of pain this kind. However, residual pain and a decrease in pain relief in the follow-up period have been reported in 23-70% of patients. Based on the most recent studies on neuropathic pain, we modified the conventional DREZ lesioning procedure to improve clinical outcomes.

Methods

Both the original DREZ-lesioning, employing electrode insertion and coagulation technique by Nashold and microsurgical technique by Sindou, intended destruction of the dorsal horn cells at Rexed layer I & II. We extended area of microsurgical destruction deep into Rexed layer V.

Fourteen patients underwent surgery between 2011 and 2017.

Results

All patients achieved excellent (n=10, pain relief without medication) or good (n=4, pain relief with medication) pain relief post-operatively, and the recurrence was not reported in any patients (median of 28 months after surgery,6-84 months).

Twelve patients (88%) achieved total pain relief (0 or 1 on the VAS) with or without medication.

Although, intraoperative MEP amplitude attenuation down to 10% of the original level were observed in 1/3 of the cases, no motor deficit was observed.

A sensory deficit was observed in 2 patients and disappeared within one month in 1 patient. New pain at the adjacent level of DREZ lesioning was observed in 3 patients and disappeared within one month in 2 patients. In the other patient, new pain persisted and required analgesics.

The most prominent gliotic change were observed at the gray matter of the spinal segment which was compatible with the most painful area.

Conclusion

Our preliminary results demonstrated that total and persistent global pain relief was achieved with the modified DREZ lesioning procedure in 90% of patients without major neurological deficits. Our results clearly suggested that the wide dynamic range neuron in Rexed layer V played a cardinal role in pain formation in case of brachial plexus avulsion injury.

Makoto TANIGUCHI (Fucyu / Tokyo, JAPAN), Keisuke TAKAI, Hirokazu IWAMURO
16:33 - 16:45 #10496 - OP65 Deep Cerebellar Stimulation For Post-Stroke Motor Recovery: Early Trial Experience.
Deep Cerebellar Stimulation For Post-Stroke Motor Recovery: Early Trial Experience.

OBJECTIVE: To review our initial experience with a first-in-human FDA-approved trial of deep cerebellar nucleus deep brain stimulation (DBS) for post-stroke recovery, including intraoperative physiological data and observations as well as the effects of acute stimulation titration on behavior and on cortical excitability indexed by transcranial magnetic stimulation (TMS).

 

BACKGROUND: Over the past decade, our group has demonstrated that chronic electrical stimulation of the lateral cerebellar nucleus (LCN) can enhance motor recovery following cortical ischemia in preclinical rodent models. Those motor rehabilitative findings were accompanied by enhanced synaptogenesis and increased expression of markers of long-term potentiation in perilesional cortex as well as modulation of cortical excitability and motor representation.

METHODS: All data are being collected as part of a first-in-man, single-center, prospective, open-label, single-arm, safety and feasibility trial for patients with persistent (>12 months post-stroke), moderate-to-severe upper extremity hemiparesis secondary to middle cerebral artery ischemic stroke.

 

RESULTS: Two participants have been enrolled to date. In addition to safety and feasibility indices we will present measures of therapeutic efficacy as well as modulation of perilesional cortical excitability and changes in motor representations measured by TMS. Intraoperative electrophysiological data including EEG and local field potential data acquired during lead implantation will also be presented. Finally, we will review our development of patient-specific biophysical models of DBS of the dentatothalamocortical network based upon pre- and post-operative imaging data.

 

CONCLUSION: This study and its data represent the initial steps in the translation of more than a decade worth of preclinical work towards the development of deep brain stimulation of the dentatothalamocortical pathway as a therapy for post-stroke motor rehabilitation. Its review will provide an interactive forum concerning the process and timing of translating neurostimulation-based research for neurorehabilitation.

Kenneth BAKER, Ela PLOW, Scott LEMPKA, Andre MACHADO (Cleveland, USA)

15:45-16:45
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