Wednesday 28 June
Time Bellevue Glienicke Potsdam I-III Tegel Kaminzimmer
07:30
07:30-08:15
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BS4
PARALLEL SESSIONS: BREAKFAST SESSIONS
RADIOSURGERY FOR PSYCHIATRIC DISEASE, EPILEPSY, PAIN

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

Moderators: Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil), Marc LEVIVIER (Chef de Service) (Lausanne, Switzerland)
Keynote Speakers: Rees COSGROVE (Director, Epilepsy and Functional Neurosurgery) (Keynote Speaker, Boston, USA), Antonio DE SALLES (Professor - Chief) (Keynote Speaker, SÃO PAULO, Brazil), Motohiro HAYASHI (Associate professor) (Keynote Speaker, Tokyo, Japan)

07:30-08:15
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BS5
PARALLEL SESSIONS: BREAKFAST SESSIONS
CHALLENGING CASES IN EPILEPSY

PARALLEL SESSIONS: BREAKFAST SESSIONS
CHALLENGING CASES IN EPILEPSY

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

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

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

Moderators: Johannes ENSLIN (Specialist) (Cape town, South Africa), Patrick MERTENS (Head of the department) (LYON, France)
Keynote Speakers: Johannes ENSLIN (Specialist) (Keynote Speaker, Cape town, South Africa), Patrick MERTENS (Head of the department) (Keynote Speaker, LYON, France), Marc SINDOU (Professor of Neurosurgery) (Keynote Speaker, Lyon, France)

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

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

Moderators: Hidehiro HIRABAYASHI (Tokyo, Japan), Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)
Plenary Speaker: Andres LOZANO (Alan & Susan Hudson Cornerstone Chair in Neurosurgery, University Health Network) (Plenary Speaker, Toronto, Canada)

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

OPS06a PLENARY SESSION: ORAL PRESENTATIONS

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

Introduction

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

 

Methods

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

 

Results

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

 

Conclusion

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


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

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

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

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

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

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


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

Objective:

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

Materials/Methods:

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

Results:

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

Conclusions:

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


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

Objective

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

Methods

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

Results

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

Conclusion

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


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

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

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

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

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


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

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

OPS06b PLENARY SESSION: ORAL PRESENTATIONS

Moderators: Arthur CUKIERT (São Paulo, Brazil), Veerle VISSER-VANDEWALLE (Head of Dep. of Ster. and Funct. NS) (Cologne, Germany)
10:30 - 10:42 #10525 - OP31 Surgical approach to the superolateral branch of the medial forebrain bundle (slMFB) for DBS in depression.
Surgical approach to the superolateral branch of the medial forebrain bundle (slMFB) for DBS in depression.

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

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

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

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

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

 

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

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

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

 


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

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

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

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

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


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

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

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

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

 

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

 

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

 

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

 

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


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

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


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

Introduction

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

Methods

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

Results

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

Conclusion

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


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

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

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

Moderators: Arthur CUKIERT (São Paulo, Brazil), Veerle VISSER-VANDEWALLE (Head of Dep. of Ster. and Funct. NS) (Cologne, Germany)
Plenary Speaker: Bart NUTTIN (Professor) (Plenary Speaker, Leuven, Belgium)

12:00
12:00-14:00
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LIS3
LUNCH SYMPOSIUM - INDUSTRY SPONSORED

LUNCH SYMPOSIUM - INDUSTRY SPONSORED

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

WSSFN INDUSTRY COMMITTEE MEETING

12:00-14:00
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LIS4
LUNCH SYMPOSIUM - INDUSTRY SPONSORED

LUNCH SYMPOSIUM - INDUSTRY SPONSORED

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

WSSFN PSYCHIATRIC COMMITTEE MEETING

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

WSSFN SCIENCE COMMITTEE MEETING

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

WSSFN EDUCATION COMMITTEE MEETING

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

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

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

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

PARALLEL SESSIONS: KEYNOTE LECTURES
NEURAL TRANSPLANTATION

Moderators: Ethan TAUB (Head of Functional Neurosurgery) (Basel, Switzerland), Hiroki TODA (Director) (Osaka, Japan)
Plenary Speaker: Stéphane PALFI (HEAD) (Plenary Speaker, PARIS, France)

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

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

Moderator: Cristina TORRES (Staff Neurosurgeon) (Madrid, Spain)
Plenary Speaker: Bahram MOHAMMADI (Plenary Speaker, Hannovre, Germany)

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

OPS08 PARALLEL SESSIONS: ORAL PRESENTATIONS

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

Objective

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

Methods

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

Results

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

Conclusion

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


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

Purpose.

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

 

Methods.

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

Results.

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

 

Conclusions.

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

 


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

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


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

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

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

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

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


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

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

Methods

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

 Results

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

Conclusions

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


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

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

OPS07 PARALLEL SESSIONS: ORAL PRESENTATIONS

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

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


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


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


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


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

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

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

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

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


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

Introduction

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

 

Methods

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

 

Results

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

 

Conclusion

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


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

Intro:

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

Methods:

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

Results:

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

Conclusion:

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


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

Caudate Is Involved in Human Associative Learning

 

Introduction

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

Methods

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

Results

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

Conclusion

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


Sarah BICK (Boston, USA), Emad ESKANDAR

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

OPS09 PARALLEL SESSIONS: ORAL PRESENTATIONS

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

Objectives:

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

Methods:

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

Results:

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

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

Conclusions:

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


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

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

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

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

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


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

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


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

Objective:

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

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

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

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


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

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


Darko CHUDY (Zagreb, Croatia)

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

FP5 - PARALLEL SESSIONS: FLASH PRESENTATIONS

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

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

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

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

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


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

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

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

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

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


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

Introduction

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

Methods

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

Results 

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

Conclusion

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


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

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

 

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

 

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

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

 

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


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

Introduction

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

Patients and methods

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

Results

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

Conclusion

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


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

Introduction

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

Methods

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

Results

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

Conclusion

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


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

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

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

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

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


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

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

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


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

 Objective

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

Methods

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

Results

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

Conclusions

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


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

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

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

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

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


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

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

FP4 - PARALLEL SESSIONS: FLASH PRESENTATIONS

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

Introduction

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

Methods

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

Results and Conclusions

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

References

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

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

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

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


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

Introduction:

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

 

Methodology:

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

 

Results:

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

 

Conclusion:

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


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

 

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

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

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

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

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


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

Objective:

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

Materials:

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

Results:

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

Conclusions:

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


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

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


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

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

Background:

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

Methods:

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

Results:

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

Conclusion:

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


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

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

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

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

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


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

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

 

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

 

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

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

 

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


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

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

 

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

 

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

 

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


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

Introduction:

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

Methods:

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

Results:

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

Conclusions:

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


Mohammed IQBAL, Shabbar DANISH (New Brunswick, USA)

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

FP6 - PARALLEL SESSIONS: FLASH PRESENTATIONS

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

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

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

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

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


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

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

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

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

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

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


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

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


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

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

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

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

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

to provide dual  stimulation of both STN and GPi. 

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

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

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

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

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

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

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

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

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

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

Conclusion

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

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


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

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

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

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

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

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

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


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

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

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

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

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


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

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

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

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

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


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

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

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

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

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


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

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


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

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


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

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

PLENARY SESSION: WRAP UP SESSION-3 presenters

Moderators: Keyoumars ASHKAN (London, United Kingdom), Adrian LAXTON (Winston Salem, USA), Ido STRAUSS (Neurosurgeon) (Tel Aviv, Israel)

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

CLINICAL TRIALS SESSION 2

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

WSSFN

 

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

 

 

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

 

 

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


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

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


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

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


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

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

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

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

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

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


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

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

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

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

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

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

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


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

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

WFNS STEREOTACTIC AND FUNCTIONAL NEUROSURGERY COMMITTEE