Wednesday 26 September
15:00

Wednesday 26 September

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D12
15:00 - 15:30

WELCOME COFFEE

WOLFSON HALL B
15:30

Wednesday 26 September

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D11
15:30 - 18:00

Pre-congress for Psychiatrists (special event)

Moderators: Benjamin GREENBERG (USA), Keith MATTHEWS (Professor) (Dundee, UK)
15:30 - 16:30 Neurosurgery for mental disorders: Guidelines on pre- and post-surgical management. Keith MATTHEWS (Professor) (Dundee, UK), Benjamin GREENBERG (USA)
15:30 - 18:00
1. Welcome and Introductions
2. Agenda Setting
3. “Things I have learned” – brief presentations by attendees.
4. Pre-Operative Patient Assessment: lessons and suggestions
5. Post-Operative Management: lessons and suggestions
6. Educational / Training Opportunities
7. AoCB
16:30 - 16:40 #15021 - OP001 Ethics of deep brain stimulation in adolescent patients with refractory tourette syndrome.
OP001 Ethics of deep brain stimulation in adolescent patients with refractory tourette syndrome.

Introduction: Tourette Syndrome (TS) is a childhood onset disorder characterized by vocal and motor tics and often remits spontaneously during adolescence. For treatment refractory patients, Deep Brain Stimulation (DBS) may be considered. This paper deals with ethical issues associated with DBS of adolescent TS patients (10-25 years of age).

Methods: We describe our experiences with the treatment of two adolescent TS patients and systematically review the scarce literature on this subject. We discuss the ethical issues and specific difficulties that physicians may encounter when treating adolescent patients.

Results: Following surgery one patient experienced side effects without sufficient therapeutic effects and the stimulator was turned off. After a second series of behavioural treatment, he experienced a tic reduction of more than 50% after two years. The reduction may be due to natural waning of tics that often follows adolescence and due to an additional behavioural treatment for tics after the DBS. At present, he is satisfied with the level of symptoms and would not consider the surgery anymore. The second patient is responding well to the stimulation but went through a period of behavioural disturbances which are not uncommon during adolescence but interfered with optimal programming. We believe that the experienced stress before, around, and after the surgery might have provoked the excessive use of cannabis and caused the related behavioural disturbances. After one year he experienced a 70% tic reduction. Sixteen DBS surgeries in adolescent TS patients have been reported. So far, detailed case descriptions are lacking and no attention has been paid on the ethical issues and specific difficulties that physicians may encounter when treating adolescent TS patients. As such we conclude that there is yet no literature on ethical aspects of performing DBS on TS patients, let alone on adolescent TS patients (Table 1).

Discussion: Specific ethical issues arise in adolescent TS patients undergoing DBS relating both to clinical practice as well as to research. Attention should be paid to selecting patients fairly, thorough examination and weighing of risks and benefits, protecting the health of children and adolescents receiving DBS, special issues concerning patient’s autonomy, and the normative impact of quality of life. In research, registration of all TS cases in a central database covering a range of standardized information will facilitate further development of DBS for this indication.

Conclusion: DBS surgery for TS patients has lately been considered at an earlier age because more stress has been placed on the potential long lasting harmful effects of the disorder. Specific ethical issues arise in this age-group relating both to clinical practice as well as to research. Clinical practice should be accompanied by ongoing ethical reflection, preferably covering not only theoretical thought but providing also insights in the views and perspectives of those concerned, that is patients, family members and professionals. Examining the ethical issues of DBS may help to realize its entire potential for benefiting severely suffering TS patients.

Anouk SMEETS (Hulsberg, THE NETHERLANDS), Annelien DUITS, Dorothee HORSTKÖTTER , Cara VERDELLEN, Guido DE WERT, Yasin TEMEL, Linda ACKERMANS, Albert LEENTJENS
16:40 - 16:50 #16233 - OP002 Comparison of guidelines for the treatment of psychiatric disorders: a focus on neurosurgical techniques.
OP002 Comparison of guidelines for the treatment of psychiatric disorders: a focus on neurosurgical techniques.

We propose to determine the level of agreement across a set of evidence- based guidelines for management of the psychiatric disorders and with a focus on neurosurgical treatments.

Raphaelle RICHIERI (Marseille), Jean REGIS, Giorgio SPATOLA
WOLFSON HALL B
18:30

Wednesday 26 September

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A13
18:30 - 19:10

Congress Opening Ceremony

Moderator: Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
18:30 - 18:35 Chairmen’s Welcome. Marwan HARIZ (London, UK), Keith MATTHEWS (Professor) (Dundee, UK), Ludvic ZRINZO (London, UK)
18:35 - 18:45 Welcome address. Dan LEKSELL (Chairman) (Stockholm, SWEDEN)
18:45 - 19:05 The History of Medicine and Neuroscience in Edinburgh’. David Cunningham OWENS (Psychiatrist) (Edinburgh, UK)
FESTIVAL THEATRE AUDITORIUM
19:10

Wednesday 26 September

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A15
19:10 - 20:00

Welcome Reception in the exhibition area

FESTIVAL THEATRE AUDITORIUM
Thursday 27 September
08:30

Thursday 27 September

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A21
08:30 - 10:00

Plenary Session 1
Opening ceremony & special lectures

Moderators: Marwan HARIZ (London, UK), Keith MATTHEWS (Professor) (Dundee, UK)
08:30 - 08:45 Congress chairmen & Congress President: "FIRST meeting in Edinburgh in 1972". Marwan HARIZ (London, UK), Keith MATTHEWS (Professor) (Dundee, UK), Ludvic ZRINZO (London, UK), Damianos SAKAS (ATHENS, GREECE)
08:45 - 09:00 Revival of British stereotactic surgery 1974-2008; A personal perspective. T.r.k VARMA (UK)
09:00 - 09:15 Capsulotomy for depression; the Cardiff experience. Brian SIMPSON (Invited speaker) (Cardiff, UK, UK)
09:15 - 09:30 History of British stereotactic and functional Neurosurgery. Erlick PEREIRA (Consultant Neurosurgeon) (London, UK)
09:30 - 09:45 Why Psychiatry needs new treatments. Guy GOODWIN (speaker) (Oxford, UK)
09:45 - 10:00 40 years experience in Surgery for Psychiatry. Rees COSGROVE (Director, Epilepsy and Functional Neurosurgery) (Boston, USA)
FESTIVAL THEATRE AUDITORIUM
10:00

Thursday 27 September

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A22
10:00 - 10:30

COFFEE BREAK & VISIT OF POSTERS AND EXHIBITION

FESTIVAL THEATRE AUDITORIUM
10:30

Thursday 27 September

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A23
10:30 - 12:00

Plenary Session 2
Surgery for OCD

Moderators: Rees COSGROVE (Director, Epilepsy and Functional Neurosurgery) (Boston, USA), Eileen JOYCE (Consultant) (London, UK), Keith MATTHEWS (Professor) (Dundee, UK)
10:30 - 10:50 Understanding the neurocircuitry of OCD. Trevor ROBBINS (UK)
10:50 - 11:00 Patient selection for OCD. Keith MATTHEWS (Professor) (Dundee, UK)
11:00 - 11:15 #16165 - O001 Targeting deep brain stimulation in obsessive-compulsive disorder: lessons learned from 71 consecutive cases.
O001 Targeting deep brain stimulation in obsessive-compulsive disorder: lessons learned from 71 consecutive cases.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder characterised by persistent thoughts and repetitive ritualistic behaviours. Despite optimal cognitive-behavioural and pharmacological therapy, approximately 10% of patients remain treatment resistant. Since 2005 we investigated deep brain stimulation (DBS) as experimental therapy for treatment-refractory OCD. Thus far, we operated 71 patients. In the first 28 patients, quadripolar DBS electrodes (Medtronic model 3389 with 1.5 mm contacts and 0.5 mm interspace) were targeted with the lowest two contacts in the nucleus accumbens (NAc). Activation of these NAc contacts, however, did not improve OCD symptoms whereas activation of the upper two electrode contacts improved OCD symptoms by >35% in 15 patients (i.e. 54% responders). While evaluating the relationship between the anatomical location of active electrode contacts and clinical outcome, active contacts located bilaterally in the ventral part of the anterior limb of the internal capsule (ventral ALIC, vALIC) correlated with a good response to DBS whereas active contacts in or adjacent to the caudate nucleus (Cd) hardly improved symptoms. To improve the response rate, we therefore targeted the middle two contacts to vALIC in the next 39 patients. Unexpectedly, only 16 patients responded to DBS (41%). To better understand these variable results, we performed tractography analysis and found that active contacts closer to the medial forebrain bundle (MFB) correlated with better outcome. In the most recent four patients, we therefore incorporated the location of the MFB (which’ location within the ALIC varied considerably from one patient to another) into our surgical targeting plan: all four responded to DBS. These findings strongly suggest that DBS for OCD may benefit from MFB-specific electrode implantation.

Pepijn VAN DEN MUNCKHOF (Amsterdam, THE NETHERLANDS), Martijn FIGEE, Luka LIEBRAND, Maarten BOT, Matthan CAAN, Pieter OOMS, Nienke VULINK, Pelle DE KONING, Guido VAN WINGEN, Damiaan DENYS, Rick SCHUURMAN
11:15 - 11:30 Stereotactic ablation for OCD. Rees COSGROVE (Director, Epilepsy and Functional Neurosurgery) (Boston, USA)
11:30 - 11:45 The psychiatrist perspective on surgical results in OCD. Benjamin GREENBERG (USA)
11:45 - 11:55 #16322 - O002 Anterior capsulotomy for the treatment of obsessive compulsive disorder – a review of old and new literature.
O002 Anterior capsulotomy for the treatment of obsessive compulsive disorder – a review of old and new literature.

Introduction

Neurosurgery for Obsessive Compulsive Disorder (OCD) has undergone a renaissance thanks to the use of deep brain stimulation (DBS). This has, paradoxically, reinvigorated stereotactic lesional neurosurgery, especially anterior capsulotomy. However, the universally accepted scale for reporting severity of OCD, - the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was only published and validated in 1989.(1) The aim of this paper is to assess both historical and modern outcomes of anterior capsulotomy (AC) in the treatment of OCD to help direct further treatment in this highly refractory and difficult to treat population.

 

Methods

The literature on AC for OCD was extensively searched. Publications from 1961 to 2018 were scrutinized. Patients´ baseline characteristics and outcomes were noted. Patients were grouped according to whether published Y-BOCS scores were available or not. Those with a Y-BOCS score were stratified into “severity groups” according to preoperative score as follows: Moderate: 16-23; severe: 24-31 and extreme: 32-40. These groups were separated into outcome measures based on a modified version of the Christmas criteria. Remission (Group A) is defined as Y-BOCS reduction to below 8. Good response requires Y-BOCS < 16 (Group B). Response is defined as 35% improvement or more in Y-BOCS (Group C). Non-responder is when remission or response criteria are not met (Group D). Worse indicates a worsening of the Y-BOCS score (Group E). Patients without reported Y-BOCS scores were grouped according to the clinical description (Remission: symptom free, Good Response: Live independently, Response: social function improved, or No response/worse).

 

Results

A total of 500 patients were identified. In the Y-BOCS group (n=266) Three quarters of patients responded and two fifths went into remission. In the group without Y-BOCS (n=234) 90% of patients responded and 39% of patients went into remission. Common complications included weight gain (18% patients) and personality change (7% patients). The risk of significant complications was 4.9% (suicide 0.3%, attempted suicide 1.7%, intracranial bleed 1.5%, focal deficit 1.2%, epilepsy 0.3%). Surgical complications were partly dependent on the method used (Leucotome, radiofrequency coagulation, gamma-knife or Focused ultrasound).

 

Conclusion

Anterior capsulotomy is an effective procedure for medical refractory OCD. The stigma surrounding the use of anterior capsulotomy in OCD is based more on historical prejudice and possible conflation with lobotomy, than on fact.

 

1. Goodman, W.K. et al., 1989. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Archives of General Psychiatry, 46(11), pp.1012–1016.

 

Joshua PEPPER (Birmingham, UK), Ludvic ZRINZO, Marwan HARIZ
11:55 - 12:00 Discussion.
FESTIVAL THEATRE AUDITORIUM
12:00

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A25
12:00 - 13:30

LUNCH BREAK & VISIT OF POSTERS AND EXHIBITION

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B24
12:00 - 13:30

INDUSTRY LUNCH WORKSHOP

WOLFSON HALL A

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C24
12:00 - 13:30

INDUSTRY LUNCH WORKSHOP

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Thursday 27 September

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D24
12:00 - 13:30

INDUSTRY LUNCH WORKSHOP

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Thursday 27 September

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A24
12:00 - 13:30

INDUSTRY LUNCH WORKSHOP

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13:30

Thursday 27 September

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A26
13:30 - 15:00

Plenary Session 3
Surgery for Epilepsy

Moderators: Robert GROSS (Neurosurgeon, MD/PhD Dir, eNTICE Chair, SOM Faculty) (Atlanta, USA), Kai LEHTIMÄKI (Associate Professor in Neurosurgery) (Tampere, FINLAND), Richard SELWAY (Consultant Neurosurgeon) (London, UK)
13:30 - 13:45 Sir Victor Horsley: A View From Across the Pond. Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)
13:45 - 14:00 DBS Ant nucleus. Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (LISBON, PORTUGAL)
14:00 - 14:15 Centromedianum Stimulation. Richard SELWAY (Consultant Neurosurgeon) (London, UK)
14:15 - 14:30 Hippocampal stimulation. Dirk VAN ROOST (Head of Department) (Ghent, BELGIUM)
14:30 - 14:45 LITE in Epilepsy Surgery. Robert GROSS (Neurosurgeon, MD/PhD Dir, eNTICE Chair, SOM Faculty) (Atlanta, USA)
14:45 - 14:55 #16310 - O003 Vagus nerve stimulation for refractory epilepsy: two-year outcomes from a single center.
O003 Vagus nerve stimulation for refractory epilepsy: two-year outcomes from a single center.

Vagus nerve stimulation (VNS) is an established palliative therapy for refractory epilepsy patients that are not candidates for curative surgery. Despite its benefit, much remains to be understood, namely predictors of seizure control failure and of patient satisfaction. To further study these subjects, we hereby report our single-center experience.

We performed a descriptive and inferential retrospective analysis of the VNS performed at our center. Epidemiological and clinical characteristics were summarized and results were analyzed, according to Engel Outcome Scale, antiepileptic drugs (AED) reduction, complications and subjective report by patients and families.

A total of 107 VNS procedures were performed between 2000 and 2016. Patients were predominantly male (57%), with an average age at epilepsy onset of 5.6±6.6 years. Epilepsy was classified as structural in 46%, syndromic in 24%, genetic in 17%, immunologic in 0.9% and unknown in 12%.  Age and duration of symptoms at surgery were 25.7±13.6 and 20.2±11.6 years, respectively. At two-year follow-up, the majority (66.0%) of patients achieved a worthwhile improvement in seizure control, with Engel Class I attained in 12.3%, Engel II in 17.9%, Engel III in 35.8% and Engel IV in 34.0% of cases. Reduction in seizures’ frequency and duration was observed in 52.8% and 55.7%, respectively. Additionally, fall events were abolished in 15.1% of cases. An AED dose reduction was possible in 44.9%. Patients reported a subjective improvement in 60.4% of cases, no improvement/no worsening in 38.7% and worsening in 0.9%. No intra-operative complications were observed. Early and late post-operative complications occurred in 26.2% and 18.7% of cases, respectively. Specifically, voice-related side effects, cough paroxysms and infection were observed in 21.5%, 12.1% and 2.8% of cases, respectively.

On a multivariate analysis, complication occurrence was associated with a worse Engel Outcome classification (p=0.004). More specifically, complication occurrence and voice-related side effects presented an odds ratio (OR) of 8.5 (95% confidence interval [CI] 2.2-33.0) and 19.6 (CI 3.9-98.8) for Engel IV outcome, respectively. Moreover, lack of seizures frequency reduction was also associated with voice-related side-effects (OR 27.2, 95%CI 3.5-209.3). AED reduction was associated with older age at symptom onset (average 7.1 vs 4.3 years, p=0.03). Subjectively reported improvement was associated with younger age at surgery (average 22.1 vs 30.8 years, p<0.001) and shorter interval between symptom onset and surgery (average 17.4 vs 24.0 years, p=0.002). Conversely, complication occurrence was associated with older age at surgery and longer interval between symptom onset and surgery (average 23.4 vs 30.4 years, p=0.009, and 18.6 vs 23.2 years, p=0.043, respectively).

VNS represents a valuable option for refractory epilepsy. Seizure control outcomes appear to be tightly related with surgical complications, specially voice-related side effects. Additionally, both subjective improvement and complications appear to be optimal in younger patients and in those who wait a shorter time for surgery, suggesting that an earlier, lower-threshold surgical pathway might increase this procedure’s usefulness. More studies are needed to validate and further explore these results.

Vasco PINTO (Porto, PORTUGAL), Inês LARANJINHA, Sérgio SOUSA, João CHAVES, Rui RANGEL
14:55 - 15:00 Discussion.
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15:00

Thursday 27 September

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A27
15:00 - 15:30

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15:30

Thursday 27 September

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A28
15:30 - 17:00

Parallel Session 1
Rehabilitation

Moderators: Jocelyne BLOCH (Médecin Cadre) (Lausanne, SWITZERLAND), Robert BROWNSTONE (N/A) (London, UK), Ali SAVAS (NA) (ANKARA, TURKEY)
15:30 - 15:50 Spinal cord stim for repair. Jocelyne BLOCH (Médecin Cadre) (Lausanne, SWITZERLAND)
15:50 - 16:10 Neuromodulation of wakefulness. Damianos SAKAS (ATHENS, GREECE)
16:10 - 16:30 #15505 - O004 Deep brain stimulation for the early treatment of the minimal conscious sate and vegetative state.
Deep brain stimulation for the early treatment of the minimal conscious sate and vegetative state.

Introduction: An effective treatment of minimal conscious state (MCS) and vegetative state (VS), caused by hypoxic encephalopathy (HE) or traumatic brain injury (TBI), has not been yet revealed. Several studies with deep brain stimulation of thalamic nuclei in MCS and VS patients were published with most patients after TBI. The aim of our study is to find out the possibility of DBS as a therapy for patients in VS or MCS particularly in earlier phase when the irreversible changes of muscles and joints are not so pronounced.

Methods: Fourteen patients were included four patients with TBI and 10 with HE. Four of them were in MCS and 10 in VS. Entry criteria included an evaluation neurological status including Rappaport Coma/Near coma scale, electrophysiological status with multimodal evoked potential and 12/24 hours of EEG, and neuroimaging (positron emission tomography and magnetic resonance imaging).

The stimulation target was centromedian-parafascicular nucleus complex in the left hemisphere or more preserved hemisphere in patients with TBI.  Patients were stimulated daily for 30 minutes every three hours. The parameters of stimulation were as follows: monopolar, intensity to induce "arousal reaction", frequency 25-30 Hz, pulse duration 220 µs. Follow up was from 30 to 54 months. 

Results: Two MCS patients regained consciousness, walking without help, speaking fluently with impressive speech comprehension and no need for assistance in everyday life.  One MCS patient reach to the level of consciousness however she is still in wheelchair. One VS patient after ischemic lesion improved to the level of consciousness with possibility of nonverbal communication. Three VS patients died from respiratory infection or sepsis. Other 7 patients, six in VS and one in MCS, remained without substantial improvement of consciousness.

Conclusion: For the VS or MCS patients that fulfill clinical, neurophysiological and neuroimaging criteria the DBS of thalamic nuclei could be advised as an option and could be started at rather early stage. We did not figure out neurophysiologic, imaging or clinical marker(s) predicting recovery of patients having very similar features.  The studies, which could solve these dilemmas, have to be designed not only using reliable scientific methods but also solving some ethical questions which are specific and more demanding in VS and MCS patients than others.

Darko CHUDY (Zagreb, CROATIA), Vedran DELETIS
16:30 - 16:40 #16178 - O005 Minimally invasive spinal surgery in treatment of spastic paraplegia . ( 75 cases).
Minimally invasive spinal surgery in treatment of spastic paraplegia . ( 75 cases).

Introduction: The spasticity becomes very often rebel to medical and physiotherapic treatments.Neurosurgical procedures aim to re establish the tonic balance between agonist and antagonist muscles .Selective dorsal rhizotomy is today a primary treatment for spastic pararplegia.

Methods: 75 patients suffered from spastic pararplegia were selected by a multidisciplinary team using clinical,analytical and functionnal scales.They have underwent selective dorsal rhizotomy.The age of these patients varied between 23 to 61 year with a lear mal predominance .The origin of spasticity was spinal cord injury in 41 cases(54,66%), multiples sclerosis in 20 patients (26,66%),genetic hereditary disease in 10 cases (13,33%), degenerative spine in 3cases (4,1%), B12 vitamin deficiency in 1 case(1,33%).

Results: This study schows a schort ,medium and long term follow up evaluation (Mean duration11 years),that the post operative results were satisfactory in 75% of the cases who acqueried a better quality of life .

Conclusion: Selective dorsal rhizotomy is a minimally invasive spinal surgery to treat spastic pararplegia .This procedure leads to long term satisfactory improvement in confort,nursing, dressing and in some cases unmask motor performance.

Lila MAHFOUF (Algiers, ALGERIA), Brahim MERROUCHE, Benaissa ABDENNEBI
16:40 - 16:50 #16317 - O006 The impact of combined anterior and posterior lumbar rhizotomy on spinal interneuron activity one year post-operative; The indirect neuromodulation.
The impact of combined anterior and posterior lumbar rhizotomy on spinal interneuron activity one year post-operative; The indirect neuromodulation.

Background: Children with cerebral palsy (CP) may present with severe mixed forms of hypertonia and contractures of their extremities. Combined anterior and posterior lumbar rhizotomy (CAPR) is an emerging surgical technique for treatment of mixed hypertonia in cerebral palsy. Obvious improvement of function following such surgery points out to changes in central neuronal plasticity. Many trials have been made to quantify the measurements of hypertonia; the electrophysiologic assessments including the motor nerve conduction studies and its late responses (H reflex, Hmax\Mmax ratio, F wave, and F\M ratio) had been considered as an objective quantified measurements.

Objectives: In this study, we investigated the possible changes in excitability of the spinal interneurons in CP children following combined anterior and posterior lumbar rhizotomy.

Patients and methods: Children were subjected to pre-operative and 12 months post-operative clinical and electrophysiologic assessment. Clinical evaluation involved assessment of muscle tone, the modified Ashworth scale (MAS) was used, and the gross motor function measurement (GMFM-66). Electrophysiologic assessment of the H\M and F\M ratios was performed. Recording of the electrophysiologic data was obtained after tibial nerve stimulation at the popliteal fossa and the ankle.

Results: Forty children were included in this study; the mean age was 5.75 years. Significant reduction of the mean muscle tone was noted from 3.57 to 1.97. The changes in the electrophysiologic findings were significant, the H\M ratio changed from a mean of 0.518 to 0.081 (P value: 0.000), and the F\M ratio changed from a mean of 0.126 to 0.065 (P value: 0.000).

Conclusion: This study demonstrates the potentials of the combined anterior and posterior lumbar rhizotomy to improve the neuroplasticity of spinal interneurons as evidenced by both clinical as well as the electrophysiologic measurement in CP children.

Walid ABDEL GHANY (Cairo, EGYPT), Mohamed NADA, Marwa NASSEF, Tamer SABRY, Mennatallah SHATA, Ahmad SAEED ALY, Shady MAHMOUD
16:50 - 17:00 Discussion.
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Thursday 27 September

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B28
15:30 - 17:00

Parallel Session 2
Movement Disorders / Dystonia

Moderators: Joachim K. KRAUSS (HANNOVER, GERMANY), Ioannis PANOURGIAS (DOCTOR) (ATHENS, GREECE), Sarah PERIDES (Advanced Nurse Practitioner) (London, UK)
15:30 - 15:45 20 years experience of DBS for paediatric dystonia. Laura CIF (Montpellier, FRANCE)
15:45 - 15:55 #14670 - O007 Deep brain stimulation neuromodulation reduces severe dystonic pain in children and young people.
O007 Deep brain stimulation neuromodulation reduces severe dystonic pain in children and young people.

Objective - This review analyses the prevalence of painful dystonia in a cohort of children undergoing neuromodulaton. The aim was to better understand the dystonic pain experience and evaluate the improvements one year following deep brain stimulation (DBS).

Background - Dystonic pain is reported as prevalent, however it is yet to be systematically evaluated. There is an overall paucity of literature evaluating the effects of DBS on dystonic pain using validated, reliable methods. The methods that have been used are varied and at times inappropriate for the population being assessed.

Methods - Dystonic pain was assessed in a cohort of children (n= 144) undergoing DBS. Assessment was multi-modal, six different pain assessment methods were used; intendity (proxy - Paediatric Pain profile and self-report - Numerical rating scale-11), parental perception (CPChild Questionnaire), pain frequenct, pain severity and analgesia use. SPSS version 21 was used to analyse the data. Data was analysed on the whole cohort, but also by aetiological sub-classification; inherited DYT positive dystonias (n=8), inherited heredodegenerative dystonias (n=9), acquired dystonias (n= 37) including cerebral palsy (n=21) and idiopathic dystonias (n= 8).

Results - 44.5% (63/144) of this cohort reported dystonic pain. Pain improved after DBS surgery in each group. Clinically significant improvements P<0.001 were noted in whole cohort, using NRS-11 (n=27/63), PPP (n=17/63) and the CPCHILD (n=48/63 assessments. Subjective reductions in frequency and severity were also reported. Very severe pain fell in 9/28 (30%) cases. Constant pain fell from 27/63 to 11/63, a 40.7% reduction and 18/63 (28.6%) became pain free. We found a 40% reduction in children receiving daily analgesia and an increase in 46.1% not requiring any. Whole cohort finds were comparable with the sub-classification except the heredodegenerative group, where subjective improvements were noted only.

Conclusion - This is the first evaluation focussing on the impact of DBS surgery on dystonic pain in children. This unique dataset illustrates the specific improvements from DBS on dystonic pain. Together, intensity, frequency, duration and experience of pain was reportedly improved following DBS, these effects were sustained at one year post surgery. Whilst this sample is small it is actually larger then has been reported internationally elsewhere. Additionally a multi-assessment approach in pain research reduces the risk of bias in an otherwise challenging population. By employing a more thorough and systematic approach to pain assessment and by using both objective (analgesia use) and subjective (self-reort / proxy report) measures results can be considered both clinically and meaningfully important, which is the priority for patients experiencing pain.

Longitudinal data collection and the consideration of a multi-centre research project would improve validity and reliability further. However a reduction in dystonic pain should remain a goal for DBS surgery, particularly given the relationship between pain and poor quality of life, social isolation, self-perception and overall poor health status.

Sarah PERIDES (London, UK), Jean-Pierre LIN, Geraldine LEE, Hortensia GIMENO, Daniel LUMSDEN, Richard SELWAY, Keyoumars ASHKAN, Margaret KAMINSKA
15:55 - 16:00 #16148 - O008 Dystonic Tremulous Spasmodic Torticollis Treated by bilateral Deep Brain Stimulation. Case Series.
O008 Dystonic Tremulous Spasmodic Torticollis Treated by bilateral Deep Brain Stimulation. Case Series.

Background: The aim of the present study was to present a case series of 3 patients with longstanding debilitating dystonic tremulous spasmodic torticollis. Pharmacological treatment including benzodiazepines as well botulinum toxin injections failed to adequately control dystonic jerking movements of the head and  neck. The patients were referred for deep brain stimulation (DBS) surgery.

Material and Methods: Two patients underwent bilateral implantation of DBS leads into the posterolateral segment of the globus pallidus internus (GPi). 1 patient received implantation of left lead in the nucleus ventralis intermedius of the thalamus (Vim) and the right DBS lead in the GPi. All surgeries were uneventful. The formal preoperative objective assessment included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the motor score of Tremor Rating Scale (TRS). The postoperative TWSTRS and TRS assessments were done at 2 months postoperatively and every 6 months up to 36 months after surgery.

Results: At the last follow-up visit, the severity, disability and pain scores of TWSTRS were improved by 50 %, 54 % and 58 % respectively. The TRS improved by 72 % when compared to baseline TRS score.  There were no hardware-related complications over follow-up period.

Conclusion: Our preliminary experience gathered in 3 patients indicates that bilateral DBS can be an effective treatment for disabling tremulous spasmodic torticollis.

 

 

Michał SOBSTYL (Warsaw, POLAND), Tomasz PASTERSKI , Marta ALEKSANDROWICZ
16:00 - 16:05 #16172 - O009 A registry of real-world outcomes using deep brain stimulation for the treatment of dystonia.
O009 A registry of real-world outcomes using deep brain stimulation for the treatment of dystonia.

Objective: The objective of this device registry entails collecting clinical outcomes, economic value and technical performance of a Deep Brain Stimulation (DBS) system capable of multiple independent current control (MICC) for use in the treatment of dystonia. 

Background: Several studies have now published clinical outcomes using DBS for the treatment of dystonia encompassing a range of dystonic conditions including primary generalized, cervical dystonia, tardive dystonia, and other types of secondary dystonia, and all have reported effective results with use of DBS for the treatment of dystonia.  Here we report the initial outcomes from a multi-center registry of dystonia patients implanted with an MICC-based DBS system.

Methods: This is a prospective, on-label, multi-center, international registry study consisting of up to 200 patients implanted with a DBS system (Vercise, Boston Scientific) for use in the treatment of dystonia followed out to 3 years (post-implant) at up to 40 sites in Europe. Study assessments conducted will be based on dystonia sub-group, classification, and age and include (but not limited) to the following: Burke-Fahn-Marsden Dystonia Rating Scale, Clinical Global Impression of Change, Global Dystonia Scale, SF-36v2 or SF-10v2 Health Survey, and Toronto Western Spasmodic Torticollis Rating Scale. 

Results: Initial results of this on-going registry of DBS outcomes in dystonia patients will be reported. 

Conclusions: Large patient data registries may facilitate insights regarding real-world, clinical use of DBS. This registry represents the first comprehensive, large scale collection of outcomes associated with dystonia patients implanted with a DBS system capable of multiple independent current control (MICC) and will include assessment of economic value and device technical performance.

Joachim KRAUSS (HANNOVER, GERMANY), Claire NICHOLSON, Michael T. BARBE, Veerle VISSER-VANDEWALLE, Andrea KÜHN, Monika PÖTTER-NERGER, Alberto ALBANESE, Roshini JAIN, Heleen SCHOLTES, Nic VAN DYCK
16:05 - 16:10 #16180 - O010 Bilateral Deep-Brain Stimulation of the internus Globus Pallidus in Dystonia.
O010 Bilateral Deep-Brain Stimulation of the internus Globus Pallidus in Dystonia.

INTRODUCTION

Dystonia is a rare movement disorder. It is characterized by involuntary patterned sustained or repetitive muscle contractions of opposing muscles, causing, twisting movements and abnormal posturing. Dystonia is typically classifed by age of onset, origine, and affected body region.

When the cause is not defined or unknown, the dystonia is referred to as idiopathique or primary dystonia. Primary dystonia can be familial. Medical treatment rarely relives symptoms. Deep brain stimulation is an effective treatment of generalized dystonia.

 

MATERIAL AND METHODS

35 patients (20 males and 15 females) underwent this surgical technique.

We have : 27 patients suffering from generalized dystonia, 06 patients with cervical dystonia and 02 patients with hémidystonia.

Etiology : 20 cases : primary dystonia, 15 cases had  secondary dystonia including: 09 cases: Pkan syndrome. 01 cases : posttraumatic dystonia, 02 cases : postneuroleptic dystonia, 01 cases: mitochondrial cytopathy, 02cases post IMC.

Electrodes were bilaterally implanted under stereotactic guidance and connected to neurostimulateur. The varaition of brain impedance and current measurements was activated. Efficacy was evaluated by comparing scores on the clinical and functional Burke-Marsden-Fahn dystonia rating Scales before and after implantation (3 and 6 months and 1 year postopertively). The operation was performed under standard general anesthesia.

 

RESULTS

Optimal stimulation paramters vary between patients, however, the clinical response varied from patient to patient depending on several factors, including etiology and severity of the dystonia.  After 3 months the improvement of the clinical score was 45%, the functional score was improved by 30%. After that, at 6 months was respectively: clinical: 56% and functional: 41%. Finally at one year : the improvement concerned the clinical score : 80% and the functional score: 85%.

 

CONCLUSION

Bilateral chronic electrical stimulation can be proposed as first line treatment generalized dystonia.It is conservative,adaptable, reversible and well tolerted by the pediatric population. It must be applied as soon as possible,especially in primary dystonia.Tolerance is excellent and the complication’s rate remains low.The dystonic syndrom partiel contrôle and the significant improvement of pain symptomatology justify this treatment for secondary dystonia in selected patients.

Brahim MERROUCHE (ALGIERS, ALGERIA), Benaissa ABDENNEBI , Lila MAHFOUF
16:10 - 16:15 #16220 - O011 Adaptive deep brain stimulation in the internal globus pallidus of a dystonia and a Parkinson’s disease patients.
O011 Adaptive deep brain stimulation in the internal globus pallidus of a dystonia and a Parkinson’s disease patients.

Background:

Beta oscillations (13-30Hz) have been utilized as feedback signal for adaptive Deep Brain Stimulation (aDBS) in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients.1 In dystonia, low-frequency oscillations (LFO, 4-12Hz) have been found to be correlated with the presence of dystonic symptoms, measured with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), 2 making LFO a potencial biomarker for adaptive stimulation. Up to now, the applicability of aDBS in the internal globus pallidus (GPi) using beta oscillations (PD) or LFO (dystonia) is yet to be addressed.

Objective:

To test the safety of aDBS applied in the GPI of a dystonia and a PD patient and its effect in the oscillatory activity used for stimulation feedback.

 

Materials & Methods:

Bilateral intraoperative local field potentials (LFPs) were recorded in the GPi of one PD patient and one patient with craniocervical dystonia. A 30-second recording segment was used to obtain power spectral density estimates (PSD). LFPs were then filtered around the frequency peak registered in order to make either LFO or beta oscillations evident. Filtered LFPs were rectified and smoothed and stimulation was programmed to respond to increments in amplitude of the selected frequency band. A stimulation segment of approximately 200 seconds per disease was obtained. [Figure1]. Stimulation fractions per condition were calculated by dividing the total duration of the aDBS run into 20 segments. For each segment, the amount of time in which stimulation was turned on was calculated. Correlations between fraction of stimulation and time were conducted using Spearman’s rho.

 

Results

 

PSDs revealed a peak around 10 Hz in dystonia and a peak around 18Hz in PD. Stimulation voltages were set according to the voltages used in clinic, being in dystonia 1 V and 2.3 V in PD. GPi-aDBS was well tolerated in both patients and only elicited paresthesias at supraliminal voltages in the extremities contralateral to the stimulation side. aDBS was provided in such a way that it stimulated on average 34% of the time in the dystonia patient and 26.7% of the time in the PD patient. From the beginning to the end of the aDBS condition, despite fixed thresholds, the stimulation fraction dropped significantly, both in PD (ρ = -0.42, p = 0.04) and dystonia (ρ = -0.45, p = 0.04). [Figure2] This implies that the total amount of time that the signal remained above the threshold was progressively reduced by aDBS.

  

Conclusions

 

In this proof-of-principle report, aDBS was safely applied in the GPi of both a dystonia and a PD patient. They showed different oscillatory GPi profiles, namely a LFO peak in dystonia and a beta peak in PD. This provides a rationale for formally trialing aDBS in the GPi based on beta (PD) or LFO (dystonia) oscillations.

 

Bibliography

 

1.        Beudel, M. & Brown, P. Adaptive deep brain stimulation in Parkinson’s disease. Parkinsonism Relat. Disord. 22 Suppl 1, S123-6 (2016).

2.        Neumann, W.-J. et al. A localized pallidal physiomarker in cervical dystonia. Ann. Neurol. (2017). doi:10.1002/ana.25095

Figure 1.  Example of the application of adaptive DBS based on low-frequency oscillations in dystonia. Upper row: bipolar local field potential (LFP) derived from the internal part of the Globus Pallidus (GPi) filtered between 3 and 37 Hz. Second row: LFP filtered between the peak in low-frequency oscillations ± 3 Hz (i.e. 10 ± 3 Hz). Third row: average low-frequency amplitude envelope over 400ms moving average. The red line depicts the threshold determined for providing stimulation, i.e. when the amplitude is exceeding the red line stimulation is provided. Lower row: Stimulation trigger showing at which moments high frequency stimulation was provided.

 

Figure 2. A. Relation between the fraction of time that stimulation is turned on (Fraction of Stimulation) and the advancement of the application of aDBS in a dystonia patient and its least square line. B. Similar relation in a PD patient.

Dan PIÑA-FUENTES (Groningen, THE NETHERLANDS), J. Marc C. VAN DIJK, D.l. Marinus OTERDOOM, Martje VAN EGMOND, Teus VAN LAAR, Marina A. J. TIJSSEN, Martijn BEUDEL
16:15 - 16:20 #16222 - O012 Deep brain stimulation of the globus pallidus interna (gpi) with microelectrode recording for secondary dystonia: clinical reports and review of the literature.
O012 Deep brain stimulation of the globus pallidus interna (gpi) with microelectrode recording for secondary dystonia: clinical reports and review of the literature.

Background/Aim: Deep brain stimulation (DBS) has been used successfully in various forms of dystonia. However, there was no clear consensus on whether the globus pallidus interna (GPi) was an effective anatomic structure for secondary dystonia cases. In this study, we reported long-term results of secondary dystonia patients treated with GPi-DBS with microelectrode recording, and the results of our cases compared with the literature results.

Methods: Patients who underwent GPi-DBS for the diagnosis of secondary dystonia between the years of 2011-2017 were evaluated retrospectively. Burke-Fahn-Marsden Dystonia Rating Scale (BFM) scores, clinical improvement rates, follow-up period, stimulation parameters and the need of internal pulse generator replacement were analyzed. The PubMed database was searched carefully for articles describing GPi-DBS only for secondary dystonia. Keywords were ‘dystonia’, ‘deep brain stimulation’, ‘GPi’. In addition, the same database was searched for articles describing STN-DBS only for secondary dystonia. Keywords were ‘dystonia’, ‘deep brain stimulation’, ‘STN’.

Results: A total of 9 secondary dystonia patients (5 male, 4 female) underwent GPi-DBS with microelectrode recording. The mean follow-up period is 30 months. The average BFM score was 58.2 before the surgery, whereas the mean value was 36.5 at the last follow-up of the patients (mean improvement 39%, min: 9%, max: 63%). In the literature review, 63 cases (mean follow-up 18 months) of GPi-DBS treatment were reached in 18 different publications in the presence of microelectrode recording in the case of secondary dystonia. Detailed analysis of BFM scores showed worsening in one case after GPi-DBS, nine had no clinical improvement, and four cases had limited improvement. The number of cases with a 50% ≥ decrease in BFM scores was 21. In the remaining 23 cases, the healing rate was 11-49%.

Conclusion: GPi DBS has long-term efficacy and safety in secondary dystonia patients.

Sait OZTURK (Elazig, TURKEY), Dursun AYGUN, Yasin TEMEL, Ersoy KOCABICAK
16:20 - 16:25 #16248 - O013 Psychiatric symptoms, body concept and quality of life in patients with idiopathic dystonia.
O013 Psychiatric symptoms, body concept and quality of life in patients with idiopathic dystonia.

Abstract

In the past few years the occurrence of non- motor symptoms has been increasingly recognized in patients with a variety of movement disorders. Patients with dystonia experience unusual postures and disfigurement which is visible while they move in public. Few reports are available about the self perception of their body and its association with quality of life. The aim of this study was to examine the body concept in relation to quality of life, the severity of dystonia, and mood and anxiety in a series of 20 patients with idiopathic and inherited dystonia prior to deep brain stimulation (generalized, segmental and cervical dystonia). Patients suffered from mood instability and anxiety symptoms except social interaction anxiety. Depression was significantly correlated to the motor scores and to social phobia. Furthermore, impairments of body concept was evident in both cognitive and affective subscores. Mood and body concept negatively influenced the physical and mental domains of quality of life. Deep brain stimulation improved not only dystonia but also associated non-motor symptoms. It is important to recognize such non-motor symptoms in dystonia since they may contribute as well to reduced quality of life.

Assel SARYYEVA (Hannover, GERMANY), Lejla PARACKA, Florian WEGNER, Claus ESCHER, Martin KLIETZ, Mahmoud ABDALLAT, Joachim K. KRAUSS
16:25 - 16:30 #16249 - O014 Thalamic deep brain stimulation for dystonic head tremor.
O014 Thalamic deep brain stimulation for dystonic head tremor.

Background: Deep brain stimulation (DBS) of the internal globus pallidus (GPi) has become an accepted treatment for segmental and generalized dystonia. In severe tremor syndromes the thalamic ventral intermedius nucleus (Vim) is usually the DBS target of choice. Few case reports on thalamic DBS in dystonia have been reported. Patient with dystonic tremor might as well benefit from thalamic DBS.

Objectives: We aimed to evaluate the clinical benefit of Vim DBS in patients with dystonic head tremor.

Methods: Patients with dystonic head tremor were scheduled for Vim DBS. All patients were clinically characterized according to the Burke-Fahn-Marsden (BFM) motor and  disabilityrating scale (BFM-M/BFM-D) and the modified Fahn-Tolosa-Marin Tremor Rating Scale (mFTMTRS) (0-12 point scale for head tremor) pre- and postoperatively. Statistical analysis for significant pre- and postoperative changes in BFM-M/BFM-D and mFTMTRS was performed using the Wilcoxon Rank test for paired variables.

Results: 15 consecutive patients with dystonic head tremor underwent Vim DBS (6 male, mean age at DBS 49.7 +/- 11.8 years). Mean follow-up (FU) duration was 41 months (median 17 months). The mean preoperative BFM-M was 21.8 +/- 11.5, which improved to 12.2 +/- 10.5 at last FU (-44.5%, p<0.05), and the mean preoperative BFM-D was 5.1 +/- 2.9, which improved to 3.4 +/- 4.1 at last FU (-33.3%, p<0.05), while the mean preoperative mFTMTRS was 8.7 +/- 2.5, which improved to 3.5 +/- 2.7 at last FU (-59.8%, p<0.005).

Conclusions: Thalamic DBS should be considered as a primary therapeutic option in patients with segmental dystonia with prominent tremor. Indeed, patients experienced a significant relief of their tremor but also other dystonic symptoms improved significantly as reflected by the BFM.

Assel SARYYEVA (Hannover, GERMANY), Marc E. WOLF, Christian BLAHAK, Joachim RUNGE, Joachim K. KRAUSS
16:30 - 16:35 #16259 - O015 Efficacy and safety of deep brain stimulation for pantothenate kinase-associated neurodegeneration: a systematic review and meta-analysis.
O015 Efficacy and safety of deep brain stimulation for pantothenate kinase-associated neurodegeneration: a systematic review and meta-analysis.

Introduction

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder, characterized by progressive neurodegeneration associated with brain iron accumulation. Deep brain stimulation (DBS) has been trialed to treat PKAN-associated movement disorders, particularly dystonia. We studied outcome and safety of DBS for PKAN.

 

Methods

We performed a systematic review and meta-analysis, using independent participant data (n=99) from 38 articles. Primary outcome variables were change in Movement and Disability Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-M and –D) 1 year postoperatively. Secondary outcomes were response rate and complications.

 

Results

Patients with classic (n=58) and atypical (n=15) PKAN were operated at the median age of 11 and 31 years, respectively (p<.001). Globus pallidus internus (GPi) was primarily targeted (n=88). Mean BFMDRS-M change following GPi-DBS (-26%; 95%CI[-37,-15%]) was more pronounced in atypical vs. classic cases (-45 vs. -15%, respectively, p<0.001). >30% BFMDRS-M improvement at 1 year was observed in 35% of classic vs. 73% of atypical cases (p=0.04). Higher preoperative BFMDRS-M and atypical type were associated with higher BFMDRS-M reduction 1 year after GPi-DBS. Neither age at onset or surgery nor the presence of skeletal deformities and/or muscle contractures predicted outcome. GPi-DBS improved BFMDRS-D only in atypical cases. Longer follow-up suggests benefit decline.

Prevalence of surgical infections (6%) and hardware complications (7%) was similar to other dystonia aetiologies. Two patients died within 3 months. omplication rate was higher when operated in status dystonicus.

 

Conclusions

This meta-analysis provides level 4 evidence that GPi-DBS reduces BFMDRS in PKAN at 1 year postoperatively; however, this benefit may not be sustained in the long-term.

 

Philippe DE VLOO, Philippe DE VLOO (Leuven, BELGIUM), Darrin LEE, Robert DALLAPIAZZA, Mohammad ROHANI, Alfonso FASANO, Renato MUNHOZ, George IBRAHIM, Mojgan HODAIE, Andres LOZANO, Suneil KALIA
16:35 - 16:40 #16308 - O016 Parkinsonian signs in patients with cervical dystonia treated with pallidal deep brain stimulation: a controlled and observer-blinded study.
O016 Parkinsonian signs in patients with cervical dystonia treated with pallidal deep brain stimulation: a controlled and observer-blinded study.

Introduction

Pallidal deep brain stimulation is an established treatment in patients with dystonia. However, anecdotal evidence suggests that it may lead in some patients to specific parkinsonian symptoms such as freezing of gait, micrographia, and bradykinesia.

 

Methods

We investigated parkinsonian signs using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale motor score by means of observer-blinded video ratings in a group of 29 patients treated with pallidal stimulation for predominant cervical dystonia and a non-surgical control group of 22 patients with predominant cervical dystonia. Additional assessments included MRI-based models of volume of neural tissue activated to investigate areas of stimulation related to symptom control and those likely to induce parkinsonian signs as well as an EMG analysis to investigate functional vicinity of stimulation fields to the pyramidal tract.

Results

Compared with controls, stimulated patients had significantly higher motor scores (median, 25th–75th percentile: 14.0, 8.0–19.5 versus 3.0, 2.0–8.0; p<0.0001), as well as bradykinesia (8.0, 6.0–14.0 versus 2.0, 0.0–3.0; p<0.0001) and axial motor subscores (2.0, 1.0–4.0 versus 0.0, 0.0–1.0; p=0.0002), while rigidity and tremor subscores were not different between groups. Parkinsonian signs were partially reversible upon switching stimulation off for a median of 90 minutes in a subset of 19 patients tolerating this condition. Furthermore, the stimulation group reported more features of freezing of gait on a questionnaire basis. Quality of life was better in stimulated patients compared with control patients, but parkinsonian signs had a significant negative impact on quality of life. In the imaging analysis maximum efficacy for dystonia improvement projected to the posteroventrolateral internal pallidum with overlapping clusters driving severity of bradykinesia and axial motor symptoms. The severities of parkinsonian signs were not correlated with functional vicinity to the pyramidal tract as assessed by EMG. 

Conclusion

Parkinsonian signs, particularly bradykinesia and axial motor signs, due to pallidal stimulation in dystonic patients are frequent and negatively impact on motor functioning and quality of life. Therefore, patients with pallidal stimulation should be monitored closely for such signs both in clinical routine and future clinical trials. Spread of current outside the internal pallidum is an unlikely explanation for this phenomenon, which seems to be caused by stimulation of neural elements within the stimulation target volume.

Philipp MAHLKNECHT, Dejan GEORGIEV (Ljubljana, SLOVENIA), Harith AKRAM, Florian BRUGGER, Saman VINKE, Ludvic ZRINZO, Kailash BHATIA, Gunn Marie HAIRZ, Peter WILLEIT, John ROTHWELL, Thomas FOLTYNIE, Patricia LIMOUSIN
16:40 - 16:45 #16339 - O017 Globus pallidus stimulation for dystonia: single-center global experience and particularities of the NBIA group.
O017 Globus pallidus stimulation for dystonia: single-center global experience and particularities of the NBIA group.

Internal globus pallidus stimulation (GPi-DBS) is an established therapeutic tool for medically refractory dystonia. However, treatment success predictors and patient satisfaction modulators remain poorly understood. To further study these subjects, we hereby report our single-center experience. We performed a descriptive and inferential retrospective analysis of the GPI-DBS performed at our center. Epidemiological and clinical characteristics were summarized and results were analyzed, according to the Burke-Fahn-Marsden for movement (BFMDRS-M) and dysability (BFMDRS-D) and, additionally, according to a scale of patient/family subjective self-reported benefit.

A total of 8 isolated dystonia cases (5 generalized, 3 cervical), 4 dystonia in neurodegeneration with brain iron accumulation (NBIA), two myoclonic dystonia and one dystonic cerebral palsy case were submitted to GPi-DBS at our institution. Average age at procedure was 36.3 years, ranging from 7 to 65. Average follow-up time was 52±9.8 months. Average pre-operative BFMDRS-M and BFMDRS-D scores were 44.5±8.8 and 12.7±2.4, respectively. On multivariate analysis, older age at procedure, shorter symptom duration before surgery and idiopathic etiology were associated to lower motor and disability scores (p<0.05).  After intervention, a statistically significant decrease of motor and disability scores was observed, with mean absolute reductions of 19.2±5.6 and 5.9±1.7 points, and mean relative reductions of 48.6±8.9% and 54.2±8.6%, on the respective scales at at last follow-up (p<0.05). On multivariate analysis, idiopathic etiology was associated with a decreased absolute motor benefit (p=0.025), but increased proportional benefit relative to pre-operative score (p=0.032). Additionally, higher pre-operative scores were associated to a greater absolute motor ad disability benefit (p=0.033 and p=0.005, respectively). At last follow-up, two thirds of patients/families reported a good or excellent benefit. Subjective benefit was associated to increased relative benefit as measured by BFMDRS-M and BFMDRS-D (p=0.026 and p=0.012), but not to absolute benefit. On multi-variate analysis, NBIA dystonias were associated to higher pre-operative scores (average BFMDRS-M 83.37±25.3 and BFMDRS-D 23.0±9.2); increased absolute benefit at last follow-up (average 36.0±10.2 motor and 10.5±4.1disability benefit); on the other hand, this group achieved lower relative benefits (average 35.63±10% increase for BFMDRS-M and 41.4±12% for BFMDRS-D) and lower subjective benefit (p<0.05).

GPi-DBS is an effective option for improving dystonia patients’ motor and functional performance. Isolated dystonias presented a greater absolute and subjective benefit. The NBIA group might be associated with a greater absolute - but not proportional – benefit, contrasting with isolated dystonia cases. Finally, BFMDRS relative change might be more important than absolute variations for subjective benefit as perceived by the patient and families.

Vasco PINTO (Porto, PORTUGAL), Eduardo CUNHA, Joana DAMÁSIO, Carla SILVA, Alexandre MENDES
16:45 - 16:50 #16363 - O018 Deep brain stimulation in primary and in NBIA-related dystonia. Comparision of clinical and quality of life improvement. A two year follow-up study.
O018 Deep brain stimulation in primary and in NBIA-related dystonia. Comparision of clinical and quality of life improvement. A two year follow-up study.

Materials and methods:  32 patients (18 male, 16 female) age from 6 to 64  (mean 27,3) affected by dystonia were treated with DBS GPi. 18 patients were diagnosed with idiopathic general dystonia and with 15 NBIA- related general dystonia. The patients were evaluated with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Unified Dystonia Rating Scale (UDRS) and the SF-36 scale before treatment and 9 and 24 months after the procedure. The permanent electrodes were implanted  to GPi in all patients. The target was identified with direct and indirect method. Intrasurgical macrostimulation and microrecording were used for neurophysiological evaluation of the target.

Findings: No serious morbidity or mortality were reported in the group.  Local chest hematoma was reported at the region, where internal pulse generator was implanted. One patient died at the follow-up period (not related to the DBS procedure or treatment). A significant improvement in all scales were reported in both, generalized dystonia and NBIA. The differences between the groups are presented. Better results were achieved in generalized dystonia group. 

Conclusion: DBS GPi is a safe and effective method of dystonia treatment. Application of this method of treatment in generalized dystonia and dystonia in neurodegeneration with brain iron accumulation is legitimate. The improvement in both functional and quality of life scales were significant in both groups. The response to therapy may depend on clinical diagnosis. DBS GPi improves quality of life in dystonia patients.

Krzysztof SZALECKI (warszawa, POLAND), Tomasz KMIEĆ, Henryk KOZIARA, Tomasz MANDAT
16:50 - 17:00 Discussion.
WOLFSON HALL A

Thursday 27 September

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C28
15:30 - 17:00

Parallel Session 3
Surgery for Tourette

Moderators: Terry COYNE (Neurosurgeon) (Brisbane, AUSTRALIA), Tom FOLTYNIE (Professor of Neurology) (London, UK), Veerle VISSER-VANDEWALLE (Köln, GERMANY)
15:30 - 15:50 Overview of Tourette. Eileen JOYCE (Consultant) (London, UK)
15:50 - 16:10 Thalamic DBS in Tourette syndrome: where is the best target? Veerle VISSER-VANDEWALLE (Köln, GERMANY)
16:10 - 16:30 DBS for Gilles de la Tourette syndrome. Tom FOLTYNIE (Professor of Neurology) (London, UK)
16:30 - 16:40 #16221 - O019 Our experience of stereotactic radiofrequency pallidotomy for the treatment of Tourette syndrome.
O019 Our experience of stereotactic radiofrequency pallidotomy for the treatment of Tourette syndrome.

         OBJECTIVES. Tourette syndrome (TS) is a complex neurological and neurobehavioral disorder characterized by motor and phonic tics and a variety of behavioral comorbidities. Surgical treatment is used when motor symptoms become troublesome despite optimal medical therapy.  Nowadays DBS is a method of choice in treatment of severe TS but ablative surgical procedures remain important neurosurgical interventions in view of economical, geographical and some other reasons. The purpose of the study is to evaluate the effectiveness of unilateral stereotactic pallidotomy  for TS. 

         METHODS. In Romodanov Neurosurgery Institute 9 patients with TS underwent stereotactic radiofrequency GPi lesioning, among them were 8 males and 1 female. Patient’s age ranged from 16 to 36 years (mean 23.3 years). For measuring severity of tics, OCB, quality of life, and depression before and after treatment were used Yale Global Tic Severity Scale (YGTSS), Global Assessment of Functioning (GAF) Scale and Gilles Tourette Syndrome Quality of Life scale (GTS-QOL), HDRS and Beck's Depression Inventory scales. 

         Surgery performed on CRW stereotactic system, using FraimLink (Medtronic) and iPlan (BrainLab) softwares. Postero-ventro-lateral globus pallidus GPi has been the target of lesion.  Intraoperative macrostimulation was used to delineate the optimal target location.Postoperative follow-up ranged from 6 months to 10 years (mean 3.3 years).

         RESULTS. The mean duration of disease before surgery was 7.3 years. All patients had severe motor symptoms: chronic isolated or chronic multiple motor tics or/and phonictics which were resistant to drug treatment. Symptoms of obsessive-compulsive disorder were present in 5 of 9 patients (55.6%). 

         All patients have undergone surgery well. There were no postoperative complications and patients were discharged on fourth or five day after surgery. The improvement in tics began in one month after treatment and was progressive with time postoperatively. Most patients noted maximum improvement in five months after surgery.  

         At one year follow-up the YGTSS score mean improvement was 55% and the GAFscore improved by 22%. There were no regression of motor symptoms in two years after treatment. The patient was also found to have improvement in depressive and anxiety symptoms. 

         CONCLUSION. Our results demonstrate that stereotactic pallidotomy is a promising safe therapeutic alternative for treating medically refractory TS. Unilateral GPi lesion significantly reduced motor and vocal tics, as well reduced behavioral disturbances, increased patient’s daily living activity and improved quality of life. Postero-ventro-lateral globus pallidus seems to be a good target for lesioning for treatment TS in patients who have dominant severe motor symptoms. At the same time pallidotomy improves not only tics but also some of the behavioral comorbidities.

Vitaliy TSYMBALIUK, Kostiantyn KOSTIUK (Kyiv, UKRAINE), Yuri MEDVEDEV, Andriy POPOV, Nazar VASYLIV, Maxim SHEVELOV, Varelii CHEBURAKHIN, Sergii DICHKO
16:50 - 16:55 #16212 - O021 Deep brain stimulation for tic disorders: cohort from a single centre.
O021 Deep brain stimulation for tic disorders: cohort from a single centre.

There are many types of tic disorders of which the most commonly known is Tourette Syndrome (TS). In TS, more than 50% of cases are associated with other psychiatric disorders such as OCD, ADHD, anxiety and other mood disorders. Around 20% of patients have very severe manifestations with great repercussions in quality of life due to significant social and professional impairment. Deep brain stimulation (DBS) for the treatment of tic disorders is still experimental and has been performed on at least 9 described targets, including thalamic, striatal and internal capsule. The evidence regarding its efficacy and safety is still sparse and studies analysing the effects of stimulation in different targets is essential.

The objective of this study was the evaluation of the clinical benefit and adverse events of DBS in patients with tic disorders while also analysing the targets used and its influence on different pre-operative symptoms.

To do so, a retrospective analysis of a cohort of patients undergoing DBS for the treatment of tic disorders in a single centre was made. The patients were clinically assessed using the Yale Global Tic Severity Scale (YGTSS). Information regarding demographics, pre- and post-operative clinical status, targets used, stimulation parameters and adverse events was collected.

Three patients were identified, one with tardive neuroleptic syndrome with tics and dystonia (case 1) and two with Tourette Syndrome with obsessive-compulsive disorder and anxiety (case 2 and 3). Mean age was 25 years and all patients were male. The targets used was anteromedial Gpi in case 1 and 2 and ALIC plus ventral striatum with interleaving stimulation in case 3. The mean coordinates for the antero-medial Gpi were left: x= -15,37; y= 10,48; z= -2,99; right: x= 15,72; y=9,91; z=-3,02. For Case 3, the coordinates were left: x= -6,09; y= 11,95; z= -2,97; right: x= 6,34; y= 12,06; z= -3,03. Both patients with Tourette syndrome had an improvement with stimulation of more than 50% (maximum 81% in case 3) on the YGTSS and a total resolution of associated obsessions and compulsions. The patient with tardive syndrome did not have a significant improvement (21% on the YGTSS). The mean follow-up was 19,9 months. The adverse reactions reported were weight disturbances in two cases and insomnia in one. In case 1, there was an infection of the system, caused by picking of the IPG and lead trajectory. Total removal of the system was necessary 2 months after implantation, with no re-implantation so far.

To summarise, tics may benefit with DBS, with up to 80% improvement. Resolution of OCD symptoms was an additional benefit in these patients. The choice of the target accordingly to the type of neurologic and psychiatric symptoms may help to maximize the clinical benefit. In one case, the ALIC was specifically targeted to treat OCD symptoms with success. Infection is a serious concern in TS patients undergoing DBS.

Pedro DUARTE BATISTA (Lisboa, PORTUGAL), Miguel COELHO, Patrícia LOBO, Herculano CARVALHO, Maria BEGOÑA CATTONI, Group MOVEMENT DISORDERS
16:55 - 17:00 #16229 - O022 Differential structural connectivity during thalamic DBS in Tourette syndrome.
O022 Differential structural connectivity during thalamic DBS in Tourette syndrome.

Introduction

In 1999, DBS was introduced for Tourette syndrome (TS) with the target in the first patient being located at the anteromedial border of the centromedian nucleus (CM) (as part of the intralaminar thalamic nuclei), with the upper contacts of the quadripolar electrode being located in the nucleus ventro-oralis internus (Voi) (as part of the ventrolateral thalamic nuclei). This attempt to stimulate different nuclei with one electrode was motivated by the thalamotomies performed by Hassler in 1970, during which multiple lesions were performed in the intralaminar thalamic nuclei and the ventrolateral nuclei. After this first case, other studies have shown the efficacy of DBS of CM/Voi in alleviating symptoms in otherwise intractable TS patients. However, the complexity of this target with the different connections of the CM and Voi respectively within the the cortico-striatal-thalamo-cortical (CSTC) circuits and subcircuits, makes our understanding of CM/Voi DBS in TS difficult. Tractography is a relatively new technique applied in DBS to optimize targeting pre-operatively, or to optimize the understanding of the anatomical substrate of DBS postoperatively, by defining the fibers modulated by the active contacts of the implanted leads. In this study, we made a first step in elucidating the mechanisms of CM/Voi DBS in TS, and specifically in the differential role of the subparts of this target structure, based on tractography. 

 

Methods

Five patients suffering from refractory TS who underwent implantation of bilateral electrodes (Medtronic, Model 3389) for thalamic DBS were included in this study. The targeted areas were the CM and the Voi. Tics were measured with the Yale Global Tic Severity Scale (YGTSS) pre-, and postoperatively with long-term follow-up at different time points. Postoperatively the exact location of the active contacts within the thalamus was assessed by fusing preoperative MRI planning scans with postoperative thin-sliced CT scans. Diffusor tension imaging (DTI) was used to trace the fibers at the active contacts used for stimulation.

 

Results

Reduced number of vocal and motors tics were documented in all patients already three months after surgery. At long-term follow-up (ranging between 3 and 12 months), there was a tic reduction varying between 20 and 50% on the YGTSS. Stimulation-induced side-effects only included a temporarily mild lack of energy reported by two patients. The patients with the most dorsal active contacts, the ones related to the Voi, showed a higher connectivity to the mesial part of the prefrontal cortex through the anterior limb of the internal capsule ipsilaterally, as well as contralaterally following a transcallosal pathway. On the other hand, the patients with the most ventral active contacts, the area related to the CM, followed a connectivity pattern to the premotor cortex through the internal capsule, and to the striatum ipsilaterally.

 

Conclusions

These findings suggest that stimulation of the Voi of the thalamus acts through a modulation of the connectivity between thalamus and the ipsi-, and contralateral prefrontal cortex, while stimulation of the CM modulates the ipsilateral premotor cortex through the thalamostriatal pathway. The former can be explained by the more direct connections between the ventrolateral complex of the thalamus and the frontal cortex, the latter by modulation of the excitatory feedback loop between the intralaminar thalamic nuclei and the striatum.

Pablo ANDRADE (Cologne, GERMANY), Moritz HOEVELS, Veerle VISSER-VANDEWALLE
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Thursday 27 September

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D28
15:30 - 17:00

Parallel Session 4
Pain Surgery

Moderators: Tipu AZIZ (Professor) (Oxford, UK), Vladimir SHABALOV (Nicosia, RUSSIA), Ido STRAUSS (Neurosurgeon) (Tel Aviv, ISRAEL)
15:30 - 15:40 #14992 - O023 Occipital nerve stimulation for refractory chronic cluster headache: long-term efficacy and predictive factors.
O023 Occipital nerve stimulation for refractory chronic cluster headache: long-term efficacy and predictive factors.

Background: Chronic cluster headache (CCH) is a rare and disabling primary headache condition. Chronic electrical stimulation of the occipital nerves (ONS) is an accepted treatment for refractory CCH patients, but its efficacy has been evaluated only in small short-term series of cases. Our objective was to evaluate the long-term efficacy of ONS in a large series of CCH patients and to identify predictors of response.

Methods: We prospectively studied 105 patients with refractory CCH, treated by ONS from 2012 to 2015 within the ONS French national observatory (10 participating centers). Efficacy was evaluated by frequency, duration and intensity of CH attacks; quality of life (EQ-5D); functional (HIT-6, MIDAS) and emotional (HAD) impacts; medication consumption. Predictors of the response (defined as attack frequency decrease > 50%) were studied.

Results: At last follow-up (mean 43.8 months), attack frequency was reduced >50% in 69% of the patients. Median weekly attack frequency decreased from 20 (+/-22) attacks/w to 6 (+/- 12) attacks/w between baseline and last follow-up (p <0.001). Preventive and abortive medical treatments were significantly decreased. Most of the patients (61%) were satisfied (PIGC score). In the whole cohort, functional impact (HIT-6 and MIDAS scores), anxiety (HAD-A) and health-related quality of life (EQ-5D) significantly improved after ONS. In the group of excellent responders (59% of the patients), quality of life improved dramatically (median EQ5D VAS score increased from 40 to 75). Significant predictors of response in multivariate analysis were younger age, attacks strictly unilateral and preoperative low HAD Depression score. Adverse events occurred in 59% of the procedures and consisted in lead migration, infection, local pain and hardware dysfunction.

Conclusion: Efficacy of ONS in CCH was maintained over time and resulted in dramatic improvement of quality of life in responders. Although not severe, surgical complications were numerous, which requires optimization of hardware and surgical techniques. Predictors of good response to ONS were younger age, strictly unilateral attacks and absence of preoperative depression.

Aurelie LEPLUS (NICE), Serge BLOND, Jean REGIS, Sylvie RAOUL, Bechir JARRAYA, Stéphane DERREY, Stephan CHABARDES, Jimmy VOIRIN, Jocelyne BLOCH, Sophie COLNAT-COULBOIS, Francois CAIRE, Michel LANTERI-MINET, Denys FONTAINE
15:40 - 15:50 #16280 - O024 Congruence of preoperative MRI images with intraoperative findings in trigeminal neuralgia.
O024 Congruence of preoperative MRI images with intraoperative findings in trigeminal neuralgia.

The authors of this report sought to review their outcomes with microvascular decompression (MVD) in patients with idiopathic trigeminal neuralgia (TN), and the success of preoperative magnetic resonance imaging (MRI) in identifying the offending vascular compression on the trigeminal nerve. The goal of this report is twofold. The first is to evaluate the correlation of vascular compression with outcomes after MVD. The second, to assess the accuracy of preoperative MRI in identifying the offending vascular compression.

Eighty-nine patients (53 women, 36 males), with ages of 57 ± 13years underwent MVD for TN. TN was on the left side in 39 cases, and on the right in the rest. Length of hospitalization was 2 ± 1 day, and patients were followed for 23 ± 30 months.

Eighty five patients had an excellent outcome with 3 scoring 4 on the VAS scale,  2 patients 3, and the rest less than 2/10.  Arterial compression was the offending vessel in 65 patients, a vein in 16, and none in 4. Four patients continued to experience pain after surgery scoring in excess of 5/10 on the VAS scale. Three of the 4 had arterial compression and one venous. The latter ultimately required stereotactic radiosurgery (SRS) for pain control. Three of the 4 were on medications, including 2 on narcotics.

At surgery, arterial compression was encountered in 68 cases, venous in 17, and none in 4. MRI studies were available for review in 55 cases. The intraoperative findings were congruent with the MRI interpretation in 47 cases and incongruent in 8. In the latter, arterial compression was identified at surgery in 4, venous in 2, and no offending vessel in the remaining 2. The MRI for the 4 arterial and 2 venous compressions identified at surgery, did not reveal an offending vessel preoperatively. For the 2 cases where no offending vessel was identified at surgery, the MRI was interpreted as showing an artery in one, and a vein in the second.

In summary, MVD in medically unresponsive TN should be based on the clinical diagnosis.  An excellent and pain free outcome can be encountered with MVD irrespective of whether the offending vessel is an artery or vein, and even in the absence of either.  Preoperative studies are not always conclusive regarding the presence or absence of an offending vessel. Though vascular compression was identified at surgery in 94% of our cases, and the source of  compression was congruent with MRI in 85% of cases, MRI is mandatory to eliminate other compressive etiologies of TN such aneurysm or tumor. Conversely, however, the presence of vascular compression by MRI should encourage the surgeon to persevere in search of the offending vessel particularly when it proves elusive.

Patrick HITCHON (Iowa City, USA), Marshall HOLLAND, Jennifer NOELLER
15:50 - 16:00 #16324 - O025 Normalisation of Sensory Function in Patients with Neuropathic Facial Pain Syndromes and Deep Brain Stimulation against Neuropathic Pain.
O025 Normalisation of Sensory Function in Patients with Neuropathic Facial Pain Syndromes and Deep Brain Stimulation against Neuropathic Pain.

Introduction: Neuropathic facial pain syndromes due to lesions to the trigeminal nerve system are associated with permanent sensory deficit with numbness in the related trigeminal area including deficits to touch sensation and pain. Following non responsiveness of medical treatment surgical methods as motor cortex stimulation and deep brain stimulation of sensory thalamic nuclei and or periventricular or periaqueductal grey matter were utilized. But under consideration long term treatment results are less than 50% in the literature. Only gasserian ganglion stimulation procedures exhibited better results. But due to discontinuation of production of the electrodes for gasserian ganglion stimulation there was a treatment vacuum which was filled by motor cortex stimulation unsuccessful on long term run and deep brain stimulation of sensory thalamic nuclei and periventricular or periaqueductal grey matter with afore mentioned mediocre results. Applying surgical procedures against pain the results have to be higher than in medical treatments otherwise we treat in an range of effectiveness of placebo. I changed 2012 dramatically our targeting against neuropathic pain by using a combination of sensory thalamic stimulation and a stimulation of the posterior limp of the capsula interna.

Material and Methods: Out of 46 treated patients with neuropathic pain syndromes we had a group of 12 patients with neuropathic pain of the face. 50% of the patients showed preoperatively a severe sensory deficit for touch-, pain-, warmth- and cold sensation. They exhibited pathological reaction on touch (allodynia, hyperpathia, dysesthesia) and repeated touch. All patients had pre- and postoperative neurophysiological-, neuropsychological examination beside of a pain questionnaire consisting of McGill Pain Questionaire – German version, Oswestry questionnaire – German version, SF-36 German version 1.0, EQ-5D German version, Eisner Body Region VAS. Further physiological testing was performed utilizing the test battery of quantitative sensory testing (QST) in neuropathic areas and normal area in the contralateral face side. The level for detection of cold sensation, warmth sensation, pain due to cold, pain due to heat, tactile detection, mechanical pain, pin prick, wind up ratio including VAS at the beginning and at the end were recorded in all patients.  We examined 6 women from 29 to 65 years of age with pure trigeminal neuropathia according to rhizotomy, exhearse, 2 x maxilla fracture with maxilla facial surgical treatment, maxilla mobilisation due to disontogenesis, infection of the ear and the petrous bone. All patients were treated with 2 electrodes in the same side of the pain. One electrode was reaching from a precoronal approach the vpm thalamic area and one electrode was inserted from a parietal approach into the posterior limp of the capsula interna. Riechert & Mundingers stereotactic frame got utilized. 3T MRT and stereotactic computed tomography angiography were fused by Tatra Med Stereoplan Plus 4.0 planning software and the brain suite of brainlab with an intraoperative CT scanner by Siemens. Operation was performed under intubation anesthesia. Tractography was showing motor and sensory fiber tracts. All patients got neuropsychological testing of memory and cognition pre- and one year postoperatively to detect stimulation induced changes.

Results: All 6 patients lost allodynia, hyperpathia and dysesthesia. Pain was not existing anymore. Touch and repeated touch was not provoking pain anymore. One patient with rhizotomy of the retrogasserian trigeminal nerve was still not able to feel touch, pain, cold and heat but the extremely burning pain in the face is not existing for 5 years. All other patients gained a relief of the permanent burning pain followed by normalisation of sensory function in the face as it has been before the neural trauma. Neuropsychological testing showed no change in memory and cognition before and one year after surgery.

Conclusion: Our method against neuropathic facial pain is high effective and safe. We have more than 5 years of stable and successful treatment. Beside of pain relief a normalisation of sensory function in the previous painful area. Our findings support a maximum improvement of quality of life in our patients. We see similar results in other neuropathic pain syndromes like in post stroke pain.

Wilhelm EISNER (Innsbruck, AUSTRIA), Sebastian QUIRBACH, Ralf BECKER, Johannes KERSCHBAUMER, Julia WANSCHITZ, Wolfgang LÖSCHER, Raphael REHWALD
16:00 - 16:10 #16365 - O026 NEUROSURGICAL ABLATIVE PROCEDURES FOR INTRACTABLE CANCER PAIN.
O026 NEUROSURGICAL ABLATIVE PROCEDURES FOR INTRACTABLE CANCER PAIN.

Background:

A subset of patients with cancer experience severe refractory pain and suffer tremendously during their last months of life. Some of these patients may benefit from targeted neurosurgical procedures aimed to disconnect the pain pathways in the spinal cord (cordotomy) or the brain (cingulotomy). Patients were evaluated by an interdisciplinary team composed of a specialist in palliative care, a pain specialists and a neurosurgeon. We present our experience and considerations in patient selection and outcome of  these interventions.

Methods:

Retrospective review of all patients who underwent neurosurgical interventions in the Tel Aviv Medical Center between March 2015 and March 2018. All patients had advanced metastatic cancer with limited prognosis and suffered from intractable oncological pain.

Results:

Fifty-nine patients were operated during the study period.

Thirty-nine patients with localized pain underwent disconnection of the spinothalamic tract: Thirty-two underwent percutaneous cervical corodotomy, 5 open thoracic, and 2 patients underwent stereotactic mesencephalotomy. Excellent pain relief was achieved immediately post operatively in 36/39 patients (92%). At 1 month this improvement was maintained in 28/33 patients available for follow-up (85%). We had 1 major morbidity.

Twenty patients with diffuse pain underwent stereotactic cingulotomy. 19/20 patients reported substantial pain relief immediately after the operation. Good pain relief was achieved in 12/16 (75%) available for 1-month follow-up and in 8/13 (62%) of patients available for 3-months follow-up. We had no major morbidity or mortality. Transient confusion/apathy was present in 9/20 (45%).

Conclusions:

Our experience indicates that neurosurgical procedures are safe and effective in alleviating  suffering in patients with intractable cancer pain.

Ido STRAUSS (Tel Aviv, ISRAEL), Assaf BERGER, Uri HOCHBERG, Alexander ZEGERMAN, Rotem TELLEM
16:10 - 16:20 #16417 - O027 An Open-Label, Analgesic Efficacy and Safety of Pituitary Radiosurgery for PatientsWith Opioid-Refractory Pain: Study Protocol and preliminary results for a Randomized Controlled Trial.
O027 An Open-Label, Analgesic Efficacy and Safety of Pituitary Radiosurgery for PatientsWith Opioid-Refractory Pain: Study Protocol and preliminary results for a Randomized Controlled Trial.

BACKGROUND: Hypophysectomy performed by craniotomy or percutaneous techniques leads to complete pain relief in more than 70% to 80% of cases for opioid refractory cancer pain. Radiosurgery could be an interesting alternative approach to reduce complications. The objective is to assess the analgesic efficacy compared with standard of care is the primary goal. The secondary objectives are to assess ophthalmic and endocrine tolerance, drug consumption, quality of life, and mechanisms of analgesic action.

METHODS: The trial is multicenter, randomized, prospective, and open-label with 2 parallel groups. This concerns patients in palliative care suffering from nociceptive or mixed cancer pain, refractory to standard opioid therapy. Participants are randomly assigned to the control group receiving standards of care for pain according to recommendations, or to the experimental group receiving a pituitary radiosurgery (160 Gy max dose) associated with standards of care. The primary endpoint is evaluated at D4. Further evaluation assessments are taken at baseline, D0, 4, 7, 14, 28, 45, month3, and 6.

Results: Since June 2016, 15 patients have been screened, 4 included. The two patients randomized for the best medical treatment have been subsequently treated. The first patient randomized in the radiosurgery arm was a 67 years old women presenting with a sacrum chordoma with osteolytic pelvis invasion and major side effects of the opioids (prurit ++). The pain scale at inclusion was 10/10, DN4 was 7/10, the NPSI 42/100 and the medical treatment was including Hypnovel 4.8mg/d ; oxynorm PCA bolus dose 5mg/30min ; morphine intrathecal 800mg/d in oral equivalent; Dexchlorpheniramine ; Hydroxyzine ; Pantoprazole ; Pregabaline ; Paracétamol 4g/d; Dalteparine ; Kabiven. Supine position was unsustainable for the patient and SRS was performed under general anesthesia. The pain scale went to 0 at D0 few hours after SRS and was still 0 at D4. Antalgic drugs were completely stopped at D4 for hypnotic, D14 for level III and D45 for the others. Patient have died at month 3 from cancer progression, pain free, with no side effect of SRS.

DISCUSSION: The design of this study is potentially the most appropriate to demonstrate the efficacy and safety of radiosurgery for this new indication. Preliminary results are impressive.

Jean REGIS, Anne BALOSSIER (Marseille), Pierre Yves BORIUS, Marie FICHAUX, Stephanie RANQUE GARNIER, Sebastien SALAS
16:20 - 16:25 #14555 - O028 Prospective Randomized Feasibility Study Comparing Manual vs. Automatic Position-Adaptive Spinal Cord Stimulation with Surgical Leads.
O028 Prospective Randomized Feasibility Study Comparing Manual vs. Automatic Position-Adaptive Spinal Cord Stimulation with Surgical Leads.

Introduction

 

It was previously identified that the majority of patients experience uncomfortable stimulation associated with posture changes, especially when lying down. Position-adaptive neurostimulation was designed to accommodate for positional changes and eliminate the need to manually adjust the stimulation parameters.  The purpose of this study was to establish the extent that chronic pain patients implanted with surgical, laminectomy-type leads experience position-related variations in spinal cord stimulation therapy and to investigate the effects of manual versus automatic position-adaptive spinal cord stimulation on clinical outcome.

 

Methods

 

A total of 18 patients completed a single-center, prospective, randomized feasibility clinical study with a two-arm crossover design. A manual stimulation adjustment mode was used for all patients for the first two months, after which the patients were randomized to one of the two study arms: manual or automatic position-adaptive stimulation. All patients were followed for a total of 5 months with threshold and therapeutic stimulation parameters (amplitude, impedance, pulse width and rate) collected in different postures (lying right, left, prone or supine and upright or upright active).  Clinical outcomes, patient satisfaction, and complications were also assessed. Data were collected at baseline, surgery, 2-months, 3.5-months, and 5-months follow-ups.

 

Results

 

Clinical outcomes improved significantly at all time points for ODI (p.0039), VAS leg (p.0082), Pittsburg Sleep Quality Index,  (p.034), and at 2 months for VAS back pain scores compared with baseline scores. There were no statistically significant changes in pain medication scores (p=.73). In addition, we did not detect any statistically significant differences for medication use (6.8 vs. 6.6; p=.77), ODI , (33.4 vs. 31.5; p=.28), VAS for back (4.3 vs. 3.5; p=.16) or leg pain,  (3.3 vs. 3.3; p=1.0), and PSQI (8.9 vs. 8.6; p=.65) scores in manual vs. automatic patient groups. The patients reported higher Likert scale satisfaction rates with automatic stimulation (mean 1.7; 95% CI = 1.1 – 2.3). There were no statistically significant amplitude or impedance differences found between manual and automatic stimulation in any of the body positions. The highest reduction in therapeutic stimulation amplitudes was recorded in the supine position: 74% of the upright body position for manual (95% CI = 64% – 83%) and automatic (95% CI = 65% – 83%) stimulation.

 

Conclusions

 

Similar variations were reported for manual or automatic stimulation intensity in response to positional changes, but the patients were much more satisfied when using position-adaptive stimulation for relief of their back and leg pain.

 

Kara BEASLEY (Boulder, USA), Christie ZAKAR, Vinod KANTHA, Steven HOBBS, Sigita BURNEIKIENE
16:25 - 16:30 #14678 - O029 Bridging Veins and Veins of the Brain Stem in Microvascular Decompression Surgery for Trigeminal Neuralgia and Hemifacial Spasm.
O029 Bridging Veins and Veins of the Brain Stem in Microvascular Decompression Surgery for Trigeminal Neuralgia and Hemifacial Spasm.

Object: In microvascular decompression surgery for trigeminal neuralgia and hemifacial spasm, the bridging veins are dissected to provide the surgical corridors, and the veins of the brain stem may be mobilized in cases of venous compression. Strategy and technique in dissecting these veins may affect the surgical outcome. We investigated solutions for minimizing venous complications and reviewed the outcome for venous decompression.

Methods: We retrospectively reviewed our surgical series of microvascular decompression surgery for trigeminal neuralgia and hemifacial spasm, between 2005 and 2017. Our surgical strategies included preservation of the superior petrosal vein and its tributaries, thorough dissection of the arachnoid sleeve that enveloped these veins, cutting of the inferior petrosal vein over the lower cranial nerves, and mobilization or cutting of the veins of the brain stem that compressed the nerve roots. We summarized the patient characteristics, operative findings, and postoperative outcomes, according to the vascular compression types as follows: artery alone, artery and vein, and vein alone. We analyzed the data using chi-square and one-way ANOVA tests.

Results: The cohort was composed of 121 patients with trigeminal neuralgia and 205 patients with hemifacial spasm. The superior petrosal vein and its tributaries were preserved with no serious complications in all patients with trigeminal neuralgia. Venous compression alone and arterial and venous compressions were observed in 4% and 22% of the patients with trigeminal neuralgia and in 1% and 2% of those with hemifacial spasm, respectively (P < 0.0001). In patients with trigeminal neuralgia, 35% of those with artery and venous compressions and 80% of those with venous compression alone had atypical neuralgia (P = 0.015). The surgical cure and recurrence rates of trigeminal neuralgias with venous compression were 60% and 20 %, respectively, and those with arterial and venous compressions were 92% and 20% (P < 0.0001, P = 0.04), respectively. In patients with hemifacial spasm of arterial and venous compressions, their recurrence rate was 60% and significantly higher, compared to other compression types (P = 0.0008).

Conclusion: Dissection of the arachnoid sleeve that envelopes the superior petrosal vein may help to reduce venous complications in surgery for trigeminal neuralgia. Venous compression may correlate with worse prognosis even with thorough decompression, in both trigeminal neuralgia and hemifacial spasm.

Hiroki TODA (Osaka, JAPAN)
16:35 - 16:40 #16315 - O031 Spinal cord stimulation for microcirculation improvement in the treatment of ischemic pain.
O031 Spinal cord stimulation for microcirculation improvement in the treatment of ischemic pain.

Objectives: Refractory angina pectoris (RAP) and peripheral vascular disease (PVD) is a chronic pain condition caused by occlusive artery diseases, which can't be adequately controlled neither by a combination of medical therapy nor by vascular surgery treatment (angioplasty or bypass surgery). Since 1976 spinal cord stimulation (SCS) appears to be an effective and safe treatment for these patients. SCS has been used for treating refractory angina since the 1980s. It alleviates angina symptoms without masking the symptom of acute myocardial infarction. The anti-ischaemic effect has been demonstrated by a number of studies from different centers. The efficacy of SCS is supported by one placebo-controlled study, two larger randomized controlled trials, and several small controlled studies. According to systematic reviews, there is strong evidence that SCS gives rise to symptomatic benefits and improves functional status in patients with angina pectoris. Cook et al. were the first investigators to use SCS in patients with the peripheral vascular disease. The efficacy of technology in pain relief not only for the neuropathic but ischemic genesis of pain is obvious. Besides, it can result in microcirculatory improvement in the myocardium and limbs' tissues.

Methods: We conducted a prospective analysis of patients with non-reconstructable RAP (n=19) and PVD (n=58) who underwent SCS in our facility between 2012 and 2017. Conventional SCS was applied with rechargeable and nonrechargeable IPGs. The lead placement in the RAP group was C7-Th1-Th4, in the PVD group - Th12-L1. Preoperative and follow-up myocardium perfusion scintigraphy (MPS), transcutaneous oximetry (TCO) and laser-doppler flowmetry (LDF) were performed on admission and in 1 year after the procedure. Pain relief was assessed by visual analog scale (VAS) in all patients.

Results: The patients showed 9,37±0,13 marks according to VAS before the procedure and pain relief to 1,27±0,09 marks (p<0,01) in a 1-year follow-up. All patients in RAP and PVD group demonstrated the rise of tolerance to the physical activity. MPS detected the decrement of perfusion's defect from 13,36±4,16 to 10,14±3,35 units (increase in coronary reserve up to 24%). TCO detected the microcirculatory improvement (n=42): tissue oxygenation increased from 10,5 to 39,5 mm Hg (p=0,045). LDF detected the improvement in microcirculation that manifested in increasing of functional reactivity of microcirculatory vessels. The mean value of microcirculation speeds in the postocclusion test at third minute increased from 5,91 ml/min per 100 g to 7,59 ml/min per 100 g (that contributed 28,4%, p=0,05), in the Valsalva's probe - from 3,48 ml/min per 100 g to 6,32 ml/min per 100 g (81,6%, p=0,05). There were two patients (3.4%) who had required postoperative amputation and 1 patient's death from cardiac infarction.

Conclusions: Spinal cord stimulation is the efficient neuromodulation modality for patients with ischemic pain syndrome. But microcirculatory improvement is also evident. Our experience confirms that SCS can reduce the pain and improve quality of life with vascular reserve enhancement in patients with ischemic pain syndrome.

Vladimir MURTAZIN (Novosibirsk, RUSSIA), Roman KISELEV, Andrey ASHURKOV, Kirill ORLOV, Alexey KRIVOSHAPKIN, Vladimir SHABALOV
16:40 - 16:45 #16326 - O032 The importance of somatotopy to achieve clinical benefit in motor cortex stimulation for pain relief.
O032 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
16:45 - 16:50 #16332 - O033 Medial thalamotomy - radiofrequency thermocoagulation for intractable pain.
O033 Medial thalamotomy - radiofrequency thermocoagulation for intractable pain.

Objective: Ablative procedures still have their place in the treatment of intractable pain despite the boom of neuromodulation techniques. Here we present the results of medial thalamotomy performed by radiofrequency thermocoagulation (RT) in various pain syndromes.

Methods and Patients: Between 1996 and 2017 we performed unilateral RT in 41 patients (F:M=24:17, age ranged 30-85, median 67 yrs) suffering from different severe pain syndromes (10x thalamic pain, 8x resistant classic trigeminal neuralgia /TN/, 8x postherpetic TN, 8x secondary TN, 5x atypical TN, 2x amputation pain)  in whom conservative treatment had failed. The median follow up was 12 months (range 4 -120  months).  In twenty four patients some invasive procedures for pain release preceded: gamma knife irradiation of trigeminal nerve, balloon compression or glycerolysis in cavum Meckeli, microvascular decompression. The Leksell Sterotactic Frame, SurgiPlan Software (Elekta) and T1- and T2-weighted sequences acquired at 1.5 T (Siemens Avanto) were used for target localization of medial thalamus – centrum medianum (CM) and nucleus parafascicularis (Pf). CM/Pf were localized 7 mm lateral to the wall of the 3rd ventricle, 8 mm behind the mid-point and 3 mm above intercommisural line. RT was performed by unipolar radiofrequency electrode with applied temperature ranged from 75° to 80°C. The neurological status and pain relief after electrocoagulation were evaluated. A decrease of the pain intensity under 50 % of the previous level has been considered as a successful treatment.

Results: Initial successful results were achieved in 10 (46 %) of the patients, with complete pain relief in 5 (12 %) of them. Pain recurred in 2 (5 %) of patients 5 and 6 months after RT.  Transient facial paresthesia  have been observed in 1 patient.

Conclusions: These results suggest that RT for patients suffering from severe pain syndromes is a relatively successful and safe method that can be used in patients even if they are in poor condition. The main risk of RT for our patients was failure of treatment, because we have experienced only one transient  clinical side effects. Supported by MH CZ – DRO (NHH, 00023884)-IG151201, IG161201.

Dusan URGOSIK (Prague, CZECH REPUBLIC), Roman LISCAK
16:50 - 16:55 #16370 - O034 Clinical outcomes and comparison of Burst, 1 kHz and 10 kHz subperceptinal spinal cord stimulation for chronic back pain.6 months multicentre, double blinded study.
O034 Clinical outcomes and comparison of Burst, 1 kHz and 10 kHz subperceptinal spinal cord stimulation for chronic back pain.6 months multicentre, double blinded study.

Spinal Cord Stimulation (SCS) is a commonly recommended procedure to treat several pain syndromes with a focus on pain relief an functionality. Stimulation parameters have been investigated and manipulated for years to optimize pain therapy. A wide range of frequencies used in commercially available SCS devices have been explored for various indications. With a recent focus on novel waveforms, such as 1kHz -10 kHz and burst stimulation, there is a growing appreciation for the impact of energy delivery on the nervous system. The aim of this study was to assess long term outcomes and compare clinical effects of 3 types of high frequency stimulation: Burst Stimulation, 1kHZ and 10 kHz in patients with chronic pain of back and legs.

Material and methods 

19 Subjects were recruited  from June 2016 to January 2018.  following criteria were used for inclusion: A good indication for SCS and reporting pre-dominant back pain. All patients were implanted with a permanent wireless, Freedom SCS system (Stimwave, Pompano Beach, Florida) at thoracic (TH9-TH10) or cervical (C2-C4) levels.  Subjects experiencing at least 30% reduction of pain intensity were allowed to continue past an initial trial period. Patients were offered 3 different waveforms in the 2nd phase of this study:  Burst (500-Hz spike mode), 1kHz and 10kHz.

Program parameters:

 Burst (500 Hz in 5 peaks, 1 us), bipolar, amplitude based on patient’s preference;

1KHz, 20 us, bipolar DS TH9-TH10, amplitude based on patient’s preference not greater than 3mA

10KHz, 20us, bipolar DS TH9-TH10, amplitude based on patient’s preference not greater than 3 mA

Each waveform was tested for 1 week. Both researcher and subject were blinded to treatment. each subject had 2-4 programming session to optimize therapy. In the third phase of study objects evaluated their long term results with preferred waveform.

Outcomes measurements:

Key outcome measurement included VAS for back and leg pain, Oswestry Disability index measuring functionality, Laitinen Scale and subject preference. Subjects tested all three programs for one week, up to the first evaluation visit at 1-month post-trial. After 3 and 6 months objects evaluated their long term results with preferred therapies.

Results

 All 19 patients finished observation with general pain relief of at least 50% or greater in VAS scale. The therapy effect was stable and there were no significant changes during 6 months.

The analysis of the Laitinen questionnaire showed more than 50% of improvement in all  4 accessed areas of life. Laitinen analysis showed stable improvement during 6 months.

Oswestry Disability index were significantly reduced compared with baseline value. Effectiveness of 3 different modes of HF stimulations:

The 6 months observation showed that all HF modes were effective on the beginning of therapy. After the first follow up  - 1 month - majority of patients had chosen stimulation mode of 1KHz.

The second follow up (3 months) showed shift to higher frequency – 10 KHz. After 3 months almost no patients were using burst mode.

The third follow up (6 months) showed that significant number of patients had chosen 10KHz mode.

- adjustment of other programming parameters was not significant and mostly related to the increase of amplitude up to 4,5 mA.

 Conclusion

 Our case series study showed superior efficacy of higher frequency stimulation modes which had been more frequently chosen option by patients due to lack of troublesome paresthesia and better analgesic effect.

The study showed patients’ preferences to switch to higher frequency mode. In the first month after operation the best improvement was observed after 1 kHz stimulation and after 6 months of observation 10 KHz was the most preferred by patients.

 Higher frequency showed better tolerance, stability and required less programming procedures. Additionally – no paresthesia, no postural effect and general good pain improvement in all areas of the body was observed in HF SCS.

HF stimulation seems to work more precisely and allows to reach difficult areas.  However various patients reported different preferences of 1 kHZ or 10 kHZ which had been changed in time to receive  better coverage of feet or/and low back pain. The major advantage of the wireless system is to deliver all kind of available waveforms of stimulation and adjust them to every single patient.

 

Aleksandra MAJ-KESICKA (BYDGOSZCZ, POLAND), Pawel SOKAL, Marek HARAT, Leszek HERBOWSKI, Zennar KHEDER, Jacek NACEWICZ
16:55 - 17:00 #16414 - O035 Extended DREZ-lesion for Relieving Intractable Arm Pain Following Brachial Prexus Avulsion Injury. What occurs at the Injured dorsal horn.
O035 Extended DREZ-lesion for Relieving Intractable Arm Pain Following Brachial Prexus Avulsion Injury. What occurs at the Injured dorsal horn.

Background: Dorsal root entry zone (DREZ) lesioning has been the most effective surgical treatment for the relief of intractable pain due to root avulsion injury; 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.

Method: Fourteen patients underwent surgery between 2011 and 2017. The detailed surgical procedure will be reported in the presentation.
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. 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.

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
WOLFSON HALL B
17:00

Thursday 27 September

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A29
17:00 - 19:30

Parallel Session 5
Renaissance of Lesioning

Moderators: Jin Woo CHANG (Seoul, KOREA), Marwan HARIZ (London, UK), Kostiantyn KOSTIUK (Neurosurgeon) (KYIV, UKRAINE), Juergen VOGES (Head of the Department) (Magdeburg, GERMANY)
17:00 - 17:15 Cingulotomy for depression. Rees COSGROVE (Director, Epilepsy and Functional Neurosurgery) (Boston, USA)
17:15 - 17:30 Pros & cons // Lesioning using RF vs GK vs HIFU. Takaomi TAIRA (faculty, speaker) (Tokyo, JAPAN)
17:30 - 17:45 MRgFUS capsulotomy for psychiatric illness. Jin Woo CHANG (Seoul, KOREA)
17:45 - 18:00 STN HIFU in Parkinson's disease. Marta DEL ALAMO (Neurosurgeon) (Madrid, SPAIN)
18:00 - 18:15 Gamma Knife Capsulotomy for OCD. Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
18:15 - 18:25 #14475 - O036 Bilateral stereotactic anterior nucleothalamotomy in humans for treatment of intractable epilepsy.
O036 Bilateral stereotactic anterior nucleothalamotomy in humans for treatment of intractable epilepsy.

Objectives: Anterior thalamic nucleus (ANT) chronic stimulation showed great results in frontal and temporal epilepsy control because of their wide spread projections to various cortical and subcortical structures and involvement in the process of generation and spreading of epileptic activity. Several animal studies demonstrated the efficacy of bilateral lesions and stimulation of ANT in prevention of seizure propagation with superiority of lesions in terms of epilepsy control. The first report on unilateral stereotactic lesion of the anterior thalamus in humans for the treatment of epileptic seizures was published in 1967 by S. Mullan and co-authors. In their series the seizure-freedom achieved in 2 out of 9 patients, a significant improvement in 4 cases with 1 non-responder. Based on these researches, we proposed the stereotactic anterior nucleothalamotomy as an option for treatment of pharmacoresistant epilepsy in humans.

Methods: The bilateral stereotactic radiofrequency lesions of ANT performed in 21 patients suffering from pharmacoresistant epilepsy (table 1).  Due to lack of clear anatomical borders of ANT on MRI, the patients were scanned day before surgery to visualize well defined anatomical structures - subthalamic nucleus, red nucleus and substantia nigra. Targeting was based on stereotactic atlas information with correction of the final coordinates according to the location of anatomical landmarks and intraoperative microelectrode recording data. All surgeries was performed under a local anesthesia through bilateral 14 mm bur holes located 3 – 3.5 cm posteriorly to the coronal suture and 4 cm from midline. The electrode trajectory was trans-ventricular in all cases. Microelectrode recording performed in 20 patients to confirm the passing of electrode through the lateral ventricle and the thalamus and define the length of ANT. For lesioning we used CSK-3M radiofrequency electrode with tip diameter 1.1 mm connected to G4 Four-Electrode RF Generator. Two lesions were done along the track: one on the target and one 0.5 mm above the target 70°Celcius 70 second each.

Results: MRI showed structural abnormalities in 3 patients: in 1 case posttraumatic gliotic changes, in 1 – transmantle FCD and in 1 - multiple FCD not eligible for surgical resection.  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. The clear signal from ANT was obtained in 38 trajectories. According to the MER data, the average length of ATN was 4.1 mm on the left (range - 4.0-5.2 mm) and 4.5 mm on the right (range - 3.1-4.7 mm). Postoperative MRI confirmed the location of the lesions zones within ANT on both sides with average diameter of the lesion zone 4.1 mm (range - 3.8-5.2 mm) (Fig. 1). After surgery 17 of the 21 patients experienced a significant reduction in seizures ranging from 50 to 90%. The average seizure frequency reduction among the responders with available follow up exceeded 91.2 %. Currently, 5 patients remain completely seizure-free with 4 non-responders. No neurological complication including memory disturbance were noted.

Conclusions: Stereotactic anterior thalamotomy is an effective option for seizure control in epilepsy originated from frontal and temporal lobes. ANT lesions more effective for secondary generalized seizures compared to simple partial seizures.

 

Andrey SITNIKOV (Moscow, RUSSIA)
18:25 - 18:35 #16237 - O037 Six year outcome of focused ultrasound thalamotomy for essential tremor.
O037 Six year outcome of focused ultrasound thalamotomy for essential tremor.

Introduction.  Focused ultrasound thalamotomy has been recently proposed as another treatment option for medication-refractory essential tremor, but the long term outcome is unknown.  

Methods.  A pilot study of 15 ET patients, treated with unilateral FUS Vim thalamotomy, was conducted in 2011.  Clinical outcomes were assessed for tremor, disabilities, quality of life, MRI, and adverse event reporting.   These patients were recently assessed at six years with CRST, QUEST, and global impression of clinical change.  A correlation analysis of their long term clinical outcomes was conducted.

Results.  Thirteen patients (87%) were assessed at 6 years post thalamotomy.  One patient was lost to followup and another died from breast cancer.  There was no additional, latent procedural morbidity.

Mean hand tremor scores (baseline: 20.4+5.2), which were improved by 74% (5.2+4.8) at one year, remained improved by 36% (12.5+11.4) at 6 years but with some loss of effect.  Six of the thirteen patients available for followup had over 50% reduction of hand tremor at 6 years.  

Mean disability scores remained improved from baseline by 50% at long term.  Additional outcomes including total CRST, simulated eating task, and quality of life from the QUEST are improved at long term. 

Conclusion.  FUS thalamotomy can provide long term benefit for ET, but recurrence occurs.  These long term results from an early stage pilot study demonstrate that additional refinements of the procedure are needed to improve the durability of FUS thalamotomy.   

W. Jeff ELIAS (Charlottesville, USA), Diane HUSS, Tony WANG, Aaron BOND, Binit SHAH
18:35 - 18:45 #15790 - O038 The STN and Hemiballismus. Historical review.
O038 The STN and Hemiballismus. Historical review.

Introduction. The presentation is an historical review of the subthalamic nucleus (STN) and the hemiballismus (HCB) as surgical complication.

For many years the STN had a poor reputation among neurosurgeons due to the acute movement disorder that is developed after its lesion.  

Material and Methods. In the presentation we describe the HCB from early studies in monkeys (1940-50´s), as a surgical complication in functional neurosurgery (1950-60´s), the pathophysiology of HCB (1980-90´s) to current subthalamic lesions in parkinsonian patients.

Results. Volume and placement of lesions in the STN may be correlated with the complication and this topic will be developed during the presentation.  The capital role of the pallido-thalamic pathway maintaining the dyskinesia are also described during the presentation.

The STN, an anatomical structure, which was discovered more than 100 years ago is now generating interest in the stereotactic field.

Jorge GURIDI (Pamplona, SPAIN), Rafael RODRIGUEZ-ROJAS, Olga PARRAS
18:45 - 18:55 #16357 - O039 Focused ultrasound thalamotomy outcomes in 60 consecutive patients with refractory tremor: A 3 year to 6 month follow-up single center study.
O039 Focused ultrasound thalamotomy outcomes in 60 consecutive patients with refractory tremor: A 3 year to 6 month follow-up single center study.

Objetive
The efficacy of focused ultrasound thalamotomy with magnetic resonance imaging guidance
(MRIgFUS) for the treatment of essential tremor has been supported by one randomized trial and
several uncontroled trials. To date, more than 1000 patients have underwent this procedure
worldwide. We present a descriptive series of 60 consecutive patients treated at a single center with
MRgFUS Thalamotomy to control their drug-refractory tremors.


Methods
From March 2015 to November 2017, sixty consecutive patients suffering from chronic,
drug-refractory tremor (DRT) were treated with unilateral MRgFUS Thalamotomy. The target
was the Ventral intermediate (Vim) nucleus contralateral to the dominant hand side (three
right Vim Thalamotomies). Primary relief assessment indicator was the Essential Tremor Rating Scale (Fahn,
Tolosa, and Marin) (ETRS) taken at follow-up (6 to 36 months) with accent on the hand function
subscores and handwriting. We also gathered detailed recording of the procedure steps and of
adverse effects, immediate and along follow-up.


Results
The mean ETRS relief at maximum follow-up available was 47.8% (36-57). The mean number of
sonications was 17.3 (11-27), with a mean maximal temperature achieved at target of 57.9 Celsius
((53-64). Neurological exploration at 6 months showed improvement not only in arm tremor but
also in coexisting tremors of the head, chin, and leg, although to a lesser degree. The most frequent
adverse effects were equilibrium and gait disturbances. Such adverse effects were transient, and
none of our patients had any adverse event that lasted for more than 4 months. Admission mean
time was of 16,8 hours after the procedure.


Conclusions
The outcomes in our series support the reproducibility of previous trials: that MRIgFUS Thalamotomy reduced hand tremor and improved the quality of life in patients with
DRT with a remarkable safety profile. Side effects included sensory and gait disturbances, wich were transient in all cases. No serious complications were encountered. Further studies will
be needed to validate the long term effect of the treatment beyond three years.

Jordi RUMIÀ (BARCELONA, SPAIN), Javier TERCERO, Núria BARGALLÓ, Meritxell AZANUY, Alberto ALOMAR, Francesc VALLDEORIOLA
18:55 - 19:05 #16416 - O040 Bilateral GammaKnife Thalamotomy for severe Essential Tremor: Preliminary results of a prospective study.
O040 Bilateral GammaKnife Thalamotomy for severe Essential Tremor: Preliminary results of a prospective study.

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 RF 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 Knife 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), Axel CRETOL, Romain CARRON, Louise MERLY, Jean Philippe AZULAY, Tatiana WITJAS
19:05 - 19:15 #16284 - O041 Cryosurgical method in modern functional and neuro-oncology stereotactic neurosurgery.
O041 Cryosurgical method in modern functional and neuro-oncology stereotactic neurosurgery.

Cryosurgery as a method for the ablation of deep subcortical structures in functional stereotactic neurosurgery was proposed by I.Cooper in 1960. Later, E.I.Kandel used the cryosurgical technique for the purposes of functional stereotaxy and neuro-oncology for the destruction of deep brain tumors. Subsequently, however, cryoablation was almost completely replaced by other methods of stereotactic destruction, including thermoablation with radio-frequency alternating current, radiosurgery, etc. At the same time, cryosurgery successfully develops for many years in other fields of surgery – hepatosurgery, urology, gynecology, etc. In our opinion, the main reason for the pushing out of cryosurgery from neurosurgical practice is that the most of the cryodevices is based on use of liquid nitrogen. Such devices are not suitable for neurosurgery because of the inability to control the stable temperature of the cooling chamber of the cryoprobe, impossibility to provide a safe temperature of reversible cooling in target points as well as the risks of "icy fractures" that occur in the brain tissue at temperatures below -100 ºC.

At the same time, the cryosurgical method according to its characteristics – the possibility of exploratory effects at target points during the trial cooling, the predictability of the size of destructions subject to standard cryoexposure parameters, clear demarcation of foci of ablation – fully meets the requirements for stereotactic impacts. Moreover, this is the only method of stereotactic ablation, which allows real-time control of the size of destruction using intraoperative ultrasound which visualize the ice-ball at the target zone. In this regard, stereotactic cryosurgery can be regarded as a more accessible and no less effective alternative to laser interstitial thermal ablation under MRI control, used in recent years for the treatment of deep brain tumors and temporal epilepsy.

Previously, we have shown that stereotactic cryodestruction of nervous tissue and intracerebral tumors can be achieved at temperatures of -60-70 ºC. The destruction occurs because of the destroying of cell membranes by ice crystals, as well as due to ischemia of tissue at the zone of freezing. In this regard, for the purposes of stereotactic neurosurgery we have designed cryosurgical apparatus working with the temperature of solid carbon dioxide -78 ºC. As a refrigerant for cooling the working chamber at the tip of a cryoprobe, acetone is used, circulating under pressure in a closed circuit. The instrument is equipped with an indicator of temperature in the refrigerating chamber of the cryoprobe. Cooling of acetone to the operating temperature can be achieved both by means of cool exchanger, in whom dry ice is loaded, and by means of compressors. The diameter of the frozen zone inside a brain depends on the size of the cooling chamber of cryoprobe and duration of freezing. But there is a maximum diameter of freezing, which is achieved in about 4 minutes of cryoexposure. While used device able to form foci of destruction up to a volume of 7 cm3 each, while the destruction using apparatus for radio frequency thermoablation does not exceed 1 cm3. The thawing of the frozen tissue occurs spontaneously within 5 minutes after the termination of cycle. The advantages of this device above an equipment working with the liquid nitrogen include easy control of temperature at an active tip of a cryoprobe, its good adhesion to a tissue, absence of “icy fractures” of a frozen tissue, the possibility of reversible (diagnostic) cooling in target points in temperatures -20-30 ºC, and also simplicity and safety of work.

Due to the ablative and immunostimulating effect of cryoablation, this device is used by us for stereotactic multi-position destruction of deep intracerebral tumors, inaccessible for open removal. To date, 196 patients have been operated on with average volume of total destruction about 23 cm3. Stereotactic cryodestructions in mediobasal temporal structures with total volume of 6-18 cm3 with a good result were performed by us also in the treatment of 7 patients with temporal epilepsy related to medial temporal sclerosis. Operations are carried out under local anesthesia. MRI and MRI/PET, frame and frameless stereotactic devices are used for targeting and guidance at intracerebral target points. Thus, the cryogenic method now allows to solve successfully tasks of both functional and non-functional stereotaxis.

Vladimir NIZKOVOLOS, Natalia STERLIKOVA (Saint Petersburg, RUSSIA), Andrey KHOLYAVIN, Victor BONDARENKO, Jaroslav BELYAEV, Andrey MYAGKOV, Boris MARTYNOV, Alexander GURCHIN
19:15 - 19:20 #16135 - O042 Safety of bilateral thalamotomy for essential tremor.
O042 Safety of bilateral thalamotomy for essential tremor.

Background: Essential tremor (ET) can be quite debilitating with significant diminution of quality of life, more so in patients having bilateral and/or midline/axial tremor besides effective treatment for bilateral symptoms remains unproven. Verification of bilateral thalamotomy for medication refractory bilateral and/or midline/axial tremor is often dismissed with apprehension for occurrence of adverse effects.

Objectives: To study the impact of any manifested adverse effects on the quality of life and the overall functional improvement along with patient satisfaction in medically refractory bilateral essential tremor patients treated with staged bilateral ventral intermediate nucleus (Vim) thalamotomy.
Methods: Eight patients were selected for the study and subjected to a specially prepared questionnaire. The questionnaire studied the patient's disability on the scores of mild, moderate and severe and their contentment with the result. The scores obtained thereof were analyzed. Results: Out of 8, 1 patient had moderate disability and 4 patients had mild disability due to residual neck tremor. No patient had severe disability in any aspect. All patients could dress, groom themselves and eat using chopsticks. There was good improvement in quality of life reducing dependence on family members or caring staff for daily life activities.
Conclusions: Staged bilateral Vim thalamotomy definitely improves quality of life of ET patients with bilateral symptoms with acceptable adverse effects.

Takaomi TAIRA (Tokyo, JAPAN), Ghate PRAJAKTA, Shiro HORISAWA
19:20 - 19:25 #16211 - O043 Unilateral pallidothalamic tractotomy for Parkinson's disease.
O043 Unilateral pallidothalamic tractotomy for Parkinson's disease.

Pallidothalamic tract connects globus pallidus internus and ventrolateral portion of the thalamus, and ablation of pallidothalamic tract (pallidothalamic tractotomy: PTT) have been reported to have antiparkinsonian effect. However detailed clinical course have yet to be reported. The patient is a 68-year-old previous healthy woman. After 14 years of beginning the oral medications, she experienced a wearing off phenomenon. The levodopa 300mg/day was required to maintain her daily activities. Rigidity and peak dose dyskinesia were predominantly observed in right side of the body. Right foot dystonia with pain also manifested. Preoperative Unified Parkinson’s Disease Rating Scale (UPDRS) score Part1, Part2 (off medication/on medication), Part3 (off medication/on medication), Part4 were 7, 26/4, 41/23, 13 respectively. Preoperative Unified Dyskinesia Rating Scale (UDysRS) and Parkinson’s Disease Questionnaire-39 (PDQ-39) were 102 and 46, respectively. She underwent left-side PTT, and no perioperative complications were observed. At 1 year postoperatively, she has maintained the daily dose of 200 mg levodopa without off condition all day. The 1-year UPDRS score Part1, Part2, Part3, Part4 were 5, 9/1, 20/12, and 5 respectively. The 1-year UDysRS and PDQ-39 were 20 and 20, respectively. Although larger sample sizes are needed, pallidothalamic tract can be an alternative treatment target in PD patients.

Shiro HORISAWA (Shinjyuku, JAPAN), Takakazu KAWAMATA, Takaomi TAIRA
19:25 - 19:30 Discussion.
FESTIVAL THEATRE AUDITORIUM

Thursday 27 September

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B29
17:00 - 19:00

Parallel Session 6
Mouvement Disorders

Moderators: Patric BLOMSTEDT (Neurosurgeon) (Umeå, SWEDEN), Joseph CANDELARIO-MCKEOWN (Deep Brain Stimulation Nurse Specilaist) (London, UK), István VALÁLIK (head of department) (Budapest, HUNGARY)
17:00 - 17:20 Asleep DBS in the Zona Incerta for PD and ET. Patric BLOMSTEDT (Neurosurgeon) (Umeå, SWEDEN)
17:20 - 17:30 #14909 - O044 The increase of dopamine transporter density in the ventral striatum and its correlation with motor improvement in patients with Parkinson’s disease after subthalamic nucleus deep brain stimulation.
O044 The increase of dopamine transporter density in the ventral striatum and its correlation with motor improvement in patients with Parkinson’s disease after subthalamic nucleus deep brain stimulation.

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. Furthermore, we also examined the relationship between CFT binding and motor function before and after 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). Motor function was also evaluated by the Unified Parkinson’s Disease Rating Scale (UPDRS) part III pre- and post-operatively (at around the same time as the PET study). Spearman’s correlation coefficient by rank tests were used to compare the DBS-induced changes in UPDRS III with DBS-induced changes in [11C]CFT binding.

 

 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 ipsilateral anterior-ventral putamen, contralateral ventral caudate and bilateral nucleus accumbens although it did not reach statistical significance. The magnitude of the percentage of reduction in UPDRS III (improvement of the motor function) was significantly correlated with that of increase in [11C]CFT binding in the ipsilateral anterior-ventral putamen and ipsilateral ventral caudate. Although the same tendency was observed in the contralateral ventral caudate and contralateral nucleus accumbens, statistical significance did not reached.

 

Conclusions.

Our result showed that STN-DBS increases dopamine transporters in the ventral striatum, which is different from natural course of PD. The ventral striatum (anterior-ventral putamen and ventral caudate) ipsilateral to the clinically more affected side was significantly correlated to the the degree of motor improvement after STN-DBS, and contralateral ventral striatum (ventral caudate and nucleus accumbens) showed same tendency although it did not reach statistical significance. This dorsal-to-ventral shift of dopamine transporter density 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
17:30 - 17:40 #16171 - O045 Five year outcomes of a prospective, multicenter trial evaluating deep brain stimulation with a new multiple source, constant current rechargeable system in parkinson's disease.
O045 Five year outcomes of a prospective, multicenter trial evaluating deep brain stimulation with a new multiple source, constant current rechargeable system in parkinson's disease.

Objective: To evaluate the long term follow up of patients in the VANTAGE Study that employed a Deep Brain Stimulation (DBS) system with multiple independent current control (MICC) in the management of symptoms of Parkinson's disease.

Background: We postulated that a multiple source, constant current DBS device (CE marked) permitting a well defined distribution of current would lead to motor improvement in patients with Parkinson's disease (PD). The 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 five year, long term results. 

Methods: VANTAGE is a prospective, multicenter, nonrandomized, open label trial sponsored by Boston Scientific. Forty subjects with idiopathic PD were implanted bilaterally with a DBS system (Vercise, Boston Scientific) targeting the subthalamic nucleus and followed up to five years post lead placement. Assessments included UPDRS III scores in the meds off condition, quality of life such as Parkinson's Disease Questionnaire (PDQ39), Modified Schwab and England (SE), etc. Adverse events were collected. 

Results: At four years post lead placement, quality of life as assessed by PDQ39, SE continued to show improvement as compared to baseline. Additionally, the usage of antiparkinsonian medications continued to show a similar trend as reported earlier. This report will present the long term motor outcomes and quality of life results at 5 years post lead placement. 

Conclusions: The collected outcomes from the VANTAGE clinical trial will inform clinicians on use of this system, and its flexibility to manage 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
17:40 - 17:50 #16195 - O046 Brain networks predicting impulsivity after subthalamic deep brain stimulation for Parkinson’s disease.
O046 Brain networks predicting impulsivity after subthalamic deep brain stimulation for Parkinson’s disease.

Introduction

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an important advanced therapy for Parkinson’s disease (PD), which alleviates motor symptoms and improves quality of life. However, some individuals develop postoperative neuropsychiatric symptoms such as impulsivity and mood elevation. This is believed to arise from the central role of the STN in cognitive and affective, as well as motor, inhibition. Our group has previously demonstrated that the locus and distribution of subthalamic stimulation is a key determinant of postoperative neuropsychiatric symptoms; here we sought to delineate brain networks responsible for this phenomenon. 

Methods

Forty-five, non-demented persons with PD undertook high-resolution diffusion brain imaging prior to subthalamic DBS. Each participant was assessed with a battery of neuropsychiatric instruments at baseline and at four postoperative intervals up to six-months post-DBS. Participants also played a played a slot-machine in a virtual casino prior to subthalamic DBS (whilst on medication) and three-months postoperatively (whilst on stimulation).  This provided information on gambling behaviour and furnished Bayesian estimates of a participant's confidence in the winning probability and volatility (likelihood that a machine would switch between "hot" and "cold" states) of the slot machine.

Results

We delineated core structural brain networks implicated in cognitive control, response inhibition and reward valuation. At baseline, using multivariate path analysis with partial least squares regression, the connectivity (defined as apparent fibre density) of the STN with cortical regions pre-SMA (supplementary motor area), IFG (inferior frontal gyrus) and ACC (anterior cingulate cortex) was significantly associated with inhibitory errors and ‘double or nothing gambles’ on the slot machine. The connectivity of the ventral striatum (nucleus accumbens) with cortical regions 10-medial, OFC (orbitofrontal cortex) and ACC was significantly associated with impulsive-compulsive behaviours (as rated by the Questionnaire for Impulsive- Compulsive Disorders in PD–Rating Scale), delay aversion (as scored by the delay discounting task), bet size and uncertainty about winning probability on the slot machine. We then generated an individual volume of activated tissue (VAT) for each hemisphere in each participant based upon subthalamic electrode positioning and individualised stimulation parameters. We found that connectivity between the site of stimulation and these cortical targets significantly modulated these behavioural and cognitive measures.

Conclusions

In summary, we identify core subcortical-cortical networks underlying impulsivity and valuation in Parkinson's disease, and demonstrate the interaction between electrode targeting and neuroanatomy in the modulation of post-DBS impulsivity. These data underscore the importance of accurate electrode targeting, contact selection and device programming to reduce postoperative neuropsychiatric impairment. The ability to predict neuropsychiatric symptoms based on subthalamic data may permit anticipation and prevention of these occurrences, improving safety and tolerability.

Philip MOSLEY (Brisbane, AUSTRALIA), Saee PALIWAL, Alistair PERRY, David SMITH, Peter SIBURN, Terry COYNE, Marc TITTGEMEYER, Klaas STEPHAN, Michael BREAKSPEAR
17:50 - 18:00 #16228 - O047 Does the degree of improvement after deep brain stimulation surgery for parkinson’s disease meet the patient’s expectations?
O047 Does the degree of improvement after deep brain stimulation surgery for parkinson’s disease meet the patient’s expectations?

Objective: This research is a quantitative, exploratory study, which aims to identify the symptoms that patients with Parkinson's disease (PD) expect to improve with deeep brain stimulation (DBS) and whether the expected levels of improvement are met after DBS surgery.

Background: DBS is an effective surgical treatment that improves patient quality of life in advanced PD. It is an essential part of patient care in DBS treatment to identify and manage expectations from the assesment of suitability for DBS to the lifelong care after DBS surgery. The DBS outcome is influenced by patients' varying expectations on how DBS can improve their symptoms after DBS.

Research Methods: 28 participants with advanced PD were recruited and have completed a visual analogue (VAS) questionnaire designed to capture patient's expectations prior to surgery (pre-DBS) and at 6 months to 2 years follow up (post -DBS). 20 patients had subthalamic nucleus (STN) DBS and 8 patients had globus pallidus interna (Gpi) DBS.

Results: For the group as whole, there was a significant reduction in total levodopa equivalent daily dose (mg/day) by 50.45% in the STN group after DBS and the motor symptoms for both STN and Gpi group have improved on the UPDRS III off (p 0.001), mobility (p 0.0048), ADL (p 0.008) and stigma (p 0.014) after DBS. This objective symptomatic improvement was also mirrored in the patients expectations being generally met for the motor symptoms at least. In general expectation of patients in DBS, there was no significant difference (z value (-0.158), two tailed p value 0.875) between the pre-DBS expectation of general improvement in PD symptoms and perceived general improvement 6 months to 2 years after surgery, which confirms that general expectations of  improvement were met after DBS. Most patients reported that expectations of improvement after DBS were met: 64% for motor symptoms, 71% and 83% for quality of life and reductions in medication daily dose (respectively). Only 25% of the expected levels of improvement were met for the non-motor  symptoms and for the social domain. Between STN and Gpi DBS targets, the expectations from DBS were satisfied 6 months to 2 years after the surgery: in Gpi-DBS group, 100% were satisfied in the reduction of dyskinesias, 83.3% for motor symptoms and 66.70% for quality of life. STN-DBS patients were satisfied with the reduction in medication (84.20%), 78.90% for motor symptoms and 73.70% for quality of life.

Conclusions: DBS did meet the perceived expected level of improvement in motor symptoms, quality of life, and reduction in medication within 6 months to 2 years after DBS surgery for the majority of patients which corresponded to the objective clinical outcome. The pre-DBS expected improvement of non-motor symptoms and social domain was not met after surgery. Overall, both STN-DBS and Gpi-DBS patients were satisfied that DBS had met their expectations of surgery.

Joseph CANDELARIO-MCKEOWN (London, UK), Maryam TORKAMANI, Hannah SHERIDAN, Alison COUTTS, Catherine HARTIGAN, Maricel SALAZAR, Patricia LIMOUSIN, Marwan HARIZ, Ludvic ZRINZO, Jonny HYAM, Tom FOLTYNIE, Marjan JAHANSHAHI
18:00 - 18:10 #16258 - O048 Outcome and complications of surgical retreatments for essential tremor. The Toronto experience and a systematic review of the literature.
O048 Outcome and complications of surgical retreatments for essential tremor. The Toronto experience and a systematic review of the literature.

Introduction

Despite the excellent improvement following deep brain stimulation (DBS) of the thalamus and adjacent white matter tracts, or thalamotomy by radiofrequency, radiosurgery or focused ultrasound thalamotomy in medication-refractory cases of essential tremor (ET), recurrences are observed either early (

We aim to systematically review the Toronto Western Hospital experience as well as the literature on surgical retreatments for ET.

 

Methods

We searched the surgical database of the Toronto Western Hospital for ET patients with at least 1 year follow-up and assessed the number of surgeries. Further, we performed a systematic literature search and screened publications on ET surgery for recurrence and re-treatment. We collected data on outcome and complications, and constructed a flowchart for decision making in cases of postoperative ET recurrence.

 

Results

In Toronto Western Hospital, 13/144 (9%) ET patients were retreated at least once, in line with the literature. We found >200 retreatment cases in the literature. DBS failures were mostly treated by lead repositioning or addition of a second lead in a different target, with good outcome and low complication rate. Repeated ablations after failed thalamotomies generally improved tremor but were associated with much higher complication rates.

Microelectrode recording can still be helpful in retreatment cases, independent of the first treatment modality.

Early failures are often due to suboptimal targeting, while late relapses can be attributed to disease progression or DBS tolerance.

 

Conclusion

Surgical retreatment appears to be not uncommon in ET. Although any treatment modality can be successful independent of the previous treatment, the complication rate appears higher in re-treatment cases, especially in cases of repeated thalamotomy.

Philippe DE VLOO, Philippe DE VLOO (Leuven, BELGIUM), Robert GRAMER, Darrin LEE, Robert DALLAPIAZZA, Alfonso FASANO, Renato MUNHOZ, Suneil KALIA, Mojgan HODAIE, Andres LOZANO
18:10 - 18:20 #16312 - O049 Differential effect of frequency of STN DBS (80 vs. 130 Hz) on oculomotor and cognitive task performance: an exploratory, double blind study.
O049 Differential effect of frequency of STN DBS (80 vs. 130 Hz) on oculomotor and cognitive task performance: an exploratory, double blind study.

Objectives: Deep Brain Stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for patients with advanced Parkinson’s disease (PD). The role of the frequency of stimulation is not fully understood. We compared  the effect of 80 Hz and 130 Hz on functions mediated by the associative and oculomotor fronto-striatal loops by assessing several oculomotor tasks and a cognitive test (the Stroop test), in a randomised double blind design.

Methods: After overnight withdrawal of dopaminergic medication, 20 patients received 80Hz and 130 Hz stimulation in a randomised order during 24 hours. The amplitude of stimulation was adjusted to keep the energy delivered stable.  The assessments included:  Unified PD Rating Scale motor score (UPDRS-III), pro-saccade (S) and anti-saccades (AS) task and Stroop test.  Horizontal eye movements were collected using an eye-tracking system consisting of an infrared camera and padded helmet (Mobile EBTH, e(ye)BRAIN. 24 horizontal saccades across 3 visual angles (5°,10°,20°) were registered for both S and AS.

Results: Mean UPDRS-III was not different between the two frequencies (130Hz: 19.2 (9.1), 80Hz: 16.9 (10.5), p=0.2) . Tremor did not deteriorate. The saccade latencies and gain were similar for the two frequencies of stimulation during the S task. However, for AS, the error rate (10.2±6.3 vs. 12.2±5.73, p=0.02) and the latencies (326.0±101.6 ms vs. 381±135 ms, p= 0.03) were higher at 80Hz. The Stroop test revealed less errors in the more complex task at 80Hz (2.5±3.1 vs. 1.1±1.4 p=0.02).

Conclusions: The acute change of frequencies did not affect the clinical benefit measured with UPDRS III. However, antisaccade performance was superior at 130Hz stimulation, while performance on the complex Stroop task was comparatively better at 80Hz. This discrepancy might be related to interference with neural circuits differentially involved in lower-order oculomotor function versus higher-order cognitive tasks.

André ZACHARIA (Genève, SWITZERLAND), Diego KASKI, Dejan GEORGIEV, Matthieu BEREAU, Walid BOUTHOUR, Philipp MAHLKNECHT, Thomas FOLTYNIE , Ludvic ZRINZO, Marwan HARIZ, Marjan JAHANSHAHI, John ROTHWELL, Patricia LIMOUSIN
18:20 - 18:25 #14606 - O050 Ventro-lateral motor thalamus abnormal connectivity in essential tremor before and after thalamotomy: a resting-state fMRI study.
O050 Ventro-lateral motor thalamus abnormal connectivity in essential tremor before and after thalamotomy: a resting-state fMRI study.

Objective: To evaluate functional connectivity (FC) of the ventro-lateral thalamus, a common target for drug-resistant essential tremor (ET), resting-state data were analyzed before and 1 year after stereotactic radiosurgical thalamotomy (SRS-T), and compared against healthy controls (HC).

Methods: 17 consecutive patients and 10 HC were enrolled. Tremor network was investigated using ventro-lateral ventral (VLV) nucleus as region-of-interest (ROI), extracted using automated segmentation from pretherapeutic diffusion MRI. Temporal correlations of VLV at whole brain level were evaluated by comparing drug-naïve ET with HC, and longitudinally, 1 year after SRS-T. Thalamotomy volume was always located inside VLV, and did not correlate with any of FC measures (p>0.05). This suggested presence of longitudinal changes in VLV FC independently of thalamotomy volume.

Results: Pretherapeutic ET displayed altered VLV FC with left primary sensory-motor cortex, pedunculopontine nucleus, dorsal anterior cingulate, left visual association and left superior parietal areas. Pretherapeutic negative FC with primary somatosensory cortex and pedunculopontine nucleus correlated with poorer baseline tremor scores (Spearmann=0.04 and 0.01). Longitudinal study displayed changes within right dorsal attention (frontal eye-fields and posterior parietal) and salience (anterior insula) networks, as well as areas involved in hand movement planning or language production.

Conclusion: Our results demonstrated that ET and HC differ in their VLV FC to primary somatosensory and supplementary motor, visual association, or brainstem areas (pedunculopontine nucleus). Longitudinal changes display reorganization of dorsal attention and salience networks after thalamotomy. Beside attentional gateway, they are also known for their major role in facilitating a rapid access to the motor system. 

Constantin TULEASCA (Pully, SWITZERLAND), Jean RÉGIS, Elena NAJDENOVSKA, Tatiana WITJAS, Nadine GIRARD, Jerome CHAMPOUDRY, Mohamed FAOUZI, Jean-Philippe THIRAN, Meritxell BACH CUADRA, Marc LEVIVIER, Dimitri VAN DE VILLE
18:25 - 18:30 #14720 - O051 Connectivity of effective electrode contacts to unexpected fiber tracts in deep brain stimulation for parkinsonian tremor.
O051 Connectivity of effective electrode contacts to unexpected fiber tracts in deep brain stimulation for parkinsonian tremor.

Objective

The aim of our study was to investigate which cerebral fiber tracts are involved in the alleviation of parkinsonian tremor in deep brain stimulation.

 

Methods

21 patients with Parkinson´s disease and bilaterally implanted electrodes in the subthalamic nucleus were investigated. In 6 of those patients parkinsonian tremor was present in 11 hemibodies contralateral to the investigated brain-hemispheres. Diffusion weighted images (DWI) with 64 gradient directions were included in the routine preoperative imaging procedure for deep brain stimulation. Post-operative CT scans were fused to the DWI data set and the position of the individual contacts of the electrodes were determined. Probabilistic fiber-tracking was performed with seed regions based on each individual contact of the electrodes and the resulting anatomical fiber tracts were determined. We compared the depicted fiber tracts between contacts, which effectively (<=2V) reduced the tremor (> 50%) with the fiber tracts of contacts that did not.

 

Results

14 (31.8%) of the 44 contacts achieved a reduction of the contralateral tremor (>50%) with an amplitude <= 2.0V. Effective contacts were significantly more often associated with the fasciculus thalamicus, the ansa and fasciculus lenticularis, the medial and lateral branches of the anterior limb of the internal capsule and fibers passing through the zona incerta (p<0.05) than non-effective contacts. Fibers of the ipsi- and contralateral dentate-rubro-thalamic tract were not depicted differently between effective and non-effective contacts.

 

Conclusion

As opposed to essential tremor, in parkinsonian tremor the dentate-rubro-thalamic tract does not seem to be the anatomical structure involved in tremor reduction. More likely, stimulated pallido-thalamic and prefrontal-thalamic fibers play the major role concerning the alleviation of parkinsonian tremor.

Juergen SCHLAIER (Regensburg, GERMANY), Quirin STROTZER, Judith ANTHOFER, Claudia FELLNER, Alexander BRAWANSKI, Anton BEER
18:30 - 18:35 #16182 - O052 Optimizing tremor control by exploring random combinations of deep brain stimulation parameters.
O052 Optimizing tremor control by exploring random combinations of deep brain stimulation parameters.

Background: Despite more than 30 years of applying deep brain stimulation (DBS) for tremor, optimal stimulation parameters remain elusive and clinical outcomes inconsistent. Addressing the individual anatomy and tremor characteristics may be key to deriving the most clinical benefit. In practice, however, the virtually infinite amount of parameter combinations and patient fatigue hinder an individualized, comprehensive exploration of the parameter space. The insufficiently understood relationship between the stimulation parameters (voltage, pulse width and frequency) further emphasizes the need for a robust programming strategy.

Objective: We aimed to test the effect of unexplored DBS settings and hypothesized that applying random combinations of stimulation parameters could lead to improved tremor suppression and reduce side-effects. The main advantage of this approach would be that the DBS parameter space is more thoroughly explored in limited time and the stimulation parameters are independent from each other.

Methods: Ten individual random combinations of stimulation parameters were tested on eleven patients (64 ± 16 y.o.) reporting suboptimal tremor reduction following DBS in the Vim, ZI or GPi for either essential, orthostatic, or Holmes tremor. The effects of the random combinations were documented by means of patient reported outcomes and accelerometer recordings. Clinical follow-up after 6-17 weeks was obtained telephonically.

Results: The experimental paradigm was conducted within 23.8 ± 8.03 minutes per patient and afforded significantly (p = 0.017) improved tremor suppression (.21 ± .12 a.u.) compared to baseline (.93 ± .79 a.u.). Upon medium term follow-up, tremor suppression was retained (p = .01), with prolonged resolution of side-effects in three out of four patients. Noteworthy, optimal titration was achieved with significantly broader pulse widths (Z = -2.81, p = .005) and lower frequencies (Z = -2.14, p = .032) compared to baseline, which is in line with the deleterious effect we observed for maximal stimulation frequencies (U = 486, p = .008).

Conclusion: Random DBS-parameter exploration yielded significant tremor suppression compared to baseline in the short and medium term, with reduced side effects. Our paradigm is a safe, highly effective and time-efficient approach for improving DBS-programming that may provide a basis for closed-loop DBS programming algorithms. Moreover, these findings add to the current understanding of the working mechanisms of DBS and may guide further research.

I. Daria BOGDAN (Groningen, THE NETHERLANDS), Gea DROST , D.l.marinus OTERDOOM, Teus VAN LAAR , J. Marc C. VAN DIJK, Martijn BEUDEL
18:35 - 18:40 #16367 - O053 Atlas-independent mapping of the optimal locus of subthalamic deep brain stimulation for the motor symptoms of Parkinson disease.
O053 Atlas-independent mapping of the optimal locus of subthalamic deep brain stimulation for the motor symptoms of Parkinson disease.

Introduction: Deep brain stimulation (DBS) in the subthalamic nucleus (STN) region reduces the motor symptoms of Parkinson’s disease (PD). However, symptomatic improvement among patients is variable, perhaps due to inconsistency of the active electrodes location relative to some unknown optimal locus of stimulation. In this study, we mapped the optimal locus of DBS stimulation for bradykinesia, tremor, and rigidity in a mathematically defined and atlas-independent manner.

Methods: In 37 patients treated with STN DBS for PD, we mapped active electrode position to Unified Parkinson’s Disease Rating Scale (UPDRS) improvement, as well as individual scales for tremor, rigidity, and bradykinesia. We then applied a novel computational electrical field model of neuronal activation to provide an independent prediction of optimal lead location for each motor sign across patients.

Results: Using this combined outcomes analysis and our electrophysiological model, we mapped the optimal locus of DBS stimulation to a tightly-defined region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. Interestingly, using our atlas-independent computational model, we determined the optimal sties for the 3 hallmark symptoms of PD, and found them to be statistically the same as the overall optimal site of stimulation.

Conclusions: Our results suggest that one locus of stimulation in DBS for PD is in a region dorsal, posterior, and lateral to the anatomical midpoint of the STN optimally improves the overall symptoms of PD as well its major motor components.

James MOSSNER, Kelvin CHOU, Parag PATIL (Ann Arbor, USA)
18:40 - 18:45 #16379 - O054 Long term outcomes of Spinal Cord Stimulation in Primary Progressive Freezing of Gait.
O054 Long term outcomes of Spinal Cord Stimulation in Primary Progressive Freezing of Gait.

Background

In recent years, studies in patients with gait disorders have suggested that Spinal Cord Stimulation might have positive effects on locomotion. Herein, we report the case of a patient with primary progressive freezing of gait who underwent SCS for thirty three years. To the best of our knowledge, it‘s the longest follow-up published for SCS in the treatment of motor disorders.

Case report

In 1987, a 60-year-old woman presented gait disturbance characterized by stepping troubles and motor blocks without pain. She was initially diagnosed as lumbar spinal claudication A SCS test was proposed to improve her symptoms. A trial was positive and a neurostimulation system (Medtronic *) was implanted at T10 spinal level. The gait returned to normal. In 1997, a similar event of severe walking disorders returned, corresponding to a battery depletion. Abnormal gait pattern included shuffling, waddling and freezing of gait. A Parkinson disease (PD) was suspected but neurological examination was normal as DAT SPECT scan and Levodopa was ineffective.The device was replaced and, again, gait troubles vanished. The same events repeated in 2005, 2012 and 2017, occurring at the time of a battery depletion and disappearing following its replacement. SCS parameters based on our experience in lower limbs pain treatment were 80Hz, 300 micros, cycling mode (“off“ 1min, “off“ 2min) and 2.5 v, subthreshold value for paresthesia.

The clinical condition remained stable. She was subjected to an evaluation during the replacement periods, in Off and On stimulation condition including PD scales  (UPDRS III - motor items, Freezing of Gait Questionnaire (FOG-Q), quality of life PDQ 39 and minimental test), a walking test, the SWS Test (“stand-walk-sit“) documented on videotapes and a laboratory analysisto evaluate temporospatial gait parameters.

Results

During this 30 years follow-up period, course of disease was mildly progressive. During “on“ stimulation, patient experienced significant improvement in motor scores and quality of life criteria and the gait parameters were all dramatically improved when compared with Off condition : the completion time was almost four times faster with four times less number of steps and no freezing episodes.

Discussion 

Our patient presented with a pure progressive FOG with shuttling that started 30 years earlier. Otherwise, neurological examination was normal during this time course with no additional signs in keeping with PD or PD plus. This syndrom fit with “Primary Progressive Freezing of Gait“(PPFG) or “Syndrom of Gait Ignition Failure“ (SGIF). The recurrent gait troubles and their recovery by SCS were very similar several years apart. Indeed, the lesion was indolent but sufficient to keep its potential effect. A placebo effect needed to be taken into account.The expectation of clinical improvement which had been found to activate reward mechanisms unlikelysustained at long-term.

On the other hand, directly experiencing the SCS on gait improvement withstimulation-induced paresthesia could establish a learning effect which contributed to the sustained effect.

The mechanisms of SCS efficacy were not elucidated. Trouble originated by a lesion on the gait control pathway whatever the level, resulted in an abnormal modulation on the spinal CPG, that could be reversed by the SCS. Indeed, the SCS could induce supra spinal activation, but the key point was the CPG. Hence, an optimal lead placement at the CPG level seemed crucial for successful stimulation.

Conclusion

SCS remained effective during this very long time without tolerance. Two other cases of PPFG were publishd and two cases of freezing in Supranuclear paralysis. Well Studied in depth cases could disentangled gait disorders in PD. That’s an important point in support of conducting larger randomized studies as new paresthesia free SCS systems are promising.

 

Disclosure 

The authors have no conflicts of interest relevant to this study. 

 

Vincent D'HARDEMARE (Paris), Cécile HUBSCH, Jean Philippe BRANDEL, Nathalie PATTE-KARSENTY, Marc ZIEGLER, Jean-Baptiste THIEBAUT
18:45 - 18:50 #16405 - O055 Levodopa reduces the Phase lag Index of Parkinson’s disease patients,A MEG study.
O055 Levodopa reduces the Phase lag Index of Parkinson’s disease patients,A MEG study.

Objectives: As a method of measuring the phase difference between two signals, the phase lag index (PLI) of the alpha and beta bands in patients with Parkinson’s disease (PD) was investigated by using magnetoencephalography (MEG).

Methods: 18 PD patients were measured by MEG in the state of overnight withdrawal of Levodopa and after Levodopa treatment; meanwhile, UPDRS III scale was evaluated.

Results: Compared with healthy controls, alpha (8-13 Hz) PLI in the frontal and parietal areas elevated in PD patients, while the elevation was reversed by the Levodopa treatment. The alterations of the UPDRS III total scale (rs = 0.552, p = 0.013, n = 16) and the changes of akinesia scale (rs = 0.622, p = 0.005, n = 16) were correlated to the change of beta (13-30 Hz) PLI in the left parietal area. The change of the UPDRS total scale was negatively correlated to duration of disease (rs = 0.432, p = 0.047, n = 16). There was a negative correlation between the age of PD patients and the change of alpha PLI in the left frontal area (rs = 0.519, p = 0.020, n = 16). 

Conclusions: PD patients showed a higher Mu PLI in the sensorimotor area relative to the healthy controls. The improvement of motor symptoms of PD patients by levodopa was correlated to the inhibition of beta PLI in the sensorimotor area.

Chunyan CAO (Shanghai, CHINA), Dianyou LI, Peng HUANG, Yixin PAN, Shikun ZHAN, Bomin SUN
18:50 - 19:00 Discussion.
WOLFSON HALL A

Thursday 27 September

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C29
17:00 - 18:30

Parallel Session 7
Epilepsy

Moderators: Allan HALL (Surgical Trainee) (Glasgow, UK), Krassimir MINKIN (Head of Center of Functional Neurosrgery) (Sofia, BULGARIA), Dirk VAN ROOST (Head of Department) (Ghent, BELGIUM)
17:00 - 17:10 #16143 - O056 Ictal intracranial electroencephalography using wavelet analysis of high-frequency oscillations in patients with refractory epilepsy.
O056 Ictal intracranial electroencephalography using wavelet analysis of high-frequency oscillations in patients with refractory epilepsy.

Introduction

Epilepsy is a neurological disease that places a heavy burden on society. One-third of these patients have seizures that are refractory to medical treatment. Surgery may provide a cure in due course, but identification of seizure focus is necessary for success. In patients with a clear and resectable structural lesion, surgery may proceed after video electroencephalography, magnetic resonance imaging, and clinical psychological testing. Nonetheless, some patients do not appear to have a resectable lesion according to these methods. High-frequency oscillations (HFOs) refer to electrographic activity of 80 to 500Hz. It is hypothesised that HFOs can be biomarkers for epilepsy. Wavelet transformation may accurately depict HFOs. We propose that detection of wavelet-transformed HFOs may help determine the seizure-onset zone that is essential for epilepsy surgery.

 

Methods

A total of 128 patients from the study sites between 7/2013 and 6/2015 with refractory epilepsy underwent resective surgery. Of these patients,34 gave informed consent to undergo intracranial electroencephalography. These patients (mean age 34 years, female 45%) underwent implantation of grid or strip electrodes with a range of configurations to delineate seizure foci. Episodes of stereotypic seizure with clinical manifestations were recorded in 3-minute epochs, adopting bipolar montage and good technical quality. Each epoch covered the entire seizure and centred on a quarter of its own length from the onset of seizure. Electroencephalographic findings for each seizure were first analysed visually by a neurologist, followed by off-line export of data for wavelet analysis. The number of scales that corresponded to the range of 80 to 500Hz was used. The algorithm was generated using a MATLAB platform. The mother wavelet used was biorthogonal 6.8. The density of HFOs was calculated by a peak-to-trough power ratio of 50 to 70. If the ratio fell below 10, the electrode position might not have represented the seizure onset zone. A previous cohort served as a pilot control group in which the percentage of patients eligible for resective surgery was 70% and the rate of good surgical outcome was 57%. During the recording procedures, conventional frequency ictal patterns, hyperexcitability, and radiological lesion were also recorded. An ancillary study included the technical aspect of electroencephalographic data. Hyperexcitability was defined as the appearance of after-discharges or clinical seizures following electrical stimulation (50Hz, biphasic, pulse width of 0.5ms, 5s, 5mA). The mean proportion of HFOs among resected channels was compared with that of the conventional frequency ictal pattern, hyperexcitability, and radiological lesion.

 Results

The proportion of patients who attained good surgical outcome with accurate identification of seizure-onset zone was 71.4% following review of wavelet-transformed HFOs. This represented an increase of 17% to 18% when compared with no analysis of HFOs, and an increase of 30% when compared with no intracranial electroencephalography. By testing for HFOs, we demonstrated a safe and fast methodology to determine the laterality of onset for patients with bilateral mesial temporal sclerosis. In patients in whom electrographic signals were sampled in the greater curvature of a neocortical surface, the number of channels involved initially may have been so extensive that rapid identification of foci was not feasible. Our mathematical representation identified the distinctive region with HFOs and added strength to information not visible to the naked eye. In addition, our analysis showed additional evolution of discharges throughout the seizure epoch that was not uniform. Fast activity was evident at the very first moment of the seizure, followed by a decrease in power towards the mid-portion. As the seizure epoch concluded, spectral power was regained, culminating in final, abrupt cessation of seizure. This phenomenon was not observable byvisual analysis of HFOs. Hyperexcitability co-occurred with HFOs, conventional frequency ictal patterns, and radiological lesions. Combining two or more modalities may improve selection of candidates for surgery. Our data suggest that when both wavelet-transformed HFOs and hyperexcitability are used, sensitivity can be maintained at 100% (95% confidence interval [CI]=0.52-1) and specificity may be increased from 66.7% (95% CI=0.31-0.91) to 75% (95% CI=0.36-0.96), compared with wavelet-transformed HFOs alone.

Conclusion

Our study demonstrated that by testing for wavelet-transformed HFOs, patients who would otherwise be denied surgery may receive a potential cure. Our study has provided an effective research platform in electroencephalography whose results concur with those of other studies. We are interested in ictal HFOs because they have been revealed during intracranial recordings. Identifying the moment of seizure provides researchers with the strongest evidence of localisation and lateralisation. Surgery improves seizure outcome and is feasible in refractory epilepsy, and patient quality of life can be improved.

H LEUNG (Hong Kong, CHINA), Xl ZHU
17:10 - 17:20 #16183 - O057 SUrface-PRojected FLAIR (SUPR-FLAIR) statistical analysis: a novel tool for advanced imaging of epilepsy.
O057 SUrface-PRojected FLAIR (SUPR-FLAIR) statistical analysis: a novel tool for advanced imaging of epilepsy.

Objective. The objective of this pilot retrospective study is to describe the SUrface-PRojected FLuid-Attenuation-Inversion-Recovery (SUPR-FLAIR) statistical analysis, a novel method mainly aimed at revealing cortical areas with subtle signal hyper-intensity.

Methods. Images from 101 healthy controls and ten patients suffering from drug-resistant partial epilepsy were retrospectively post-processed. Brain surface was reconstructed from a 3D T1-weighted fast field echo (3D T1W-FFE) MRI scan. A turbo spin echo FLAIR axial scan was registered to the 3D T1W-FFE scan and its intensity values were normalized. The cortical intensity signal was “projected” onto the brain surface, and surface-based analysis was performed, comparing each patient against the 101 controls. The localization of the first Positive Lower P-value Cluster (PLPC) peak and of the resection zone (RZ) were compared. We studied five patients with focal cortical dysplasias (FCD) (three of them with negative MRI), and five with hippocampal sclerosis.

Results. SUPR-FLAIR statistical analysis localized the first PLPC peak in the RZ in all cases. Since all patients have been seizure free since surgery, it can be assumed that the epileptogenic zone (EZ) was included in the RZ. Thus, SUPR-FLAIR statistical analysis correctly aligned with the EZ, with 100% sensitivity. More in details, we obtained four major results. 1) SUPR-FLAIR analysis allowed lesion detection also in patients with MRI-not-visible, histologically proven FCDs. 2) The dynamic mapping (by means of P-value shifting) depicted a progressive enlargement of the detected area mirroring the seizure spreading in one patient. 3) Our method revealed a subtle FLAIR hyper-intensity in the ipsilateral temporal pole of patients suffering from HS.4) Visual inspection of SUPR-FLAIR mapping allowed simple and efficient topographic definition of MRI-visible FCDs in 3D reconstructions of the brain. The major limitation of this technique is the difficulty of obtaining optimal surface reconstructions in very young subjects (< 3 years) and when previous surgeries or other particular situations make particularly difficult the estimation of grey/white matter interface.

Conclusions. SUPR-FLAIR statistical analysis is a non-invasive technique potentially helpful for the detection of subtle FCDs and for the definition of the EZ. Its use could reduce the indications for invasive EEG or could provide essential data to refine the strategy of intracerebral electrode implantation in the most challenging cases. Moreover, the estimation of temporal neocortex involvement in Hippocampal Sclerosis (HS) cases could be helpful for indicating an antero-mesial temporal lobectomy or a selective amygdalo-hippocampectomy (SAH). Since SAH is re-gaining popularity thanks to minimally invasive Laser Induced Thermal Therapy (LiTT), the latter aspect can be particularly valuable. 

Francesco CARDINALE (Milano, ITALY), Piergiorgio D'ORIO, Martina REVAY, Francesca GOZZO, Veronica PELLICCIA, Valeria MARIANI, Luciana GENNARI, Maurizio SBERNA, Michele RIZZI
17:20 - 17:30 #16409 - O058 SEEG outcomes in a regional neurosurgical centre over the past 14 years: a review as part of good medical practice.
O058 SEEG outcomes in a regional neurosurgical centre over the past 14 years: a review as part of good medical practice.

Introduction: Stereoelectroencephalography (SEEG) is an invasive technique allowing localisation of the site of onset of seizures, and identification of eloquent cortex  in patients with refractory focal epilepsy, where non-invasive methods have failed. It is a relatively safe tool , but given its invasive nature it is important, as part of good medical practice, to review SEEG outcomes within neurosurgical centres.

Objective: To review the safety and efficacy of SEEG studies in the presurgical evaluation of focal epilepsy in the Glasgow Regional Neurosurgical Centre

Methods: We retrospectively reviewed 42 SEEG implantations in our centre from 2002 to 2016. Efficacy of SEEG was assessed by number of satisfactorily placed electrodes (trajectory and position across axial, sagittal and coronal planes), the idenitifcation of seizure focus and post operative seizure outcomes (using the Engel classification). Safety was assessed by any post-procedure complications. 

Results: Mean age at implantation was 39 years (range 22-64). The patient population consisted of 17 male patients (40%) and 25 female patients (60%). There were a total number of 272 electrodes placed with an average of 6 electrodes per patient. The number of satisfactory placed electrodes was 252 (92.6%), and the number of unsatisfactory placed electrodes was 20 (7.4%). The presumed epileptogenic zone was identified in 39 patients (92%), 31 patients (73%) went on to have resective surgery. Outcomes post operatively at 2 year follow up using Engel’s classification were:, 18(58%) Class I, 4 (13%)  Class II, 3 (10%) Class III, and 6 (19%) Class IV. Morbidity related to SEEG implantation occurred in 9 patients (21%). Eight (19%) suffered small SEEG related subclinical haemorrhage/contusion and one patient had presumed infection (which fully resolved with antibiotics). One patient had a bleed at time of attempted implantation which had to be subsequently abandoned. There were no mortalities or severe permanent deficit as a result of electrode implantation at 2 year follow-up.

Conclusion:  Our review shows that SEEG in our centre is an effective and relatively safe  method for identifying the  epileptogenic zone,  resulting in a good seizure outcome in 71% of patients at 2 year follow up. However, there is some scope for improved electrode placement and minimisation of  post-SEEG complications.

Allan HALL (Glasgow, UK), Patricia LITTLECHILD, Veronica LEACH, Shona LIVINGSTONE
17:30 - 17:35 #14640 - O059 RADIOFREQUENCY ABLATION OF THE CENTROMEDIAN NUCLEUS IN THE TREATMENT OF PHARMACORESISTANT EPILEPSY. A PILOT STUDY FOR A SELF-CONTROLLED PROSPECTIVE CLINICAL TRIAL.
O059 RADIOFREQUENCY ABLATION OF THE CENTROMEDIAN NUCLEUS IN THE TREATMENT OF PHARMACORESISTANT EPILEPSY. A PILOT STUDY FOR A SELF-CONTROLLED PROSPECTIVE CLINICAL TRIAL.

We present the results of a pilot study for a self-controlled prospective clinical trial in patients with generalized drug-resistant epilepsy. Patients were selected with diagnosis of generalized epilepsy refractory to medical treatment according to ILAE criteria and electroencephalogram compatible with generalized activity, three patients were included who met the inclusion criteria, prior informed consent a beseline counting of seizures three moths before surgery was performed, posteriorly they underwent  bilateral radiofrequency ablation of the centromedian nucleus guided by the published work on electrical stimulation of this nucleus. Each ablation consisted in the stereotactic location of the nucleus, taking as a reference the anterior border of the posterior commissure 10 mm lateral to the midsagittal plane and at the level of the AC-PC line. By obtaining characteristic recruiting responses, the position of the nucleus was electrophysiologically confirmed bilaterally and a radiofrequency lesion was performed on each side with a monopolar electrode at 80 degrees Celsius for 60 seconds. A follow-up of up to 24 months was carried out with a scheduled seizure count, as well as a surface electroencephalogram every 3 months. There was a reduction in the frequency of seizures greater than 80% statistically significant after the radiofrequency ablation, but not in the interictal and slow wave activity in the surface electroencephalogram. We conclude that both electric stimulation and radiofrequency ablation have similar clinical effects by inhibiting the nucleus which seems to be related in propagation and generalization of seizures.

 

Gustavo AGUADO CARRILLO (Ciudad de México, MEXICO), Francisco VELASCO CAMPOS, Ana Luisa VELASCO MONROY, Julian E. SOTO ABRAHAM, Jose Luis NAVARRO OLVERA, Pablo SAUCEDO ALVARADO, Juan Manuel ALTAMIRANO
17:35 - 17:40 #16206 - O060 Stereotactic electrode placement for SEEG: Advanced 3D-visualization planning and predictors of accuracy.
O060 Stereotactic electrode placement for SEEG: Advanced 3D-visualization planning and predictors of accuracy.

Background: Intracranial recordings with stereoelectroencephalography (SEEG) aims at defining the epileptogenic zone in patients with pharmacoresistant epilepsy. Currently used techniques for depth electrode implantation include stereotactic frame-based and navigated frameless applications, both either conventional or robot-assisted. Safety and diagnostic efficacy depends on accuracy of implantation.

Objective: Evaluation of a technique combining stereotaxy with sophisticated three-dimensional (3D) planning software and to calculate accuracy of electrode placement as well as accuracy predictors.

Methods: Retrospective study of 15 consecutive patients that received depth electrodes using a stereotactic frame (Leksell G frame, Elekta, Stockholm, Sweden), after planning with Elements (Brainlab, Munich, Germany). For each electrode, we calculated the entry point error (EPE) as lateral deviation and target point error (TPE) both as lateral deviation and euclidian distance. Multivariate regression analysis and computation of 95% confidence intervals using the bootstrap method were applied for statistical analysis and evaluation of accuracy predictors.

Results: Fifteen patients received 136 depth electrodes (average 9; range 6-13). Eleven patients received unilateral (8 right/3 left) and 4 bilateral electrodes. Overall there were 40 left-sided and 96 right-sided electrodes. There were 12 amygdalar, 15 hippocampal, 9 parahippocampal, 16 insular, and 84 lobar electrodes (37 frontal, 30 temporal, 2 occipital, 3 parietal, 9 temporo-occipital and 3 temporo-parietal). There was no mortality. One patient had a small intracerebral hematoma in the occipital lobe at the entry point with a volume of 3.42ml. The patient was asymptomatic. Rate: 1/15 patients (6.7%); 1 in 136 electrodes (risk of hemorrhagic complication per electrode: 0.7%).

The mean EPE, lateral TPE and euclidian TPE were 0.6 +/- 0.5 mm, 1.1 +/- 0.7 mm and 1.5 +/- 0.8 mm respectively. According to the formula to calculate the “safe distance” proposed by Cardinale et al. (EPE + 3sd + probe radius) our safety margin when planning SEEG trajectories therefore should be 2.6 mm. 

Order of implantation (1-6 vs. >6) is predictor for the euclidian TPE and length of electrode predictor for the lateral TPE. Localization of electrode generally did not correlate to error but insular electrodes were significantly less accurate than lobar ones. 

Conclusion: With respect to the implantation of multiple depth electrodes, the need for better and sophisticated visualization does not preclude the accuracy of a frame-based stereotaxy system. Safe distance, as calculated by mean error and standard deviation, reflects the accuracy and precision of a SEEG implantation method and should be regarded as the best safety indicator regardless of the used method (frame-based or frameless). Accuracy predictors should be considered for the improvement of safety in SEEG methods. 

 

Figure 1: 

SEEG Electrode planning with the aid of different views (Planning software: Elements, Brainlab, Munich, Germany):

A. In-line view of the planned electrode including the planned positions of the contacts (contrast enhanced T1 weighted MRI).

B. Planned trajectory with safety margin in probe’s eye view (left upper corner) and standard anatomical planes (contrast enhanced T1 weighted MRI).

C. Three-dimensional reconstruction of the automatically segmented anatomical structures (hippocampus - blue, amygdala - orange) and different perspectives, with and without segmented brain surface and ventricles to give an overview of the 3D-configuration of the planed electrodes.

D. Relation of the planned electrodes to the surface (skin, ear).

 

Figure 2: 

Safety margins necessary for trajectory planning depend on the accuracy of the implantation method (EPE + 3sd + probe radius, according to Cardinale et al., 2013):

A. Safety margin of 2.6 mm considering our EPE of 0.6 mm +/-  0.5 mm.

B. In-line view of the trajectory with safety margin calculated for our implantation method.

C. Same trajectory with a safety margin of 9.4 mm considering the results of a reported frameless navigated method in children (Budke et al., 2017) with EPE of of 3.64 +/- 1.78 mm. 

D. In-line view of the trajectory with safety margin calculated for their implantation method. 

Peter C. REINACHER (Freiburg, GERMANY), Evangelos KOGIAS, Dirk-Matthias ALTENMÜLLER, Kleanthis KARAKOLIOS , Karl EGGER, Volker A. COENEN
17:40 - 17:45 #16224 - O061 SEEG guided monopolar radiofrequency thermocoagulation for drug-resistant epilepsy.
O061 SEEG guided monopolar radiofrequency thermocoagulation for drug-resistant epilepsy.

SEEG guided monopolar radiofrequency thermocoagulation for drug-resistant epilepsy

 

Background: Radiofrequency thermocoagulation (RFTC) at the end of stereoelectroencephalography (SEEG) is a treatment and diagnostic procedure for patients with drug–resistant epilepsy. All published series include patients with bipolar RFTC between adjacent contacts of the SEEG electrodes. We present a series of monopolar RFTC and assess its effectiveness and complications rate.

Material and Methods:  Our material includes 18 patients (age: 6-42 years) treated between 2014 to 2017 by SEEG-guided RFTC in the Epilepsy Surgery Center of University Hospital “St. Ivan Rilski”, Sofia. Four to 65 monopolar RFTC per patient (mean 16) were performed by applying 4.5 W current for 30 sec. between one contact of the SEEG electrode and a referent electrode on the inferior extremity.

Results: Three patients (16.7%) were seizure free after SEEG-guided RFTC, 7 patients (38.8%) experienced  ≥ 75% seizure reduction, 5 patients (27.8%) experienced > 50% decrease of seizure frequency after RFTC and 6 patients (33.3%) did not benefit from RFTC (mean follow-up of 13 months). Transient seizure freedom for 2 months was achieved in 11 patients which was an excellent prognostic factor for seizure freedom after open surgery. RFTC was performed in 7 patients with insular epilepsy and seizure reduction was achieved in 6. There was only one complication – small intraventricular hemorrhage after hippocampal RFTC that did not require any treatment.

Conclusions: Our study find that monopolar RFTC can be used as diagnostic and therapeutic option at the end of SEEG. Definitions of the best indications will need larger series.

Krasimir MINKIN (Sofia, BULGARIA), Kaloyan GABROVSKI, Yoana MILENOVA, Petar KARAZAPRYANOV, Marin PENKOV, Petya DIMOVA
17:45 - 17:50 #16309 - O062 Cingulate cortex involvement in frontal lobe epilepsy - exploration using Stereo-encephalography (SEEG).
O062 Cingulate cortex involvement in frontal lobe epilepsy - exploration using Stereo-encephalography (SEEG).

Objectives: We aim at describing cingulate cortex (CC) involvement in frontal lobe seizures and the approach of the cingulum with intracranial electrodes by means of SEEG method for a better definition of the seizure onset zone as well as for functional mapping using direct electrical stimulation.

Methods: We included patients with SOZ location in the frontal lobe and at least 1 year follow up explored by SEEG in the Romanian Program for Drug Resistant Epilepsy (2012–2017) that had minimum one electrode sampling the CC (anterior-ACC, middle-MCC or posterior-PCC). We systematically reviewed seizures recorded and functional stimulations (bipolar, 50Hz, 0,25-3 mA). Electrodes exploring the cingulum were implanted with oblique parasagittal trajectories, so each electrode had at least 3 contacts in the cingulate cortex.

Results: We selected 20 patients from a series of 75 consecutive patients explored with intracranial electrodes during pre surgical work up. All recorded seizures in this population showed an early involvement (within first 5 seconds after seizure onset) of the electrode contacts exploring the cingulate gyrus. Four patients were not treated due to functional reasons. In 14 patients parts of the cingulum were included in the surgical resection (n=11) and/or received radiofrequency thermocoagulation in the CC (RFTC, n=8) at the end of the implantation procedure. DES elicited mainly emotional behavioural or elementary sensory-motor effects. Seizure freedom rate was 68%. No complication of the implantation procedure were reported.

Conclusion: Cingulate cortex is frequently involved early in frontal lobe seizures. Therefore exploring the cingulum is mandatory during pre surgical workup. Intracranial electrode placement in the cingulum with oblique trajectories and parasagittal approach is safe and effective in SOZ definition and functional mapping.

 

 

 

 

Ioana MANDRUTZA, Jean CIUREA (Bucharest, ROMANIA), Irina POPA, Andrei BARBORICA, Donos CRISTI , Maliia MIHAI DRAGOS, Arbune ARBUNE, Rasina ALIN
17:50 - 17:55 #16337 - O063 Concordance of scalp electroencephalography (EEG) with stereo-electroencephalography (SEEG) in the pre-surgical investigation of patients with intractable epilepsy: influence on surgical outcome.
O063 Concordance of scalp electroencephalography (EEG) with stereo-electroencephalography (SEEG) in the pre-surgical investigation of patients with intractable epilepsy: influence on surgical outcome.

Concordance of scalp electroencephalography (EEG) with stereo-electroencephalography (SEEG) in the pre-surgical investigation of patients with intractable epilepsy: influence on surgical outcome.

 

 

Mahmoud Abdallat1,2, MD

Holger Joswig1, MD, FMH

Jonathan C. Lau1, MD, MEng

Andrew G. Parrent1, MD, FRCSC

Keith W. MacDougall1, MD, FRCSC

Jorge Burneo1, MD, MSPH, FAAN

David A. Steven1, MD, MPH, FRCSC, FACS

 

Epilepsy Program, Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London ON, Canada

Department of Neurosurgery, Hannover Medical School, Hannover, Germany

 

abdallat@me.com

holger.joswig@gmail.com

jonathan.c.lau@gmail.com

andrew.parrent@lhsc.on.ca

keith.macdougall@lhsc.on.ca

jorge.burneo@lhsc.on.ca

david.steven@uwo.ca

 

Purpose: To assess the concordance of the scalp-electroencephalography (EEG) pre-implantation hypothesis with stereoelectroencephalography (SEEG) findings in patients with drug-refractory temporal and extratemporal lobe epilepsy (TLE and eTLE) in relation to surgical seizure outcome.

 

Methods: A retrospective analysis of 125 patients who underwent SEEG from 2011 until 2018. The pre-implantation hypothesis of the seizure onset zone (SOZ) based on the scalp-EEG, seizure semiology and positron emission tomography (PET) findings, was compared to the SEEG findings. Surgical seizure outcome at last follow-up was assessed according to the Engel classification.

 

Results: The pre-implantation scalp-EEG hypothesis was confirmed by SEEG in 52/125 (41.6%) of cases. The SOZ was found to be temporal in 74/125 (59.2%) and extratemporal in 51/125 (40.8%) of the cases. 35/74 (47.2%) patients with TLE underwent anterior temporal lobectomy, and 24/51 (40.8%) patients with eTLE proceeded to resective epilepsy surgery and had complete follow-up data at a median of 24 months (range 6 – 36 months).

 

One year seizure-freedom (Engel 1) after anterior temporal lobectomy was achieved in 08/12 (66.6%) in those with concordant scalp-EEG and SEEG findings as compared to 13/16 (81.2%) with discordant findings (p=0.377).

 

One year seizure-freedom (Engel 1) after resective surgery for eTLE was achieved in 7/7 (100%) in those with concordant scalp-EEG and SEEG findings as compared to 8/11 (72.7%) with discordant findings (p=0.130). 65/125 patients also underwent PET scan as part of their pre-implantation investigation. A hypometabolic focus was seen in 39 patients and in 35 (89.7%) of these, the PET was concordant with the SEEG hypothesis. In the 21 PET-SEEG concordant patients who have undergone surgery, 16/18 (88.8%) became seizure-free (p-value 0.017) in one year follow-up.

 

Conclusions: SEEG in combination with PET has good merits in the confirmation of the SOZ and identification of surgical candidates.

Mahmoud ABDALLAT (Amman, JORDAN)
17:55 - 18:00 #16361 - O064 Adverse events in anterior temporal lobectomy: analysis of 100 consecutive cases.
O064 Adverse events in anterior temporal lobectomy: analysis of 100 consecutive cases.

Introduction

Approximately 30% of epileptic patients are estimated to be drug-resistant. Many studies demonstrated the effectiveness of surgical therapy in terms of remission from seizures in this category of patients. Despite this, only a small part of them undergo surgical treatment. This may be partly attributable to the perplexity of physicians and patients regarding morbidity / mortality of epilepsy surgery. Anterior temporal lobectomy is the most performed epilepsy surgery in the IRCCS Neuromed of Pozzilli (Italy). The aim of the present study is to evaluate the morbidity and mortality resulting from the intervention of anterior temporal lobectomy (ATL) in a consecutive series.

Patients and methods

We retrospectively analyzed the medical records of 100 patients treated with ATL at the IRCCS Neuromed Center for Epilepsy Surgery in Pozzilli (Italy) by the same operator (E.V.). All of them underwent a pre-surgical study using Video-EEG, brain MRI, neuropsychological study, psychiatric evaluation. In doubtful cases, PET and / or invasive study by positioning subdural grids have also been performed. The surgical procedure was achieved according to the standard cortico-amigdalo-hippocampectomy. The extent of the neocortical resection was determined by clinical data (dominant side, characteristics of seizures, duration of  epilepsy), neuropsychological, electrophysiological and radiological data, as well as intraoperative findings (increased consistency of sclerotic tissues), in order to obtain the best clinical outcome, avoiding the removal of neocortex not involved in the seizures. Temporal pole, amygdala and hippocampal samples were sent to Neuropathology for histological examination. After surgery, the patients were admitted to intensive care unit and underwent CT scan before re-admission to the neurosurgical clinic. One month after surgery, the patients performed MRI control and standard EEG at 1 and 6 months. Additional inpatient controls with video-EEG, neuropsychological evaluation and possibly psychiatric evaluation were conducted at 1, 2 and 5 years. Furthermore, the clinical outcome was evaluated as well as the progress of every deficit due to the intervention was recorded.

Results

We considered 100 patients (52 F, 48M), mean age at surgery 39.4 years. Complications occurred in 9 patients. In 4 cases they resolved spontaneously, without treatment:  two cases of palpebral ptosis, one right hemiparesis and one subdural hematoma. In 3 cases the complications resolved completely but they needed an appropriate rehabilitative treatment: two cases of diplopia and one case of transient aphasia. In 2 cases the complications resolved not completely despite medical treatment : one case of aphasia (delayed ischemic disturbance) and one case of diplopia. There were no surgical deaths.

Conclusions

Post-surgical complications following anterior temporal lobectomy (ATL) occur in a low percentage of cases and often resolve spontaneously or following medical treatments. The intervention of anterior temporal lobectomy should be considered a safe treatment.

Francesco PAOLONI (Padova, ITALY), Giancarlo DI GENNARO, Roberta MORACE, Valentina BARO, Andrea LANDI, Domenico D'AVELLA, Vincenzo ESPOSITO
18:00 - 18:05 #16380 - O065 Initial Experience using the Visualase MRI-guided stereotactic laser ablation system for epileptogenic Lesions.
O065 Initial Experience using the Visualase MRI-guided stereotactic laser ablation system for epileptogenic Lesions.

Background:

MR-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive technique for ablating soft tissue lesions. The technique allows the surgeon real-time feedback and control of the ablation process and is increasingly used in recent years by neurosurgeons to treat epileptic brain lesions.

The Medtronic Visualase system, which uses a 980 nm,15 Watt laser energy, was recently approved for use in Europe and Israel. We report our initial technical experience using the system in the first 5 cases in which the system was used to ablate focal epileptic lesions in adults.

 

Methods:

Five patients with intractable epilepsy underwent MRgLITT ablation of epileptogenic lesions in Tel Aviv Medical Center between March and May 2018. One cooling catheter/laser fiber assemblies were placed per patient. The catheters were placed using frame-based technique using the Leksell G frame. LITT was performed using the 10mm exposed tip and 15 Watt laser, while monitoring MRI thermometry using 3T scanner.

 

Results:

All 5 patients underwent the procedure without complications. The indications for surgery were intractable epilepsy due to mesial temporal lobe epilepsy (n = 2), cortical dysplasia (n=1) and low-grade glioma (n=1) and one case of non-lesional frontal epilepsy.

Ablations were made using 50% to 70% of the 15 Watt maximal energy of the Visualase system, for a mean 122 sec ± 63 sec. The maximal diameter of the lesion using these parameters ranged between 12.6 and 18.4 mm. We used serial ablations as needed along the tract of the catheter by pulling back the optic fiber, the length of the lesion ranged between 19.4 and 38 mm.

 

Immediate post ablation MRI demonstrated good ablation of the epileptic lesion in both MTS cases and the cortical dysplasia. Near complete ablation of the tumor was achieved due to limitations of the approach. Of special interest is the case of non-lesional epilepsy where the ablation zone was determined based on FDG PET-CT combined with stereo-EEG recordings. Mean volume of the lesion as measured on post-operative DWI and contrast enhanced images was 4.4cc and 3.4cc respectively.

 

Short term follow-up clinical outcome data regarding seizures will be presented.

 

Conclusions:

MRgLITT is a promising technique and can be used safely as an alternative to open resection in both lesional and non-lesional intractable epilepsy cases. Using one catheter, lesions in diameter of up to 18mm, and volumes up to 4.4cc could be ablated.

 

Ido STRAUSS (Tel Aviv, ISRAEL), Firas FAHOUM, Daniel HAYAT, Assaf BERGER, Ben-Bashat DAFNA, Eisenstein ORNA, Itzhak FRIED
18:05 - 18:10 #16388 - O066 Electrical stimulation of subiculum for temporal lobe epilepsy with hippocampal sclerosis.
O066 Electrical stimulation of subiculum for temporal lobe epilepsy with hippocampal sclerosis.

Objective The aim of this study was to evaluate the effect of subiculum DBS in cases of mesial temporal lobe epilepsy with hippocampal sclerosis, and whether it is superior to hippocampus stimulation in these patients.

 

Materials and methods.  We designed a study in two phases: a double-blind randomized trial and a longitudinal study for follow-up. Six patients with mesial temporal lobe epilepsy with hippocampal sclerosis were implanted DBS electrodes in the subiculum. Basal seizure count (BL) consisted of 4 months before surgery; one week before DBS implantation all patients were implanted diagnostic depth electrodes to lateralize and identify the epileptic focus. During the first month after implantation (M0) all patients were kept OFF stimulation. After this, one group of patients started stimulation immediately, and the other group, three months later.  DBS parameters were: 3V, 450 ms, 130 Hz, cyclic stimulation consisting of 1 minute ON, 4 minutes OFF.  After the double-blind phase all patients completed an 18-months follow-up period. During both phases, patients attended to monthly consultations for seizure count by the clinical team, and DBS system check by the unblind team; AEDs were maintained at the same doses as before surgery. After this, patients attended every 3 months for long term follow-up.

 

Results Phase 1: There was a significant reduction of total number of seizures and generalized seizures (p<0.05) in M0 in comparison to BL; in M1 numbers went almost back to baseline. There was no significant difference between groups during the double-blind phase. Phase 2: There was a significant reduction of generalized seizures from month 2; there were no differences in overall seizure count. There were no differences in Neuropsychological evaluation.

 

Discussion

Electrode placement at the subiculum had a transitory one-month effect on seizure reduction, being more significant on generalized seizures. In the follow-up phase, subiculum stimulation seems to have very good effect on generalized seizures, but moderate response in complex partial seizures. There was no neuropsychological impairment. The subiculum as target has good effects, but it is not superior to hippocampal stimulation in patients with hippocampal sclerosis.

Daruni VÁZQUEZ-BARRÓN (Mexico City, MEXICO), Ana Luisa VELASCO, Francisco VELASCO, Manola CUÉLLAR-HERRERA, Marysol MONTES DE OCA
18:15 - 18:20 #16410 - O068 Deep brain stimulation for seizure control: a role for white matter.
O068 Deep brain stimulation for seizure control: a role for white matter.

Background: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) can improve seizure control for patients with drug-resistant epilepsy. Yet, responder rates vary highly which is possibly explained by crucial differences in brain stimulation sites.

 

Objective: We hypothesized that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) results in increased seizure control in DBS for drug-resistant epilepsy.

 

Methods: We retrospectively analysed the location of the active contacts and ANT-MTT junction of 11 patients treated with ANT-DBS for drug-resistant epilepsy. Coordinates and Euclidean distance of the active contact relative to the ANT-MTT junction were calculated and compared between 5 responders (≥50% reduction in seizure frequency) and 6 non-responders (<50% reduction in seizure frequency). Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generation of stimulation heat-maps.

 

Results: The mean Euclidean distance of the active contacts to the ANT-MTT was 30% smaller in responders to DBS. VTA models and heat maps indicate that the stimulation hot-spot of responders is located at the medio-ventral ANT in closer vicinity to the ANT-MTT junction compared to the hot-spot of non-responders, located at the dorsal ANT. The Euclidean distance between the centres of stimulation hot-spots was a substantial 3.8 mm.

 

Conclusions: Our findings suggest that there is a relationship between stimulation site and therapy response in ANT-DBS. The ANT-MTT junction is a potential brain stimulation site for increased seizure control.

Fred SCHAPER, Birgit PLANTINGA, Albert COLON, Louis WAGNER, Paul BOON, Erik GOMMER, Govert HOOGLAND, Linda ACKERMANS (Sittard, THE NETHERLANDS), Rob ROUHL, Yasin TEMEL
18:20 - 18:25 #16415 - O069 SIMULATED VOLUME OF NEURAL ACTIVATION IN ANTERIOR NUCLEUS OF THALAMUS IN DEEP BRAIN STIMULATION FOR INTRACTABLE EPILEPSY.
O069 SIMULATED VOLUME OF NEURAL ACTIVATION IN ANTERIOR NUCLEUS OF THALAMUS IN DEEP BRAIN STIMULATION FOR INTRACTABLE EPILEPSY.

Deep brain stimulation of anterior thalamic nucleus (ANT-DBS) is one of the well-tolerated and promising procedures for treating epilepsy based on the data from both the experimental models and limited clinical trials. These preliminary evidences are encouraging enough to design more comprehensive controlled studies.

Our aim was to identify the location of the active contact potentially stimulated, volume of tissue activation (VTA) and consequently involved in the therapeutic or adverse effects, using stereotactic localization of the stimulating contacts projected on stereotactic anatomic atlases by SureTune software provided by Medtronic. We designed prospective randomized multicenter trial of high‐frequency electrical stimulation of the ANT in 40 patients with intractable epilepsy.

SureTune provides patient-specific comprehensive visualization of lead location and simulated volume of neural activation (VTA) that can help for making decisions on how to program, or tune, ANT-DBS therapy. We will present maps of location of the stimulating lead and VTA on the thalamus anatomy.

Hussein HAMDI ABOUELGHEIT (Marseille), Stephan CHABARDES, Claire HAEGELEN, Marc GUENOT, Fabrice BARTOLOMEI, Jean REGIS
18:25 - 18:30 Discussion.
DEACONS SUITE

Thursday 27 September

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D29
17:00 - 18:30

Parallel Session 8
Psychiatry

Moderators: David CHRISTMAS (Consultant Psychiatrist) (Dundee, Scotland, UK), Sameer SHETH (Associate Professor of Neurosurgery) (Houston, USA), Giorgio SPATOLA (Neurosurgeon) (Marseille, FRANCE)
17:00 - 17:10 #16151 - O070 Stereotactic radiosurgical capsulotomy for obsessive-compulsive disorder: initial results using a “Goldilocks” 5-shot radiosurgical plan.
O070 Stereotactic radiosurgical capsulotomy for obsessive-compulsive disorder: initial results using a “Goldilocks” 5-shot radiosurgical plan.

Introduction

Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2 to 3%, and many patients are refractory to conventional pharmacological and behavioral treatments. Neurosurgical options including stereotactic radiosurgical capsulotomy (SRSC) have been used for decades in refractory patients, with symptomatic response rates of 40-65%. The most significant adverse event from these procedures is radionecrotic cyst formation and frontal lobe edema causing a dysexecutive syndrome, which is radiation dose dependent. We employed a radiosurgical plan with a novel 5-shot dose distribution, designed to be large enough to recapitulate the efficacy of earlier 2-shot procedures but conformal enough to reduce the chance of cyst/edema formation.

 

Methods

The radiosurgical plan consists of 5 4-mm shots per hemisphere, with 150 Gy maximum dose. The vertically stacked shot configuration uses sector blocking and weighting to produce a distribution elongated in the superior-inferior direction (Fig 1). The ventral-most shot is placed in the ventral portion of the anterior limb of the internal capsule bordering the ventral striatum in the coronal plane, and near the posterior putaminal border in the axial plane. Response was defined as >35% reduction in Yale-Brown Obsessive Compulsive Scale (YBOCS) score.

 

Results

Six patients with severe, refractory OCD have undergone the 5-shot SRSC (Figure 1). Of the 4 patients who are >6 months out, all 4 are responders, with mean YBOCS reduction of 50% (range 36-68%) at mean follow-up interval of 9 months (range 7-13). Dose-volume histograms demonstrated conformality, and low volumes at mid-range doses (~0.6 cc at 60 Gy). Thus far, follow-up MRIs have demonstrated minimal edema and no cyst formation (Fig 2). Other than brief (~1 month) mild fatigue, no other adverse events have occurred.

 

Conclusions

SRSC strives to deliver the “just right” dose of radiation: enough to create an effective lesion, but not enough to cause adverse events. Our initial results show response rates at least as high as those produced using previous treatment plans with higher radiation dose. Longer follow-up interval in more patients will determine whether the adverse event profile is improved with this plan. SRSC remains an attractive neurosurgical option for refractory OCD.

Figure. Top: Example 5-shot showing isodoses from 120 Gy (smallest) to 12 Gy (largest). Bottom: T1 non-contrast MRI at 3 months demonstrating a robust lesion in the desired location.

Sameer SHETH (Houston, USA), Yagna PATHAK, Ian PADDICK, Deepti ANBARASAN, Tony WANG, Antonio LOPES, Marcelo HOEXTER, Benjamin GREENBERG, Steven RASMUSSEN, Euripedes MIGUEL, Nicole MCLAUGHLIN, Garrett BANKS
17:10 - 17:20 #16235 - O071 Cognitive and emotional effects of antero-ventral STN DBS in refractory OCD.
O071 Cognitive and emotional effects of antero-ventral STN DBS in refractory OCD.

Background : Deep brain stimulation (DBS) targeting the associative-limbic subthalamic nucleus (STN) has been shown to be effective for obsessive compulsive disorder (OCD). The STN is a critical relay within the indirect pathway of fronto-striatal circuitry receiving inputs also via the cortical hyperdirect pathway, thus being involved in response inhibition. Additionally, behavioural and electrophysiological studies in Parkinson disease showed responses of the STN to emotional stimuli, impairments in recognition of negative affective states and modulation of the intensity of subjective emotion. As the mechanisms underlying clinical benefit of STN DBS in OCD are poorly understood, we performed a study assessing the effects of STN DBS on critical cognitive and affective functions in OCD patients: decisional impulsivity, as well as emotional response, i.e. emotional ratings of positive and negative valenced images. 

Methods: Twelve OCD subjects were recruited from Grenoble University Hospital, tested on and off associative-limbic STN DBSin a double-blind randomized mannerand compared with 24 healthy volunteers. Both groups were assessed for two different forms of decisional impulsivity: reflection impulsivity or evidence accumulation using the Beads Task and delay discounting using the Monetary Choice Questionnaire. Ten OCD patients also performed a second assessment of the emotional responses toa set of low and high valence emotional images (International Affective Picture System). OCD patients had undergone bilateral STN DBS for mean 38.1±18.8 months prior to testing (duration of the stimulation range prior to the study: 5-71 months). Patients had at least five years of treatment-resistant, severe, disabling OCD before DBS surgery. Related samples Wilcoxon Signed Rank Test was used to compare on and off DBS in the decisional impulsivity tasks; independent samples Kruskal Wallis test was used to compare more than two groups and independent samples Mann-Whitney U-test for post hoc analyses if the Kruskal Wallis test was significant. Results were corrected for multiple comparisons. For the affective task, we compared the scores for affective ratings (emotional valence) and arousal ratings separately using a repeated measures ANOVA with a within-subject ON-OFF factor and within-subject Affect factor (Neutral, Pleasant and Unpleasant). This was separately conducted for the high valence and low valence stimuli.

Results : We highlight that anterior associative-limbic STNstimulation enhances decisional impulsivity with less accumulation of evidence during probabilistic uncertainty (related-samples Wilcoxon Signed Rank Test, P = 0.04)and enhances delay discounting (p=0.03). We also found that STN DBS increases positive ratings to positive stimuli and decreased negative ratings to negative stimuli, but only for images of low valence intensity (main effect of Valence (F(1,8)=36.66, p<0.0001) and of DBS (F(1,9)=6.23, p=0.034). Moreover, the change in severity of OCD symptoms pre- versus post-operatively interacts with valence ratings. 

Conclusion : We show that STN DBS leads to a more adaptive behavior in subjects with OCD by shifting for a functional cognitive less cautious style, closer to that of healthy controls. These effects highlight the hub role of STN in multimodal information processing and may contribute to explain STN DBS mechanisms of the clinical efficacy. Interestingly, these results may contribute to improve selection of patients candidate for the STN DBS procedure.

Mircea POLOSAN (Grenoble cedex 09), Stephan CHABARDES, Astrid KIBLEUR, Julien BASTIN, Fabien DROUX, Eric SEIGNEURET, Alexandre KRAINIK, Olivier DAVID, Paul KRACK, Valerie VOON
17:20 - 17:30 #16271 - O072 Gamma Knife Anterior Capsulotomy for refractory obsessive-compulsive disorder: results in a series of 10 consecutive patients.
O072 Gamma Knife Anterior Capsulotomy for refractory obsessive-compulsive disorder: results in a series of 10 consecutive patients.

Object:

Obsessive-compulsive disorder is a severe psychiatric condition. We present our experience with Gamma Knife Radiosurgery in the treatment of patients resistant to any medical therapy.

Methods:

Patient with severe OCD resistant to any pharmacological and psychiatric treatments treated with anterior gamma knife capsulotomy were retrospectively reviewed. These patients were submitted to a physical, neurological, and neuropsychological examination together with a structural and functional MRI pre-and post-radiosurgery treatment. Strict inclusion criteria have been applied. Radiosurgical capsulotomy was performed using two 4-mm isocenters targeted at the mid-putaminal point of the anterior limb of the capsule. A maximal dose of 120 Gy was prescribed for each side. Clinical global changes were assessed by the Clinical Global Impression (CGI) Scale, Global Assessment of Functioning (GAF) and Quality of life (EQ-5D), the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI). Obsessive compulsive symptoms were determined by the Y-BOCS. 

Results:

10 patients with medical refractory OCD (5 women and 5 men) treated from 2006 to 2015 were included in this study. Median age at diagnosis was 22,5 years, median duration of illness at the time of radiosurgery was 14.5 years, median age at treatment was 38 years. Before GKRS, the median Y-BOCS score was 34.5 with a median obsession score of 18 and compulsion score of 17. Seven out of 10 patients (70%) achieved a full response at their last follow-up, 2 patients were non-responder, 1 patient was a partial responder. Evaluation of Y-BOCS, BDI, STAI-T, STAI-S, GAF, and EuroQoL showed statistically significant improvement at the last follow-up after GKRS. Neurological examinations were normal in all patients at each visit. At last follow-up, none of the patients experienced any significant adverse neuropsychological effects or personality changes.

Conclusion:

GKRS anterior capsulotomy is effective and well tolerated with a maximal dose of 120 Gy. It reduces both obsessions and compulsions, improves quality of life and diminish depression and anxiety.

Giorgio SPATOLA (Marseille), Roberto MARTINEZ ALVAREZ, Nuria MARTINEZ, Raphaelle RICHIERI, German REY, Jean Marie REGIS
17:30 - 17:40 #16297 - O073 Results from six years experience of deep brain stimulation in the bed nucleus of stria terminalis in obsessive-compulsive disorder.
O073 Results from six years experience of deep brain stimulation in the bed nucleus of stria terminalis in obsessive-compulsive disorder.

Background: Obsessive-compulsive disorder is characterized by persistent obsessive thoughts that generate anxiety and the related compulsions with the aim of neutralizing the distress. OCD affects approximately 2% of the population and half of the patients develop a chronic form of the disorder. Up to 10% of patients with OCD continue to demonstrate severe therapy-refractory symptoms despite trying available treatments; pharmacological and psychoterapeutic therapies. Hence, deep brain stimulation (DBS) is under investigation for severe therapy refractory OCD. This invasive and probably life‑long treatment, differs considerably from the established therapies for OCD. There are still very few reports on the long-term effects of DBS in OCD. We present here data ranging from 1 to 6 years follow up from 10 patients with severe therapy refractory OCD treated with DBS in the bed nucleus of the stria terminalis (BNST).

Methods: 10 patients with severe therapy refractory OCD were included in a study of DBS in BNST for OCD. The patient group consisted of 6 females and 4 males with the average age of 37 at surgery. The patients underwent bilateral electrode implantation in the BNST and the stimulation was started immediately after surgery. The patients were evaluated at baseline, 6 and 12 months after surgery and therafter yearly. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Scale (YBOCS).

Results: One year after surgery the mean YBOCS had improved from 33 to 20 points, meaning an average of 39% symptom reduction. Thus, the severity of the OCD after one year had decreased from extreme to moderate on average. Similar results were seen long-term with follow-up ranging from 1 to 6 years, where the mean YBOCS had improved from 33 to 19 (42%). The adverse effects observed during this period of 6 years was one case of re-implantation due to an skin infection at the battery site and minor signs of hypomania, reversed with a change of stimulation parameters seen in two patients. Additionally one patient reported a reaction of  severe rebound in anxiety after on own accord turning off stimulation at home. Similar effects with an acute increase of anxiety have been observed in 8 of the 10 patients in our study with functional magnetic resonance imaging (fMRI), where the DBS in this patient group is switched off for two hours prior to the off DBS fMRI scan. The patient with the longest follow-up at 6 years had at the last follow-up 0 points on YBOCS and is therefore currently on gradual cessation of the stimulation.
 
Conclusions: The long-term results and experiences from this study of BNST DBS in severe therapy-refractory OCD are promising. The greatest improvement  of OCD symptoms was seen after 1 year of stimulation and the results were generally stable over-time, with further improvement in some induvidual patients after years of stimulation. The observed acute increase in anxiety when stimulation is turned off suggests that gradual stimulation cessation should be considered in OCD patients who wish to discontinue DBS treatment.
Matilda NAESSTRÖM (Umeå, SWEDEN), Patric BLOMSTEDT, Marwan HARIZ, Owe BODLUND
17:40 - 17:50 #16329 - O074 Brain networks implicated in ventral capsule and anteromedial subthalamic nucleus stimulation for refractory obsessive-compulsive disorder.
O074 Brain networks implicated in ventral capsule and anteromedial subthalamic nucleus stimulation for refractory obsessive-compulsive disorder.

Background 

Pathophysiological models of obsessive compulsive disorder (OCD) point to a dysfunction within the cortico-striato-thalamo-cortical networks. The ventral capsule (VC) and anteromedial subthalamic nucleus (amSTN) are distinct deep brain stimulation (DBS) targets, individually effective in reducing OCD symptoms. This study investigates the neural circuits modulated by DBS in these two nodes.

Methods 

A randomized controlled trial compared VC-DBS and amSTN-DBS within the same six patients. Patients underwent high angular resolution diffusion-MRI at 3T preoperatively. Volume of tissue activated (VTA) models, corresponding to active DBS electrodes (located on intraoperative stereotactic MRI) were estimated. Probabilistic tractography streamlines were then generated using each DBS-VTA as seed. Group average networks, produced from resulting individual streamlines, are described. 

Results 

OCD symptoms significantly improved with DBS in both targets. However, only VC DBS had a positive effect on mood, as measured by Montgomery Asberg and Beck Depression Scales. Conversely, only amSTN had a positive effect on cognitive flexibility with significant reduction in extra-dimensional set-shifting errors. VC-VTA streamlines were connected to medial orbitofrontal cortex, mediodorsal thalamus, amygdala and habenula. amSTN-VTAs streamlines were connected to lateral orbitofrontal cortex, dorso-anterior cingulate cortex and dorsolateral prefrontal cortex. Common streamlines connect VC and amSTN networks in a central pathway, passing through the internal capsule and midbrain via the medial forebrain bundle.

Conclusions

VC-DBS and amSTN-DBS independently improve OCD symptoms by influencing different neural circuits. This may also explain the differential effects of VC-DBS and amSTN-DBS on mood and cognition.

Harith AKRAM (London, UK), Trevor W. ROBBINS, Himanshu TYAGI, Annemieke M. APERGIS-SCHOUTE, Tom FOLTYNIE, Patricia LIMOUSIN, Lynne M. DRUMMOND, Naomi A. FINEBERG, Keith MATTHEWS, Marjan JAHANSHAHI, Barbara SAHAKIAN, Eileen JOYCE, Ludvic ZRINZO
17:50 - 18:00 #16343 - O075 Anatomic Description of the Ventral Capsule and Orbitofrontal Radiation Confluence as a possible hot spot for OCD DBS.
O075 Anatomic Description of the Ventral Capsule and Orbitofrontal Radiation Confluence as a possible hot spot for OCD DBS.

Background: Dysfunction of the reward system and consequent hyperactivity of cortico-striato-thalamo-cortical loops has been accepted as the potential mechanism for obsessive-compulsive disorder (OCD). Ablation or deep brain stimulation (DBS) of ventral portions of anterior limb of internal capsule (ALIC) and the adjacent ventral striatum (‘VC/VS’) are currently the most frequently interventions for the treatment for refractory OCD. ALIC is supposedly comprised by fibres from the prefrontal areas that connect to the striatum, thalamus and brain stem. However, evidence from early anatomical studies suggests that mesial orbitofrontal cortex may use another connection route. Insufficient similarities between primate and human frontal lobes and methodological shortcomings of diffusion tensor imaging may have precluded accurate anatomic description of this particular region.

Aim and Method: The current study aimed to investigate the 3D anatomy of this region using reconstructed data from high field MRI and brain histological sections corregistered into MNI space (São Paulo-Würzburg Electronic Atlas of the Human Brain). We also present preliminary results of two refractory OCD patients who had bilateral DBS leads placed in the confluence of VC and orbitofrontal radiation (hot spot).

Results: We found that the ALIC contains fibres from most of frontopolar, central and lateral orbitofrontal and dorsolateral prefrontal cortices, corroborating neuronal labelling data from non-human primates and MRI-DTI human studies. However, fibres from the mesial orbitofrontal and ventromedial prefrontal cortex apparently take a different route. As a continuum, the white matter of gyrus rectum gives rise to a band that reaches the ventral striatum. Coursing laterally and adjacent to the uncinate fasciculus, in a trajectory parallel to the anterior commissure, these fibres cross and join the ones from the ventral ALIC towards the thalamus and brainstem. Lateral to this confluence, the same fibres reach the ventral pallidum and follow the path towards the substantia inominata and the amygdala in the temporal lobe. Two patients with ALIC DBS electrodes implanted near this fibre region experienced significant acute improvement on the day following surgery. This pronounced insertion effect lasted for almost one week, after which symptoms subsided. During the first 3 months of the programming phase, patients Y-BOCS improvements were in the order of 26-59% and 50-60% respectively. Once the best stimulation parameters were set, they experienced significant and stable improvement up to the last follow up (12mo). At that time, patient 1 was in complete remission of OCD symptoms and patient 2 had 78% improvement in the Y-BOCS.

Conclusion: A detailed appraisal of the anatomy of the region of the ALIC and VC/VS is now possible with novel computerized reconstructions of histological sections. Although our results are preliminary and based on two cases, DBS in this target apparently yields promising results.

Figure Legend

The figure shows a drawing of an axial section of the human hemisphere showing the fiber projections from frontal region through the ventral capsule (blue doted arrows) and medial orbitofrontal radiation (red doted arrows) and their confluence in the spot (yellowish circle) right below the anterior commissure (AC), which has ascending trajectory towards midline. Image reference: Dejerine J. Anatomie des Centres Nerveux.  Anatomie du cerveau – Anatomie du rhomencephale, pg22, J Rueff Editeur, 1901, Paris.

José Francisco PEREIRA, Eduardo Joaquim ALHO, Clement HAMANI, Helmut HEINSEN, Antonio Carlos LOPEZ, Fabio GODINHO, Jacobsen Teixeira MANOEL, Marcelo BATISTUZZO, Marcelo Q HOEXTER, Euripides Constantino MIGUEL, Fonoff ERICH (Sao Paulo, BRAZIL)
18:00 - 18:05 #14821 - O076 Clinical Characteristics of Obsessive-Compulsive Disorder: Focusing on Psychiatric Diagnosis and Comorbidities.
O076 Clinical Characteristics of Obsessive-Compulsive Disorder: Focusing on Psychiatric Diagnosis and Comorbidities.

Objectives Several clinical trials of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) have been performed internationally with sufficient therapeutic results to attract strong interest. OCD-DBS is a form of neurosurgery for psychiatric disorders (NPD). Therefore, making an accurate diagnosis before performing this invasive procedure is important. Methods We surveyed OCD patients in our hospital and reviewed their psychiatric diagnosis and comorbidities. Two certified psychiatrists interviewed 44 OCD patients, recorded their clinical characteristics, and diagnosed their condition using DSM4 TR, M.I.N.I. (The Mini-International Neuropsychiatric Interview) and psychological test etc. Based on their diagnosis, patients were subdivided into those with only OCD (Group A) or those with comorbidities other than OCD (Group B). Group B patients were further divided into patients with psychotic disorders (Group B1) or patients with non-psychotic disorders (Group B2). We first statistically compared groups A and B, then compared group B1 with groups A and B2 combined. This study was approved by the ethical committee of Tokyo Metropolitan Matsuzawa Hospital, and all ethical aspects have been fully considered. ResultsThe patients were allocated to the following groups: Group A (n=8) and Group B (n=36), which was further subdivided into Groups B1 (n=15) and B2 (n=21). The non-psychotic comorbidities were: autism spectrum disorder (n=7), mood disorder (n=4), etc. Patients in Group B tended to score more highly on the Hamilton Depression Scale while patients in Group B1 tended not to experience a trigger event before the onset of OCD symptoms compared to patients in Groups A and B2. ConclusionWe speculate that OCD patients with certain comorbidities experience a severer depressive state and that patients who have no trigger event before the onset of OCD symptoms might have a psychotic comorbidity such as schizophrenia. Ascertaining the extent of depression and accurately identifying OCD triggers may aid in accurately diagnosing the psychiatric disorder and selecting patients for whom NPD is appropriate.

Yasushi OKAMURA (Tokyo, JAPAN), Katsushige WATANABE, Tatsuya SUGIMOTO, Hirohiko HARIMA, Masahiko SAITO, Yoshio HIRAYASU, Makoto TANIGUCHI
18:05 - 18:10 #16142 - O077 Modulation of oscillatory neuronal activity by high frequency deep brain stimulation in the bed nucleus of the stria terminalis/ internal capsule in obsessive compulsive disorder.
O077 Modulation of oscillatory neuronal activity by high frequency deep brain stimulation in the bed nucleus of the stria terminalis/ internal capsule in obsessive compulsive disorder.

Objective: Deep brain stimulation (DBS) of the bed nucleus of the stria terminalis/ internal capsule (BNST/ IC) is successfully used for treatment of patients with obsessive compulsive disorder (OCD). The mechanisms of action of DBS remain unclear in OCD. We here investigate the effect of stimulation of the BNST/ IC on oscillatory neuronal activity in patients with OCD implanted with DBS electrodes.

 

Methods: We recorded the oscillatory activity of local field potentials (LFPs) from DBS electrodes (contact +0/-3; bipolar configuration; both hemispheres) from the BNST/ IC parallel with frontal cortical electroencephalogram (EEG) one day after DBS surgery in four patients with OCD. BNST/ IC and frontal cortical EEG oscillatory activities were analysed before stimulation as baseline and after three periods of stimulation with different voltage amplitudes (1V, 2V and 3.5V) at 130Hz.

 

Results: Overall, high frequency DBS suppressed theta (4-8Hz) and increased beta (12-30Hz) LFP oscillatory power both in BNST/ IC and in the frontal cortex (P<0.01). Stimulation increased the percentage of alpha band (8-12Hz) LFP oscillatory power differently on the left (2V and 3.5V; P<0.05) and the right side (1V and 2V; P<0.01) without changes in the frontal cortex. Further, after stimulation the percentage of gamma band (30-100Hz) LFP oscillatory power in the left BNST/ IC was increased with 1V (P<0.05) and 2V (P<0.01), and in the frontal cortex with 1V, 2V and 3.5V (P<0.01).

 

Conclusion: Our findings indicate that stimulation of the BNST/ IC in OCD modulates oscillatory activity in brain regions that are involved in the pathomechanisms of OCD.

Mesbah ALAM (Hannover, GERMANY), Saryyeva ASSEL , Hans E. HEISSLER, Winter LOTTA, Ivo HEITLAND, Kahl KAI, Kerstin SCHWABE, Joachim K KRAUSS
18:10 - 18:15 #16375 - O078 Robot assisted guide tube insertion and radiofrequency lesioning for psychiatric disorders and epilepsy.
O078 Robot assisted guide tube insertion and radiofrequency lesioning for psychiatric disorders and epilepsy.

Introduction

Precisely localised radiofrequency thermal ablation has been successfully utilised in treatment of conditions including treatment resistant depression, obsessive compulsive disorders, movement disorders and epilepsy. We present an image-directed, robot-assisted, guide tube insertion and delivery of thermal electrocoagulation, which allows accurate target localization, facilitates accurate lesioning with submillimetre accuracy, and future repeat lesioning to optimise benefit without the need for repeat stereotactic procedure. We present a series of eight cases who underwent guide tube facilitated thermal lesioning for severe treatment resistant depression (TRD), OCD and epilepsy.

Methods

Skull mounted guide tubes were inserted, assisted by a robot arm (Renishaw PLC) under general anaesthesia. Trajectories were planned based on pre-operative MRI images over a shortest distance avoiding blood vessels.  Radio-opaque stylettes inserted into the target enable verification of target accuracy with either intraoperative CT angiogram or MRI. Thermal lesions were created using a five millimetre tipped probe at 70◦C for 90 seconds (Cosman Medical), and repeated along desired target depth. The stylette was reinserted into the guide tube prior to closure to maintain patency and enable repeat lesioning as required.

Results

For TRD, 4 patients underwent primary bilateral anterior cingulotomy (AC) (procuring remission n=1; response n=1; transient response n=1; and no response n=1 and despite repeat lesioning); and one patient has received primary stereotactic subcaudate tractotomy (SST) and is awaiting follow-up. Two patients with TRD beyond sustained failure of DBS underwent lesioning, procuring remission in one with AC, and response in another with sequential AC and SST (Limbic Leucotomy). One patient with resistant severe OCD has received bilateral AC beyond historical capsulotomies and SST. One patient underwent a unilateral insula lesioning following a stereotactic EEG for epilepsy; and has remained seizure free for two months, following which the nocturnal seizures returned but with a much lower frequency; and may be considered for repeat lesioning to optimise response. None of the patients have had any neurological deficit post operatively.

Conclusions

This novel image-directed, robot-assisted, guide tube technique facilitates accurate delivery of the thermocoagulation probe to the target, with a minimal patient morbidity, and in a standardised fashion. Moreover, this method allows minimally invasive repeat lesioning to optimise benefit, with minimal risk and reduced cost.

Reiko ASHIDA (Bristol, UK), Angelo PICHIERRI, Neil BARUA, Malizia ANDREA L, Nikunj K PATEL
18:10 - 18:15 Discussion.
WOLFSON HALL B
18:30

Thursday 27 September

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C29B
18:30 - 19:05

Parallel Session 9
Other & Oncology

Moderators: Brigitte GATTERBAUER (physician) (Vienna, AUSTRIA), Chris HONEY (Vancouver, CANADA), Sadaquate KHAN (UK)
18:30 - 18:35 #16136 - O079 Application accuracy of the frameless neuro stereotaxy based on non-invasive fiducial systems.
O079 Application accuracy of the frameless neuro stereotaxy based on non-invasive fiducial systems.

OBJECTIVE: To compare the application accuracy of the stereotactic robot for Deep Brain Stimulation (DBS) procedures using frameless and frame-based registration systems.

METHODS: 112 patients underwent bilateral STN lead implantations for the treatment of Parkinson’s disease with DBS using the Neuromate® robot (Renishaw PLC). In all cases, MRI images were acquired under general anaesthesia and surgical planning was carried out using the neuro|inspireTM software days or weeks before surgery.

In 67 cases, registration of the patients MRI surgical plan to the patient within stereotactic space was achieved by obtaining a stereotactic CT angiogram of the patient in a Leksell stereotactic frame and co-registering this with the plan using vessel registration between the CT angiogram and the T2 MRI image volumes. Registration of the patient and their plan to the robot was then achieved by 3-point fixation of the Leksell frame to a known location on the robot stand.  

In 45 cases registration of a patient and their surgical plan to the Neuromate® was achieved intraoperatively using 3D angiogram images from the O-arm Imaging System (Medtronic Inc.) with the patient’s head fixed to the robot stand and the frameless neuro|locateTM fiducial system held over the head within the imaging field by the robot arm.

The neuro|locateTM fiducial system comprises an array of five X-ray/ CT visible ruby balls held in a known relationship by carbon-fibre rods that are mounted as a device on to the robot arm during image acquisition. The array was constructed such that only three fiducials could be found on a single imaging plane. The relative distance between fiducial pairs ranged between 57.5, and 137.1 mm.

Both registration systems were powered by fully-automated fiducial detection and recognition algorithms implemented in neuro|inspireTM, which approximates the spatial position of the fiducial captured in the image volume, and assesses the best-of-fit to a calibrated model, i.e. fiducial registration error (FRE). In case of high FRE, i.e. above 1mm, a neurosurgeon was encouraged to review the fiducial detection, and recognition results and to provide necessary corrections.

A total of 224 trajectories were retrospectively analysed regarding a Euclidean distance between the planned and delivered target position (i.e. localisation error), and its perpendicular (i.e. radial error) and parallel (i.e. depth error) components. The errors obtained from the cases facilitated with the frameless and frame-based system were compared using the Wilcoxon rank sum test.

RESULTS: The median target point localization errors for neuro|locateTM-based and frame-based trajectories were 0.695 (IQR 0.332 mm) and 0.889 (IQR 0.509 mm), respectively (Z = -2.997, p = 0.0027). The median radial errors at a target point for neuro|locateTM-based and frame-based trajectories were 0.556 (IQR 0.338 mm) and 0.631 (IQR 0.376 mm), respectively (Z = -2.225, p = 0.026). The median depth errors at a target point for neuro|locateTM-based and frame-based trajectories were 0.293 (IQR 0. mm) and 0.889 (IQR 0.509 mm), respectively (Z = -2.267, p = 0.0234). The boxplots results are presented below. All the surgical procedures were successful and uneventful.

CONCLUSIONS: DBS procedures facilitated with the neuro|locateTM are more accurate than the frame-based Leksell system, whilst keeping the safety profile of the frame-based registration. 

Mariusz PIETRZYK (Miskin, UK), Max WOOLLEY, Catherine MORAN, Neil BARUA, Steven GILL
18:35 - 18:40 #16153 - O080 Does microelectrode recording increase haemorrhage? A comparative study in a large patient cohort over 20 years.
O080 Does microelectrode recording increase haemorrhage? A comparative study in a large patient cohort over 20 years.

Objective:

 

Microelectrode recording (MER) of single neuron activity is a common and useful technique in functional stereotactic neurosurgery. Since many years, however, controversial debates are ongoing regarding the necessity of MER and a potentially increased risk of intracranial haemorrhage. Here we aimed to investigate whether there is an increased risk of haemorrhage in a large series of patients operated over two decades.

 

Methods:

 

This is a retrospective study on 585 patients who underwent functional stereotactic neurosurgery (DBS electrode implantation or radiofrequency lesioning) over a period of 20 years. Procedures were performed or supervised by the same neurosurgeon in three different centers using the same technique. The target was determined with CT-stereotactic surgery and approached via a guiding cannula. MER was performed via a single channel technique, supplemented by additional trajectories if decided necessary. Single unit recording was mainly used for targeting the subthalamic nucleus (STN) and the internal globus pallidus (GPi), while thalamic targets like the nucleus ventralis intermedius (VIM) were mainly approached without MER. Postoperative CT scans obtained within 24 hours after surgery were searched for haemorrhage of any size at any site.

 

Results:

 

A total of 244 women and 341 men with a median age of 55 years were operated for movement disorders (509), pain syndromes (52) or psychiatric disorders (24). The majority of patients underwent DBS (565), while a subset had radiofrequency lesioning procedures (20).

Overall, in 361 patients surgery was performed with MER, and thereof in 12 patients an intracranial haemorrhage was detected (3,32 %). The other 224 patients were operated without MER. Of these, 7 patients had intracranial haemorrhage (3,13 %). In the MER group haemorrhage manifested as small haemorrhage at the target site (7), subdural haematoma (3) or ventricular bleeding (2). In the non-MER group haemorrhage was found as haematoma at the target site (4) or ventricular bleeding (3). Haemorrhage was asymptomatic in all patients except in 1 patient in the MER group, who had a persistent mild hemiparesis on the right side.

 

Conclusions:

 

In this large patient series the use of MER with appropriate techniques did not significantly increase the risk of intracranial haemorrhage. Single unit recording can help to further define the target for DBS electrode placement or radiofrequency lesioning without incurring an additional risk for the patient.

Joachim RUNGE (Hannover, GERMANY), Assel SARYYEVA, Marc WOLF, Christian BLAHAK, Christoph SCHRADER, Holger H. CAPELLE, Hansjörg BÄZNER, Mahmoud ABDALLAT, Joachim K. KRAUSS
18:40 - 18:45 #16164 - O081 Concurrent hemi-laryngopharyngeal spasm (HELPS) and glossopharyngeal neuralgia: the first two cases and a review of the literature.
O081 Concurrent hemi-laryngopharyngeal spasm (HELPS) and glossopharyngeal neuralgia: the first two cases and a review of the literature.

Background

Hemi-laryngopharyngeal spasm (HELPS) is a recently described condition due to unilateral vascular compression of the Xth cranial nerve. Symptoms include progressive, intermittent throat contractions and cough without pain. Glossopharyngeal neuralgia is a rare but well recognized intermittent, unilateral throat pain that can be due to a vascular compression of the IXth cranial nerve. With a similar etiology and a close proximity of these two nerves, one would expect that these two conditions would occasionally be found concurrently in the same patient.

Methods

We present the first two reported cases of concurrent hemi-laryngopharyngeal spasm and glossopharyngeal neuralgia and review their symptomology, imaging, intra-operative findings and outcome following microvascular decompression. Presentation of these cases followed approval from our institution’s Clinical Research Ethics Board. We then review all previous reports concerning glossopharyngeal neuralgia in the Dutch, English, French, German, and Russian literature to determine if these symptoms have been previously recognized.

Results

Both our cases had microvascular decompression of the IX-X cranial nerve complex. The painful symptoms related to glossopharyngeal neuralgia resolved immediately. The choking and coughing symptoms related to HELPS improved much more slowly.  Our literature review found several previously described but unrecognized cases of concurrent hemi-laryngopharyngeal spasm and glossopharyngeal neuralgia.

Conclusions

Hemi-laryngopharyngeal spasm is a newly described condition that causes intermittent throat contractions with coughing and can progress to severe stridor. It is often misdiagnosed as a psychogenic illness. Neurosurgeons with a familiarity of microvascular decompression (MVD) may cure this condition. This report adds to the growing knowledge of this condition and highlights that compression of the lower cranial nerves results in predictable and recognizable symptoms with a surgical cure. The condition has been described but not recognized in many languages.

Christopher HONEY (Vancouver, CANADA), Murray MORRISON
18:45 - 18:50 #16325 - O082 Stereotactic Cisternal Lavage Therapy Reduces DCI and Improves Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.
O082 Stereotactic Cisternal Lavage Therapy Reduces DCI and Improves Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose: 

Delayed cerebral infarction (DCI) is a major source of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Stereotactic catheter ventriculocisternostomy (STX-VCS) and continuous fibrinolytic/spasmolytic lavage therapy is a new method for DCI prevention. We compare neurological outcome (Modified Rankin Scale, mRS), DCI incidence and DCI volume of all consecutive poor grade aSAH patients (WFNS grade 3-5) before and after introduction of STX-VCS in our institution. 

Methods: 

We analyzed all consecutive poor grade aSAH patients admitted 2.5 years before and 2.5 years after introduction of STX-VCS in our department (September 2015). On the basis of individual treatment decisions STX-VCS (Figure 1) was performed using a Leksell G-frame (Elekta, Stockholm, Sweden). Continuous fibrinolytic cisternal lavage using urokinase (Medac, Wedel, Germany) at a concentration of 100 IU/ml and a rate of 50ml/h was applied for 5-10 days. In case of sonographic vasospasm nimodipine (Bayer, Leverkusen, Germany) was applied via STX-VCS at a concentration of 0.005 mg/ml. Patient demographics, characteristics of aSAH and treatment were collected. Neurological outcome was assessed by mRS at 6 months and dichotomized for analysis (0-3 = favorable, 4-6 = poor). DCI rating was performed by an interdisciplinary board (neurologist, neurosurgeon, neuroradiologist) according to international guidelines. DCI volumes were determined using a stereotactic planning software (Elements, Brainlab, Munich, Germany). 

Results:

A total of 160 patients were included: 80 patients before implementation of STX-VCS and 80 patients after implementation of this technique. 

Baseline and treatment characteristics of both groups were highly comparable: Female 65% vs. 69% (p=0.74); median age 58.7 vs 58.8 years (p=0.74); WFNS grade 3: 9% vs. 8%, WFNS grade 4: 23% vs. 31%, WFNS grade 5: 69% vs. 61% (p=0.46); Fisher score 2: 8% vs. 9%, Fisher score 3: 5% vs. 8%, Fisher score 4: 88% vs. 84% (p=0.76); clipping/coiling: 45% / 55% vs. 44% / 56%; median aneurysm size: 6.1mm vs. 6.0mm (p=0.61); mean Charlson Comorbidity Index: 1.9 vs. 2.0 (p=0.54)

40 of 80 patients were selected for STX-VCS.  Procedures were performed without surgical complications. One adverse event due to cisternal lavage was without sequelae.

The DCI rate was 28% before and 13% after STX-VCS was introduced (p=0.029). The total DCI volume was reduced by 78% (from 5900ml to 1279 ml). 

Poor neurological outcome (mRS 4-6) at 6 months occurred in 45 (66%) and 31 (39%) of patients, respectively (p=0.039).  

In the 40 STX-VCS patients the DCI incidence was 10%, the total DCI volume was 295 ml and poor neurological outcome (mRS 4-6) at 6 months was 28%.

Conclusions: 

STX-VCS was feasible and safe in patients with severe aSAH. Performing STX-VCS in high-risk patients reduced the DCI incidence from 28% to 13% and the total DCI volume by 78%. Poor neurological outcome was significantly reduced from 66% to 39%. 

Peter C. REINACHER (Freiburg, GERMANY), Volker A. COENEN, Christian SCHEIWE, Karl EGGER, Wolf-Dirk NIESEN, Christine STEIERT, Roland ROELZ
18:50 - 18:55 #16349 - O083 The Neurosurgical Treatment of Spasmodic Dysphonia: Preliminary results of a Prospective, Randomized, Sham-Controlled (DEBUSSY) Trial.
O083 The Neurosurgical Treatment of Spasmodic Dysphonia: Preliminary results of a Prospective, Randomized, Sham-Controlled (DEBUSSY) Trial.

Introduction:

Spasmodic dysphonia (SD) is a neurological speech disorder characterized by sudden, involuntary contractions in the laryngeal musculature during speech production. The current standard of care for SD involves botulinum toxin (BTX) injections into the laryngeal muscles. Unilateral deep brain stimulation of the ventral intermediate nucleus has demonstrated to be effective in voice disorders including adductor SD. This trial has been designed to test the hypothesis that Vim-DBS can improve the vocal dysfunction of SD.

Methods:

Institutional ethics (H15-02535) and clinicaltrials.gov (NCT02558634) registration were completed. The inclusion criteria were as follows: Clinically diagnosed isolated laryngeal dystonia (adductor spasmodic dysphonia), patient able to give informed consent, patients who fall into the age range of 18-75 years old, patients with inadequate medical and BTX management of SD. The exclusion criteria included: Dystonia present in other body parts in addition to the larynx, history of laryngeal denervation surgery for SD, history of intracranial pathology (such as multiple sclerosis, tumors, or aneurysms) that may account for dystonia or essential tremor, history or evidence of ongoing psychiatric or neurodegenerative disorders (such as Parkinson's disease, Alzheimer's disease), Incompetent adults or those unable to communicate. Six right-handed patients with isolated adductor SD with inadequate response to BTX were included in this trial. Here, we present the preliminary results of the first 4 patients. The left medial Vim was targeted on pre-operative T1 imaging with intraoperative neurophysiological confirmation. Six weeks after surgery, patients were programmed over a 14-day period in a variety of acoustic, stressful, and pragmatic conditions. 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. The secondary outcomes included: Beck depression inventory, Voice handicap Index, and Montreal Cognitive assessment. The timeline of the study is illustrated in the figure 1.

Results:

Preliminary results will be presented of the first four patients after the cross-over phase. We will present the effectiveness of DBS on the overall severity of SD and its components (dystonic spasm, dystonic tremor, and muscle tension dysphonia). We will analyze the effect of Vim DBS in different measures of quality of life. We also analyze the volume of activated tissue and the circuits modulated by effective stimulation. Finally, we will present a protocol for postoperative management of these patients.

Conclusions:

Unilateral Vim DBS significantly reduce the overall severity of SD and improve the overall quality of life as same as the Vr-QoL. The improvement of this condition with medial Vim DBS is probably related with the modulation of the speech circuit. After the open phase of this trial, we will provide robust evidence of the effectiveness of Vim DBS in normal life conditions in SD patients. 

Christopher HONEY (Vancouver, CANADA), Anujan POOLOGAINDRAN, Murray MORRISON, Rammage LINDA, Nancy POLYHRONOPOULOS, Josue AVECILLAS-CHASIN
18:55 - 19:00 #16372 - O084 Optical tool for stereotactic brain tumor biopsy guidance.
O084 Optical tool for stereotactic brain tumor biopsy guidance.

Background and Aim

Biopsy procedures are common in intracranial tumors. Complications occur in up to 12% of the interventions, intracerebral hemorrhage is the most frequent [1, 2]. To ensure sampling of diagnostic tissue and to minimize risk of hemorrhage, a combined optical tool was developed to identify malignant tumor tissue and vascular structures.

Material and Methods

The guidance tool comprises an in-house developed fluorescence system [3, 4] and laser Doppler flowmetry [5]. A probe (ø=2.2 mm) incorporating forward looking optical fibers was used for recording together with a hand driven insertion device [5] adapted to the Leksell Stereotactic System. Fourteen patients (11 male, 3 female, age 65±11) were included in the study (No. 2015/138-32). Prior to surgery they were given 20 mg/kg 5-ALA. Intraoperative optical measurements were done in 1 mm steps from the cortex along the planned trajectories to the preplanned biopsy sites. The probe was retracted and a side-cutting biopsy needle (ø=2.1mm) was inserted and several tissue samples assessed at the predefined positions along the trajectory. The samples were sent for intraoperative smear-based examination. Depending on the outcome, surgery was closed or another trajectory chosen. Definite diagnosis was placed postoperatively by a neuropathologist. Detailed analysis in three cases is included in this abstract.

Results

Measurements were registered along 19 trajectories. PpIX-fluorescence was visible in real-time for all patients and in 17/19 trajectories in the tumor region during insertion of the optical probe. The PpIX-peak increased on entering the tumor. Intraoperative histopathology of the tissue samples showed 12 high grade tumors and 2 lymphomas. Analysis of three patients confirmed availability of tumor cells in the fluorescence positive biopsies [4]. Elevated blood flow was found in 6,3% of the measurement sites, mainly in the cortical region. There was no increase in blood flow in the tumor compared to the surrounding tissue. The recording time varied 15-40 min. depending on the trajectory lengths. Waiting time for pathological results during the operation was about 1 hr. 

Discussion and Conclusion

For all cases the surgeons received immediate feed-back of blood flow status along the trajectory and fluorescent response indicating malignant tissue. The optical probe enables real-time detection of malignant tumor tissue and can guide the surgeon to the best spot for the biopsy. Increased blood flow signals can alert increased risk of bleeding during the insertion of the guide. 

The procedure was safe and reduced the necessity of repeated insertions of the needle and shortened the time until confirmation of diagnostic tissue samples.

 

References

1.  Grossman, R., S. Sadetzki, R. Spiegelmann and Z. Ram, Haemorrhagic complications and the incidence of asymptomatic bleeding associated with stereotactic brain biopsies.Acta Neurochir (Wien), 2005. 147(6): p. 627-31; discussion 631.

2.  Malone, H., J. Yang, D.L. Hershman, J.D. Wright, J.N. Bruce and A.I. Neugut, Complications Following Stereotactic Needle Biopsy of Intracranial Tumors.World Neurosurg, 2015. 84(4): p. 1084-9.

3.  Haj-Hosseini, N., J. Richter, S. Andersson-Engels and K. Wårdell, Optical touch pointer for fluorescence guided glioblastoma resection using 5-aminolevulinic acid.Lasers Surg Med, 2010. 42(1): p. 9-14.

4.  Haj-Hosseini, N., J. Richter, P. Milos, M. Hallbeck and K. Wårdell, 5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy.Biomedical Optics Express, 2018. 9(5), 1 May, 2284.

5.  Wårdell, K., P. Zsigmond, J. Richter and S. Hemm, Relationship between laser Doppler signals and anatomy during deep brain stimulation electrode implantation toward the ventral intermediate nucleus and subthalamic nucleus.Neurosurgery, 2013. 72(2 Suppl Operative): p. ons127-40.

Johan RICHTER (Linköping, SWEDEN), Neda HAJ-HOSSEINI, Peter MILOS, Martin HALLBECK, Karin WÅRDELL
19:00 - 19:05 #16377 - O085 Hyperbaric Oxygen Therapy as adjuvant treatment for hardware-related infections in neuromodulation.
O085 Hyperbaric Oxygen Therapy as adjuvant treatment for hardware-related infections in neuromodulation.

Background: Neuromodulation utilizes implantable medical devices to deliver drugs or provide electrical stimulation to the nervous system to reduce symptoms or restore neurological functions. In the last decades, new indications combined with increased availability have resulted in an exponential numbers of patients with implanted devices. However, one major drawback in the field of neuromodulation is hardware-related infections reported to be as high as 23%. Hardware used in neuromodulation may be affected by biofilm formation causing persistent foreign body infections resistant to treatment with antimicrobial agents. Consequently, partial- or total removal of neuromodulation hardware, followed by aggressive antimicrobial therapy, has been necessary in 60-100% of the reported cases, and is considered the standard treatment for hardware-related infections. This management implies the interruption of neuromodulation therapy, causing distress for the patient, additional surgical interventions and increased economic costs. Hyperbaric Oxygen therapy (HBOT) has been shown to have beneficial effects in the treatment of neurosurgical infections, such as spontaneous brain abscesses and complicated postoperative cranial and spinal wound infections. HBOT is considered safe, improving clinical outcome in patients with surgical and non-surgical CNS infections by reducing the need for reoperations, and allowing infection resolution without removal of foreign material. HBOT decreases tissue hypoxia and acidosis in tissues with microcirculatory dysfunction.

Objective: The aim of this retrospective study was to assess the effects of HBOT as an adjuvant treatment to antibiotics in postoperative hardware-related infections in neuromodulation therapies. Time to infection resolution (with a minimum follow-up of 14 months), treatment characteristics and clinical outcome regarding the need for partial- or total hardware removal were also investigated.

Methods: The patient cohort consisted of a) seven patients with a DBS implant, b) four patients with intrathecal-pumps for drug delivery and c) one patient with a vagal nerve stimulator. 14 hardware-related infection events in 12 consecutive patients between 2002 and 2015 were treated with antibiotics and adjuvant HBOT at the Karolinska University Hospital, Stockholm, Sweden. Two time-independent infection events related to hardware replacements occurred in two patients. Infection resolution and the need for hardware removal were assessed.

Results: 12/14 events of hardware-related infections were successfully treated without hardware removal (86%). The two patients treated twice with HBOT on two time-independent occasions could retain their hardware in both cases. Hardware was removed following HBOT failure in 2 infection events, with long-term infection control achieved in all patients. Further, an intrathecal pump malfunction caused by HBOT at 2.8 bars was observed, leading to a change in the manufacturer’s guidelines.

Discussion and conclusions: The present study introduces a novel strategy to treat hardware-related infections in neuromodulation with adjuvant HBOT. We found that HBOT was an efficient and safe adjuvant to antibiotics in the treatment of hardware-related infections, which allowed continued neuromodulation treatment and preservation of hardware following 12 out of 14 (86%) infectious events in 10 out of 12 (83%) patients. This is a remarkable improvement in comparison to the outcome in previous reports, where hardware removal was undertaken for infection resolution in almost every instance. In conclusion, this study indicates a potential benefit of adjuvant HBOT in the treatment of hardware-related infections in neuromodulation. However, prospective studies are warranted to establish the role of adjuvant HBOT in the treatment of hardware-related infections in neuromodulation.

Jiri Jr BARTEK, Simon SCHYRMAN, Tiit MATHIESEN, Folke LIND, Gastón SCHECHTMANN (Stockholm, SWEDEN)
DEACONS SUITE

Thursday 27 September

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D29B
18:30 - 19:00

Parallel Session 10
Imaging & Neuronavigation

Moderators: Harith AKRAM (Neurosurgeon) (London, UK), Juan Antonio BARCIA (Neurosurgeon) (MADRID, SPAIN), Cameron MCINTYRE (speaker) (Cleveland, USA)
18:30 - 18:35 #16163 - O086 Automatic segmentation of the subthalamic nucleus: a viable option to support planning and visualization of patient-specific targeting in deep brain stimulation.
O086 Automatic segmentation of the subthalamic nucleus: a viable option to support planning and visualization of patient-specific targeting in deep brain stimulation.

Background: Automatic segmentation is gaining relevancy in image-based targeting of neural structures. 

Objective: To evaluate its feasibility, we retrospectively analyzed the concordance of MRI-based automatic segmentation of the subthalamic nucleus (STN) and intraoperative microelectrode recordings (MER). 

Methods: Electrodes (n=60) for deep brain stimulation were implanted in the STN of patients (n=30; median age 57 years) with Parkinson’s disease (n=29) or rapid-onset dystonia parkinsonism (n=1). Elements (Brainlab, Munich, Germany) was used to segment the STN, using two volumetric T1 (+/- contrast) and volumetric T2 images as input. The stereotactic CT was co-registered with the imaging, and the original stereotactic coordinates were imported. Microelectrode recordings (0.5-1 mm steps) along the anterior, central and lateral trajectories were used to determine differences between the image-segmented STN boundary and MER-based STN entry and exit. 

Results: Of 175 trajectories, 105 penetrated or touched (≤0.7 mm) the STN. The overall median deviation between the segmented STN boundary and electrophysiological recordings was 1.1 mm for MER-based STN entry and 2.0 mm for STN exit. The electrophysiological border was sometimes deeper (closer to target) than the segmented boundary.  Overall there was a high level of concordance between the borders of STN determined using MRI-based automatic segmentation and the electrophysiological trajectories analyzed with intraoperative MER.

Conclusion: MRI-based automatic segmentation of the subthalamic nucleus is a viable, patient-specific targeting approach that can be used alongside traditional targeting methods in deep brain stimulation, to support preoperative planning and visualization of target structures and aid postoperative optimization of programming.

 

Figure 1:

A. Sagittal and coronal view of Microelectrode (MER) recording trough the segmented structures (red: red nucleus (RN); green: subthalamic nucleus (STN); blue: substantia nigra (SNr). 

B. 3-dimensional reconstruction of the segmented nuclei and the MER trajectory.

C. Electrophysiological recordings at different points on the executed trajectory with typical signals for STN and SNr. 

Images created using Elements (Brainlab AG, Munich, Germany), electrophysiological MER recordings exported from Leadpoint (V5.12, Medtronic, Inc., Minneapolis, MN, USA).

Peter C. REINACHER (Freiburg, GERMANY), Bálint VÁRCUTI, Marie T. KRÜGER, Tobias PIROTH, Karl EGGER, Roland ROELZ, Volker A. COENEN
18:35 - 18:40 #16231 - O087 Accuracy of Different Three-Dimensional Subcortical Human Brain Atlases for DBS –Lead Localisation.
O087 Accuracy of Different Three-Dimensional Subcortical Human Brain Atlases for DBS –Lead Localisation.

Background: Accurate interindividual comparability of deep brain stimulation (DBS) lead locations in relation to the surrounding anatomical structures is of eminent importance to define and understand effective stimulation areas. The objective of the current work is to compare the accuracy of the DBS lead localisation relative to the STN in native space with four recently developed three-dimensional subcortical brain atlases in the MNI template space. Accuracy is reviewed by anatomical and volumetric analysis as well as intraoperative electrophysiological data.

Methods: Postoperative lead localisations of 10 patients (19 hemispheres) were analysed in each individual patient based on Brainlab software (native space) and after normalisation into the MNI space and application of 4 different human brain atlases using Lead-DBS toolbox within Matlab (template space). Each patient`s STN was manually segmented and the relation between the reconstructed lead and the STN was compared to the 4 atlas-based STN models by applying the Dice coefficient. The length of intraoperative electrophysiological STN activity along different microelectrode recording tracks was measured and compared to reconstructions in native and template space. Descriptive non-parametric statistical tests were used to calculate differences between the 4 different atlases.

Results: The mean STN volume of the study cohort was 153.3 ± 40.3 mm3 (n = 19). This is similar to the STN volume of the DISTAL atlas (166 mm3; p= 0.22), but significantly larger compared to the other atlases tested in this study. The anatomical overlap of the lead-STN-reconstruction was highest for the DISTAL atlas (0.56 ± 0.18) and lowest for the PD25 atlas (0.34 ± 0.17). A total number of 47 MER trajectories through the STN were analysed. There was a statistically significant discrepancy of the electrophysiogical STN activity compared to the reconstructed STN of all four atlases (p < 0.0001).

 

Conclusion: Lead reconstruction after normalisation into the MNI template space and application of four different atlases led to different results in terms of the DBS lead position relative to the STN. Based on electrophysiological and imaging data, the DISTAL atlas led to the most accurate display of the reconstructed DBS lead relative to the DISTAL-based STN.

Andreas NOWACKI, Anh Khoa NGUYEN (Bern, SWITZERLAND), Ines DEBOVE, Katrin PETERMANN, Gerd TINKHAUSER, Roland WIEST, Claudio POLLO
18:40 - 18:45 #16288 - O088 Using 21st century tools to rebuild Talairach atlas.
O088 Using 21st century tools to rebuild Talairach atlas.

Introduction

Stereotactic surgery, specially deep brain surgery, is expanding its field in recent years, but targets in use are, in many cases, not visualized completely with MRI. Indirect targeting with atlas based stereotactic coordinates is still a valid tool nowadays. Those atlases were built, in a large majority of cases, with single or multiple hemispheres that have been cut in one of the orthogonal planes, perpendicular or parallel to AC-PC line. With different specimens, atlases cannot give the correct position between different orthogonal planes.

We present a new pipeline to build a volumetric atlas from cryomicrotome slices.

Method

Human brains are scanned on a 1,5T MRI after formaldehyde fixation during at least 1 month. Using external landmarks from the brains, blocks are created containing the most important deep structures with cuts oriented parallel or perpendicular to AC-PC line. The blocks are then embedded in OCT compound, frozen at -20ºC and then cut with 50 μm slices. Orthogonal high-resolution photos are taken from a fixed position after removal of each slice. The photos are then aligned to correct some translational deviation using a MATLAB algorithm and a stack is built using ImageJ. Voxel dimensions are introduced, and the stack is then transferred to 3D Slicer where it can be reoriented to align slices to AC-PC line. Two independent observers measure different structures both on MRI and on volumetric block to look for distortions.

Results

The block obtained has a voxel size of 0,046 x 0,046 x 0,05 mm. The measures taken between MRI, physical block and volumetric block were very similar. The boundaries between gray and white matter are clearly seen in all orthogonal planes which allow us to delineate some structures like the anterior nucleus of thalamus, mamillothalamic tract, mamillary bodies, striatum and fornix. This delineation is used to build 3D objects and to measure distances. 

Conclusions

With this pipeline created, it will be possible to improve the accuracy of classic atlases. This work was started to study the anterior nucleus of thalamus, a promising target for epilepsy surgery, but it can be used to improve our knowledge of many other deep structures and to improve planning of stereotactic surgery.

Alexandre RAINHA CAMPOS (Lisbon, PORTUGAL), Lia NETO, Sara FERREIRA, Guilherme VILHAIS, Pedro HENRIQUES, António GONÇALVES-FERREIRA
18:45 - 18:50 #16303 - O089 Magnetic resonance fingerprinting for target identification in deep brain stimulation.
O089 Magnetic resonance fingerprinting for target identification in deep brain stimulation.

Traditional MRI acquisitions are restricted to qualitative “weighted” measurements of tissue properties where the signal intensities are dependent upon many factors, including the type and set-up of the scanner.  Magnetic Resonance Fingerprinting (MRF) is a revolutionary new approach to collecting and analyzing MRI data that permits simultaneous quantification of multiple tissue properties (e.g. T1 and T2).  MRF uses a pseudorandomized acquisition that causes the signals from different materials or tissues to have a unique signal evolution or ‘fingerprint’ that is simultaneously a function of the multiple material properties under investigation.  MRF processing after acquisition involves a pattern recognition algorithm to match the fingerprints to a predefined dictionary of predicted signal evolutions that are derived directly from the Bloch equations.  These results can then be translated into quantitative maps of the magnetic parameters of interest.  We used MRF in a Siemens 3T scanner to collect a fully quantitative 3D image of a whole human brain within a Leksell Vantage MRI compatible stereotactic frame.  T1, T2, and proton density maps were created at 1.2 mm isotropic resolution.  Basic tissue clusters were then calculated using k-means analysis and used to segment anatomical structures within the subthalamic region.  The whole brain MRF scan time was less than 12 min, including a B1 mapping scan to correct for inhomogeneity, making acquisition of these quantitative MRI measurements clinically plausible.  MRF represents a new imaging tool that can quantitatively standardize MRI-based tissue segmentation and surgical target identification.

Dan MA, Angela NOECKER, Mark GRISWOLD, Cameron MCINTYRE (Cleveland, USA)
18:50 - 18:55 #16373 - O090 Implementation of intraoperative flat panel (O-arm) CT for stereotactic imaging during DBS procedures.
O090 Implementation of intraoperative flat panel (O-arm) CT for stereotactic imaging during DBS procedures.

Background Optimal lead placement is a critical factor for outcome of DBS procedures and preferably confirmed during surgery. Intraoperative flat panel (O-arm) CT allows for rapid stereotactic imaging and lead localisation. However, it is unknown whether this imaging technique offers sufficient accuracy for stereotactic procedures.

Methods DBS surgery was performed using the Leksell stereotactic G frame. All patients underwent a pre-operative non-stereotactic 3-Tesla MRI, stereotactic 1.5-Tesla MRI, intraoperative stereotactic O-arm CT, intraoperative post implantation O-arm CT and CT scan on the postoperative day. We compared stereotactic coordinates of the anterior commissure (AC), the posterior commissure (PC) line and midline reference (MR) between MRI and O-arm. For bottom electrode contact localisation comparison, stereotactic coordinates of lead tip on postoperative CT coregistered to stereotactic MRI was compared to intraoperative post implantation O-arm CT coregistered to stereotactic O-arm CT.

Results A total of 20 patients were evaluated. The absolute average difference in stereotactic X, Y and Z coordinates of AC, PC and MR was 0.4 ± 0.4 mm, 0.4 ± 0.4 mm and 0.7 ± 0.5 mm. The absolute average difference in stereotactic X, Y and Z coordinates for electrode localisation was 0.4 ± 0.4 mm, 0.4 ± 0.4 mm and 0.7 ± 0.5 mm. Found differences were small enough not to be considered clinically relevant.

Conclusion Stereotactic MRI and O-arm CT show equivalent  accuracy. Intraoperative O-arm CT enables direct start of DBS after stereotactic registration and evaluation of electrode placement. This increases patient comfort and simplifies the neurosurgical workflow during the day of surgery.

Roos HOLEWIJN, Maarten BOT (Amsterdam, THE NETHERLANDS), Pepijn VAN DEN MUNCKHOF, Rick SCHUURMAN
18:55 - 19:00 #16382 - O091 Comparison of intraoperative CT accuracy with postoperative CT scan for DBS lead verification.
O091 Comparison of intraoperative CT accuracy with postoperative CT scan for DBS lead verification.

Background

Accurate lead placement is crucial to maximize efficacy of Deep Brain Stimulation (DBS). 3D imaging for lead verification in the intended target consists of postoperative CT (poCT) or MRI in some centres. For spinal surgery intraoperative CT (iCT; Medtronic O-arm) is an established modality in our center to navigate and instantly verify surgical results. iCT can be used to verify lead localization in DBS surgery and could replace routine postoperative imaging. Before implementation, a validation of (sub)millimetric accuracy of iCT compared to poCT is required.

 

Aim

To verify accuracy of iCT in DBS surgery by determining lead tip coordinates on iCT and to compare results with poCT and preoperative stereotactic targeting.

 

Methods

Between June 2017 and March 2018 26 patients were operated. Stereotactic coordinates for 52 DBS leads could be calculated for iCT and poCT. In all patients the Leksell stereotactic G frame was used, no revision surgery was performed. Lead tip served as reference point. Differences between iCT and poCT were calculated and results were compared to the initial target on preoperative stereotactic MRI. We used absolute differences in X, Y and Z to calculate the Euclidean distance between the chosen reference points for all comparisons.

 

Results

12 patients (46,2%) were male and 14 patients (53,8%) were female. The mean age at time of surgery was 61 years (range 38-75). STN DBS was performed for 21 patients (81%) with Parkinson’s disease (PD); GPi DBS in 4 patients (15%) for dystonia and for 1 patient with PD (4%). Mean difference in Euclidean distance between iCT and poCT was 1.0mm ± 0.5 (SD). Compared to preoperatively determined MRI target, the Euclidean distance for iCT was 3.3mm ± 1.2, and 3.6mm ± 1.2 for poCT. Pairwise comparison of absolute stereotactic coordinates between iCT and poCT only showed for the dorsoventral direction a significant difference (mean 0.4mm ± 0.09 (SEM), P <0.001).

 

Conclusion

Based on these results iCT for DBS surgery can be considered an alternative to routine poCT, our current gold standard. A statistically significant but small difference was only found for the dorsoventral direction. Further research and external validation in other series are needed for confirmation.

Yara WILLEMS, Carel HOFFMANN , Arne MOSCH, Maria Fiorella CONTARINO, Niels VAN DER GAAG (The Hague, THE NETHERLANDS)
WOLFSON HALL B
Friday 28 September
08:30

Friday 28 September

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A31
08:30 - 10:00

Plenary Session 4
Movement Disorders

Moderators: Miroslav GALANDA (Kosice, SLOVAKIA), Alex GREEN (Consultant Neurosurgeon) (Oxford, UK), Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)
08:30 - 08:40 #14471 - O092 Resting-state fMRI relates to clinical response after Vim radiosurgery for essential tremor.
O092 Resting-state fMRI relates to clinical response after Vim radiosurgery for essential tremor.

Introduction: Essential tremor (ET) is the most common movement disorder. Drug-resistant ET can benefit from standard procedures (deep brain stimulation, thalamotomy) or minimally invasive high-intensity focused ultrasound (HIFU) or ventro-intermediate nucleus (Vim) radiosurgery (RS). Resting state fMRI (rs-fMRI) is a non-invasive imaging method acquired in absence of a task. We examined whether rs-fMRI correlates with tremor score on the treated hand (TSTH) improvement 1 year after Vim RS.

Methods: We included 17 consecutive patients treated with left unilateral Vim RS in Marseille, France. Tremor score evaluation and rs-fMRI were acquired at baseline and 1 year after Vim RS. Resting-state data (34 scans) were analyzed without a priori hypothesis, in Lausanne, Switzerland. We used data-driven multivariate analysis (i.e., independent component analysis (Calhoun et al., 2001; Beckmann et al., 2005) to conduct whole-brain analysis without prior assumptions. Statistical investigation was implemented in Statistical Parametric Mapping (London, UK; version 12) as an analysis of variance (Anova) flexible factorial model, on each separate component, by using individual subject-level maps, to take into account time point (pretherapeutic versus 1 year after Vim RS), clinical response (less or equal versus more than 50% improvement of the TSTH), as well as the interactions between. Bonferoni correction was used to deal with number of models (20). We then reported corrected p-values using conventional cluster-level family wise error (FWE) correction. For relevant interconnectivity values, there was no influence of age or disease duration (p>0.05). Based on degree of improvement in TSTH, to consider Vim RS at least as effective as medication, we separated two groups: 1, <= 50% (n=6, 35.3%); 2, > 50% (n=11, 64.7%). They did not differ statistically by age (p=0.86), duration of symptoms (p=0.41) or MR signature volume at 1 year (p=0.06).

Results: We report TSTH improvement correlated with interconnectivity strength between salience network with left claustrum and putamen, as well as between bilateral motor network, frontal eye-fields and left cerebellum lobule VI with right visual association area (pFWE= 0.001; the former also correlated with lesion volume). For this former network, both pretherapeutic interconnectivity, as well as difference between 1 year and baseline, related to TSTH improvement after Vim RS. Furthermore, patients who alleviated less presented negative pretherapeutic interconnectivity (which increased to median positive values one year later), while those who alleviated more, had already positive pretherapeutic values (which decreased to a median of zero one year later) Longitudinal changes in time, between pretherapeutic state and 1 year later, showed additional associations in inter-connectivity strength between right dorsal attention network with ventro-lateral prefrontal cortex and salience network with fusiform gyrus (pFWE<0.001). At the opposite with the results described in the previous visuo-motor network, overall interconnectivity values decreased from slightly positive to the opposite slightly negative values 1 year after Vim RS. Furthermore, patients who alleviated less presented slightly positive pretherapeutic interconnectivity (which decreased to median of slightly negative symmetric, close to zero, one year later), while those who alleviated more, had pretherapeutic negative median values (close to zero, which slightly increased to a median of zero one year later).

Conclusions: Brain interconnectivity measured by resting-state fMRI relates to clinical response after Vim RS. There is a widespread visual network, which responds to Vim RS. Vim RS seems to bring interconnectivity in the visual areas back to normal for all patients, but the ones who had this region more functionally integrated pretherapeutically had much larger benefit. Beside this visual network, a major role is played by motor and attention systems. Inter-connectivity between visual and motor areas is a novel finding, revealing implication in movement sensory guidance. Whether the visual areas should be involved in the surgical targeting in the near future remains an open question. 

Constantin TULEASCA (Pully, SWITZERLAND), Jean RÉGIS, Elena NAJDENOVSKA, Tatiana WITJAS, Nadine GIRARD, Jerome CHAMPOUDRY, Mohamed FAOUZI, Jean-Philippe THIRAN, Meritxell BACH CUADRA, Marc LEVIVIER, Dimitri VAN DE VILLE
08:40 - 08:50 #16190 - O093 A prospective trial of MRIgFUS thalamotomy for ET: 2 year follow-up results.
O093 A prospective trial of MRIgFUS thalamotomy for ET: 2 year follow-up results.

Background: Magnetic resonance (MR) guided focused ultrasound (MRgFUS) has recently been demonstrated to be a safe and effective treatment for patients with medication refractory essential tremor (ET), but the long term durability of the procedure has not yet been evaluated. This study reports the results of MRgFUS thalamotomy for ET at the 2- year follow-up.

Methods: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy (NEJM 375(8):730-9,2016) and evaluated using the clinical rating scale for tremor (CRST). Sixty-three of the patients continued in the open-label extension phase of the study with monitoring for 2 years.

Findings: Mean hand tremor scores improved by 53% at 1 year and by 55% at 2 years (from 19·8±4·9 to 9·0±5·1, mean change in CRST tremor score from baseline to 2 years, 10·8 points; 95% confidence interval, 7·7 to 10·2; p<0·001). Furthermore, the CRST disability score was improved by 64% at 1 year and by 60% at 2 years (from 16·4±4.5 to 6·5±5·0, mean change in the score from baseline to 2 years, 9·9 points; 95% confidence interval, 5·3 to 7·7; p<0·001). Two adverse events that occurred at the time of the original treatment resolved. There were no new delayed complications at 2 years.

Conclusion: MRIgFUS thalamotomy provides a significant and sustained improvement in contralateral tremor for patients with ET and improves their overall quality of life. Latent or delayed complications did not develop after surgery.

Jin CHANG, Rees COSGROVE (Boston, USA), Chang Kyu PARK, Nir LIPSMAN, Michael SCHWARTZ, Pejman GHANOUNI, Jaimie HENDERSON, Ryder GWINN, Travis TIERNEY, Takaomi TAIRA, Andres LOZANO, Howard EISENBERG, Jeff ELIAS
09:10 - 09:20 #14799 - O096 Optimizing stereotactic coordinates of Prelemniscal Radiations as target for the treatment of Parkinson’s disease. II. Individual variations in stereotactic location of fiber components: A probabilistic tractography study.
O096 Optimizing stereotactic coordinates of Prelemniscal Radiations as target for the treatment of Parkinson’s disease. II. Individual variations in stereotactic location of fiber components: A probabilistic tractography study.

Objective. To determine individual variations of Prelemniscal radiations fiber components as target to treat motor symptoms of Parkinson’s disease.

Material and Methods.Fiber composition of Raprl was determined in the two hemispheres of a group of 15 PD patients and 15 controls paired in sex and age, for a total of 60 hemispheres, using 3Tesla Magnetic Resonance imaging (MRI) and probabilistic tractography, Diffusion Weighted Images (DWI) with high angular resolution and constrained spherical deconvolution (CSD). Stereotactic position, regarding AC-PC length and level and midsagittal plane, of fiber tracts for “x”, “y” and “z” was evaluated regarding right and left hemispheres in the same person and among individuals. 

Results.Three fiber components of Raprl were identified with different connectivity: cerebellar-thalamic-cortical, Globus pallidum-peduncle-pontine nucleus and Orbital frontal cortex-mesencephalic. Fiber stereotactic position did not vary between right and left hemisphere in the same person. In contrast, variations of HPC location were significant for all tracts among subjects and more prominent for the orbitofrontal-mesencephalic tract. Such variations can be only determined by probabilistic tractography that could be used for planning electrodes’ trajectories in the future.

Conclusion.Individual optimum target to approach Raprl is better defined by probabilistic tractography. Tractography provides a platform for planning the stereotactic approach and conform volumes for DBS and lesions.

Mauricio ESQUEDA-LIQUIDANO, María Guadalupe GARCÍA-GOMAR, Luis CONCHA, Gustavo AGUADO CARRILLO, Ernesto ROLDÁN-VALADEZ, Francisco VELASCO CAMPOS (MEXICO, MEXICO)
09:20 - 09:30 #16170 - O097 INTREPID: a prospective, double blinded, multicenter randomized controlled trial evaluating deep brain stimulation with a new multiple source, constant current rechargeable system in parkinson’s disease.
O097 INTREPID: a prospective, double blinded, multicenter randomized controlled trial evaluating deep brain stimulation with a new multiple source, constant current rechargeable system in parkinson’s disease.

Objective: INTREPID is designed to assess the improvement in motor function and quality of life in patients with Parkinson's disease (PD) following Deep Brain Stimulation (DBS) using a new device with multiple independent current sources that allowed for selective activation of individual contacts on the DBS lead thereby permitting a defined distribution of applied current. 365 characters 

Background: Deep Brain Stimulation (DBS) is an effective treatment for the motor signs and fluctuations associated with Parkinson's disease (PD). Although DBS efficacy has been substantiated by several randomized controlled trials (RCT), the degree of improvement varies significantly. The INTREPID Trial assessed improvement in motor function and quality of life in PD patients following bilateral subthalamic nucleus (STN) DBS using a new device with multiple independent current sources that allowed for selective activation of individual contacts on the DBS lead thereby permitting a defined distribution of applied current. 

Methods: INTREPID is a multicenter, prospective, double blinded RCT sponsored by Boston Scientific. Subjects were implanted bilaterally in the STN with a multiple source constant current DBS System (Vercise System). Blinded subjects were randomized to either receive active vs. control settings for a 12 week period. All assessments were completed by a blinded assessor. Following the blinded period, subjects received their best therapeutic settings. Improvement in motor function and quality of life was evaluated using PD diary, UPDRS, PDQ- 39, and a battery of neuropsychological assessments. Adverse events were recorded. 

Results: The study successfully met the primary endpoint (p < 0.001) with a mean difference of 3.03 ± 4.2 hours from baseline to 12 weeks between the active and control groups in ON time (PD diary), with no increase in antiparkinsonian medications. The study also met several of the secondary endpoints. The incidence of infection was 2.7% and peri-operative intracranial hemorrhage was 1%. 

Conclusions: The results of the INTREPID Trial demonstrate that the use of a multiple source, constant-current DBS System is safe and effective in the treatment of Parkinson's disease symptoms. 

Jerrold VITEK (Minneapolis, USA), Intrepid STUDY GROUP, Roshini JAIN, Lilly CHEN, Philip A. STARR
09:30 - 09:40 #16307 - O098 Has deep brain stimulation changed the natural history of Parkinson’s disease? A case control longitudinal study.
O098 Has deep brain stimulation changed the natural history of Parkinson’s disease? A case control longitudinal study.

Introduction

Deep brain stimulation (DBS) is often regarded as the second therapeutic breakthrough after L-Dopa in the history of Parkinson’s disease (PD) therapies. However, the impact of DBS on the long-term course of PD has not yet been evaluated in a controlled manner.

 

Methods

We collected retrospective information on key disease milestones (recurrent falls, psychosis, dementia, and nursing-home placement) and death from clinical notes of PD patients treated with chronic subthalamic DBS >10 years (1999–2007) at our centre. A control group of PD patients similar in age at onset and age at baseline was extracted from a registry study (EuroPa) performed in 2003/2004 with corresponding retrospective data collection on long-term outcomes. Cox regression models were used to calculate hazard ratios (HR), adjusted for potential confounding variables.

 

Results

Fifty-four patients with DBS and 54 patients without DBS at baseline were included. Groups were not significantly different with respect to age at onset, age at baseline, sex-distribution, and number of comorbidities at baseline. Compared to patients without DBS, patients treated with DBS were at lower risk of recurrent falls (HR=0.6; p=0.035) and of psychosis (HR=0.4; p=0.031). There was no significant difference in risk for dementia (HR=1.2, p=0.67), nursing home placement (HR=0.6; p=0.26), or death (HR=1.1; p=0.73).

 

Conclusion

Treatment with chronic subthalamic DBS was associated with longer intervals to recurrent falls and onset of psychotic symptoms. There was no evidence for beneficial effects of DBS on the long-term evolution of dementia, need for nursing home placement, or on overall survival.

Philipp MAHLKNECHT (Innsbruck, AUSTRIA), Marina PEBALL, Katherina MAIR, Mario WERKMANN, Michael NOCKER, Elisabeth WOLF, Wilhelm EISNER, Cecilia PERALTA, Sabine ESCHLBÖCK, Gregor WENNING, Peter WILLEIT, Klaus SEPPI, Werner POEWE
09:40 - 09:50 #16374 - O099 Deep brain stimulation for Parkinson’s Disease: refining the optimal location within the subthalamic nucleus.
O099 Deep brain stimulation for Parkinson’s Disease: refining the optimal location within the subthalamic nucleus.

Background: Individual motor improvement after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson’s disease varies considerably. Recently the medial STN border proved superior compared to MCP as anatomical reference for correlation of DBS location and motor improvement, and enabled defining an optimal DBS location within the nucleus. In order to confirm the superiority of the medial STN border as anatomical reference we again evaluated this new anatomical reference in a recent cohort of patients at our institution.

Methods: Motor improvement after six months of 74 STN DBS electrodes was categorized into non-responding, responding and optimally responding body-sides. Stereotactic coordinates of optimal electrode contacts relative to both medial STN border and MCP served to define theoretic DBS ‘hotspots’.

Results: Using the medial STN border as reference, significant negative correlation (Pearson -0.27, p < 0.02)  was found between the Euclidean distance from the centre of stimulation to this DBS hotspot and motor improvement. This hotspot was located at 2.4 mm lateral, 0.7 mm anterior and 1.5 mm superior relative to the medial STN border. Using MCP as reference, no correlation was found.

Conclusion: This is a second, larger, cohort of Parkinson’s disease who underwent STN DBS in which the medial STN border proved superior compared to MCP as anatomical reference for correlation of DBS location and motor improvement. The percentage of optimally responding body-sides (39%) in current cohort enabled further refinement of the optimal DBS location. Implementing the optimal point of location in our DBS workflow has possibly contributed to more optimal, and thus less variable, motor improvement for individual PD patients following STN DBS.

Maarten BOT (Amsterdam, THE NETHERLANDS), Rick SCHUURMAN, Rob DE BIE, Vincent ODEKERKEN, Pepijn VAN DEN MUNCKHOF
09:50 - 10:00 Discussion.
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Plenary Session 5
Surgery for Depression

Moderators: Benjamin GREENBERG (USA), Marwan HARIZ (London, UK), Andres LOZANO (Chairman of Neurosurgery, University of Toronto) (Toronto, CANADA)
10:30 - 10:50 Genetic and Functional Architecture of Mood Disorders. Andrew MCINTOSH (Professor of Biological Psychiatry) (Edinburgh, UK)
10:50 - 11:10 DBS for depression. Volker COENEN (Head of Department) (Freiburg, GERMANY)
11:10 - 11:30 Stereotactic ablation (capsulotomy & cingulotomy) for depression. David CHRISTMAS (Consultant Psychiatrist) (Dundee, Scotland, UK)
11:30 - 11:50 The psychiatrist perspective on surgical results for depression. Keith MATTHEWS (Professor) (Dundee, UK)
11:50 - 12:00 #16347 - O100 Retrospective and prospective evaluation of tractography for bilateral anterior capsulotomy in patients with depression.
O100 Retrospective and prospective evaluation of tractography for bilateral anterior capsulotomy in patients with depression.

Introduction: Bilateral anterior capsulotomy (BAC) is an effective surgical procedure for patients with treatment-resistant major depression. The anterior limb of the internal capsule (ALIC) carries circuits associated with emotion and neurocognition. We analyzed the connectivity of the BAC lesions to identify ‘fingerprints’ associated with clinical outcomes. We also analyzed the feasibility of tractography to guide the selective ablation (or preservation) of pathways within the ALIC.

Methods: Ten patients were retrospectively analyzed following BAC surgery. These patients were divided into ‘responders’ or ‘partial responders’ based on the Beck Depression Inventory (BDI) score at one-year follow-up. These patients were matched with ten subjects obtained from a neuroimaging sample connectome. The lesions were segmented and transferred to the native space of the matched subjects to generate group-averaged probabilistic ‘fingerprints’ associated with a given outcome. We also generated the major fibers going through the ALIC (mesocorticolimbic , anterior thalamic radiations [ATR], limbic, and associative) and analyzed if the overlap of the lesions with either of these pathways were associated with outcome. Two patients, one patient with TRD and the other with treatment resistant obsessive compulsive disorder (TROCD) and co-morbid depression were treated with tractography guided capsulotomy of the limbic pathways as a proof of concept analysis.

Results: Six patients were responders (> 50% improvement in BDI) and four patients were partial responders (25-50% improvement). The responder map showed significant connections with limbic areas including ventromedial prefrontal cortex, anterior cingulate cortex, and lateral orbitofrontal cortex. The partial responder map showed significant connections with the same limbic areas and also significant stronger connectivity to associative areas including the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, and lateral orbitofrontal cortex. The overlap analysis showed that in the responder group, the involvement of the associative pathways was significantly less than the limbic pathways (p=.00). Conversely, in the partial responder group, there was no significant difference between the involvement of these pathways (p=.16). Finally, there was no significant difference in the involvement of the mesocorticolimbic tracts compared to the ATR in the two outcome groups (p=.17, p=.47). The two patients treated with tractography-guided ablation of the limbic pathways were responders after six months and no neurocognitive side effects were present after surgery. The tractography analysis showed the preservation of the associative pathways and interruption of the limbic pathways.

Conclusions: The optimum outcome following BAC surgery in this cohort was associated with interruption of key limbic areas and the relative preservation of associative pathways. Tractography is able to show patient-specific regional difference between associative and limbic pathways within the ALIC. This information is useful to identify the pathways that need to be destroyed or preserved during capsulotomy. Tractography-guided limbic capsulotomy has demonstrated to be safe and feasible and will be evaluated for long term results in patients with depression.  

Josue AVECILLAS-CHASIN, Trevor HURWITZ, Christopher HONEY (Vancouver, CANADA)
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INDUSTRY LUNCH WORKSHOP

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Plenary Session 6
Pain Surgery

Moderators: Jonathan HYAM (Consultant) (London, UK), Roman LISCAK (head) (PRAGUE, CZECH REPUBLIC), Angelo FRANZINI (MILANO, ITALY)
13:30 - 13:45 Cluster Headache & Migraine. Angelo FRANZINI (MILANO, ITALY)
13:45 - 14:00 Cortical stimulation. Patrick MERTENS (Head of the department) (LYON, FRANCE), Andrei BRINZEU (MD) (Lyon, FRANCE)
14:00 - 14:15 Update on neurosurgery for chronic pain. Tipu AZIZ (Professor) (Oxford, UK)
14:15 - 14:25 #16338 - O101 Long-term Experience with Occipital and Supraorbital Nerve Stimulation for the Various Headache Disorders – an Institutional Case Series.
O101 Long-term Experience with Occipital and Supraorbital Nerve Stimulation for the Various Headache Disorders – an Institutional Case Series.

Long-term Experience with Occipital and Supraorbital Nerve Stimulation for the Various Headache Disorders – an Institutional Case Series.

 

Mahmoud Abdallat1,3, MD

Holger Joswig1, MD, FMH

Vahagn Karapetyan1, MD

Keith W. MacDougall1, MD, FRCSC

Paul E. Cooper2, MD, FRCPC

Andrew G. Parrent1, MD, FRCSC

 

1Department of Clinical Neurological Sciences, Division of Neurosurgery, London Health Sciences Centre, University Hospital, London ON, Canada

2Department of Clinical Neurological Sciences, Division of Neurology, London Health Sciences Centre, University Hospital, London ON, Canada

3Hannover Medical School, Department of Neurosurgery, Hannover, Germany 

Objectives: To assess whether occipital and supraorbital nerve stimulation (ONS; SONS) for the various headache disorders results in clinically meaningful long-term pain alleviation.

Materials and Methods:Retrospective chart analysis of a cohort of 90 patients (age 47.2±12.3 years, 57.8% female) suffering from migraine, cervicogenic headache, cluster headache, neuropathic pain of the scalp, tension-type headache and new daily persistent headache, with a pain course of headache of 13.4±14.1 years and a HIT-6 score of 64.4±7.6 undergoing ONS (58.9%), SONS (12.2%), or a combined ONS + SONS (28.9%) stage 1 (trial) and stage 2 (definite implantation) between 2007 and 2017. Relative change in visual analog scale (VAS) pain was displayed graphically over time and significances tested using the t-test.

Results:57 out of 90 patients (63.3%) were treatment-responders to a stage 1 trial lasting 22.1±9.4 days, with reduction of their average VAS pain to 35.8±24.8% of baseline (non-responders 99.1±24.1% during the trial; p<0.01). Stage 1 percutaneous lead implantation took 27±15.8 minutes and exposed the patients to 235.1±188.1 rad*cm2. Following stage 2 (75.8±33.8 minutes surgery time; 170±116.8 rad*cm2radiation exposure), average VAS pain remained <50% of baseline on long-term follow-up for up to 10 years. 2 patients (3.5%) requested hardware explantation because of lack of treatment effect. Stage 2 complications were 1 infection (1.8%) and 4 electrode dislocations (7%).

Conclusions: After careful patient selection, based on a positive response to a stage 1 trial ONS / SONS, a clinically meaningful long-term benefit can be achieved in chronic headaches patients who had failed medical management.

Mahmoud ABDALLAT (Amman, JORDAN)
14:25 - 14:35 #14474 - O101b Trigeminal ultrasonic nucleotractotomy for treatment of deafferentation facial pain.
O101b Trigeminal ultrasonic nucleotractotomy for treatment of deafferentation facial pain.

Introduction. The deafferentation facial pain syndrome, caused by various lesions of the trigeminal sensory root is a severe pathological condition leading to patients’ disability if not controlled. Many ablative procedures at the level of trigeminal descending tract and spinal trigeminal nucleus developed for the treatment of neuropathic facial pain including open tractotomy, percutaneous stereotactic nucleotractotomy, open caudalis dorsal root entry zone lesions and pontine stereotactic trigeminal nucleotractotomy. The major indications to trigeminal nucleotractotomy at this moment are following: tumours and trauma of peripheral branches of V CN, tumours and trauma of the root of V CN (anesthesia dolorosa), post-herpetic neuralgia, cluster headache and sometimes – failed surgery for trigeminal neuralgia and glossopharyngeal neuralgia. We present our results of ultrasonic trigeminal nucleotractotomy in 50 patients suffering from deafferentation facial pain.

Method. 50 patients suffering from neuropathic facial pain underwent ultrasonic trigeminal nucleotractotomy between the 1987 – 2018.  33 patients with deafferentation pain due to various mechanical lesion of trigeminal nerve or herpes infection, 14 with migraine-induced neuralgia and 3 with trigeminal neuralgia due to multiple sclerosis. All patients experienced the painful dysaesthesias and intractable pain located in the face and oral cavity. The sensation was described as a throbbing, burning pain in half of the face with anesthesia at the same side with no effect from medication. All procedures were done in the sitting position under the general anesthesia. After small unilateral occipital craniectomy and CI hemilaminectomy on the pain side dura was cut. Vertical lesion of the trigeminal nucleus caudalis and spinal trigeminal tract performed by ultrasonic microsurgical needle along the line between the C 2 dorsal root zone and the point 2 mm dorsally to the lowest rootlet of the vagus nerve, preserving all small vessels along the way (Fig.1). The level of lesion was extended above the obex if pain was located in medial part of face, lower part of face or in oral cavity.

Results. Good immediate results (relief of baseline pain or mild pain requiring no medical therapy) achieved in 48 (96%) patients and poor results in 2 (4%). The usual side-effect – ipsilateral ataxia more prominent in upper limb due to disruption of spinocerebellar tract and posterior column was noted in 12 patients. In vast majority of cases the ataxia was well tolerated and disappeared in few weeks.

Ipsilateral paresis and contralateral hypoesthesia because of damage of corticospinal and spinothalamic tracts was seen in 3 patients. No other neurological symptoms or mortality was seen. Late follow up was available in 40 patients. Good, fair (pain control with medication), and poor results (no control of pain) were preserved in 26, 4, and 10 patients retrospectively.

Conclusions.Trigeminal ultrasonic nucleotractotomy is effective and relatively safe in relieving intractable facial pain in highly selected patients.

 

Andrey SITNIKOV (Moscow, RUSSIA), Yuri GRIGORYAN
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Parallel Session 11
Advance Imaging in Functional NS benefit & limitations of each

Moderators: Alexandre CAMPOS (Neurosurgeon - Consultant) (Lisbon, PORTUGAL), Julian EVANS (Manchester, UK), Sameer SHETH (Associate Professor of Neurosurgery) (Houston, USA)
15:00 - 15:15 Tractography for Capsulotomy. Sameer SHETH (Associate Professor of Neurosurgery) (Houston, USA)
15:15 - 15:30 Structural connectivity. Harith AKRAM (Neurosurgeon) (London, UK)
15:45 - 15:55 #16311 - O102 Holographic visualization of deep brain stimulation.
O102 Holographic visualization of deep brain stimulation.

Stereotactic neurosurgery for the placement of deep brain stimulation (DBS) electrodes is an inherently complex 3D problem.  Unfortunately, traditional tools to visualize stereotactic frame adjustments on the electrode trajectory or the electrode placement within the patient-specific neuroanatomy typically rely on 2D computer screens that require substantial degrees of imagination to resolve into a 3D understanding.  Neurosurgeons currently overcome these limitations via experience and mental visualization; however, augmented reality (a.k.a. mixed reality) provides a new medium to work with patient-specific data in a context that directly mimics the surgical environment.  Therefore, we adapted our academic neurosurgical navigation software tool, StimVision, to run within the Microsoft HoloLens platform.  Importantly, this is not virtual reality (VR), where the user is isolated in a completely artificial space.  This is augmented reality (AR), where the holograms are visible in addition to the real world and real people surrounding the model.  Our StimVision HoloLens application is capable of reading in patient imaging data, defining the stereotactic coordinate system, visualizing adjustments to the frame system, enabling interactive positioning of DBS electrodes, integrating tractographic representations of axonal pathways, and predicting the direct activation of the axonal pathways as a function of the stimulation parameter settings.  This final step is accomplished with simulations that couple DBS electric field calculations with multi-compartment cable models to predict action potential generation in the various axonal pathways as a function of the patient-specific electrode location (arc angle, ring angle, X, Y, Z position) and stimulation parameter settings (contact, pulse width, amplitude, frequency).  As such, StimVision HoloLens provides an AR DBS platform that improves the visualization and quantification of clinical therapy, all within a novel teaching environment for neurosurgical training.

Mikkel PETERSEN, Angela NOECKER, Jeff MLAKER, Mark GRISWOLD, Cameron MCINTYRE (Cleveland, USA)
15:55 - 16:08 #16319 - O103 Geometric distortions in stereotactic MR brain imaging: acquisition center sensibility and constructor distortion filtering.
O103 Geometric distortions in stereotactic MR brain imaging: acquisition center sensibility and constructor distortion filtering.

1. Introduction

Stereotactic surgery is a well-established treatment approach for both Deep Brain Stimulation (DBS) and Gamma Knife radiosurgery (GK RS). MRI-based targeting in DBS and in GK RS is a critical issue, as it aims at both providing convenient contrast to see the targets and insure non-distorted images in a clinically acceptable time. Thus, evaluation of geometric distortions in clinical MRI systems is crucial for pre-operative targeting planning.

Sources of distortions can be due to the magnet itself, to the MR sequence or to the patient. Geometric distortions come from different factors: 1) gradient non-linearity (magnet), 2) inhomogeneity of magnetic field (magnet and sequence) 3) magnetic susceptibility and chemical shift (sequence and patient). Several aspects have already been well studied in the litterature [1,2,3], but some work remains to be done.

In this study, we will use a geometric phantom and we will focus on 3D anatomical T1-weighted images used for targeting on 1.5T GE and 3T Siemens magnets. Our aim will be to evaluate how the laser positioning (used to center the object in the tunnel) influences the distortion field. In practice, we will study the distortion field as a distance to the magnet center by changing the laser position on the head coil, and evaluate the errors.

And as MR constructors include distortions-correction filters to reduce gradient non-linearities on a number of sequences, we will also evaluate these errors on corrected images, allowing  to quantify the effect of these filters.

2.  Material and Methods

We used the GRID 3D phantom (MODUS QA Inc.), a rectilinear grid (10 mm spacing) of 140 x 130 x 110 mm3, filled with acrylic plates, a solution of copper sulphate and deionized water.

We acquired FSPGR (GE Optima MR 450W, 1.5T) and MP2RAGE (SIEMENS Skyra, 3T) images, twice. First, the laser was centered relative to the phantom, second it was positioned on the superior part (approximately 55 mm) of it .The acquisitions were done with and without distortions-correction filters provided by GE and Siemens (see Table 1).

An in-house Python-based module was developed and implemented in 3D Slicer [4] for the automatic assessment of geometric distortions with the phantom. All images were preprocessed by cropping, denoising [5] and resampling to 0.5 mm iso-voxel.

Detection of the intersections was performed by the convolution of the image with a kernel (3D cross with r=3 mm and bars width 1.5 mm [6]). Convolution images were thresholded. A regular grid of control points was then placed, and residual tilts were removed [7]. We could then create the distortion field by calculating vectors between control and measured points. In case of missing measured points, interpolation was applied [8].

3. Results

More than 95 % of 2002 vertex were detected in all acquisitions. Fig. 1 shows the distortion field as a 3D heat map that includes 3 planes where the isocenter is visible. Graphs show errors of phantom points in mm as a function of the radial distance to the iso-center. Scattered points, in blue and red, correspond to,  respectively, the center and superior laser positioning. While the laser marking was on the phantom center, mean error was 0.55 mm (without filter) and 0.42 mm (with filter) for FSPGR, 0.59 mm and 0.41 mm for MP2RAGE. For the superior laser marking, mean error was 0.79 mm and 0.59 mm for FSPGR, 1.48 mm and 0.68 mm for MP2RAGE.

4. Conclusion

Positioning of the object to be imaged is critical in terms of geometric distortions. Centering in the tunnel should definitely be done with respect to the region of the interest when the aim is to accurately target in stereotaxy procedures. Moreover, constructors’ distortions-correction filters helps efficiently to reduce the geometric distortions due to the gradient non-linearities and should be systematically activated.

Acknowledgments

This study was partially supported by General Electric.

References

[1] K Wachowicz et al., Medical Physics, 39.5, 2659-2668, 2012

[2] Weygand et al. , International Journal of Radiation Oncology,95.4 1304-1316, 2016

[3] Baldwin and Lesley N. et al. Medical Physics,34.2, 388-399, 2007

[4] Fedorov, Andriy et al. Magnetic resonance imaging,30.9,1323–1341, 2012

[5] Mirebeau, Jean-Marie et al. arXiv: 1503.00992., 2015

[6] Huang, Ke et al. Physics in Medicine and Biology, 61.2, 774-790, 2016

[7] Besk, McKay et al. IEEE Trans. Pattern Anal. Mach. Intell, 14.2, 239–256,1992

[8] Shepard. ACM ’68 New York, 517-524, 1968



Gizem TEMIZ, Fernando PÉREZ-GARCÍA, Sara FERNÁNDEZ-VIDAL, Catherine JENNY, Marguerite CUTTAT, Romain VALABRÈGUE, Carine KARACHI, Didier DORMONT, Stéphane LEHÉRICY, Nadya PYATIGORSKAYA, Eric BARDINET (PARIS)
16:05 - 16:15 #16333 - O104 Single-subject connectomics with morphometric similarity networks in patients with Parkinson’s disease prior to deep brain stimulation.
O104 Single-subject connectomics with morphometric similarity networks in patients with Parkinson’s disease prior to deep brain stimulation.

Introduction

 

Over the past decade there has been a universal movement within the neuroscience community seeking to describe the brain’s wiring diagram or ‘connectome’. Numerous advances have been made through this endeavour including the understanding that broad rules govern network function over a range of scale, species, and phenotypes. Application to clinical practice however has been made difficult by the requirement for specialist neuroimaging data and the lack of methods for single subject analysis. Recently, Morphometric Similarity Networks (MSN) have been proposed, based upon shared variance in structural features of the grey matter, as a proxy for network connectivity at the single subject level. This study seeks to validate the use of MSNs in clinical practice for the first time in a cohort of patients with Parkinson’s disease prior to deep brain stimulation. The aim was to derive the core connectomic features of these MSNs and quantitatively validate them against universal network features described in the literature.

 

Methods

 

A retrospective cohort study was performed of a consecutive series of patients with Parkinson’s disease due to undergo deep brain stimulation of either the GPi or STN. All patients had 3 Tesla MRI scans with MPRAGE sequences. Cortical surface reconstructions were performed with Freesurfer (v6.0) and parcellated with the Desikan-Killiany 68 node template. Morphometric Similarity Networks were constructed based upon surface area, grey matter thickness, mean curvature, Gaussian curvature, intrinsic curvature, and folding index. Connectome construction was based on statistical dependencies (e.g. Pearson correlation) between network nodes with bootstrap-based thresholding using the false discovery rate. General network features were computed including degree distribution fit and small worldness. Weighted network measures were computed including consensus hubs, optimised modularity, and node versatility. 

 

Results

 

In total 28 participants (17 STN, 11 GPi) met the inclusion criteria (12 female). Mean age was 63 years, mean disease duration was 12 years, and mean follow-up was 11 months. Network features were generally robust to construction methods including methods of statistical dependency and thresholding. Small world features were present throughout (Humphries ~2.0, Latora ~1.8, Telesford 0.2) indicating numerous closely connected local communities interconnected by short-cuts between them, thereby balancing features of both lattice-based and random graphs. A variety of hubs were identified predominantly in higher association cortices, consistent with their role in global network integration and higher cognitive function. Consensus modularity and node versatility were used to define an optimal community partition of the network into approximately 5-10 modules. 

 

Conclusions

 

Single subject structural connectomics in patients with Parkinson’s disease awaiting deep brain stimulation is practical using clinically acquired data and offers realistic network representations or connectomes. Analysis of Morphometric Similarity Networks identifies the quintessential network features of small worldness, higher association area hubs, and distinct community partitions. These described network features are consistent with those described in other networks and connectome over a range of imaging modalities. Additionally, they are robust to variation in the network analysis construction. With these models there is the potential to describe and ultimately predict a range of clinical features not hitherto accessible including for example neuropsychiatric symptoms and higher cognitive function. 

 

Michael HART (Cambridge, UK), Rafael ROMERO-GARCIA, Philip BUTTERY, Robert MORRIS, Jakob SEIDLITZ
16:15 - 16:25 #16401 - O105 Tractography reconstruction of hyperdirect pathway fibers connecting the primary motor cortex to the subthalamic nucleus.
O105 Tractography reconstruction of hyperdirect pathway fibers connecting the primary motor cortex to the subthalamic nucleus.

Introduction Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is an established therapy to relieve motor symptoms in advanced Parkinson’s disease patients. The treatment is likely to affect white matter fibers of the hyperdirect pathway that convey excitatory effects from cortical motor areas to the STN. Recent studies using single tensor deterministic tractography and multi-fiber probabilistic tractography have demonstrated the feasibility of identifying the hyperdirect pathway in diffusion MRI (dMRI) data (1-4). Through the Human Connectome Project (HCP), multi-shell dMRI data have been made available for mapping white matter anatomy at an unprecedented resolution (5). We propose to investigate the use of multi-fiber deterministic tractography in high-resolution HCP data to reconstruct the trajectory of hyperdirect pathway fibers connecting the primary motor cortex to the STN.

Methods We used T1, T2 and dMRI datasets acquired on five HCP subjects (5). The dMRI scans were acquired using single-shot 2D spin-echo multiband EPI sequence using 90 gradient directions, 3 b-values (1,000 s/mm2, 2,000 s/mm2, 3,000 s/mm2), 1.25 mm slice thickness and 1.25 image resolution. For each subject, we used the 3D Slicer open-source software (www.slicer.org) to define regions of interest (ROIs) in the primary motor cortex, internal capsule and STN on the T1 images for tractography purpose. We used an automated atlas-based segmentation approach based on the Yeb Atlas to generate 3D meshes of the STN (6-7), and we post-processed the 3D meshes to integrate anatomical information contained in the dMRI data. A tractography workflow using a multi-compartment model of diffusion and multi-fiber deterministic tractography was used to reconstruct the tracts (8). Fiber tracking was performed with 20 seeds/voxel, step size of 0.5 mm and curvature threshold of 55 degrees. The anatomical accuracy of the reconstructed tracts was evaluated by four neuroanatomical experts using the DTI challenge methodology (http://dti-challenge.org).

Results Hyperdirect pathway fibers connecting the primary motor cortex to the STN were successfully reconstructed in all five subjects (Fig.1). The evaluation of the tracts by neuroanatomical experts demonstrated that the tractography results were in agreement with the expected anatomy.

Conclusion We have demonstrated that multi-fiber deterministic tractography combined with high-resolution multi-shell dMRI data can be used to reconstruct the three-dimensional trajectory of hyperdirect pathway fibers in individual subjects. Advanced tractography techniques combined with cutting-edge dMRI data have the potential to provide novel clinical research tools for personalized white matter mapping in the DBS treatment of Parkinson’s disease.

 

References

1.Chen Y et al. The role of the cortico-subthalamic hyperdirect pathway in Deep Brain Stimulation for the treatment of Parkinson's Disease: A diffusion tensor imaging study. World Neurosurgery 2018. 2.Avecillas-Chasin JM et al. Tractographical model of the cortico-basal ganglia and corticothalamic connections: Improving our understanding of Deep Brain Stimulation. Clin Anat 2016;29(4):481-92.

3.Lambert C et al. Confirmation of functional zones within the human subthalamic nucleus: patterns of connectivity and sub-parcellation using diffusion-weighted imaging. Neuroimage. 2012;60:83-94.

4.Akram H et al. Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson's disease. Neuroimage 2017;158:332-345.

5.David et al. The WU-Minn Human Connectome Project: An overview. NeuroImage 2013;80:62-79.

6.D'Albis T et al. PyDBS: an automated image processing workflow for DBS surgery. Int J Comput Assist Radiol Surg 2015;10(2):117-28.

7.Bardinet E et al. A 3D histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease. J Neurosurgery 2009;110(2), 208–19.

8.Pujol S et al. In vivo Exploration of the connectivity between the subthalamic nucleus and the globus Pallidus in the human Brain using multi-fiber tractography. Front Neuroanat 2017;19;10:119.

Figure. 1 Multi-fiber tractography reconstruction of hyperdirect pathway fibers. The figure shows the trajectory of white matter fibers connecting the primary motor cortex to the STN. An axial T1 image with 3D surface models of the STN (light orange), GPi (dark orange) and GPe (green) are displayed for anatomical reference.

Sonia PUJOL, Ryan CABEEN, Sophie SEBILLE, Jérôme YELNIK, Chantal FRANÇOIS, Sara FERNANDEZ VIDAL, Carine KARACHI, Yulong ZHAO, Pierre JANNIN, Michael HAYES, Ron KIKINIS, Eric BARDINET, G. Rees COSGROVE (, )
16:20 - 16:30 #16159 - O106 Deep brain stimulation: Patient-specific electrical field simulation and tractography.
O106 Deep brain stimulation: Patient-specific electrical field simulation and tractography.

Introduction

Electrical field (EF) simulation is used to evaluate the volume of tissue activated (VTA) for patients undergoing deep brain stimulation (DBS). The aim is to develop a workflow for patient-specific EF simulation which integrates tractography reconstruction of the dentato-rubro-thalamic tract (DRT).

Method

Preoperative diffusion MRI (dMRI) (b=800s/mm2, 32 directions, voxel size=1.75x1.75x2 mm) and stereotactic T2-weighted scans (TR=8000ms, TE=80 ms, voxel size=0.5x0.5x2 mm) using Leksell stereotactic system (Elekta instrument AB, Sweden) were acquired on a patient with essential tremor (ET). The study was approved by the local ethics committee (2012/434-31).

The dMRI data were corrected for eddy current distortion and diffusion models were created with bedpostx (fibres/voxel=2). Probabilistic tractography reconstruction of the DRT was generated using probtrackx2 (FSL v.5.0, FMRIB Analysis Group, University of Oxford, UK). Tracts were seeded in the precentral gyrus (number of samples=5000, curvature threshold=0.2), and the superior cerebellar peduncle and dentate nucleus were used as waypoint masks. Projections to contralateral cerebrum or ipsilateral cerebellum were excluded.

An in-house software ELMA (Ver. 2.4, Dept. of Biomedical Eng., Linköping University, Sweden) was used for intensity-based tissue segmentation of the preoperative T2 images, with a volume of interest of 100x100x42 mm3. The tissues were assigned tabulated conductivity values: grey matter (0.123 S/m), white matter (0.0754 S/m), CSF (2.0 S/m) and blood (0.7 S/m)[1]. SurgiPlan (Elekta instrument AB, Sweden) was used to co-register the preoperative MRI with postoperative CT. From the co-registered images, Leksell coordinates from the artefacts were retrieved and used for positioning the DBS-leads during simulation. A model of the DBS lead was created (6172, Abbott Lab., Il., USA) [2]. The EF was simulated, using the finite element method (Comsol Multiphysics Ver. 5.2, COMSOL AB, Sweden). The workflow was exemplified with the ET patient operated in Zona incerta (Zi). Simulations were performed in ring mode (L: contact 2, R: contact 10, Fig. 1a) and by using each segment of the contacts separately (n = 8). Stimulation parameters were set to: pulse width=60 µs, frequency=140 Hz, amplitude L=1.3mA and R=1.0mA. The rotation of the electrodes within the patient was not known meaning the evaluation from different contact segment is only theoretical. An isolevel of 0.2 V/m, corresponding to axon diameters of approximately 3 µm and larger [3], was used to visualize the VTA together with the generated DRT. The VTA and its expansion was evaluated for all simulations as well as the common volume with the generated DRT.

Result

A workflow for patient-specific EF simulation using tractography reconstruction of the DRT was developed. The generated DRT tracts were passing through Zi and crossed in the lower part of the midbrain (Fig. 1b). The size of the VTA for left side (ring mode and each segment) varied between 55-62 mm3 and for right side 34-37mm3. One segment of the contact will steer the EF and expand VTA further in that direction compared to ring mode. The variation in the common volume of VTA and DRT was higher than the variation of the VTA (L: 18-33 mm3, R: 6-21 mm3). For both sides the highest common volume of VTA and DRT was retrieved using one of the segments.

Conclusion

A first version of a workflow for combined patient-specific EF simulations and tractography reconstructions has been developed. Further work will focus on improvement of the dMRI protocol and refinement of the patient-specific simulation method. As the DRT is being considered as a potential DBS target, this study indicates that the steering electrode could be beneficial in activating as many of the fibres within the tract as possible.

References

[1] M. Åström, L.U. Zrinzo, S. Tisch, E. Tripoliti, M.I. Hariz, K. Wårdell, Method for patient-specific finite element modeling and simulation of deep brain stimulation, Medical & Biological Engineering & Computing 47(1) (2009) 21-28.

[2] F. Alonso, M.A. Latorre, N. Göransson, P. Zsigmond, K. Wårdell, Investigation into Deep Brain Stimulation Lead Designs: A Patient-Specific Simulation Study, Brain Sciences 6(3) (2016) 39.

[3] M. Åström, E. Diczfalusy, H. Martens, K. Wårdell, Relationship between Neural Activation and Electric Field Distribution during Deep Brain Stimulation, IEEE Transactions on Biomedical Engineering 62(2) (2015) 664-672.

Teresa NORDIN (Linköping, SWEDEN), Peter ZSIGMOND, Sonia PUJOL, Carl-Fredrik WESTIN, Karin WÅRDELL
16:30 - 16:35 #16234 - O107 Infusion-enhanced, MRI-guided surgery for deep brain stimulation.
O107 Infusion-enhanced, MRI-guided surgery for deep brain stimulation.

Background.  Image-guided surgery is becoming increasingly utilized in neurosurgery with the availability of intraoperative CT and MRI.  Now neurosurgeons are relying on image-guided technologies for laser interstitial thermal therapy (LITT), focused ultrasound (FUS), deep brain stimulation (DBS) and brain tumor resections.  Since initial clinical observations in patients with edema, we have been developing a technique to enhance the MRI visualization of deep brain structures with convection-enhanced delivery (CED) of CSF.  Preclinical testing in the laboratory suggests feasibility and safety; and has provided the rationale for an FDA-approved clinical trial in eight patients with Parkinson disease (PD).    

Methods.  MRI-guided DBS was planned for patients with PD under general anesthesia.  Target coordinates were first planned based on traditional methods using direct visualization and a stereotactic atlas.  Infusion of 500 microliters of the patients own CSF, obtained from a lumbar puncture, was then performed at 5 microliters / min while obtaining serial MR images.  Following infusion, the target was reassessed based on direct visualization of the target.

Results.  In our first patient, CED of 500 microliters of CSF into the globus pallidus was safe and highlighted the border of the internal nucleus.  The target was adjusted 0.6mm posterior, 1.0mm lateral, and 0.9mm superior - altering the vector in positioning by 1.5mm. 

Conclusion.  The convective infusion of autologous CSF seems safe and improves MRI visualization during deep brain stimulation (DBS) electrode placement.  This could supplant the need for inference from published atlases and potentially improve image-guided DBS surgical outcomes.

Aaron BOND, Tony WANG, W. Jeff ELIAS (Charlottesville, USA)
16:35 - 16:40 #16383 - O108 Probabilistic mapping of the cortical connections of the active contact regions in Vim deep brain stimulation (continuation of the previous study).
O108 Probabilistic mapping of the cortical connections of the active contact regions in Vim deep brain stimulation (continuation of the previous study).

Objective: The ventralis intermedius nucleus (Vim) of the thalamus has been known as a notorious target of stereotactic surgery. At the present, the mechanism of action and connectivity of the Vim and the ventralis oralis posterior (Vop) are still unidentified. The aims of this continuation of the previous study are to collect more information about active contact regions in successfully treated cases. Furthermore, with the calculated and averaged cortical connectivity maps, we probably able to create more usable individual tractography for Vim-DBS targeting. 

Methods: In this recent study all of our 18 patients have suffered from Essential tremor and they have been treated with Vim-DBS (19 operations, 30 leads). In this group, the tremor amplitude reduction reaches 90%. The position of the active contact(s) have been allocated by preoperative MR - postoperative CT fusion, after registration in the MNI152 standard-space. The number of connections of the cortical voxels to the active contact region were calculated by MRIB Software Library with 5000 cycle number.

Results: In our investigation the active contacts are located mainly below the AC-PC plane (MD –1,33mm, SD±1,68). It seems that the active contacts draw a pathway instead of a spherical target volume. The probabilistic classification’s determined motor and premotor thalamus did not contain the Roi of the active contacts. With the utilization of the Harvard-Oxford cortical structural atlas, the frontal projections of the Roi did not correspond to the motor and premotor connections of the thalamus. The connectivity to the supplementary motor cortex and to the medial part of the superior frontal cortex seemed to play more significant role for the efficient stimulation than we previously thought.

Conclusions: In our investigation the drawn tractography is consistent with the published anatomical studies, for example the dentato-rubro-thalamo-cortical pathway, but the pattern of cortical connection reveals that the non-invasive Diffusion tensor imaging (DTI) based thalamus segmentation still needs some modifications to help us for Vim-DBS targeting.

Peter SZLOBODA (Budapest, HUNGARY), Ferenc PONGRACZ, Istvan VALÁLIK
16:40 - 16:55 Image-verified DBS as The Standard of Care. Ludvic ZRINZO (London, UK)
16:55 - 17:00 Discussion.
FESTIVAL THEATRE AUDITORIUM

Friday 28 September

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B38
15:00 - 17:00

Parallel Session 12
Movement Disorder

Moderators: Stephan CHABARDÈS (head of the unit) (GRENOBLE, FRANCE), Claudio POLLO (Deputy Chief Doctor) (Bern, SWITZERLAND), Erlick PEREIRA (Consultant Neurosurgeon) (London, UK), Jordi RUMIA (Coordinator. Adult and Paediatric Functional Neurosurgery Program) (Barcelona, SPAIN)
15:00 - 15:15 Directional electrodes. Stephan CHABARDÈS (head of the unit) (GRENOBLE, FRANCE)
15:15 - 15:20 #14911 - O109 Changes of functional and dysfunctional impulsivities after deep brain stimulation of the subthalamic nucleus : predictive factors and electrodes location.
Changes of functional and dysfunctional impulsivities after deep brain stimulation of the subthalamic nucleus : predictive factors and electrodes location.

Background: Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is routinely proposed to treat Parkinson’s disease (PD) patients with motor fluctuations, its influence on postoperative global impulsivity or impulse control disorders (ICD) is controversial. We studied changes of impulsivity in PD patients treated by DBS-STN, by considering the two dimensions of impulsivity defined by Dickman, namely functional (“physiological”) impulsivity (FI) and dysfunctional (“pathological”) impulsivity (DI).

Methods: We studied retrospectively pre and postoperative data of 33 idiopathic PD patients with levodopa related-motor complications treated by DBS-STN, including UPDRS score, treatment (including dopaminergic agonists intake), cognitive functions (FAB and Mattis scales, apathy inventory), mood (MADRS) and occurrence of ICDs. Impulsivity was assessed using the Dickman scale, who distinguishes two dimensions: the FI that reflects the ability to react quickly when the situation requires it, and the DI who reflects the absence of preliminary reflection in the action, even when the situation requires it. Localization of the stimulating contacts was studied using a deformable histological basal ganglia atlas merged on postoperative MRI. 

Results: Six months after surgery, we observed a significant increase (p<0,001)of DI (mean pre- and post-operative DI scores 9 +/-1,6 and 3,5 +/-2,4) but no change in FI (mean pre- and post-operative FI scores 6,2 +/-2,7 et 5,8 +/-2,6). Factors associated with DI score’s increase >2 were: low preoperative FAB score (p=0,03), high preoperative UPDRS III score (p=0,02) and location of the left electrode in the ventral STN (p=0,012). 

 Conclusion: Our study suggests that DBS-STN might influence differently the two dimensions of impulsivity, by worsening the pathological impulsivity without modifying the physiological impulsivity. Severity of the PD, preoperative impairment of frontal functions and ventral location of the electrode favored worsening of dysfunctional impulsivity. Patients with these contributing factors should beneficiate from a closer psychiatric monitoring. 

Robin KARDOUS, Bruno GIORDANA, Caroline GIORDANA, Michel BORG, Jean Jacques LEMAIRE, Denys FONTAINE (Nice)
15:20 - 15:25 #14952 - O110 The influence of brain atrophy on targeting accuracy and outcome in robot-assisted, guide tube-directed DBS for Parkinson’s Disease.
O110 The influence of brain atrophy on targeting accuracy and outcome in robot-assisted, guide tube-directed DBS for Parkinson’s Disease.

Background

 

Traditionally brain atrophy has been considered a relative contraindication to DBS surgery due to an increased risk of CSF egress, brain shift, targeting error and surgical complications. The aim of this study was to determine the effect of brain atrophy on targeting accuracy and outcome in a cohort of PD patients undergoing DBS surgery using a highly accurate robot-assisted and guide-tube directed method designed to minimised CSF loss and brain shift.

 

Methods

 

All surgical procedures were performed using a robot-assisted guide tube-directed method (Renishaw PLC, Gloucs., UK) with on-table fluoroscopic scanning for image-guided targeting verification (O-arm, Medtronic, MN, USA). The drilling process utilised a 1.8mm diameter drill which was intended to minimise the risk of CSF egress and subsequent brain shift. Guide tubes were inserted using a track dilation technique in order to create a pre-formed track. Brain atrophy was quantified by determining the brain parenchymal fraction (BPF) in 113 consecutive PD patients using the MICO method for segmentation of grey matter, white matter and CSF, with a low BPF reflecting increased brain atrophy. Targeting accuracy was determined by comparing the planned guide tube and stylet position with intra-operative fluoroscopic scans following implantation. Vector, radial and depth targeting errors were determined and correlated with BPF using Matlab software (Mathworks, Cambridge, UK) and Spearman's rank correlation analysis. Clinical outcome data was prospectively collected and BPF correlated with UPDRSIII scores at 6 months following surgery. Brain shift was also quantified in a subgroup of 73 patients by comparing the pre-operative and intra-operative position of blood vessels, and correlated with the degree of brain atrophy.

 

Results

 

Using the MICO method for brain segmentation, the BPF of PD patients within this cohort ranged from 0.53 to 0.89 (mean 0.78). There was a weakly significant correlation between increased brain atrophy and both radial and vector targeting error, with a trend towards greater error in patients with BPF<0.7. However, the maximum vector and radial targeting error was less than 1.6mm in all patients, with a mean error of 0.78mm. There was no correlation between the degree of brain atrophy and percentage change in UPDRSIII scores at 6 months. No correlation could be found between the degree of brain atrophy and intra-operative brain shift (r=0.18). Two patients suffered brain haemorrhages within this cohort – the BPF in one patient was high (0.82) and lower in the second patient (0.67).       

 

Conclusions

 

Using a robot-assisted and guide tube-directed surgical technique designed to minimise CSF egress, targeting remained highly accurate in patients with low BPF and increased brain atrophy, with no correlation found between the degree of atrophy and clinical outcome at 6 months post-operatively. Furthermore, the degree of brain atrophy could not be correlated with intra-operative brain shift in this cohort. Further studies are required to determine whether patients with BPF<0.7 should be counselled for increased risk of targeting error, or whether a “threshold” BPF can be identified which may be used as a selection criterion for patients considered for DBS.  Comparative studies of the effect of brain atrophy on targeting accuracy and outcome when DBS surgery is performed using conventional burr holes with the robot-assisted guide tube-directed method described here are also warranted.

Neil BARUA (Bristol, UK), Mariusz PIETRZYK, Catherine MORAN, Max WOOLLEY, Steven GILL
15:25 - 15:30 #15046 - O111 Bilateral Deep Brain Stimulation in the caudal Zona incerta for Parkinson's disease - 1-year evaluation.
O111 Bilateral Deep Brain Stimulation in the caudal Zona incerta for Parkinson's disease - 1-year evaluation.

Background: Deep brain stimulation (DBS) is an established treatment for advanced Parkinson’s disease (PD). The most commonly used targets are the subthalamic nucleus, the pallidum and the ventrolateral thalamus. The area below the thalamus, known as the posterior subthalamic area (PSA)/caudal Zona incerta (cZi) has been shown to alleviate PD symptoms such as rigidity and tremor, when subjected to ablation or high-frequency stimulation. The published experience is, however, limited and consists to a large part of unilateral procedures in patients with tremor dominant symptoms.

Aim: To evaluate the effect of bilateral cZi-DBS in a group of patients with PD fulfilling the criteria for bilateral STN-DBS.

Method: The patients in this study were previously included in a randomised blinded trial of cZi DBS versus best medical treatment, with a 6 months follow-up (Blomstedt P, Stenmark Persson R, Hariz G, et al. Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson’s disease: a randomised blinded evaluation. JNNP 31 January, 2018; Epub ahead of print). In the present study we analysed the results of surgery for the whole cohort at 6 and 12 month after surgery. Main outcomes were differences in motor symptoms (Unified Parkinson’s Disease Rating Scale, UPDRS-III) and in quality of life (Parkinson’s Disease Questionnaire , PDQ-39) between baseline and follow-ups. The patients were evaluated on/off medication at baseline before surgery and on/off medication, on/off stimulation at 6 and 12 months. Preoperative T2-weighted images was used for intensity-based image segmentation and conductivity assignment (ELMA Version 2.4, Department of biomedical engineering, Linköping University, Sweden) based on tabulated conductivity values resulting in a brain model. Patient-specific electrical field simulation of the brain model will be performed using the finite element method (Comsol Multiphysics Ver 5.2, COMSOL AB, Stockholm, Sweden). Friedman’s test was used for statistical evaluation of non-parametric values and the Wilcoxon signed rank test as a post-hoc analysis. Analysis of variance for repeated measurements was used for continuous variables with the Bonferroni correction method as a post hoc test. A p-value ≤0.05 was considered statistically significant.

Results: 
Fifteen patients (4 females) were included. The mean age at surgery was 58.6±2.5 years. Levodopa-equivalent daily dosage (LEDD) were 1248±685 mg at baseline.  The presented results are means ± standard deviation in off-medication state, unless stated otherwise.  
UPDRS-III scores improved from 37.5±11.2 at baseline to 21.2±6.6 (44%) and 22.7±7.5 (40%) on stimulation at 6 and 12 months, respectively (p≤0.0005). Scores of on versus off stimulation showed  an improvement of 49% at 6 months and 47% at 12 months (p≤0.0001).  
Tremor score improved from 9.4±5.4 at baseline to 0.8±1.1 (92%) and 1.2±1.3 (87%) on stim, at 6 and 12 months after surgery (p≤0.0001). Rigidity scores improved from 7.6±2.7 to 5.4±2.7 (29%) and to 5.5±2.5 (28%) (p≤0.005). Akinesia scores improved from 13.0±5.0 to 9.0±4.3 (31%) at 6 months and 9.9±4.8 (24%) at 12 months (p≤0.01). Axial scores improved by 19% at 6 months (p≤0.02) but were no longer significantly changed at 12 months. For PDQ-39, ADL was improved from 28.1±22.2 to 20.8±19.1 (26%, p≤0.05). Stigma improved from 23.4±19.3 to 11.3±15.9 (52%, p≤0.01).

There were no significant changes concerning dyskinesia scores or LEDD. Mean stimulation parameters were 2.3±0.5 V, 66±12.2 µs and 148±13.4 Hz at 6 months and did not change over time. In relation to the midcommissural point, the active contacts were 11.8±1.2 mm lateral, 6.4±1.4 mm posterior and 1.9±1.7 mm inferior.

 
Discussion: The cZi has been suggested as an alternative target for DBS for tremor, including for PD. In this study there was robust effect at one year on tremor, and moderate on akinesia, as well as improvement in ADL and stigma. At 12 months cZi DBS did not affect axial symptoms, dyskinesia scores or LEDD. The cZi as a target for DBS in PD is an addition to the established targets, allowing perhaps to tailor the surgery to the needs of the individual patients. Further analysis in the project will include evaluation of activation volume in reference to the anatomy. Further longer term studies are needed to determine the role of cZi DBS in the surgical therapeutic armamentarium of PD.


Rasmus STENMARK P. (Umeå, SWEDEN), Teresa NORDIN, Gun-Marie HARIZ, Patric BLOMSTEDT
15:30 - 15:35 #16134 - O112 Fiber-tracts associated with the alleviation of bradykinesia in deep brain stimulation for Parkinson´s disease.
O112 Fiber-tracts associated with the alleviation of bradykinesia in deep brain stimulation for Parkinson´s disease.

Objective

Deep brain stimulation becomes increasingly important in treating the motor symptoms of Parkinson’s disease. To improve target planning in deep brain stimulation, we investigated the connectivity between the stimulated volume and cerebral white matter tracts to find out, which tracts have a positive effect on bradykinesia in Parkinson’s disease.

Methods

This retrospective study was based on 21 patients with Parkinson’s disease who received bilateral deep brain stimulation in the subthalamic nucleus. 18 of these patients initially presented with bradykinesia symptoms existent in 31 hemibodies. Since each lead electrode has four contacts, 124 lead contacts in the associated contralateral brain hemispheres were investigated. The effectiveness in reducing bradykinesia was individually assessed for every lead contact. Furthermore, we performed probabilistic tractography to visualize cerebral fiber-tracts showing connectivity to the stimulated brain volume of each individual electrode contact. Our calculations were carried out using preoperatively acquired diffusion weighted magnetic resonance imaging (64 gradient directions, 12-channel head-coil).

Results

Out of the 124 contacts, 92 (74.2%) showed a reduction of the contralateral bradykinesia symptoms of 50% or more and were therefore considered clinically effective. Clinically effective and ineffective contacts were compared for their connectivity patterns using the computed fiber-tracts. The statistical analysis showed that the effective contacts were significantly (p < 0.05) more often associated with the ipsilateral superior cerebellar peduncle and the ipsilateral dentate nucleus, which partly define the course of the ipsilateral, non-crossing part of the cerebello-thalamo-cortical pathway. Furthermore, the anterolateral fasciculus, the medial forebrain bundle, the zona incerta, the pedunculopontine nucleus and the medial part of the internal capsule’s anterior limb were significantly positively associated. Significant negative correlations existed with the contralateral medial cerebellar peduncle, the central pons and the motor cortex representing the descending cortico-ponto-cerebellar pathway.

Conclusion

A connectivity-based approach may improve target planning in deep brain stimulation. In the case of bradykinesia in Parkinson’s disease, the cortico-cerebellar loop seems to play a key role. Our results showed that a connection to its ascending portion, the ipsilateral cerebello-thalamo-cortical pathway, strongly correlated with the alleviation of bradykinesia, while stimulation of the descending cortico-ponto-cerebellar pathway had no positive influence.

Quirin STROTZER (Regensburg, GERMANY), Judith ANTHOFER, Rupert FALTERMEIER, Alexander BRAWANSKI, Claudia FELLNER, Anton BEER, Juergen SCHLAIER
15:40 - 15:45 #16194 - O114 Are there advantages of dbs on the awake pd patient for the clinical outcome?
O114 Are there advantages of dbs on the awake pd patient for the clinical outcome?

Objective

The need of using multiple trajectories and intraoperative testing in an awake patient during DBS for Parkinson´s disease is discussed controversially. In our department it was done in all cases. We aimed to find out if there is a benefit of such procedure in the clinical outcome.

Methods

We retrospectively analysed all data of patients, who have undergone DBS-surgery for Parkinson`s disease in our department in 2012 and 2014. We recorded the number of microelectrodes, the trajectory of the permanent electrode, the reasons for avoiding the central trajectory and the clinical outcome (UPDRS Part III). The intraoperative effect was defined as the improvement of the rigor estimated in % by a neurologist. The clinical outcome was measured as the difference of the preoperative UPDRS III under L-dopa medication and the postoperative UPDRS III under L-Dopa medication and stimulation. Possible influencing factors on the clinical outcome were estimated with a linear regression model (p<0,05).

Results

In the study period 67 patients were treated with bilateral DBS of the STN because of Parkinson`s disease (134 implantations of permanent electrodes). In 92,88% of the 134 implantations 3 or more trajectories were used for microrecording and intraoperative testing. For implantation of the permanent electrode the central trajectory was used in 58%. In the remaining patients (42%), we used in 56,36% the anterior, in 1,81% the medial and in 41,81% the lateral trajectory. The reason for not using the central trajectory was a better intraoperative effect in 65,38%. Changing the trajectory due to a better intraoperative effect was found to be an independent, significant (p= 0,001) predictor for the clinical outcome with the coefficient factor 8,32 on the right and 9,93 on the left side.

Conclusion

Using multiple trajectories lead to a deviation from the central trajectory in 42 % of the implantations, predominantly due to a better intraoperative effect. This intraoperative testing has turned out to be significantly positively correlated with the clinical outcome (even after controlling for the other variables). This result is in line with the hypothesis that deviating from the central trajectory due to intraoperative testing leads to a better clinical outcome. However, a matched pair analysis between the operation with awake and intubated patients, which would allow to test for a causal relationship, has not been done yet but belongs to our agenda.

Soeren K. HAUCK (Hannover, GERMANY), Steffen PASCHEN, Jan VOGLER, Michael SYNOWITZ, H. Maximilian MEHDORN, Daniela FALK
15:45 - 15:50 #16198 - O115 Bilateral thalamic deep brain stimulation for post-encephalitic movement disorders: A case report.
O115 Bilateral thalamic deep brain stimulation for post-encephalitic movement disorders: A case report.

Introduction: Deep brain stimulation (DBS) is an established treatment for essential tremor, Parkinson’s disease and dystonia. DBS is also effective in several symptomatic movement disorders, yet, its therapeutic effect on post-encephalitic symptoms has been under-reported.

A case description: A 47–year-old man presented with progressive severe axial and limb tremors for 6 months after resolution of his autoimmune encephalitis. On examination, he showed resting, intentional, and task-related tremors in his trunk and bilateral limbs. He also had dysarthria and moderate torticollis to the right side. His preoperative TETRAS scale score was 44. As the tremors being medically refractory, he underwent bilateral ventral intermediate nucleus (Vim) DBS surgery. The coordinates for Vim were 13.5mm lateral and 5.8mm posterior to the midcommissural point on the anterior and posterior commissural plane. Intraoperative microelectrode recording showed tremor cells from 8.4mm to 2.0mm above the target. The DBS electrodes were implanted to the targets to stimulate these recorded points. After an initial DBS programming, postoperative TETRAS scale score improved to 30.5 by ameliorating his tremor. His dysarthria persisted, yet moderate torticollis disappeared.

Discussion: Bilateral Vim DBS can be an effective treatment for severe post-encephalitic movement disorders.

Yusuke NAKAJIMA (Seidocho, Nakagyo-ku, Kyoto-shi, Kyoto, JAPAN), Namiko NISHIDA, Shigeto NAGAO, Akihiko OZAKI, Koichi IWASAKI, Hiroki TODA
15:50 - 15:55 #16199 - O116 Endoscopic third ventriculostomy for parkinsonism due to hydrocephalus caused by aqueductal stenosis after midbrain hemorrhage: A case report.
O116 Endoscopic third ventriculostomy for parkinsonism due to hydrocephalus caused by aqueductal stenosis after midbrain hemorrhage: A case report.

Introduction: Movement disorders related to hydrocephalus are frequently expressed as Parkinsonism, yet anatomical substrates are fairly unclear. We report here a case of post- hemorrhagic aqueductal stenosis and discuss about the origins of symptoms.  

A case description: A 23–year-old man presented with progressive bradykinesia, ataxia and gait disturbance 1.5 months after acute-phase ventricular drainage treatment for left midbrain hemorrhage ruptured into third ventricle. On examination, he showed masked face, vertical gaze palsy and resting, intentional, and task-related 3-4 Hz tremors in his right upper limb. He also had dysarthria and pyramidal tract sign of right side. His preoperative MDS_UPDRS 3 score was 68. MRI showed triventricular hydrocephalus due to edematous obstruction of aqueduct surrounding ruptured hematoma cavity, which was confirmed endoscopically. Dopamine transporter scan showed decreased uptake in left putamen. After third ventriculostomy, both ventriculomegaly and midbrain edema subsided. His symptoms were alleviated, and MDS_UPDRS 3 score improved to 19 at discharge. Dopaminergic agent was precluded due to its adverse effect. He returned to the work within a year, with residual minimum gaze palsy.

Discussion: Hydrocephalic Parkinsonism is composed of complex symptoms according to affected white matter tracts. In this case, pyramidal tract, medial longitudinal fasciculus, dentate-rubro-thalamic tract and nigrostriatal tract were possibly affected by edema, and their dysfunctions were partially reversible.

Namiko NISHIDA (Osaka, JAPAN), Yasunori NAGAI, Naoya YOSHIMOTO, Hirokuni HASHIKATA, Masanori GOTO, Kenichi KOMATSU, Hidemoto SAIKI, Hiroki TODA, Sadayuki MATSUMOTO, Koichi IWASAKI
15:55 - 16:00 #16203 - O117 Correlation between the volume of activated tissue, its overlap with the pyramidal tract, and the intra-operative side effect threshold.
O117 Correlation between the volume of activated tissue, its overlap with the pyramidal tract, and the intra-operative side effect threshold.

Background: The volume of activated tissue (VAT) virtualize the current provide to the DBS lead on brain structures. The objective of the present study was to assess the correlations between the VAT, activation of the corticospinal tract, and the intra-operative side effect (ISE) threshold.

Methods: This double-blind, single-center study was performed between September, 2016, and July, 2017. We identified two groups for statistical analysis: the entire study population, and a subset of patients with additional diffusion tensor imaging (DTI) data for determining the location of the pyramidal tract. We determined the intensity threshold at which the VAT reached the border of the target nucleus (referred to as VATn) and the intensity threshold when the VAT reached the pyramidal tract (referred to as VATndti). In each group of patients, we studied the correlation between the ISE threshold and the VATn or VATndti threshold.

Results: Fifteen patients were included in the study. In both groups, there was a significant correlation between the VAT intensity threshold and the ISE threshold (p=0.018; r=0.31 for VATn in the entire study population). In the subset of patients with valid tractography data, the correlation was stronger (p=0.002; r=0.5 for VATndti).

Conclusion: The present study is the first to show a relationship between the intensity threshold as determined by the use of the VAT and the intra-operative side effect threshold. The correlation between the clinical features and the VAT appear stronger when the model was based on a combination of high-resolution anatomic data and interpretable DTI data.

 

Katia BUNAUX (Amiens), Mélissa TIR, Jean-Marc CONSTANS, Jean-Michel MACRON, Pierre KRYSTKOWIAK, Michel LEFRANC
16:00 - 16:05 #16219 - O118 Pallidotomy and pallidal deep brain stimulation in 2 patients with post-hyperglycaemic chorea-ballism.
O118 Pallidotomy and pallidal deep brain stimulation in 2 patients with post-hyperglycaemic chorea-ballism.

Introduction

Hyperglycaemia has recently gained attention as the second most common cause of chorea-ballism. Although usually a self-restricted movement disorder resolving with glycemic correction, persistent chorea-ballism can be difficult to manage medically.

 

Case report

We report on 2 patients with post-hyperglycaemic chorea-ballism treated surgically.

A 70-year old female initially developed left-dominant chorea-ballism with typical diabetic striatopathic alterations on imaging during a nonketotic hyperglycemic state resulting from unknown type 2 diabetes. Three years later, after spontaneous improvement but not complete resolution of her left-sided chorea-ballism, she developed severe right-sided chorea-ballism following a new hyperglycemic state with improper antidiabetic medication compliance. She underwent a left-sided pallidotomy with immediate benefit and a favorable outcome on both the chorea-ballism and the quality of life after 8 months.

A 64-year old female who developed right-sided chorea-ballism after a hyperglycemic episode due to unknown type 2 diabetes was treated three years later with left pallidal deep brain stimulation (DBS), with good short-term response.

 

Discussion

Although pallidotomies and pallidal DBS have been used to treat hyperkinetic movement disorders for 70 and >20 years respectively, these patients are amongst the first to undergo pallidal RF ablation and DBS in post-hyperglycemic chorea-ballism. Contrary to previous descriptions in post-hyperglycemic and post-stroke chorea-ballism, pallidal neuronal firing rates were similar to those recorded in patients with Parkinson’s disease.

 

Conclusions

We present patients undergoing pallidal RF ablation and DBS for post-hyperglycemic chorea-ballism, with excellent short-term results, suggesting a possible role in medication-refractory cases.

Philippe DE VLOO (Leuven, BELGIUM), Robert DALLAPIAZZA, Darrin LEE, Luka MILOSEVIC, William HUTCHINSON, Alfonso FASANO, Renato MUNHOZ, Anthony LANG, Suneil KALIA, Andres LOZANO
16:05 - 16:10 #16230 - O119 Directional deep brain stimulation of the subthalamic nucleus: towards defining the best directionality and anatomical stimulation site.
O119 Directional deep brain stimulation of the subthalamic nucleus: towards defining the best directionality and anatomical stimulation site.

Background: Directional deep brain stimulation of the subthalamic nucleus for treatment of Parkinson´s disease offers new possibilities of current steering towards clinically effective locations and thereby increasing the therapeutic window. The objective of the current work is to understand the relation between the anatomical stimulation site of directional stimulation and clinical effects.

Methods: Postoperative clinical mapping after 6 months was performed in a prospective, consecutive series of 28 patients. Stimulation effect and side effect thresholds of DBS lead contacts were systematically assessed using the UPDRS motor subscores and compared to baseline in the medication-off state. DBS lead positions and their corresponding volume of tissue activation (VTA) were normalized into the MNI space and integrated into a three-dimensional human brain atlas to construct a stimulation map. Non-parametric statistical tests were applied to test for differences between subgroups.

Results: In 24 of 56 (43%) analysed hemispheres directional stimulation provided a larger therapeutic window compared to omnidirectional stimulation. The mean therapeutic window of the best directional contact was increased by 6.8 ± 60% compared to omnidirectional stimulation whereas it was significantly decreased by 33.2 ± 84% for the worst directional contact (p< 0.001). Clinically effective contacts and their associated VTA projected onto the dorsolateral aspect of the normalized STN. Electrode contacts with a low side effect threshold (< 3.0 mA) projected onto the dorsolateral STN and pointed posterolateral towards the internal capsule.

Conclusion: According to our postoperative mapping results, directional stimulation provides a slightly increased therapeutic window compared to omnidirectional stimulation. The dorsolateral STN seems to be the optimal stimulation site, although stimulation of this subregion is also associated with a low side effect threshold. Follow-up data of chronic stimulation is needed to confirm these preliminary results.

Andreas NOWACKI (Bern, SWITZERLAND), Anh Khoa NGUYEN, Ines DEBOVE, Gerd TINKHAUSER, Katrin PETERMANN, Roland WIEST, Claudio POLLO
16:10 - 16:15 #16275 - O120 Perceived intraoperative stress of movement disorder patients undergoing awake deep brain stimulation surgery.
O120 Perceived intraoperative stress of movement disorder patients undergoing awake deep brain stimulation surgery.

Background: Patients with movement disorders undergoing implantation of deep brain stimulation (DBS) electrodes are typically awake during surgery. Albeit commonly referred to as a highly stressful event, little is hitherto known about how the conscious patient perceives the different stages of awake DBS surgery and which preoperative and perioperative factors shape this intraoperative experience.

Objectives: Here, we set out to identify key factors determining the subjectively perceived intraoperative level of psychological distress in patients with different movement disorders undergoing awake bilateral microelectrode-guided implantation of DBS electrodes at our institution (Department of Neurosurgery, University Medical Center Hamburg-Eppendorf).

Methods: Based on a pre-defined set of constituent surgical phases, patients were asked to report their current level of distress on a verbally administered numerical rating scale from 0 (equal to no stress) to 10 (equal to worst possible stress) throughout the whole surgical procedure. In addition, heart rate and arterial blood pressure were monitored as indices of autonomic stress. A reference group of 67 patients with Parkinson´s disease (PD; mean age, 62 years; mean duration of disease, 12.8 years; average Hoehn & Yahr stage, 2.8) undergoing bilateral DBS of the subthalamic nucleus in the OFF medicated state was compared with 12 essential tremor patients (mean age, 64 years; mean disease duration, 18 years) and 11 dystonia patients (mean age, 56 years; mean disease duration, 15.5 years) undergoing DBS surgery in the ventrointermediate thalamic nucleus and internal globus pallidus, respectively. We employed linear mixed modelling to test for the effects of several preoperative demographic (e.g., gender and age at surgery) and clinical variables (e.g., disease duration and -severity) and perioperative factors (such as surgical phase, duration of surgery, analgosedation) on the dependent variable ‘level of distress’.

Results: Across all patient groups, the average distress score during awake bilateral DBS surgery generally ranged between 4 and 5 on the numerical rating scale from 0 to 10. PD patients reported significantly higher stress levels compared to patients with essential tremor and dystonia (p = 0.012). Subjectively perceived distress levels were critically dependent on surgical phase (p < 0.001), clearly peaking during periods of test stimulation with high frequency (130Hz; pulse width, 60µs). Furthermore, titration of analgosedation with low-dose remifentanil had a significant, time-delayed, effect (p = 0.038). The subjectively perceived distress level did not depend on any other factors including sex, age at surgery, disease duration and duration of surgery (all p > 0.05). The factor ‘disease duration’ was still non-significant (p = 0.081) following separate mixed-effects modelling for the group of parkinsonian patients. However, a median split of the PD sample revealed that patients with longer disease history (>11 years) reported higher distress levels than those with shorter disease duration, presumably paralleling differential motor deterioration following presurgical levodopa withdrawal. Objective stress measures (heart rate, blood pressure) were highly and positively correlated with the reported distress scores.

Conclusions: The verbally administered numerical distress rating scale is a simple and practical tool to monitor the patient´s distress level throughout the course of awake DBS interventions. Our results suggest that distress level is maximal during surgical steps that require the active cooperation of the patient, such as intraoperative test stimulation for unwanted side effects. Furthermore, our results also show that peak stress periods during awake DBS surgery can effectively be countered by careful titration of analgosedation with remifentanil.

Johanna SIEGER, Alessandro GULBERTI, Johannes KOEPPEN, Hans O PINNSCHMIDT, Rainer NITZSCHKE, Miriam SCHAPER, Carsten BUHMANN, Andreas K ENGEL, Anja MEHNERT, Christian GERLOFF, Manfred WESTPHAL, Monika POETTER-NERGER, Wolfgang HAMEL, Christian Ke MOLL, Christian Ke MOLL (Hamburg, GERMANY)
16:15 - 16:20 #16276 - O121 Assessment of directional deep brain stimulation in essential tremor.
O121 Assessment of directional deep brain stimulation in essential tremor.

Background and Objective     

Deep brain stimulation (DBS) applied with directional leads within the ventrolateral thalamus and subthalamic region may lead to differential effects on tremor suppression, and it may alter the threshold for eliciting paraesthesias.

 

Methods         

Nine patients suffering from essential tremor (mean age 68,5 yrs, average disease duration 23 yrs) were implanted uni- (1) or bilaterally (8) with directional leads for deep brain stimulation of the ventrolateral thalamus and subthalamic region. Acute effects elicited by stimulation in different directions via bipolar activation of corresponding segments pointing into the same direction (lower segment = cathode) were assessed intraoperatively. Monopolar review (stimulation with 60 usec, 130 Hz) was performed after postoperative microlesioning effects (mean 240 days) had vanished. This involved clinical ratings of tremor suppression, including quantitative accelorometer measurements, and the assessment of the threshold and intensitiy of paraesthesias. The patients and raters were blinded with regard to the direction of stimulation that was chosen in random order and stimulation amplitude.

 

Results            

None of the patients experienced adverse events related to the surgical procedure or the implanted hardware. All patients exhibited a microlesioning effect and sustained tremor suppression with chronic stimulation. Intraoperative assessments revealed a lower threshold for paraesthesia when stimulation was performed into the posterior (medial and lateral) direction compared to stimulation into the anterior direction. Monopolar review revealed that thresholds for tremor suppression and paraesthesias (all transient) were very variable among patients, and for three electrodes paraesthesia thresholds did not differ between directions. For 73% of the contacts, directional stimulation via segments increased the therapeutic window compared to ring mode stimulation, in particular, if stimulation was applied into the anterior and medial direction. The maximum difference between stimulation amplitudes required for tremor suppression and those eliciting paraesthesias ('therapeutic window') was 2 mA. Based on these assessments, in four patients directional stimulation was commenced and rated superior by the patients at follow-up visits.

Conclusions

The influence of directional DBS on tremor suppression and paraesthesia thresholds is highly variable. Although stimulation in the anterior and medial direction appeared superior in several cases, a uniform pattern among patients could not be observed. Clinical responses may depend on the location of contacts, individual anatomy and biophysical characteristics of directional DBS that required further investigation. 

Miriam SCHAPER (Hamburg, GERMANY), Christian Ke MOLL, Alessandro GULBERTI, Ute HIDDING, Carsten BUHMANN, Andreas Ak ENGEL, Christian GERLOFF, Manfred WESTPHAL, Johannes A KOEPPEN, Monika POETTER-NERGER, Wolfgang HAMEL
16:20 - 16:25 #16287 - O122 Phase resetting mechanism of thalamic oscillatory activity contributes to the generation of the somatosensory evoked potentials in Vim thalamus in patients with essential tremor and Parkinson’s disease.
O122 Phase resetting mechanism of thalamic oscillatory activity contributes to the generation of the somatosensory evoked potentials in Vim thalamus in patients with essential tremor and Parkinson’s disease.

Objectives:

    In the past few years it has become increasingly acknowledged that large scale oscillatory activity in sensorimotor system plays an important role in physiological brain function as well as pathophysiology of neurological disorders. Thalamic oscillations were commonly reported in Parkinson’s disease (PD). On the other hand, previous studies demonstrated median nerve stimulation evoked potentials in the nucleus ventralis intermedius (Vim) of the thalamusin PD patients (Hanajima R et al, 2004). In fact, the Vim is believed to receive kinesthetic projections including muscle afferent projections (Ohye et al., 1989).

    In the first conventional view, the stimulus presentation evokes new event-related neural activity strictly time-locked to the stimulation which is superimposed on the background activity. And response averaging removes background activity (considered to be noise), whose time course is presumed to be independent of median nerve stimulation. Recently, by contrast, SEP features arise from alterations in the dynamics of ongoing neural synchrony generating thalamic LFP. By these accounts, SEP features are produced through stimulus-induced phase resetting of ongoing field potential oscillations, a phenomenon observed in vitro.

    To address this question, we investigated whether reorganization of background thalamic oscillatory activity contributes to the generation of the evoked potentials in Vim thalamus triggered by median nerve stimulationin patients with essential tremor and Parkinson’s disease.

Methods:

    We recorded mediannerve stimulation-elicited somatosensory evoked potentials (SEPs) from the ventralis intermedius (Vim) thalamus with semi-microelectrodes during stereotactic surgery in 10 patients with Parkinson’s disease (n=3) and essential tremor (n=7). Hilbert transform was used to measure the phase of the thalamic oscillatory SEP responses for each frequency band. Then we here calculated the phase-locking factor (PLF) in order to measure the phase correlation of ongoing local field potentials (LFPs) oscillation across trials for given frequency bands in the generation of the SEPs in Vim thalamus. This measure corresponds to the inter-trial coherence, which indexes the degree of phase synchronization of trials relative to stimulus presentation. The PLF measure takes values between 0 (absence of synchronization) and 1 (perfect synchronization) (Strogatz, 2000). 

Results:

    In about two thirds of thalamic SEPs examined, we found phase-locking of γ frequency band comes first in temporal order, and subsequently that of β band, and followed by phase-locking of slower frequency band (θ and α) of ongoing thalamic LFP oscillation across trials.Transition across trials from uniform to packed phase distribution revealed temporal phase reorganization of given rhythms of thalamic LFP oscillation in relation to stimulation. Otherwise, exclusive slower frequency oscillations such as θ and α band were observed at late period in some SEPs, while no obvious higher frequency band appeared at early period. In some of the surrounding LFPs 3mm apart from those of central electrode, exclusive slower frequency oscillations such as θ and α band were observed at late period, while no obvious higher frequency band was present at early period.

Conclusions:

    The identification of a phase-locking in each rhythm of thalamic SEP trials reinforces the contribution of phase resetting model for somatosensory information processing. This may imply that phase resetting of each ongoing LFP rhythm in an appropriate temporal order at least partly participates in thalamic SEP formation. Understanding characteristic transient responses of neuronal populations to external stimulations may provide us with invaluable clues for investigating how the central nervous system such as thalamic nucleus reacts and adapts to the stimulus perturbations. For the therapeutic applications, however, it is a great challenge to design deep brain stimulation (DBS) techniquesas effective as possible.

Katsushige WATANABE (Tokyo, JAPAN), Sumito SATO, Yasushi OKAMURA, Hiromi KAMO, Makoto TANIGUCHI
16:25 - 16:30 #16295 - O123 Investigating the effect of STN-DBS stimulation and different frequencies settings on the acoustic-articulatory features of vowels.
O123 Investigating the effect of STN-DBS stimulation and different frequencies settings on the acoustic-articulatory features of vowels.

Introduction

In Parkinson’s disease (PD) in addition to motor symptoms, nonmotor symptoms and voice and speech disorders can also develop in 90% of PD patients. The aim of our study was to investigate the effects of DBS and different DBS frequencies on speech acoustics of vowels in PD patients.

Methods:

The study included 16 patients who underwent STN-DBS surgery due to PD. The voice recordings for the vowels including [a], [e], [i], and [o] were recorded at frequencies including 230 Hz, 130 Hz, 90 Hz, 60 Hz and off-stimulation. The voice recordings were evaluated by the Praat software and the effects on the first (F1), second (F2), and third formant (F3) frequencies were analyzed.

Results:

A significant difference was found for the F1 value of the vowel [a] at 130 Hz compared to off-stimulation. However, no significant difference was found between the three formant frequencies with regards to the stimulation frequencies and off-stimulation. In addition, though not statistically significant, stimulation at 60 Hz and 230 Hz led to several differences in the formant frequencies of other three vowels (Table-1).

Conclusion:

Our results indicated that STN-DBS stimulation at 130 Hz had a significant positive effect on articulation of [a] compared to off-stimulation. Although there isn’t any statistical significant stimulation at 60 Hz and 230 Hz may also have an effect on the articulation of [e], [i], and [o] but this effect needs to be investigated in future studies with higher numbers of participants.

Atilla YILMAZ (Hatay, TURKEY), Elif Tugba SARAC, Fatma Esen AYDINLI, Mustafa Turgut YILDIZGOREN, Esra OKUYUCU, Mustafa ARAS, Şükrü ORAL, Yurdal SERARSLAN
16:30 - 16:35 #16320 - O124 Outcome of Subthalamic Nucleus deep brain stimulation in Parkinson’s Disease after 15 years.
O124 Outcome of Subthalamic Nucleus deep brain stimulation in Parkinson’s Disease after 15 years.

Background and objectives:

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a proven effective and safe intervention to treat motor symptoms in Parkinson’s disease (PD). Little is known about long-term follow-up (>10 years) after implantation. Our goal is to provide an analysis of motor and cognitive outcome of  PD patients 15 years after surgery for STN-DBS. Additionally, we analysed the burden of the caregiver. To limit the loss to follow-up, patients unable to visit the hospital have been assessed at their homes.

Methods:

In this observational study, we report on the motor/cognitive outcome and caregiver burden in a cohort of 15 PD patients who underwent STN-DBS in the Maastricht University Medical Centre (MUMC+) from January 1999 to December 2003. Motor outcome has been assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) part III and cognition by the Mini-Mental State Examination (MMSE). The caregiver burden was assessed by the Zarit, without assessment before surgery. The UPDRS I and II were used to assess cognition and activities of daily life and the VAS EuroQol (EQ)5D for perception of health.

Results:

Between 1999 and 2003 43 patients were operated of which 15 patients survived follow-up. Motor function (UPDRS III) significantly worsened compared to baseline with antiparkinsonian medication (47.7 vs. 18.3, p=0.005) and was comparable to baseline without antiparkinsonian medication UPDRS III (44.7). Axial symptoms and bradykinesia are most severely affected of all motor symptoms at 15 years after surgery.

At 15 years after surgery, 40% of patients (n=6) met the diagnostic criteria of dementia and PD Mini-mental state examination (MMSE) scores non-significantly declined (baseline 28.0, 15 year FU 22.7). UPDRS II significantly worsened (p<0.01; BWM 10.5, 15 year FU 30.5). UPDRS I significantly declined (p<0.005; BWM 1.46, 15 year FU 6.7)

VAS EQ5D scores were 0.55, EQ-5D scores were 0.43 and 62% (n=8) had signs of mild mood disturbances to severe depression at FU.

A Zarit score above 16, suggestive of clinically significant caregiver burden, was reached by one third (n=5) of caregivers at 15 years after surgery. Mean Zarit scores were 17.9±9.4 and 10±4.9 for caregivers of patients living in their own residence (n=8) and in nursing homes/retirement homes (n=7), respectively, however no significance was found.

Conclusion:

Cognitive and axial symptoms are highly dominating after 15 years of follow-up, whereas tremor and rigidity show less deterioration over time. This has a significant impact on health status, quality of life and caregiver burden.

Lucas Guido WESTERINK (Rotterdam, THE NETHERLANDS), Yasin TEMEL, Linda ACKERMANS, Annelien DUITS
16:35 - 16:40 #16331 - O125 The Impact of Microelectrode Recording on Lead Placement Accuracy During Deep Brain Stimulation Surgery.
O125 The Impact of Microelectrode Recording on Lead Placement Accuracy During Deep Brain Stimulation Surgery.

Introduction

The effect of microelectrode recording (MER) on DBS placement is not well understood.  In order to assess the impact of MER on final DBS lead location in relation to the original anatomical target selected, we compared radial error of DBS lead coordinates in relation to initial target in two groups of hemispheres –Hemispheres whereby the MER resulted in an intentional deviation of DBS placement; versus hemispheres whereby MER did not result in any change in DBS placement location.  

Methods

Hemispheres of patients who underwent DBS surgery with MER at the authors’ institution from 2014-2018 were retrospectively analyzed. Targets consisted of the subthalamic nucleus (STN), ventral intermediate nucleus of the thalamus (VIM), internal globus pallidus (GPi) and zona incerta (ZI). The hemispheres were subdivided into two groups: those in which the initial MER track was chosen for final lead implantation and those where a different track from the initial was chosen. Coordinates of the intended MER-based target and final DBS lead were calculated within the same z-axis plane using intraoperative computed tomography (CT) merged to preoperative magnetic resonance imaging (MRI) studies.  Radial error between MER-based target and final DBS lead was then calculated in both groups and compared using a two-tailed T-test.  

Results

Two hundred forty-seven hemispheres were reviewed (157 STN, 57 VIM, 31 GPi, 2 ZI).  There were 96 hemispheres where the initial MER track was chosen for lead implantation and 151 where a different track was chosen.  Radial error of the DBS lead in hemispheres with lead implantation into the initial MER track was significantly (p<0.05) less than hemispheres where a different track was chosen for lead implantation (0.84±0.07 vs 1.1±0.06 mm).  Radial error broken down by target is shown in Table 1. 

Conclusion

There was a significantly higher radial error of the final DBS lead in hemispheres where a different track from the initial MER track was chosen.  While the difference reached statistical significance, the numerical value of the difference was small.

Ryan KOCHANSKI, Gian PAL, Leo VERHAGEN METMAN, Sepehr SANI (Chicago, USA)
16:40 - 16:45 #16342 - O126 Corticospinal Tract Activation Threshold Varies in Ring versus Segmented Mode Stimulation in DBS Surgery Using Motor Evoked Potential Measurements.
O126 Corticospinal Tract Activation Threshold Varies in Ring versus Segmented Mode Stimulation in DBS Surgery Using Motor Evoked Potential Measurements.

Corticospinal Tract Activation Threshold Varies in Ring versus Segmented Mode Stimulation in DBS Surgery Using Motor Evoked Potential Measurements

Ryan B. Kochanski MD, Jay Shills, PhD, Gian D. Pal MD MS, Leo Verhagen MD PhD, Sepehr Sani MD

Introduction

The introduction of segmented leads in DBS surgery promises to improve current delivery by directing current in an intended direction and perhaps more importantly, by avoiding current activation of undesired local anatomy.  The extent to which segmented stimulation away from the corticospinal tract (CST) allows for increased side effect threshold as compared to stimulation in ring mode is not well studied. 

Methods

CST activation thresholds were evaluated using motor evoked potentials (MEP).  Electrodes were placed in the contralateral muscles of the face and upper extremity for MEP measurements.  Stimulation (unipolar) was delivered by delivering current to inserted DBS leads (20 hemispheres total; 10 STN, 10 VIM) intra-operatively.  Stimulation parameters included activation of each segment of the middle two contacts followed by ring mode stimulation of all four contact while records MEP thresholds and muscle activated. 

Results

MEP thresholds were obtained from all stimulated segments and rings.  In VIM, the segment with highest threshold was noted at current that was on average 1.1mA above that in ring mode.  The abductor pollicis brevis muscle was the first MEP observed.  In STN stimulation, the results were mixed.  Variable muscle MEPs were seen at threshold stimulation.  Segmented stimulation thresholds were variable when compared to ring mode with the difference in current threshold varying between 0.6 to 1.2mA.  A likely explanation is lack of segment alignment directly opposite of CST along with the curved trajectory of CST superior and lateral to STN.

Conclusion

Segmental DBS stimulation leads to mild increase in CST activation threshold in VIM and STN.  Increased thresholds can be variable in STN likely due to imperfect segmental alignment as well as local anatomy of CST.

Ryan KOCHANSKI, Jay SHILLS, Leonard Verhagen METMAN, Sepehr SANI (Chicago, USA)
16:45 - 16:50 #16345 - O127 Activation of pallidofugal and nigrofugal fibers with effective subthalamic nucleus deep brain stimulation for Parkinson’s disease.
O127 Activation of pallidofugal and nigrofugal fibers with effective subthalamic nucleus deep brain stimulation for Parkinson’s disease.

Introduction

Deep brain stimulation of the subthalamic nucleus (STN) is an effective therapy for patients with Parkinson’s disease (PD). Different regions within the subthalamic area have been correlated with optimal clinical outcomes. In this work, we correlate the motor outcome in PD patients with the involvement of nigrofugal and pallidofugal pathways by effective stimulation.

Methods:

Fourty-three patients with STN-DBS were included and their clinical and stimulation parameters were recorded at one-year follow-up. Nigrofugal and pallidofugal pathways were obtained using constrained spherical deconvolution probabilistic tractography with imaging data from 43 PD matched subjects from the Parkinson's Progression Markers Initiative connectome. The volume of activated tissue (VAT) for all patients was modelled using finite element method within the LeadDBS software. All VATs were summed and analyzed using generalized linear models in FSL software to obtain statistically significant stimulation clusters correlated with: greater reduction of dopaminergic medication, improvement in Unified Parkinson's Disease Rating Scale (UPDRS) III, bradykinesia, rigidity, and tremor scores. Finally, we calculated the overlap coefficient of these clusters with the nigrofugal or pallidofugal fibers.  Then, these coefficients were compared with the overlap of the significant clusters with the STN.

Results:

Significant reduction of symptoms was obtained with STN-DBS in our patients (p<.05). Nigrofugal and pallidofugal pathways were traced as described in previous anatomical descriptions. Significant clusters associated with the greatest dopaminergic medication reduction, greatest UPDRS improvement overlapped with the nigrofugal fibers (coeff0.50) but not with the STN. Significant clusters associated with greater bradykinesia improvement overlapped with the nigrofugal fibers (coeff 0.55) and with the STN (coeff 0.19). Finally, significant clusters associated with greater rigidity and tremor improvement overlapped with pallidofugal fibers (coeff 0.60) and not with the STN.

Conclussions:

Electrical field involvement of the nigrofugal fibers, more than the STN, appears to produce the most improvement in UPDRS III, bradykinesia, and the most reduction of dopaminergic medications. Similarly, involvement of the pallidofugal fibers and not the STN was associated with greater tremor and rigidity improvement.

Josue AVECILLAS-CHASIN (Tarragona, SPAIN), Christopher HONEY
16:50 - 16:55 #16355 - O128 Increasing the proportion of rechargeable neurostimulators: Estimated impact on the financial sustainability of a deep brain stimulation program.
O128 Increasing the proportion of rechargeable neurostimulators: Estimated impact on the financial sustainability of a deep brain stimulation program.

Background: Deep brain stimulation (DBS) has been shown to be cost-effective in the treatment of Parkinson's disease. However, it represents a costly burden for national health systems. This situation has been aggravated by the the reduced longevity of newer non-rechargeable batteries, which has led to a rise of battery replacements costs and complications (i.e., device infections), somewhat compromising the sustainability of DBS programs. We hypothesized that investing on rechargeable devices in the short term would result in a reduction of replacements and, hence, of total DBS costs in the middle-to-long term.

Objective: 1) To estimate deep brain stimulation (DBS) material costs for a 6-year-period at our institution considering two scenarios: a conservative one focused on gradual increase of new rechargeable devices; another one with a greater initial investment in rechargeable devices (both new cases and replacements); 2) to compare these estimates to costs of the preceding three years (2014-2016), when devices had higher prices and were mostly non-rechargeable.

Methods: Descriptive analysis of the activity and material costs of DBS at our institution in 2014-2016; estimation of DBS material costs in 2017-2022 based on the aforementioned scenarios; calculation of the shortfall vs. saving resulting from comparison of the different DBS cost estimates to the costs from the 2014-2016 period.

Results: During the 2014-2016 period, the total DBS cost rose from 654.958,14€ in 2014 to 1.023.689,64€ in 2016 (56,30% increase). Regarding the estimates for the 2017-2022 period, the first scenario would benefit initially from devices price-cuts dropping to 907.665,00€ in 2017 (-11,30% compared to 2016, yet +38.58% relative to 2014), but would eventually resume the upwards trend, ending up in 2022 with a total DBS cost of 1.058.541,00€ (+3,40% vs. 2016; +61,62% vs. 2014). Conversely, the second scenario, in spite of greater cost-increase the first 3 years, would eventually lead to a reduction of replacements and subsequently of total DBS costs down to 775.676,00€ in 2022 (-24,03% relative to 2016; only +18,43% compared to 2014).

Conclusion: The cost and saving estimates of increasing the proportion of implanted rechargeable DBS neurostimulators versus primary cell devices (both new cases and replacements) support the notion that this strategy, while costly in the short term, could aid to ensure the sustainability of DBS programs in the long run.

 

References:

[1]         Eggington S, Valldeoriola F, Chaudhuri KR, et al. The cost-effectiveness of deep brain stimulation in combination with best medical therapy, versus best medical therapy alone, in advanced Parkinson's disease. J Neurol 2014; 261: 106-16.

[2]         Pepper J, Zrinzo L, Mirza B, et al. The risk of hardware infection in deep brain stimulation surgery is greater at impulse generator replacement than at the primary procedure. Stereotact Funct Neurosurg 2013; 91: 56-65.

Jordi RUMIÀ (BARCELONA, SPAIN), Yaroslau COMTA, Pedro ROLDAN, Esteban MUÑOZ, Ana CAMARA, Maria José MARTÍ, Francesc VALLDEORIOLA
16:55 - 17:00 #16359 - O129 Effects of spinal cord stimulation on postural control in Parkinson's disease patients with freezing of gait.
O129 Effects of spinal cord stimulation on postural control in Parkinson's disease patients with freezing of gait.

Background:Freezing of gait (FoG) in Parkinson’s disease (PD) is an incapacitating transient phenomenon, followed by continuous postural disorders. Spinal cord stimulation (SCS) is a promising intervention for FoG in patients with PD, however its effects on distinct domains of postural control is not well known.Aim:The aim of this study is to assess the effects of SCS on FoG and distinct domains of postural control. Methods:Four patients with FoG were implanted with SCS systems in the upper thoracic spine. Anticipatory postural adjustment (APA), reactive postural responses, gait and FoG were biomechanically assessed. Results:In general, the results showed that SCS improved FoG and APA. However, SCS failed to improve reactive postural responses. SCS seems to influence cortical motor circuits, involving the supplementary motor area. On the other hand, reactive posture control to external perturbation that mainly relies on neuronal circuitries involving the brainstem and spinal cord, is less influenced by SCS. In this short report we provide data suggesting that SCS may affect important measures in anticipation of gait that decreases the chance of FoG in gait initiation. On the other hand, our data provides evidence that SCS failed to improve reactive balance control. We suggest that SCS has distinct effects on specific postural control domains, which is important to develop and improve neuromodulation-based interventions to treat postural and gait disabilities in PD. 

Legends

Figure 1 – (A) Characterization of FoG based on spectral analysis. Schematic representation of a man representing the lumbar accelerometer as a small black box. The curve represents the vertical acceleration acquired during step initiation. The dotted square shows a 7.5s window for the frequency analysis domain (normal gait in blue and freezing in red). (B) Spectral analysis of acceleration showing one band representing the locomotor period (0 - 3Hz) and the FoG band (3 - 8Hz). (C) FoG index showing the clinical threshold (>2=FoG); FoG index is calculated by dividing the FoG band by the locomotor band (blue circle – power peak of normal gait; red circle – power peak of a period with FoG). (D) Representation of the step initiation task, showing the marker on the malleolus to detect the moment that the foot clears the floor. The sequence showed in D and E (1-4) shows: (1) beginning of the task, when the participant is in quiet standing (body weight balanced under the feet), preceding the step. (2) The red arrow shows body weight shifting toward the supporting leg (APA). (3) Once the body weight is shifted contralaterally, the moving leg can be released to take a step and finish the movement (4). The graphs showed in D and E represent the moment that each phase of the sequence (1-4) occurs: 1-quiet standing; 2- peak of APA; 3- step; 4-end of the movement. The red line represents the mediolateral force under the supporting leg, the dotted line is the displacement of the moving foot. The red line in D represents a defective mediolateral displacement of the body weight (APA), showing a relative smaller amplitude and longer APA compared to a normal APA displayed in E.

Figure 2 – Individual and mean values for % change of the outcome variables: time of gait, time of FoG, time of APA, amplitude of APA and the variables that describes reactive postural control - CoPap amplitude and CoMap amplitude. (A) Individual mean curves of the body mediolateral displacement (APA) - thin lines; and the standard deviation (thick and transparent bands) for each stimulation parameter (OFF – gray, 60 Hz – red, 300 Hz – blue). (B) Graphs showing the individual mean values of % of change for each outcome variable in 60 and 300 Hz relative to the off condition. (C) Mean values and standard deviations of % change for each outcome variable (time of gait, time of FoG, time and amplitude of APA, CoP and CoM amplitude. Asterisks highlight significant effects for 60 and 300 Hz as compared to the off condition.

Daniel Boari COELHO, Carolina DE OLIVEIRA SOUZA (São Paulo, BRAZIL), Erich FONOFF, Clement HAMANI, Dos Santos Ghilardi MARIA GABRIELA, Luis Augusto TEIXEIRA
WOLFSON HALL A

Friday 28 September

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C38
15:00 - 17:00

Parallel Session 13
Animal Models & Basic Science

Moderators: Hagai BERGMAN (Prof) (Jerusalem, ISRAEL), A Holly ROY (UK)
15:00 - 15:15 PPN in monkey. Carine KARACHI (MEDECIN) (PARIS, FRANCE)
15:15 - 15:30 Animal model for Schizophrenia - first steps towards closed-loop DBS treatment. Hagai BERGMAN (Prof) (Jerusalem, ISRAEL)
15:30 - 15:40 #16356 - O130 Higher endogenous alpha-synuclein confers greater disease susceptibility in parkinson’s; clinical-grade alpha-synuclein null human embryonic stem cells may be used to create disease-resistant dopaminergic grafts.
O130 Higher endogenous alpha-synuclein confers greater disease susceptibility in parkinson’s; clinical-grade alpha-synuclein null human embryonic stem cells may be used to create disease-resistant dopaminergic grafts.

Objective

Open-label trials in the 1990s showed that some Parkinson’s disease (PD) patients had marked improvement in motor function following ventral mesencephalic fetal graft transplantation into striatum. However, decades later on autopsy the grafts acquired Lewy pathology, a hallmark of PD, with concomitant loss of graft function. Focus is now moving towards human embryonic or induced pluripotent stem cell-derived grafts to overcome limitations of using fetal tissue, but host-to-graft spread of disease remains a major issue for these future treatments. We developed an in vitro model of disease spread using transgenic human embryonic stem cell (hESC) lines over-expressing alpha-Synuclein, the protein responsible for Lewy pathology. The aim of this work is to investigate the importance of endogenous alpha-Synuclein expression on disease susceptibility and generate disease-resistant dopaminergic grafts to test host-to-graft spread in vivo.

Methods

The Shef4 hESC line was transfected with an expression plasmid containing the human SNCA gene (and CAG promoter) to produce several clonal transgenic lines over-expressing alpha-Synuclein. Of these, the selected S37 and S8 clonal lines expressed eight-fold greater levels of α-synuclein than the parental line. These three transgenic hESC lines and an alpha-Synuclein knockout hESC (RC17) line were differentiated into cortical neurones (also affected by Lewy pathology in PD). These neurones were then seeded with recombinant monomers and pre-formed fibrils (PFFs) of alpha-Synuclein for a week. After a further 3 weeks, the neurones were fixed and stained to detect the expression of phosphorylated alpha-Synuclein at Serine-129 (pSer-129), an early marker of Lewy pathology.

Results

Monomers of alpha-Synuclein did not induce the expression of pSer-129 alpha-Synuclein in any hESC line. PFFs led to the formation of pSer-129 alpha-Synuclein structures in S37, S8 and the control Shef4 line but not in the alpha-Synuclein knockout line. The pSer-129 alpha-Synuclein immunostaining was significantly higher in S37 and S8 relative to Shef4 (p<0.001). Immunostaining was observed as short discrete axonal as well as perinuclear structures resembling Lewy body and neurite formation.

Conclusion

We show that monomeric alpha-Synuclein cannot seed Lewy body-like pathology, whereas PFFs can initiate such pathology in human cortical neurones. This is in agreement with published data on rodent models. We show that higher endogenous expression of alpha-Synuclein confers greater disease susceptibility and conversely the alpha-Synuclein knockout line does not seed any pathology. This work establishes an important human model to study PD and alpha-Synuclein knockout hESC line-derived dopaminergic grafts have been generated to test in vivo. Future experiments will aim to show such grafts can rescue the phenotype in classic lesion models of PD and that they may be resistant to PFF-induced Synucleinopathy.

Funding

Ammar Natalwala is funded by the Wellcome Trust Research Training Fellowship.

Ammar NATALWALA (Edinburgh, UK), Yixi CHEN, Karamjit DOLT, Ratsuda YAPOM, Marco KRIEK, Terry BAKER, Patrick DOWNEY, Tilo KUNATH
15:40 - 15:45 #16140 - O131 Dorsolateral striatal neuronal activity in a rat model of Parkinson`s disease with levodopa-induced dyskinesias.
O131 Dorsolateral striatal neuronal activity in a rat model of Parkinson`s disease with levodopa-induced dyskinesias.

Objective

Striatal inhibitory interneurons are important modulatory components for the direct and indirect pathways of basal ganglia (BG). However, their role in Parkinson's disease (PD) and PD with levodopa induced dyskinesias (LID) remains unclear.

Methods

Single neuron activity and local field potentials (LFPs) were recorded from the dorsolateral striatum (DLStr) together with electrocorticogram (ECoG) from the motor cortex (MCtx) area in 6-hydroxydopamine lesioned hemiparkinsonian (HP) and levodopa-primed dyskinetic (HP-LID) rats as compared to controls. Putative GABAergic interneurons (fast-spiking interneurons, FSIs) and medium spiny neurons (MSNs) were identified based on peak to trough. For the calculation of beta (13-30Hz) and gamma (30-100Hz) bursts the signals were filtered using Blackman bandpass filter and further down sampled to 100 Hz. Hilbert transformation was used to get the envelope and threshold value for burst was set at the 75th percentile of signal amplitude.

Results

The MSNs firing rate was enhanced in HP and HP-LID rats, while firing rate in FSIs were only enhanced in HP-LID rats together with reduced burst activity. The coefficient of variation (measure of firing irregularity) was only higher in HP rats in both MSNs and FSIs, with no difference in HP-LID rats. Only in HP-LID MSNs spike-triggered averaging of LFP were phase locked to beta (12-30 Hz) and gamma (30-100 Hz), while the effect in HP was less pronounced. Further, ECoG oscillatory activity in the beta and gamma burst count was enhanced in both HP and HP-LID rats, however, theta burst was higher only in HP-LID rats.

Conclusion

Our study suggests that there may be a distinct form of MSNs and FSNs firing properties and MCtx burst activity in a rat model of PD with dyskinesias, which may depend on the functional state after dopamine depletion and treatment indicating maladaptive neuroplasticity.

Xingxing JIN, Denny MILAKARA, Kerstin SCHWABE, Joachim K KRAUSS, Mesbah ALAM (Hannover, GERMANY)
15:45 - 15:50 #16149 - O132 Regulation of viral vector gene expression in the hippocampus by medial septal nucleus deep brain stimulation.
O132 Regulation of viral vector gene expression in the hippocampus by medial septal nucleus deep brain stimulation.

Introduction:

Deep brain stimulation (DBS) is a well-established treatment for several neurological diseases; however, the mechanisms by which DBS exerts its effects remain controversial. Electrical stimulation has clear effects on nearby cells but can also affect distant neuronal populations within the same circuitry. This proof-of-principle study aims to examine whether DBS can regulate gene expression from a virally delivered vector by first transducing neurons with an adeno-associated virus containing the gene for a fluorescent reporter protein downstream of a DBS-responsive promoter and then stimulating with DBS from a remote target.

Methods:

Adult Sprague-Dawley rats underwent a unilateral right hippocampal injection of adeno-associated virus serotype 5 containing a DNA construct for green fluorescent protein (GFP) under control of the chicken beta actin promoter and TdTomato (TdT) under control of the c-fos promoter  (AAV5-c-fos). Two weeks later, a stimulating depth electrode was implanted into the medial septal nucleus (MSN). In the first experiment, 1 week after implantation, rodents received no DBS, 7.7 Hz (theta frequency) DBS, or 130 Hz (gamma frequency) DBS for 1 hour, and tissue analysis was performed 1.5 hours after conclusion of stimulation. In the second experiment, rodents received DBS treatment 1 week after implantation followed by another treatment 1 week after the initial treatment with no DBS, 7.7 Hz DBS, or 130 Hz DBS. Fluorescent protein expression levels were analyzed with confocal microscopy to evaluate for spatio-temporal control of the reporter’s expression in the hippocampus.

Results:

In the first experiment, we found that, two weeks after AAV5-c-fos injection, either 1 hour of continuous 7.7 Hz, or 130 Hz MSN stimulation resulted in an increase in TdT reporter expression levels relative to no stimulation. Results from the second experiment demonstrated that TdT levels were no longer increased 1 week later with no additional stimulation, but TdT expression could be induced again with repeat 7.7 Hz or 130 Hz MSN stimulation.

Conclusions:

Here, we demonstrate that viral vector-mediated gene expression can be induced using both low- and high-frequency DBS to a distal target along a circuit. Taken together these data suggest that DBS can regulate gene expression both spatially and temporally. Successful control of gene expression by DBS will warrant further investigation into stimulation responsive promoters for use in clinical applications.

Darrin LEE (Toronto, CANADA), Chris MCKINNON, Mitch DE SNOO, Anton FOMENKO, Eun Jung LEE, Victoria AGAPOVA, Sophie NGANA, Clement HAMANI, Andres LOZANO, Lorraine KALIA, Suneil KALIA
15:50 - 15:55 #16386 - O133 The combination of experimental STN DBS and CDNF in rat model of advanced Parkinson's disease.
O133 The combination of experimental STN DBS and CDNF in rat model of advanced Parkinson's disease.

Although, several therapies are effective against the cardinal motor symptoms of Parkinson’s disease (PD), there are no disease course altering therapies currently available [1]. Several neurotrophic growth factors (NTFs) have been effective in animal models of early PD reducing or partially reversing dopaminergic cell death [2]. However, their effect has been limited in clinical trials [3]. However, most clinical NTF trials have been done in patients who have advanced PD where near total dopaminergic cell death has already happened. STN DBS is accepted therapy in advanced PD and it has shown some neuroprotective potential of its own. 

Aim: To study if CDNF can improve the effect of STN DBS in a model of advanced PD.

Methods:  Unilateral 6-OHDA injections in medial forebrain bundle were used to produce a near total dopaminergic depletion, which was verified with amphetamine induced rotations. 

Short-term STN DBS was modeled with unilateral implantation of STN electrodes combined with either CDNF (n = 15) or PBS (n= 11) injected just above substantia nigra pars compacta. The effect of STN DBS was measured by repeated cylinder tests with no stimulation (baseline) and at two stimulation amplitudes. Biochemical measured with HPLC of dopamine (DA) and DA metabolites at 4 weeks or with TH and dopamine transporter (DAT) IHC (at 7 weeks) (Figure 1A).

Long-term STN DBS was modeled with STN lesions (STNL) done with 10 µg ibotenic Acid (IBOT). Group one received PBS + PBS (n=12), group two received CDNF + PBS (n=11), group three received PBS + IBOT (n= 14), and group four received CDNF + IBOT (n=17). The behavioral effect was measured with repeated cylinder tests and apomorphine-induced rotation tests. The biochemical effect was measured by HPLC (4 weeks) or IHC (7 weeks; Figure 2A)

Results: The use of contralateral front limb increased more at 2 and 3 weeks for CDNF-treated animals compared to PBS-treated animals with both low and high stimulation amplitudes when compared to week 1 baselines (Fig 1B and C, no stimulation U = 2.18, p = 0.029, respectively, for low and high stimulation, Fig 1B-C). The optical density of TH-stained striatum was higher in CDNF + STN HFS co-treated rats compared to contralateral side than in PBS and STN-HFS treated animals, (Fig1 E-C). The DA and DA metabolite levels were similar, Fig 1 H and I. 

Only in the combination of CDNF and STNL the use of contralateral front limb use was higher (Fig 2B -C) and the number of apomorphine induced rotations were lower compared to baseline and double-sham PBS + PBS (Fig 2D). There were now differences in biochemical analysis (Fig2E-H).

Conclusions: We found additive but transient synergistic effect between STN DBS and CDNF in behavioral tests in a model of advanced PD where neurorestorative treatments have usually failed. Although there was no biochemical evidence of neuroprotection, CDNF has been previously reported to provide functional benefits without biochemical effects [4].

There are no previous reports on the combination of DBS and neurotrophic factors. This combinatory effect warrants further studies. Additionally, in human brain STN and SNpc are close and could be reached through single or adjacent trajectories. 

 

Results published in Huotarinen A, Penttinen A-M, Bäck S, et al. Combination of CDNF and Deep Brain Stimulation Decreases Neurological Deficits in Late-stage Model Parkinson's Disease. Neuroscience. 2018;374:250-263. doi:10.1016/j.neuroscience.2018.01.052.

 

 

REFERENCES

 

1.        Kalia LV, Kalia SK, Lang AE: Disease-modifying strategies for Parkinson's disease. Mov Disord 2015 Jul 24;30:1442–1450. 

2.        Airavaara M, Voutilainen MH, Wang Y, Hoffer B: Neurorestoration. Parkinsonism Relat Disord 2012 Jan;18:S143–S146. 

3.        Hegarty SV, Lee DJ, O'Keeffe GW, Sullivan AM: Effects of intracerebral neurotrophic factor application on motor symptoms in Parkinson's disease: A systematic review and meta-analysis. Parkinsonism Relat Disord 2017 May;38:19–25. 

4.        Bäck S, Peränen J, Galli E, Pulkkila P, Lonka-Nevalaita L, Tamminen T, et al.: Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson's disease. Brain Behav 2013 Mar;3:75–88. 

Antti HUOTARINEN (Kuopio, FINLAND), Anna-Maija PENTTINEN, Susanne BÄCK, Merja H VOUTILAINEN, Ulrika JULKU, Petteri T. PIEPPONEN, Pekka T MÄNNISTÖ, Mart SAARMA, Raimo TUOMINEN, Aki LAAKSO, Mikko AIRAVAARA
16:00 - 16:05 #16397 - O135 Acute Fornix DBS induces long-term depression of hippocampal synaptophysin levels.
O135 Acute Fornix DBS induces long-term depression of hippocampal synaptophysin levels.

Fornix DBS has the ability to refurbish memory function in animal models with experimental dementia. One of the possible underlying mechanisms is the acute increase of acetylcholine in the hippocampus. Another suggested hypothesis is neuroplasticity. The hypothesis that acute fornix DBS could lead to long-term positive influence on memory has been tested here.  This was done through the enhancement of histological markers of neuro- and synaptic plasticity. Rats received DBS stimulation at 100 Hz, 100 μA and 100 μs pulse width for 4 h with electrodes placed bilaterally in the fornix. The water maze was performed five weeks thereafter.  Rats were sacrificed 6.5 weeks after stimulation.  BDNF, p-CREB, SV2 and synaptophysin immunohistochemistry was performed for their brains. No differences were found in the number of BDNF, p-CREB or SV2 positive cells for fornix DBS rats when compared to sham. Nonetheless, synaptophysin immunoreactive presynaptic boutons had a significant decrease in CA1 and CA3 of the hippocampus for DBS rats. Therefore, fornix DBS might induce long-term depression related mechanisms.

Majed ALDEHRI (Maastricht, THE NETHERLANDS)
16:05 - 16:15 #15007 - O136 Nucleus basalis of Meynert neuronal activity in Parkinson’s disease.
O136 Nucleus basalis of Meynert neuronal activity in Parkinson’s disease.

Introduction

Neuronal loss within the cholinergic nucleus basalis of Meynert (nbM) correlates with cognitive decline in dementing disorders such as Alzheimer’s disease (AD) and Parkinson’s disease.  In non-human primates, the nbM firing pattern (5-40 Hz) has also been correlated with learning and memory.  In this study, we performed microelectrode recordings of the bilateral globlus pallidus pars internus (GPi) and nucleus basalis of Meynert, and implanted deep brain stimulation (DBS) electrodes in Parkinson’s disease patients to treat motor symptoms and mild cognitive impairment, respectively. Here, we evaluate the neurophysiology correlates of the nbM in Parkinson's disease patients.

Methods

Three patients (3 male, age 68±3 years) with Parkinson’s disease and mild cognitive impairment underwent bilateral GPi and nbM DBS implantation.  Microelectrode recordings were performed through the GPi and nbM along a single trajectory. Firing rates and burst index were characterized for each neuronal population at rest and during an oddball cognitive task.

Results

We characterized the firing rates of nbM cells (18±8 Hz), border cells (41±21 Hz), and GPi cells (70±46 Hz).  Firing rates of nbM cells were similar during an oddball task (13±10 Hz).  The burst index for nbM cells (1.36±0.14) was greater than border cells (1.11±0.05) but similar to GPi cells (1.24±0.14).  The nbM burst index was similar during the oddball task (1.34±0.15).

Conclusions:

The trajectory through GPi and nbM has distinct neuronal firing patterns.  The profile of nbM activity is similar to that observed in non-human primates.  Further research is necessary to characterize the role of the nbM in cognition.

Darrin LEE (Toronto, CANADA), Robert DALLAPIAZZA, Luka MILOSEVIC, Philippe DE VLOO, William HUTCHISON, Suneil KALIA, Andres LOZANO
16:15 - 16:25 #16150 - O137 Prominent temporal coding of cognitive control in human prefrontal cortex.
O137 Prominent temporal coding of cognitive control in human prefrontal cortex.

Intro

In our daily lives, we are constantly faced with situations requiring us to make rapid yet accurate decisions. For example, when approaching a traffic signal that turns yellow, we have to attend to relevant information (speed, distance to the intersection, presence of police) and ignore the irrelevant information (radio, kids arguing in the back seat) in order to choose the optimal response (hit the accelerator or brake). These elements of “cognitive control” are critical components of normal cognition, and deficiencies in these processes underlie several neuropsychiatric disorders. Many studies have broadly attributed these cognitive control processes to prefrontal cortex, yet little is known about their neurophysiological basis.

 

Methods

We recorded single neuron firing rates and local field potentials (LFP) from the dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (dlPFC) in 19 patients undergoing neurosurgical procedures requiring intracranial electrodes, including epilepsy monitoring (N=12) and DBS (N=7). Subjects performed the multi-source interference task (MSIT), a Stroop-like task with 4 categories of decision conflict.

 

Results

Neurons in both dACC (N=136) and dlPFC (N=367) demonstrated sparse firing rate coding of conflict level (dACC: 10.3%, dlPFC: 4.1%) (Figure 1). On the other hand, a majority of neurons encoded conflict level using a temporal code consisting of spike-field coupling to beta and theta oscillations (dACC: 49%, dlPFC: 52%). Spike-triggered LFP analysis indicated that firing rate encoding dACC neurons had the greatest effect on LFP in both dACC and dlPFC, suggesting that this small population of neurons may be entraining the LFP. Finally, spike-theta coherence in dlPFC predicted reaction time on a trial-to-trial basis, indicating a proximal relationship between neuronal activity and behavior (Figure 2).

 

Conclusions

The large majority of PFC neurons that do not demonstrate firing rate coding, previously assumed to be uninvolved bystanders, actually do participate in a temporal coding strategy that is both task- and behaviorally relevant. Temporal coding is emerging as a scheme used by several brain regions to facilitate communication and encode a wide dynamic range of information in a noise-robust manner. We propose that small populations of rate coding neurons (specialized “soloists”) entrain oscillatory potentials to recruit a larger population of temporal coding neurons (“choir”) that in turn stabilize and boost representations across the broader cognitive control network. These populations seem to work in concert to detect and communicate relevant information to optimize our decision-making capability.

Figure. Left: Sparse rate coding of decision-relevant variables in human dACC neurons. a, Microwire recording locations, with different colors per subject. b, Example dACC raster plot and firing rate over conflict conditions for a representative neuron that showed rate coding for decision conflict. c, Venn diagram for dACC neurons selective for specific elements of the task. Right: Reliability coding in human dlPFC neurons. a, Recording locations in the 9 patients from which dlPFC units were recorded b, Venn diagram c, Representative dlPFC neuron d, Representative coherogram for a single dlPFC neuron with no conflict and e, for both types of decision conflict. f, Difference between mean coherograms for trials with both types of decision conflict and trials without decision conflict. g, Mean difference coherograms averaged across all 367 dlPFC neurons. h, Mean difference coherogram illustrating significant difference in coherence across conflict conditions. i, Scatter plot and linear regression theta coherence predicting RT.

Sameer SHETH (Houston, USA), Guillermo HORGA, Garrett BANKS, Mark YATES, Yagna PATHAK, Guy MCKHANN, Elliot SMITH
16:25 - 16:35 #16189 - O138 Oscillatory coherent networks involving the internal Globus Pallidus and cortex.
O138 Oscillatory coherent networks involving the internal Globus Pallidus and cortex.

 Background

Internal Globus Pallidus (GPi) is part of the basal ganglia circuit and a common therapeutic target for the treatment of movement disorders. Deep Brain Stimulation (DBS) surgery affords an opportunity to study cortico-GPi coherent networks by simultaneous recording of GPi local field potential (LFP) and magnetoencephalography (MEG). The possibility to perform such recordings only exists in a few centres worldwide and to date only a single paper has been published (Neumann et al., Brain 2015). This study, done in dystonia patients, described three distinct coherent networks: pallido-temporal in the theta band (4-8 Hz), pallido-cerebellar – in the alpha band (7-14 Hz), and pallido-sensorimotor cortical – in the beta band (13-30 Hz). Here, we attempt to reproduce these results in a new and more heterogeneous patient group.

 

Methods

 

Nine patients were included in the analysis. Six of them had dystonic syndromes and three had Parkinson’s Disease but were recorded on dopaminergic medication when their symptoms were reduced.  Two of the dystonia patients had unilateral implantations resulting in 16 hemispheres with GPi recordings.

Resting MEG recordings were carried out using the Elekta Neuromag Vector View 306 channel system.

 

Coherence was computed in 0-45 Hz range between bipolar channels derived from adjacent GPi contacts and all magnetometer channels. Sensor-level statistical test was then performed in SPM12 (http://www.fil.ion.ucl.ac.uk/spm/) to identify frequency bands with significant coherence. Source analysis for three fixed bands (theta 4-8 Hz, alpha 7-13 Hz, and beta 13-30 Hz) was performed with Dynamic Imaging of Coherent Sources (DICS) beamformer implemented in the DAiSS toolbox (https://github.com/spm/daiss).  Images of coherence with left hemispheres were flipped in relation to mid-sagittal plane and all the images were included in a repeated measures ANOVA with factors frequency band and image type (original vs. surrogate). Regressors for subjects and hemispheres were included as confounding factors.

 

All results were significant with family-wise error correction (p<0.05) at the peak level. All significant coherence peaks were ipsilateral to the GPi electrode.

 

Results

 

Two contacts of the electrodes were localized inside the posterior 1/3 GPi in all subjects. The distribution of the coherent frequencies at the sensor level showed two clear peaks: in the alpha-theta band peaking at 9Hz and in the beta band peaking at 25 Hz. In the theta band the main peak was found in the hippocampus with additional peak at the fusiform gyrus. In the alpha band there were two significant clusters: in the temporal lobe with peak in Brodmann area 22 (BA22) and in the brainstem. In the beta band one cluster was peaking in the premotor cortex (BA6) and an additional cluster was in the orbitofrontal cortex (BA11).

 

Discussion:

 

Our results are only partially consistent with the previous study. We also find coherence with inferior temporal lobe in the theta band and with motor areas in beta. However, there is no clear evidence for coherence with the cerebellum, and we find a new peak at BA11 in the beta band. The coherence topography in the alpha band is very similar to previously reported for the subthalamic nucleus (STN) which might suggest that STN and GPi are part of the same alpha network.

Chunyan CAO (Shanghai, CHINA), Dianyou LI, Yixin PAN, Shikun ZHAN, Vladimir LITVAK, Bomin SUN
16:35 - 16:40 #16223 - O139 A new type of thalamic potential related to somato-sensory system.
O139 A new type of thalamic potential related to somato-sensory system.

Introduction

It has been postulated that high frequency oscillations (HFO) recorded at thalamus and elicited by somato-sensory evoked potentials (SSEP) are specific markers for the sensory ventro-caudal (Vc) nucleus. We have addressed this hypothesis by means of micro-electrode recordings (MER) during deep brain stimulation (DBS) of the centromedian nucleus (Ce) for refractory epilepsy.

Methods

SSEP elicited at contralateral median nerve were recorded in six patients anaesthetized (Propofol + remifentanil). Scalp (C3’/C4’-Fpz), cervical (C2-Fpz) and 4-leads MER recordings (bandwidth 2-5000 Hz, notch off) were averaged, starting at least 6 mm above the theoretical target at 1 mm steps. Reconstruction of MER position was done with the Schaltenbrand-Wharen atlas and using the final angles and coordinates of end DBS leads by means of MRi. Off-line analysis was performed using Matlab. Raw records were filtered at 2-200 Hz, to analyses local field potentials (LFP) and at 500-5000 Hz (Figure A), to analyses high frequency components (HFC). Spectral analysis (Fast Fourier Transform) was done onto both components (Figure 2B) and time-frequency analysis through Discrete Wavelet Transform (DWT) was applied onto HFC (Figure 2C).

Results

LFP of two phases were observed in 60.7% recordings (N = 285), three phases in 29.1% records, four in 7.7% and finally, five phases 2.5% records. The first component appeared at 66% of records with a N1 phase (upward direction). The amplitude of LFP was 2.3 ± 0.1 µV ([1.1-2.7] range P25-P75), when the first component was N1 (upward), but when the it was P1 (downward), the amplitude was -2.1 ± 0.2 µV ([-2.3 - -1.0]), with a latency onset measured at peak of 19.43 ± 0.17 ms ([18.91 – 20.36]).

High Frequency Components. Can be divided into two components:

High Frequency Oscillations (HFO). Defined as those components whose frequencies are > 1 kHz. Are the second most frequent, (N = 224). It’s quite relevant to observe that HFO appears during long trajectories (up to 8 mm) and frequently in all the four electrodes. Spectra were slightly different from point to point. The amplitude was 3.0 ± 0.5 µV ([1.2 – 3.1]), with a latency onset of 14.29 ± 0.11 ms ([13.5 – 15.2]), a latency end of 25.37 ± 0.27 ms ([22.47 – 28.22]) and a frequency of 1471 ± 35 Hz ([1074 - 1850]).

Low Frequency Oscillations (LFO). We have defined the low frequency responses LFO as those potentials whose main frequency component does not exceed 1000 Hz, exhibiting amplitudes greater than HFO. These are the less frequent potentials, appearing in only 10 cases, usually in one point of recording, except in two trajectories were appeared in two points. The amplitude was 5.2 ± 1.8 µV ([3.7 – 7.9]), with a latency onset of 17.69 ± 0.47 ms ([16.11 – 18.89]), a latency end of 21.11 ± 0.27 ms ([19.55 – 22.95]) and a frequency of 848 ± 66 Hz ([700 - 865]).

Spectral analysis shows that components lower than 1 kHz are always present. However, it’s amplitude only is higher than peaks above 1 kHz when LFO are seen in the recording.

DWT for HFC recordings containing LFO and HFO show the presence of low frequency components (

Reconstruction of trajectories shows that sources of LFP and HFO are in several nuclei, including lamina medialis, ventral intermedium, centromedian and parafascicularis. However, the LFOs only appear in the sub-nuclei of V.c (Figure D).

Conclusions

We have shown that SSEP are composed by three components. Two of them (LFP and HFO) are highly scattered along several millimeters and in all the electrodes, with reconstructed sources located in several thalamic nuclei. However, the third component, LFO only appears in a highly localized manner and sources appear only in nuclei belonging to V.c. Therefore, we propose that LFO are the real physiological markers of somato-sensory synapsis at V.c. nucleus. This fact can shed light about the physiology of human sensory processing and help to improve accuracy of DBS surgery.

Jesus PASTOR (Madrid, SPAIN), Lorena VEGA-ZELAYA, Cristina TORRES, Marta NAVAS
16:40 - 16:45 #16268 - O140 Electrophysiological characterization of the centromedian nucleus in humans.
O140 Electrophysiological characterization of the centromedian nucleus in humans.

Introduction: The centromedian (Ce) nucleus has been used as target in deep brain stimulation (DBS) surgery. However, up to date, the electrophysiological properties of this nucleus have not been described. The aim of this study was to analyse the electrophysiological properties of the Ce nucleus in anesthetized patients.

Methods: By means of the projection of the theoretical reconstruction of the real trajectory through thalamus in the Schaltenbrand-Wharen atlas, we can identify the nucleus were electrode is located. We have analysed the neuronal recordings from 6 patients with refractory epilepsy undergoing bilateral DBS of the Ce nucleus, such as parvocellular (Ce.pc) as magnocellular (Ce.mc) sub-domains. All the extracellular action potentials (AP) have been sorted by Euclidian distances using amplitude (µV) and duration (ms) of the depolarizing and repolarizing phases (2 and 3, denoted as P2 and P3 respectively), e.g VP2, durP2, VP3, durP3. Then, we identify those pertaining to the same unit (clusterization) (Figure 1A). Finally, APs were merged to get the mean action potential (mAP). For all of these mAP, we computed the number of phases (2 or 3, if P1 is present), amplitude and duration, maximum and minimum values of first derivative (dVmax and dVmin, in mV/s) (Figure 1B) and the number of components of the repolarization phase (between maximum and minimum voltages) by means of the first derivative. Besides, we analysed the properties of raw discharge (e.g, mean frequency or firing rate, modified burst index -mBI-, pause index -PI- and pause ratio -PR). To conclude, we computed the density of cells (number of units at the raw record).

Results: A total of 362 mAP (146 for Ce.pc and 216 for Ce.mc) from more than 2000 AP were obtained. We observed 3 phases in 66% y 75 % for Ce.pc y Ce.mc respectively therefore, 34% and 25% had only 2 phases, with a first negative phase (P1-) of shorter duration in most of cases, 72% in Ce.pc and 80% in Ce.mc (Figure 1C). The mean amplitude of P1- for Ce.pc was 19.8±1.4 µV and for Ce.mc 22.8±0.2 µV. The duration was 0.11 ±0.01 ms for both sub-domains. We found a first positive phase (P1+) in 28% and 20% for Ce.pc and Ce.mc respectively. The mean amplitude and duration was -17.8±1.6 µV and 0.15±0,01 ms for Ce.pc and -16.3±1.4 µV with 0.16±0.01 ms of duration for Ce.mc. Regarding the second phase (P2-), we found a mean amplitude of 68.8±2.5 µV and 83.9±2.9 µV for Ce.pc and Ce.mc, respectively (p=0.008) with a duration of 0.37±0.01 ms for Ce.cp and 0.39±0.01 ms for Ce.mc (p<0.001). The mean amplitude of the third phase (P3+) for Ce.pc and Ce.mc was -38.3±1.6 µV and -45.8±1.6 µV (p=0.005) and the duration for Ce.pc 1.59±0.04 ms and for Ce.mc 1.75±0.03 (p=0.005). When we analyse the data of the total mAP, we found values of amplitude for the Ce.pc and Ce.mc of 107.1±3.9 µV and 129.8±4.5 µV (p=0.005). As for the duration, in the Ce.pc was 2.08±0.04 ms and in the Ce.mc was 2.26±0.03 ms (p=0.0002). The dVmax (mV/s) was for Ce.pc of 5.02±0.22 and of 6.08±0.24 for Ce.mc (p=0.023). Finally, the density of cells (units/raw) was 3.06±0.20 and 3.72±0.16 for Ce.pc and Ce.mc, respectively (p=0.015). No differences in mean firing rate, mBI, PI or PR were observed between both sub-domains.

Conclusions: There were significant differences between both sub-domains for amplitude and duration for P2 and P3 and for the total amplitude and duration of the mAP. Thus, the mAPs for both sub-domains exhibit different properties in morphology what make different and, therefore, easily recognizable by the analysis of their AP characteristics. The analysis of extracellular AP’s recorded during the surgery for DBS could help to identify the different nuclei, achieving a greater exactness in the placement of electrode. Therefore, we can increase the success in DBS improving the surgical outcome and decreasing the secondary effects. This technique must be especially relevant for thalamic surgery, where a great number of different nuclei are densely packed. The absence of difference in pattern discharge between Ce.pc and Ce.mc are not completely explained, but it is very important to remind that recordings were done under the effects of anaesthesia.

Lorena VEGA-ZELAYA (Madrid, SPAIN), Jesus PASTOR, Marta NAVAS, Cristina TORRES
16:45 - 16:50 #16282 - O141 Incidence of Seizures Induced by Intracranial Research Stimulation: a Multicenter Prospective Study in 770 Sessions Across 188 Patients.
O141 Incidence of Seizures Induced by Intracranial Research Stimulation: a Multicenter Prospective Study in 770 Sessions Across 188 Patients.

Introduction: Patients with epilepsy undergoing intracranial recordings provide an increasingly utilized opportunity to study human neurophysiology. Intracranial stimulation in these patients for research purposes can provide unique and valuable information, but ethical concerns demand a thorough appreciation of the associated risks. We measured the incidence of stimulation-associated seizures in a large multi-institutional prospective study using consistent stimulation parameters and seizure monitoring criteria.

 

Methods: 188 subjects who underwent intracranial epilepsy monitoring across 10 institutions participated in 770 stimulation sessions over 3.5 years. Seizures within 30 minutes of a stimulation session were considered potentially stimulation-related. For each observed seizure, we sought to determine whether it was likely related to stimulation or likely a naturally occurring seizure. To do so, we 1) analyzed the patient’s baseline seizure frequency to determine the statistical likelihood that the observed seizure was stimulation-related; 2) visually analyzed the temporal relationship between seizure onset and stimulation onset. Based on this scheme, we assigned each observed seizure to a category of definitely, possibly, unlikely, or definitely not related to stimulation.

 

Results: In total, 14 seizures occurred during or soon after a stimulation session (1.8% of sessions). Six seizures were similar to the patient’s typical seizures in terms of semiology, onset, and spread. All events were single seizures. The majority were simple partial (64%), or complex partial (29%); only one was generalized. No adverse events occurred, and length of stay in the monitoring unit was not affected. The mean amplitude of seizure-associated stimulation was 1.125mA (range 0.25-2mA), compared to a mean amplitude of 1.055mA (range 0.1-3.5mA) delivered in sessions without seizures. Using the categorization scheme, we found that 4 seizures (0.5%) were possibly stimulation-related, and 10 seizures (1.3%) were unlikely stimulation-related.

 

Conclusion: Seizures are a known possible risk of intracranial research involving brain stimulation. Using conservative criteria, we provide an upper limit of approximately 0.5-1.5% chance of stimulation-related seizure using our parameter range. The observed seizures did not add morbidity or affect the clinical course of any patient. These results will be important for understanding the feasibility and safety of intracranial stimulation for research purposes.

Hannah GOLDSTEIN, Elliot SMITH, Robert GROSS, Barbara JOBST, Bradley LEGA, Michael SPERLING, Greg WORRELL, Kareem ZAGHLOUL, Paul WANDA, Mike KAHANA, Dan RIZUTTO, Catherine SCHEVON, Guy MCKHANN, Sameer SHETH (Houston, USA)
16:50 - 16:55 #16300 - O142 Local field potentials in the thalamus and zona incerta during urinary functions.
O142 Local field potentials in the thalamus and zona incerta during urinary functions.

Background: Control of the lower urinary tract is complex and involves the integrated activity of distributed brain and spinal regions. However, the contribution of individual brain regions to bladder control is poorly understood. Implanted deep brain stimulation (DBS) electrodes enable the measurement of local field potential (LFP) signals from localised regions in the brain. Such recordings can provide insight into neurophysiological control of organ systems and pathophysiology of disease, and thus is relevant for the study of bladder control and dysfunction. Previous work has demonstrated measurable effects of DBS at the ventral intermediate nucleus of the thalamus (VIM) on urodynamic recordings during bladder filling (Kessler et al 2008), however, LFP analysis of VIM signals with regard to lower urinary tract behaviour has not been performed. 

Aims: To investigate neuronal oscillations in the VIM during imagined voiding, pelvic floor contraction and urinary voiding as well as their association with lower urinary tract symptoms. Signals from the zona incerta (ZI) were also recorded in patients with electrodes that spanned VIM/ZI, as a comparison nucleus.

Methods: 5 patients with VIM DBS were recruited; in 3 of these the electrodes also entered the ZI. 3 had essential tremor, 1 dystonic tremor and 1 Parkinson’s disease. LFPs were recorded during three experiments: imagined voiding, pelvic floor contraction/relaxation and urinary voiding. 

Bipolar channels were created by subtracting adjacent contacts for both the VIM and ZI. The signal was down-sampled to 1000 Hz in Spike2 and exported to MATLAB. The signal was low-pass filtered at 100 Hz, high-pass filtered at 2 Hz, and band-stop filtered at 50 Hz with a Butterworth filter. Power spectral density (PSD) analysis was performed on individual trials. These were then averaged per patient and then across patients. PSDs were also created for averages normalised by total power. Frequency bands were defined as: 2-4 Hz delta, 4-8 Hz theta, 8-12 Hz alpha,12-30 Hz beta, 30-90 gamma. Statistical comparison was done using Wilcoxon rank-sum test in individual patients and signed-rank test across patients.     

Linear regression in SPSS was used to assess the correlation between beta oscillatory power during voiding normalised to rest, and urinary symptoms assessed by the International Consultation on Incontinence Lower Urinary Tract Symptoms questionnaire was explored. 

Results: Significant frequency and frequency band changes were observed in the VIM and ZI during pelvic floor contraction/relaxation and imagined void at a single subject level, however, there was no significant change in LFP power during any experimental condition when signals were averaged across participants. 

Beta power during voiding normalised by resting beta power in the VIM, but not the ZI, significantly correlated with ICIQ scores for voiding (p=0.014), frequency (p=0.036) and incontinence (p=0.015) (Figure). 

Conclusions: There was no significant change in oscillatory power in the VIM or ZI during imagined void, pelvic floor contraction/relaxation or voiding. This implies that the VIM/ZI are not involved in normal voiding, however, our small sample size and heterogeneous population may have prevented us from detecting an effect. Significant bands in individual patients suggest hidden variables. Significant correlation between VIM beta power and lower urinary tract symptom severity in this patient group suggests that the beta signal may be of pathophysiological relevance for lower urinary tract symptoms.

Holly A ROY, Savva PRONIN (Edinburgh, UK), Yongzhi HUANG, Tipu Z AZIZ, James J FITZGERALD, Alex L GREEN
16:55 - 17:00 Discussion.
DEACONS SUITE

Friday 28 September

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D38
15:00 - 17:00

Parallel Session 14
Eating disorders & addiction

Moderators: Jane MORRIS (UK), Bomin SUN (director) (shanghai, CHINA), Pawel SOKAL (head of department) (Bydgoszcz, POLAND)
15:00 - 15:15 Basics of anorexia. Jane MORRIS (UK)
15:15 - 15:30 DBS for anorexia. Rebecca PARK (Associate Professor and Consultant Psychiatrist) (Oxford, UK)
15:30 - 15:45 Stereotactic ablation for anorexia. Roberto MARTINEZ-ALVAREZ (Neurosurgeon) (Madrid, SPAIN)
15:45 - 16:00 Basics of addiction. Christelle BAUNEZ (Director of Research) (Marseille, FRANCE)
16:00 - 16:15 DBS for addiction. Juergen VOGES (Head of the Department) (Magdeburg, GERMANY)
16:15 - 16:30 Surgical treatment for anorexia: DBS or ablation? Bomin SUN (director) (shanghai, CHINA)
16:30 - 16:40 #16406 - O143 Weight stabilization, based in normalization of the body mass index in 16 patients who underwent deep brain stimulation in the posterior hypothalamus for handling refractory extreme aggressiveness.
O143 Weight stabilization, based in normalization of the body mass index in 16 patients who underwent deep brain stimulation in the posterior hypothalamus for handling refractory extreme aggressiveness.

Introduction:  The management of patients with extreme refractory aggressiveness (ERA) has shown improvement with bilateral deep brain stimulation (DBS) in the posterior hypothalamus (PH).  In our experience, 16 patients who underwent surgery, not only improved their aggressive behaviour but also stabiliezed their weight, including both overweight and underweight.  Objective:  To report the clinical stabilization in the body mass index of 16 patients who underwent (DBS) in the PH due to ERA.  Methods:  16 patients operated between March 2013 and September 2017 with (DBS) in the (PH) due to (ERA) were followed-up with for a period of 8 to 62 months. Weight and height to calculate BIM were taken before surgery and betwen 6, 12, 24, 48 and 60 months after surgery. Other scales of quality of life, health status and aggressiveness were taken. a multidisciplinary group manages the patient before, during and after surgey. With Leksell frame implanted, Phililps 3 Teslas MRI is performed and the target is planned with Surgiplan software. 3387 Medtronic electrode is implanted bilaterally. Target:  X: 2 mm lateral to the lateral wall of the third ventricle, Y:  3 mm posterior with respect to the mid comissural point, Z:  2 mm above the upper edge of the red nucleus found with Fhc microrecording system.   Results:  The quality of life  EQ-5D-5L, the state of health ESH, the simplified scale of aggressiveness MOAS, as well the body mass index BIM, improved in the post surgical between 70-90%, 60-90%, 58-90%, 70-95% respectively.  Appetite disorders such as hyperphagia or not wanting to eat improved in the patients who presented it and some have become selective in the decision to consume specific foods that they did not have before.    Conclussions:  Bilateral (DBS) in the (PH) has shown significant improvement in aggressive behaviour and also in weight stabilization based on normalization of the body mass index in both overweight and underweight patients after surgery.  More studies and more cases should be carried out.  

Adriana Lucia LOPEZ RIOS (TORONTO, CANADA), Jonathan Ricardo DE LA CRUZ PABON, Alejandro ARISTIZABAL GAVIRIA, Luisa Fernanda AHUNCA VELASQUEZ, Gloria Elena RENDON PEREZ, Katherine Johanna NARANJO PEREZ, William Duncan HUTCHISON
16:40 - 16:50 #16358 - O144 Deep brain stimulation in the treatment of a patient with severe intractable anorexia nervosa – clinical experience and short-term follow up: Case report.
O144 Deep brain stimulation in the treatment of a patient with severe intractable anorexia nervosa – clinical experience and short-term follow up: Case report.

Objective: Anorexia nervosa is ranking within the highest mortality rates of psychiatric disease. Reports on safety of deep brain stimulation in patients with anorexia nervosa have documented clinical benefits of surgical therapy in a small series of patients. We have indicated to proceed with deep brain stimulation of the subcallosal cingulate as a rescue therapy in a patient with otherwise poor prognosis of life-time.

 

Material and Methods: The treatment option of deep brain stimulation was offered to a 20-year-old patient with treatment refractory anorexia nervosa who refused parenteral nutrition as well as nasogastric feeding. Baseline body mass index was 9.8. The patient was implanted with bilateral stimulation electrodes into the white matter of the subcallosal cingulate gyrus under general anesthesia. A rechargeable impulse generator was implanted in an infraclavicular subcutaneous pocket. A period of eight weeks of postoperative in-house surveillance is available for a short-term follow-up.

 

Results: No side effects, adverse events, or complications related to the surgical procedure occurred. Eight weeks after the operation the body mass index was stabilized at 12.1. Postoperative improvement in mood was reflected in a decrease in the Beck depression inventory scoring from 51 to 42. 

 

Conclusion: Deep brain stimulation seems to be a safe treatment option. A larger number of cases and long-term follow-up needs to be established to validate the long-term efficacy of the surgical treatment option for patients with severe, life-threatening anorexia nervosa.

Klaus NOVAK (Wien, AUSTRIA), Christoph KRAUS, Richard FREY
16:50 - 17:00 Discussion.
WOLFSON HALL B
Saturday 29 September
08:30

Saturday 29 September

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A41
08:30 - 10:20

Plenary Session 7
Innovation

Moderators: Laurence DUNN (UK), Ruby MAHESPARAN (NORWAY), Stéphane PALFI (HEAD) (Créteil, FRANCE)
08:30 - 08:50 Gene therapy for neurological disorders: Current status and future propects. Stéphane PALFI (HEAD) (Créteil, FRANCE)
08:50 - 09:10 Spinal cord stimulation for Parkinson. Grégoire COURTINE (Prof. Dr. Courtine) (Geneve, SWITZERLAND)
09:10 - 09:30 The first Grenoble BMI. Alim Louis BENABID (Grenoble, FRANCE)
09:30 - 09:50 Electrical stimulation and recording of the abnormal brain cavity wall. Philippe DE VLOO (Fellow in Stereotactic and Funcitonal Neurosurgery) (Leuven, BELGIUM)
09:50 - 10:20 Predicting pain & predicting pain relief: How imaging derived structural features can help us understand trigeminal neuralgia. Mojgan HODAIE (Attending Neurosurgeon) (Toronto, Canada, CANADA)
FESTIVAL THEATRE AUDITORIUM
10:20

Saturday 29 September

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A42
10:20 - 10:50

COFFEE BREAK & VISIT OF POSTERS AND EXHIBITION

10:50

Saturday 29 September

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A44
10:50 - 12:30

CLOSING LECTURES

Moderators: Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (LISBON, PORTUGAL), Joachim K. KRAUSS (HANNOVER, GERMANY), Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
10:50 - 11:10 Adaptive stimulation for PD. TBA.
11:10 - 11:30 Ethics of DBS for disorders of mood and mind. Marwan HARIZ (London, UK)
11:30 - 11:50 25 years of STN DBS. Patricia LIMOUSIN (Professor of Neurology) (London, UK)
11:50 - 12:10 Surgery for dementia. Andres LOZANO (Chairman of Neurosurgery, University of Toronto) (Toronto, CANADA)
12:10 - 12:30 Update in surgery for Dystonia. Joachim K. KRAUSS (HANNOVER, GERMANY)
FESTIVAL THEATRE AUDITORIUM
12:30

Saturday 29 September

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A45
12:30 - 13:00

ESSFN RESEARCH GRANT AND AWARDS 2018

Moderators: Antonio GONÇALVES FERREIRA (Head of the Stereotactic and Functional Division) (LISBON, PORTUGAL), Joachim K. KRAUSS (HANNOVER, GERMANY), Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
FESTIVAL THEATRE AUDITORIUM