OBJECTIVE

Gamma knife radiosurgery (GKS) for the treatment of vestibular schwannoma (VS) introduces risks to the facial nerve and auditory perception, and may involve post-treatment complications such as pseudoprogression, hydrocephalus, and other cranial neuropathies. This study of patients with VS who underwent GKSinvestigatedradiosurgical results, focusing on post-treatment complications and identifyingthe factors that predict such complications.

METHODS

We undertook a retrospective review of all VS patients treated with the PerfexionLeksellgamma knife between November 2007 and October 2010 at our institution. Patients who had a minimum of 12months of clinical and radiological assessments before and after GKS were included.

RESULTS

The 5-year serviceable hearing and facial nerve preservation values were 84.9% and 94.3%, respectively. Following GKS, 43 patients (18.30%) showed pseudoprogression, 15(6.38%) exhibited hydrocephalus, 22 (9.36%) showed trigeminal neuropathy, 14 (5.96%) showed vertigo or balance disturbances, and 25 (10.64%) showed facial myokymia. According to multivariate analysis, solid tumor nature was significantly associated with pseudoprogression and patient age was significantly associated with hydrocephalus. Patients receiving margin dose ≥ 13Gy or who underwent no prior surgical resection had a significantly higher probability of loss of serviceable hearing.Patients with smaller tumors had a trigeminal nerve preservation rate comparable to patients harboring larger tumors. Patients receiving margin dose < 13 Gy or older patients had a significantly higher probability of vestibular nerve dysfunction.

CONCLUSIONS

Further prospective studies should be designed to provide further insight into the exact relationship between the predictive factors we investigated and post-treatment complications.

Question: Deep brain stimulation (DBS) has been investigated as potential intervention into the disease progression of Alzheimer’s disease (AD). There is an urgent need for improvement of existing dementia treatments. Any new investigational approach should adhere to high ethical requirements in order to protect participants’ safety with regard to uncertainties like unknown risk of side effects and adverse events. The assessment of such unknown risks is best conceived on a continuum from conservative protectionism to experimental adventurism (certainty-uncertainty continuum). Protectionism may impede scientific progress and can harm patients by hampering the development of new and better treatment possibilities. Because DBS involves (narrowly restricted) craniotomy, it belongs to “Class III” of medical devices implying “high risk” according to regulation by the European Parliament. This coarse classification into three classes (I, II and III) is unlikely to decompose the certainty-uncertainty continuum adequately into distinct categories. Other relevant features need also to be considered. Due to its reversibility and minimal-invasiveness, DBS paves the way for emerging new technologies and indications, although ethical justification of research rationale relying on conclusive evidence remains key. We recommend a linear relationship between risk and evidence: the riskier a novel approach, the higher the demands on quality criteria used to assess some research hypothesis.

Methods and results: We searched systematically (EMBASE and MEDLINE) for data on DBS for DBS (preclinically, case studies, investigational trials or feasibility studies and reviews), assessed the findings, and rated the published material according to established standards (AMSTAR-Checklist, Cochrane levels of evidence).

Conclusion: The first aim was to evaluate the research rationale for DBS of AD by examining the uncertainties associated with DBS’ mechanism of action, target selection and stimulation parameters specific to AD symptomatology and pathomechanism. The second aim was to classify the unknown risks and uncertainties on the basis of standardized criteria and the expert’s views held in the scientific community. Since the responsibility for novel investigational clinical trials is shared among ethics committees, researchers involved, and patients and caregivers affected, this classification will facilitate evidence-based decision-making and thus promote patients' informed consent.

Objective The operative change of generators after DBS-surgery is necessary after several years, especially in patients with non-rechargeable generators. Since 2008 the new generation of Medtronic generators is available and the non-rechargeable Activa-PC replaced the Kinetra. The change from Kinetra to Activa-PC in patients who need new generators requires an adaptor when extension cables are not changed. From a clinical view the hypothesis was generated that the battery-life of Activa-PC generators is reduced under use of an adaptor. The aim of this study was to very this. 

Methods We retrospectively investigated patients suffering from Parkinson’s disease, dystonia and tremor who had an implantation of DBS electrodes and generators in our department. We investigated times from first-implantation to change or from change to change before and after change to Activa-PC with adaptor. The battery-lifes data were compared by Wilcoxon test.

In a second step the total electrical energy delivered was calculated for each patient before and after the change to Activa-PC with adaptor. Data were again compared by using Wilcoxon test.

Results

In our department up to now 20 patients who got an Activa-PC generator connected with an adaptor had a change of their new generator. One of these patients could not be included in further investigations.

From the 19 patients 16 were suffering from PD, one from tremor and two from dystonia. 

The mean durability of the Kinetra generator was 54,58 ± 13,77 months and 29,31 ± 5,84 months of the Activa-PC generator with adaptor.

Differences were significant using Wilcoxon test (p = 0,000276).

In order to reveal reasons for this shortening of battery-life, stimulation parameters were compared. In 16 patients stimulation parameters were documented. As the impedance was not available for all patients the total electricity delivered per impedance was calculated. For the Kinetra generator TEED/impedance was 290,5834 ± 96,6859 mW * Ω and for the Activa-PC 293,7803 ± 95,0821 mW * Ω. Differences were not significant using Wilcoxon test (p = 1).

Conclusion A shorter durability of Activa-PC generators under use of adaptors was seen in this study. This could not be reasoned by higher stimulation parameters.  

Patients have to be informed that durability of generators is shortened under use of adaptors. This might lead in some cases to a recommendation of rechargeable systems or to a change of the extension cables during the exchange of the generator.

Introduction: Deep Brain Stimulation is an established treatment modality in various movement disorders including
dystonia. Due to the close proximity of the most common target point (GPi) to critical functional structures as the optic
tract and the internal capsule, therapeutic yield might be limited by side effects.
Recently, segmented DBS leads have been made available. This technique comes with the promise of increased
efficacy and side effect reduction. We hereby report on the first case of dystonia treated with directional lead deep
brain stimulation.
Materials/Methods: A 31 year old female presented with a 20 year history of generalized dystonia. The severe
additional
ataxic component left her wheelchair bound and she suffered from severe dysarthria.
The neurological complex was thought to be caused by a proven isolated Vitamin E deficiency
syndrome. MRI revealed structural changes of the basal ganglia anatomy with anatomical
distortions pronounced on the left (Image 1). Standard coordinates did not match the individual
anatomy of the patient. She therefore underwent bilateral GPi DBS surgery using direct
targeting of the left GPI. Directional leads were implanted in both hemispheres.
Results: After calculation of standard AC-PC coordinates (3.5 mm anterior, 22.0 mm lateral and 4.0 mm below MCP)
the trajectory was adapted guided by MRI anatomy to the lateral border of the optic tract. The posterior
communicating artery took a atypical course above the optical tract further limiting the approach. Targeting was
guided by three micro electrode recording tracts and a directional lead system (Vercise DBS, Boston Scientific) was
implanted in an all-in-one GA setting. Conventional stimulation caused a fast worsening of the dysarthria and painful
stimulation induced side effects. The segmented contacts were intensively tested at 90μs and 130 Hz in the
postoperative course. Distinct effect/side-effect patterns for each contact were observed.

Conclusions: Segmented leads allowing current steering offer new perspectives for DBS and will likely result in
increased treatment efficacy while reducing side effect at the same time. While this is true for well known disorders
and their targets (PD, generalized dystonia) this technique also yields the potential to treat disorders currently not
amendable to DBS as no good benefit/side-effect ratio could be achieved with conventional DBS.

Objectives

Subthalamic deep brain stimulation (STN-DBS) has been presumed closely related to dopamine system.  Levodopa responsiveness has been discussed as an important predictor for success of STN-DBS for Parkinson disease (PD).  However, the long-term outcome of the relationship between STN-DBS and levodopa responsiveness are still unclear.  It is well known that lebodopa responsiveness for PD will fall year by year, but it is unclear whether STN-DBS responsiveness also falls in accordance with the fall of levodopa responsiveness.  We tried to clarify whether STN-DBS responsiveness for PD also falls as levodopa responsiveness more than 10 years after surgery.

Methods

We compared UPDRS part III scores in four different conditions with or without medication or DBS in seven PD patients who received bilateral STN-DBS and followed up more than 10 years.  Levodopa infusion test was also carried out in six of these patients. 

Results

STN-DBS showed statistically better improvement (17.2±7.5 points) in UPDRS part III score compared to medication (4.2±4.0 points). 

STN-DBS also showed better improvement (18.0±8.1 points) in UPDRS part III score compared to levodopa intravenous infusion (6.4±4.3 points).  Two patients developed hallucination and one patient developed facial dystonia after levodopa infusion. 

Conclusions

             It showed dissociation between STN-DBS responsiveness and levodopa responsiveness more than 10 years after surgery.  It also suggested that mechanisms of STN-DBS may isolated from dopamine system.

OBJECTIVES : We investigated the effect of short pulse width on the therapeutic window in Parkinson’s disease patients with deep brain stimulation in the subthalamic nucleus (STN).

METHODS : Five pulse width values ranging from 10 to 60 microseconds were applied randomly, in a double blinded fashion, during a single programming session. Ten patients with Vercise DBS leads, Boston Scientific, were included at least 3 months after surgery. The principal outcome was the therapeutic window, i.e. the difference between the amplitude threshold for pyramidal side effects (tolerance threshold) and the amplitude threshold for rigidity suppression (efficacy threshold). The secondary outcome was the total electrical energy delivered (TEED) by the neurostimulator on different pulse width values. 

RESULTS : The therapeutic window widened when pulse width decreased, with increasing tolerance and efficacy thresholds. The widest therapeutic window was obtained at 20 microseconds. In order to achieve the same clinical efficacy at 20 microseconds as at 60 microseconds, the total electrical energy delivered (TEED) was increased.

CONCLUSION : This double-blinded study confirms that low pulse width widens the therapeutic window. Nonetheless, TEED is increased to reach clinical efficacy when pulse width is shortened. Therefore, in routine post-operative management, we advocate for lowering the pulse width only if the therapeutic window is narrow, but not systematically.

Objective The operative change of non-rechargable generators after DBS-surgery is necessary after several years. Since 2008 a new generation of Medtronic generators is available and the non-rechargeable Activa-PC replaced the Kinetra. From a clinical view the hypothesis was generated that Kinetra has a longer battery-life than Activa-PC. The aim of this study was to verify these findings.

Methods We retrospectively captured the battery-life of every single patient after implantation of DBS electrodes and generators between 2005 and 2012 in our department due to Parkinson´s disease and compared the battery-life of the Kinetra- and the Activa PC groups. To calculate the current usage, the total energy delivered (TEED) was estimated for each patient using stimulation parameters one year after electrode implantation and compared the TEED in both groups.

Results 192 patients could be included in the study, among those 105 with Kinetra generators and 86 with Activa-PC generators. The mean battery-life of the Kinetra was significant longer (5,439 ± 0,199 y) than of the Activa PC (4,438 ± 0,165 y) (p = 0,023).

The mean TEED without impedance for the Kinetra group was 219,9031 ± 121,5310 mW * Ω and for the Activa-PC group 145,1321 ± 72,6729 mW * Ω, which implied significant lower stimulation parameters in the Activa PC group (p = 0,00038).

Conclusion A significant shorter battery-life of the new generator Activa-PC in comparison to the older model Kinetra was shown. Since higher battery consuming stimulation parameters as a reason could be excluded, a shorter battery-capacity is probable. Reasons for this e.g. the smaller size of the new implant, new functions or other causes could not be revealed by this study. 

OBJECTIVES

Internal pallidal nucleus stimulation surgery for the treatment of dystonia is performed under general anesthesia in paediatric patients. The recording of evoked activity in the visual and motor cortex by intraoperative stimulation of the therapeutic electrodes could be useful to optimize their localization.

METHODS

We perform intraoperative electrical stimulation through the cerebral electrodes according to the usual therapeutic parameters while recording motor cortical and visual evoked activity. We collect the intensity in wich capsular and visual responses appear. We search for a possible correlation between the intraoperative findings and the response after the activation of the system.

RESULTS

Five patients aged between 7 and 16 years old have been operated. Visual evoked response was obtained in all of them at an intensity between 1 and 6 volts.Involvement of the internal capsule has been recorded in four of them between 4 and 6 volts. We did not change te location of the electrodes despite these findings. Postoperative CT monitoring showed the placement of the electrodes according to preoperative planning. In the patients that intraoperative motor stimulation was obtained, a lower threshold of adverse effects due to internal capsule involvement was observed in the postoperative period. In all cases we solved this using higher contacts for therapeutic stimulation.

CONCLUSIONS

Intraoperative neurophysiological monitoring may be useful to optimize the location of the internal pallidal electrodes and to predict the stimulation window due to its proximity to the internal capsule.

OBJETIVES

We have initiated a pallidal stimulation program for the treatment of paediatric patients with dystonia. For the implantation of the cerebral electrodes we use the Neuromate® (Renishaw®) robot without associating a stereotactic frame. We intend to verify the accuracy of the robot for this technique and the effectiveness of it.

METHODS

We prospectively collect the distances between the electrodes and their respective planned trajectories merging the postoperative CT with the preoperative plan. We record the clinical results comparing preopeative and postoperative BFM (Burke-Fahn-Marsden) and UMRS (Unified Motor Rating Scale) scales and the complications derived from "hardware" and from stimulation.

RESULTS

We have operated five patients with ages ranging from 7 to 16 years, three with primary dystonia and two with myoclonus-dystonia (SGCE), with a follow up from 0 to 10 months. The average precision in the placement of the electrodes has been 1mm at the target level. In all cases there has been a clear clinical improvement as well as a significant reduction in the motor (62-73%) and functional (53%) BFM scale in the dystonic patients, and in the UMRS scale for action myoclonias (90 %). Also functional tests (62.5%-72%) in the patients with myoclonus due to SGCE mutation.There have been no hardware-related complications. In the first operated patient with primary dystonia dysartria limits intensity of stimulation in lower contacts of right electrode. This is the only complication derived from stimulation, probably due to medility of the electrode.

CONCLUSIONS

The Neuromate®(Renishaw®) stereotactic robot is an accurate tool for the placement of internal pallid electrodes in children with movement disorders. This is an effective and safe technique for the treatment of these entities.

Objective: Meanwhile the DBS targeting the VIM region is a standard procedure for the treatment of medical refractory tremor. In difference to other target points a direct visualization of the VIM in standard MRI´s is not possible. Therefore the intraoperative testing of symptoms is essential. For essential tremor data for clinical outcome in larger series exist, for other indications only case reports or small series were published. Indications, intraoperative methods and the optimal target are under discussion. The aim of this study was, to control our advancement for this target point.

Methods: We retrospectively analyzed data of all patients, who have undergone DBS-surgery with targeting the VIM, in our department from 2008 until 2016. We recorded age, gender, indications for surgery, number of microelectrodes, trajectory for the permanent electrode, intraoperative reduction of symptoms, reasons for avoiding the central trajectory, the coordinates of the active contacts of the permanent electrode and compared these data with the clinical outcome. Surgeries were all performed under local anesthesia with MRI-planning and intraoperative micro recording and testing of symptoms.

Results: In the 9 years period 89 DBS-surgeries targeting the VIM were performed, indications for surgery were Essential Tremor 68.5%, MS-Tremor 15.7%, PD-Tremor 4.5%, Orthostatic Tremor 3.4%, Holmes Tremor 2.2%, and other Tremor minorities 5.6%. Mean age of the patients was 61 years ± 14.7 years (range 15 years to 81years). Bilateral stimulation was performed in 83 patients (93.2%), unilateral in 6 patients.

Within the 172 implantations of VIM-electrodes we were able to use 3 or more microelectrodes for a three-dimensional view in 76.2%, 2 in 14.5%, 1 in 4.1% and no microelectrodes in 5.2%, regarding an individual risk evaluation.  For the permanent electrode the central trajectory was chosen in 60.5% 39.5% were implanted over periphery trajectories. Reasons were a better effect (14.7 %), less side effects (27% left and 14.6%) or sometimes a combination of both (23.6%) with sometimes just slight differences.

A good reduction of the symptoms was mainly shown intraoperatively (range from 20% effect up to 100% tremor reduction) and was compared to the symptoms reduction under permanent stimulation.

Conclusion: For the optimal outcome of the patients the intraoperative testing of the tremor symptoms over multiple trajectories is an essential addition to the MRI-based target planning.

Introduction : Brain shift during deep brain stimulation (DBS) surgery result in mistargeting of electrode especially at second electrode insertion. Leakage of cerebrospinal fluid (CSF) is thought to be a cause of brain shifting.

Methods : Fourty five patients who took immediate magnetic resonance image (MRI) after DBS were retrospectively reviewed. Their air volume which represent leakage of CSF were segmented and calculated by 3D-slicer. Stereotactic coordinates of anatomical structures of anterior commissure, posterior commissure and structures that visualize better in MRI which represents location of common DBS targets (anterior thalamic nucleus (ATN), globus pallidus interna (GPi and subthalamic nucleus (STN)) are measured by Surgiplan software.

Results : Mean air volume measured was 14.7 cc. Brain shifting was most prominent in y axis (every structure, <0.01) and shift of more than 1mm in vector were seen in AC, ATN and both STN. Air volume was most contributing factor for brain shifts. Other factors such as sex, age, diagnosis for DBS, and operation time did not show significant relation in most targets. However, age seems to be related with air volume (p=0.086) and operation time showed trend toward increasing air volume (p=0.082). No significant difference was seen related to diagnosis of patients for DBS (p=0.104).

Conclusion : Though we failed to show operation time nor air volume result in brain shifting, brain seems moving toward direction of gravity. If operating elderly patients and taking long operation time, more posterior the actual target would be located.

Objective: A stimulation-induced drowning hazard has recently been described in a patient with Parkinson’s disease, who developed a profound inability to swim following treatment with deep brain stimulation (DBS) at the posterior subthalamic area. The impairment was present despite normal neurological examination, and was reversible with withdrawal of stimulation. This study aimed to systematically determine whether DBS impairs swimming ability in a larger patient cohort.

Methods: 18 participants (including index case) with Parkinson’s disease (n=13), essential tremor (n=3), Tourette’s syndrome (n=1) or post-traumatic brain injury proximal tremor (n=1), treated with posterior subthalamic area (n=15) or globus pallidus interna (n=3) DBS, were assessed in a randomized, double-blind crossover study. Ability to swim with DBS ON versus OFF was compared within each participant, during three trials of freestyle and breaststroke, in a standardized pool environment. Outcome measures were distance covered, lap time, and Aquatic Skills Proficiency Assessment (ASPA) score.

Results: Paired-sample t-tests showed no statistically significant effect of stimulation status on measures of swimming ability for freestyle or breaststroke. However, clinically observable changes were seen in three participants. The index case displayed severe persisting impairment in all measures of swimming ability with DBS ON, which normalized with DBS OFF. With stimulation ON, the index case’s freestyle trial time increased by 54% (±2.0), distance covered reduced by 40% (±10.0), and ASPA score reduced by 69% (±0.0). The impairment predominantly involved difficulty with limb coordination and postural control, rendering him unable to swim effectively. Two participants showed clinically observable improvements in trial time and ASPA scores with DBS ON during freestyle and breaststroke.

Conclusion: The index case demonstrated that DBS can induce a serious and persisting swimming impairment that is not evident during routine neurological assessment. However, systematic analysis revealed no significant swimming impairment in other participants with DBS (n=17). There were no discernable features unique to the index case regarding pathology or stimulation site. Patients should be informed that DBS may rarely worsen swimming ability to a level affecting safety, and that DBS is unlikely to improve swimming above pre-DBS baseline.

INTRODUCTION

The outcome of deep brain stimulation (DBS) depends heavily on the position of the implanted lead. After a preoperative anatomical planning, most groups collect numerous intraoperative data such as therapeutic effects induced by stimulation tests. To choose the final implant position, physicians “mentally” visualise all available data. The aim of the present work was to develop a method visualising intraoperative stimulation test results, patient’s images, electric field (EF) simulations for the patient-specific stimulation conditions and the corresponding therapeutic effects quantitatively evaluated by accelerometry. The application to five essential tremor (ET) patients should give a first idea about the optimal target position. 

METHODS

In Clermont-Ferrand University Hospital the anatomic target structure and the neighbouring structures were manually outlined, a target and a trajectory defined and two parallel trajectories per hemisphere intraoperatively evaluated. Stimulation tests were performed at 7 to 8 positions per trajectory and several stimulation current amplitudes. The therapeutic effect was evaluated using a previously published method based on accelerometry. Finite element models and simulations were performed for up to three stimulation amplitudes per position and EF isosurfaces (0.2V/mm) were extracted. For the 3D visualization of the numerous overlapping isosurfaces, we generated “improvement maps” by assigning to each voxel within the isosurfaces the highest tremor improvement. Those maps were visualized together with anatomical images, delineated structures and trajectories (Paraview, Kitware Inc). The method was applied to 5 ET patients implanted in the ventro-intermediate nucleus of the thalamus (VIM). Results were analysed by the neurosurgeon regarding the optimal implant position.  

RESULTS

The clinical teams were able to identify the optimal implant position for all patients with more ease and in less time compared to the routine discussion using pen and paper. Additionally, for 7 of the 9 improvement maps, the highest improvement region was found to be in the posterior subthalamic area, inferior and posterior to the VIM.

CONCLUSION

Improvement maps assist the clinicians in determining the optimal implant location of the chronic DBS lead. Results support findings of other studies that the fibre tracts in the posterior subthalamic area like prelemniscal radiations may be responsible for alleviating tremor in ET patients.

Diffusion-Weighted Imaging (DWI) and tractography allow noninvasive mapping of the structural connections of the brain, and may provide important information for optimizing Deep Brain Stimulation (DBS) treatment. The hyperdirect pathway (HDP), connecting the subthalamic nucleus (STN) with motor cortex, is assumed to play a key role in mediating the beneficial effects of DBS. Less is known about the HDP, connecting the STN to prefrontal regions, and whether this might play a role in adverse effects of DBS on cognitive function.

This study aims to apply recent methodological advances in DWI acquisition and analysis to generate a connectivity-based map of the STN. This can be combined with postoperative electrode position localization with the aim of guiding postoperative stimulation management.

By combining high spatial and angular resolution DWI data with state-of-the-art tractography frameworks (Constrained Spherical Deconvolution based probabilistic tractography) we delineated connections to the STN from motor cortex (MC) and prefrontal (PF) regions. Analyzing these connections, we identified regions of the STN that were dominated by MC or PF connectivity. Post-operative electrode positions were identified and correlated to manual STN segmentations and cortico-subthalamic motor connectivity using in-house Matlab tools.

Our method can delineate a motor connectivity gradient going from high in the dorsolateral aspect of the STN to low towards the antero-medial aspect. We also examined the motor connectivity gradient at each electrode contact point in seven patients with Parkinson’s Disease at 3 month follow up. We found no clear relationship between the ‘active’ (therapeutic) electrode contact and degree of STN-motor connectivity. However, when analyzing the electrode position with the manually delineated STN outline, we find that in 12/14 DBS leads the active contact is the one with the largest or second to largest STN volume coverage. Further analysis will be carried out to model the volume and connectivity of STN tissue stimulated with patient-specific stimulation parameters.

These preliminary results are promising and in line with the previously established anatomy of the STN. This framework could potentially help both neurosurgeons during pre-operative STN targeting and clinicians in optimizing the post-operative testing and management of stimulation settings.

Objective: Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms and quality of life in patients suffering from idiopathic Parkinson's disease (PD). How DBS of the STN affects neuronal network activity is not completely understood. Prepulse inhibition (PPI) of acoustic startle response (ASR) is an operational method to measure the pre-attentive filtering process known as sensorimotor gating. Changes in PPI indicate alteration in network activity as found in neuropsychiatric disorders like Parkinson’s disease. Thus in the present clinical study we investigated how STN-DBS affects sensorimotor gating in patients with idiopathic Parkinson's disease.

Methods: Nine patients with PD and treated with STN-DBS were investigated three months after implantation of the DBS-system (Medtronic, ACTIVA). The medication was stopped 12h before testing. After UPDRS measurement PPI was assessed under two conditions: without stimulation (STN-OFF) and STN high frequency stimulation (STN-ON) with the best UPDRS-III-improvement . PPI was tested with an Interval of 30, 60 and 100ms between prepulse and pulse.

Results: DBS of the STN (STN-ON) compared to no stimulation (STN-OFF) significantly increased PPI (F(1,8)=16,4; p<.01) in patients with Parkinson´s disease.

Conclusion: STN-DBS improves PPI in patients with Parkinson’s disease. Conceivably. PPI could be used as a surrogate marker to indicate how DBS modulates network activity. Our results render PPI measurement as a potential marker for disease- and target specific optimization of DBS settings independent of the examiner or the patient. Further studies integrating also results from functional imaging are warranted.

Introduction

Lead movement after deep brain stimulation (DBS) may occur and influence the area of stimulation. The cause of the displacement is not fully understood. The aim of the study was to investigate differences in lead position between the day after surgery and approximately one month postoperatively and also simulate the electric field (EF) around the active contacts.

Methods

23 patients with movement disorders underwent DBS surgery (37 leads). CT at the two time points were co-fused respectively with the stereotactic images in Surgiplan. The coordinates (x, y, z) of the lead tips were compared between the two dates (paired t-test). 8 of these patients were selected for the EF simulation in Comsol Multiphysics.

Results

There was a significant discrepancy (mean ± s.d.) on the left lead: x (0.44 ± 0.72, p < 0.01), y (0.64 ± 0.54, p < 0.001), z (0.62 ± 0.71, p < 0.001).  On the right lead, corresponding values were: x (-0.11 ± 0.61, n.s.), y (0.71 ± 0.54, p < 0.001), z (0.49 ± 0.81, p < 0.05).  No correlation was found between bilateral (n =14) vs. unilateral DBS, gender (n = 17 male) and age < 60 years (n = 8).  The lead movement affected the EF spread (Fig. 1).

Conclusion

The left lead tip displayed a tendency to move lateral, anterior and inferior and the right a tendency to move anterior and inferior. Lead movement after DBS can be a factor to consider before starting the stimulation. The differences in the area of stimulation might affect clinical outcome.

INTRODUCTION

The success of the deep brain stimulation (DBS) therapy relies primarily in the localization of the implanted electrode, implying the need of utmost accuracy in the targeting process. Intraoperative microelectrode recording and stimulation tests are a common procedure before implanting the permanent DBS lead to determine the optimal position with a large therapeutic window where side effects are avoided and the best improvement of the symptoms is achieved. Differences in dimensions and operating modes exist between the exploration and the permanent DBS electrode which might lead to different stimulation fields, even when ideal placement is achieved. The aim of this investigation is to compare the electric field (EF) distribution around the intraoperative and the chronic electrode, assuming that both have exactly the same position.

METHODS

3D models of the intraoperative exploration electrode and the chronically implanted DBS lead 3389 (Medtronic Inc., USA) were developed using COMSOL 5.2 (COMSOL AB, Sweden). Patient-specific MR images were used to determine the conductive medium around the electrode. The exploration electrode and the first DBS contact were set to current and voltage respectively (0.2mA(V) - 3 mA(V) in 0.1 mA(V) steps). The intraoperative model included the grounded guide tube used to introduce the exploration electrode; for the chronic DBS model, the outer boundaries were grounded and the inactive contacts were set to floating potential considering a monopolar configuration. The localization of the exploration and the chronic electrode was set according to the planned trajectory. The EF was visualized and compared in terms of volume and extension using a fixed isocontour of 0.2 V/mm.

RESULTS

The EF distribution simulated for the exploration electrode showed the influence of the parallel trajectory and the grounded guide tube. For an amplitude of e.g. 2 mA/2 V, the EF extension of the intraoperative was 0.6 mm larger than the chronic electrode at the target level; the corresponding difference in volume was 76.1 mm³.

CONCLUSION

Differences in the EF shape between the exploration and the chronic DBS electrode have been observed using patient-specific models. The larger EF extension obtained for the exploration electrode responds to its higher impedance and the use of current controlled stimulation. The presence of EF around the guide tube and the influence of the parallel trajectory require further experimental and clinical evaluation.

Objective: If outcome of DBS treatment does not meet expectations, identification of suboptimal lead placement needs to be placed on objective grounds, as a tool for planning lead revision and for deciding on details of the surgical procedure.

Patients and Methods: Electrode positions are routinely controlled by fusion of post-surgical CCT to pre-surgical stereotaxy CT and to the on-fused T2 and contrast enhanced T1 weighted MRI. Additional post-surgical MRI may be used for confirmation. Electrode tip and electrode catheter are compared to the the pre-surgical planning of tip and trajectory and intra-operative decision on final trajectory. Depending on clinical development, early or late lead revision is indicated in case of insufficient (unilateral) response, persistent fluctuations or walking disturbance. If a trajectory different to the first chosen is feasible, a one-step-procedure is considered whereas a serious conflict between existing site and new plan are found, a two-step procedure with explantation and new implantation is chosen. Standardized control of clinical status before and thereafter by UPDRS-III at Med-On/ Med-Off and Stim-On/ Stim-Off conditions are included in the protocol.

Results: Within a series of 130 consecutive DBS procedures for PD, indication for lead revision was set in 4 patients (3%) and in 10 further transferred after DBS elsewhere. In two patients two-step-procedures were chosen and in 12 patients single step operations were possible by fluoroscopy control of stepwise insertion of new microelectrodes and removal of old electrodes. Distance of electrode sites to planned ideal site ranged from 2mm to 8.4 mm. Except for two patients who were lately identified as suffering from multi system atrophy MSA, all the other 12 patients showed marked improvement in overall mobility and satisfaction with decision for lead revision and outcome.

Conclusion: Suboptimal outcome in DBS deserves precise investigation of lead location and may be successfully treated by lead-re-positioning. In view of severe lead artefacts on post-surgical MRI especially in the STN region, the use of the pre-surgical MRI is essential.

Objective:

The feasibility of applying new directional leads (D-leads) in standard DBS procedures, possible difficulties or complications were the focus of this study.

Background:

Deep brain stimulation is mainly used for treatment of movement disorders. Despite high precision in electrode placement, side effects can occur by stimulating adjacent fibers or nuclei by the volume of tissue activated (VTA). Leads with smaller electrode contacts by horizontal segmentation into three contacts instead of one ring contact are designed to apply and to direct smaller stimulation volumes.

Material and methods:

31 patients (23 male, Ø age 59,9, 27 PD, 1 dystonia, 3 tremor, 3 unilateral) underwent a DBS procedure with 59 segmented leads. Stereotactic planning, micro-electrode recording and testing were identical to the previous procedure. The decision for directional leads was made intraoperatively, if test stimulation through the microelectrodes indicated a narrow therapeutic window. Lateral fluoroscopy was used to control implantation of the definite DBS lead. In contrast to standard electrodes not only the depth and possible sagittal deviation from the planned trajectory was important, but also the rotation of the electrode, which was controlled by alignment of a X-ray marker above the electrode level. For placing the two middle contacts with D-lead components at the spot of best response, the lowest tip was planned to be placed about 3 mm deeper than usual.

Results:

In three cases complications occurred (1 subcutaneous hematoma, 1 electrode dislocation, 1 brain edema) not different from conventional lead implantation. Slightly longer fluoroscopy time was needed for D-leadplacement compared to conventional leads (415.53 vs. 32896 Gycm²; p=0.09). Mean operation duration did not differ between either lead type (08:59 vs. 08:55 h:min). ). In early follow-up, in most patients at least unilateral D-lead segment has been activated for chronic stimulation. 

Conclusion:

From a surgeon’s point of view, the exact implantation of the directional leads in a correct horizontal mode is slightly more challenging than a conventional DBS lead, but feasible. The higher x-ray-dose is minimal and surely acceptable in view of the estimated long-term advantage. Prospective studies to compare ring-mode-stimulation with directional-stimulation are needed and are already in process.

Evaluation of lead position accuracy may be accomplished by postoperative CT or MRI. Image distortion induced by the lead contacts in MRI question the accuracy and usefulness of this technique. Here, we compare the electrode position in postoperative CT and MRI by direct fusion of both modalities in DBS for Parkinson's Disease (PD).  Therefore, visual electrode selection and related determination of stimulation parameters in post-OP MRI or CT-MRI fusion is of rising importance

Method:

After DBS 9 subjects (2 dystonia, Ø age 57.7, 8 male)were investigated by postoperative imaging including MRI T1-MPRAGE (3Tesla, Trio, Siemens Inc, 1mm slices) and CT-scan (64-channel, Philips, 1mm axial slices) at a minimum of 4 weeks post-operatively to avoid pneumocephalus artefacts. Image analysis was performed in three steps, first direct image fusion of postoperative MRI T1-MPRAGE and postoperative CT was performed, second anterior and posterior commissure distance (AC_PC) and its midpoint were identified and third coordinates of the most distal electrode contact tip relative to AC_PC-midpoint were registered. These coordinates were compared in either modality and the average difference of the electrode position was measured taking modality induced MRI or CT artefacts into account as previously described.^1,2

Results:

18 electrodes were analyzed. Average vector distances of the distal electrode tip in post-op MRI versus CT fused images was 1.04mm (range 0.1- 2.74mm). Further statistical analysis showed special differences in z coordinates, with significant deeper electrode position in CT versus MRI by a mean of 0.61mm (SD 0.9 mm, p = 0.03*), but no statistically significant differences in other planes by either technique.

Discussion:

Comparison of electrode localization showed on average differences below pixel resolution, although, in few individuals discrepancies above 2 mm were detected. In most patients a systematic deeper localization of the most inferior electrode contact was identified by CT compared to MRI. These findings could be of clinical relevance in attempts of prediction of neurostimulation effects by VTA models. For optimal implementation of postoperative MRI into the control and programming planning work flow, these cases need further systematic analysis in order to identify a gold standard for lead localization.

Background:

Deep brain stimulation (DBS) is an established method for the treatment of movement disorders, such as in Parkinson’s disease or essential tremor. The involuntary tremor movements occur primarily in the upper limb. In clinical practice, the physician’s visual observations provide the basis for intraoperative test stimulations and stimulator reprogramming. However, this approach is highly subjective. Objective measurements may improve clinical practice by quantifying the severity of tremor and other relevant scores.

Objectives:

Sensor-based information can help physicians to fine-tune DBS parameters to suppress tremors while minimizing the energy delivered to the brain. In this context, we developed a wearable sensor with a software tool to capture, filter and analyze sensor data online.

Methods:

Our initial focus is to quantify and classify pathological hand tremor, using both commercially-available and our custom-built device. We measured kinematic and bioelectrical activity on the patient’s forearm. To assess tremor in real-time, we developed a semi-automated software tool (based on custom-written MATLAB™ software). Bandpass-filtered tremor-dominant acceleration waveforms of the respective hand tremor can be recorded and analysed online for progressive status tracking during either the intraoperative test stimulations or reprogramming sessions of the implanted pulse generator. To this end, we analyse signal components of relevant movement events in the power spectrum and statistical metrics in the time domain.

Results:

Our study focuses on the principal dynamics of DBS input–output relationships. In practical terms, we can reliably identify relations between clinical outcomes capturing tremor dynamics and changes in electrical stimulation amplitude. Our preliminary results demonstrate that the developed techniques could be utilized to help clinicians to find optimal stimulation parameter settings. In addition, multiple observations during reprogramming sessions of deep brain stimulators have shown that features extracted from the wearable sensor data correlate with clinical rating scores.

Conclusion:

This work presents a first step toward the optimization of clinical outcomes for tremor patients based on systematic data capture and analysis. The future work will focus on pathological tremor modelling and on the long run to check, if the proposed signals may be usable for self-steering feedback controlled stimulators.

Introduction: The purpose of this study was to evaluate the accuracy of stereotactic electrode placement in patients undergoing deep brain stimulation by using pre- and post-operative stereotactic computed tomography (CT).

Material & Methodes: 23 patients with movement disorders (Parkinson disease (n = 7), tremor (n = 9), dystonia (n = 7)) treated with bilateral deep brain stimulation (DBS) (overall 46 target points) were investigated. The target point of the electrode was planned stereotactically in combination with a pre-operative stereotactic helical computed tomography (CT). A post-operative CT, which was carried out still in the operating room while the patient had the stereotactic frame on the head, was performed in order to control the position of the electrodes in relation to the previously planned target point. The position of the four electrode contacts was measured according to the Talairach space (AC-PC line) and compared with the coordinates of the planned target point. Image fusion by anatomical landmarks or the next day and other electrode positions than the calculated center electrode position in the 5 electrode carrier Ben’s Gun were an exclusion criterion.

Results: The mean spatial distance of planned target perpendicular to the electrode was 1.32 ± 0.75 mm.

Discussion: These results show the high accuracy of stereotactic implantation of DBS electrodes assisted by pre-and postoperative image fusion with computed tomography (CT).

While DBS of the STN is highly effective in treating PD motor symptomatology, a subset of patients may continue to be troubled by refractory DBS-responsive symptoms, despite appropriate lead placement and clinical optimization. Out of approximately 600 deep brain stimulation surgeries performed at our center over 10 years, 6 STN DBS patients (5 bilateral, 1 unilateral, 1 of whom underwent initial surgery at a different institution) received “rescue” DBS targeting a second brain area for additional control of their Parkinson’s symptoms. All patients had reasonable lead placement and tolerability, and experienced clinical improvement with STN stimulation. Unilateral globus pallidus interna (GPI) electrodes were placed in three patients for persistent dyskinesias, and three patients underwent unilateral ventral intermediate (VIM) thalamic electrode placement for breakthrough tremor.  All patients suffered from relatively young onset PD (median age of onset 34 years old, range 17- 43). The median age at surgery was 45 years old (range 36-53 yo). The median interval from PD onset to the first DBS surgery was 9 years (7-27 years), and between the first and second surgeries was 3 years (0.5-12 years).

In the three patients who received GPI leads, the symptoms that led to the first STN surgery were painful dystonia, dyskinesia and fluctuations. Although both improved with STN stimulation, they continued to experience troublesome dyskinesias despite reasonable lead placement, extensive programming and medication adjustments. All three reported significant improvement of dyskinesia following addition of the GPI rescue lead.

In three patients requiring addition of a VIM lead, all had severe tremor and one also had dyskinesia. All experienced moderate degree of tremor improvement with STN DBS but required high settings and continued to experience tremor breakthrough. All three subsequently experienced further tremor improvement, although two patients continued to have some residual positional tremors that impacted certain activities.

These cases, along with similar reports from other centers (Cook et al. 2015; Matias et al. 2016) demonstrate the potential for a second “rescue” lead – GPI for dyskinesias and VIM for tremor - to provide additional benefit in select cases.

Emerging evidence has demonstrated DBS to be efficacious in the treatment of refractory Tourette’s syndrome (TS), although the optimal target remains a matter of debate. Pallidal DBS has been reported as effective in treating both TS as well as Tardive Dyskinesia (TD). We present a case of a patient with co-morbid TS and TD referred for surgical intervention.
A 59 YO female with TS since childhood was referred to our center. Her condition was complicated by haloperidol-induced TD, characterized by facial movements and teeth grinding. Multiple medication trials were attempted, limited by side effects including worsening of tardive movements. The frequent neck tics caused radicular symptoms of severe neck and left shoulder pain. Initial exam demonstrated recurrent bruxism with tongue movements, brow lifting and frequent neck jerking movements. YGTSS: 18+0+30=48, YBOCS: 5+4=9.
The decision made to implant both CM thalamic and pallidal leads bilaterally. She underwent staged dual-lead DBS, with the left hemispheric leads followed by the right three weeks later. The GPI leads were initially programmed alone with improvement in teeth grinding but not tics leading to introduction of thalamic stimulation one month later with subsequent improvement in tics.
Postoperatively, her tics significantly diminished and her neck and shoulder pain completely resolved. Her teeth grinding transiently improved then returned despite several programming adjustments. She experienced continued OCD behaviors. 10 months post-DBS, her YGTSS: 8+0+10=18, YBOCS: 0+8=8.

Conclusions:

1. Simultaneous GPI and CM thalamic stimulation has proven well tolerated with no apparent stimulation-related side effects beyond those typically encountered with higher stimulation parameters with either target.
2. Thalamic stimulation led to a significant and sustained improvement in tics with less impact on OCD behaviors.
3. Meige-like tardive movements initially improved when only GPI DBS was initiated but recurred without significant lasting improvement to date.
4. Determining whether GPI or CM stimulation alone or in combination is most responsible for tic improvement is challenging but it appeared that tic improvement became more apparent following introduction of CM stimulation.

Abstract title:

Limiting brain penetrations during DBS surgery using an interventional-MRI guided DBS placement platform

Background:

Deep brain stimulation (DBS) has become a well-accepted surgical treatment option for medically refractory Parkinson’s disease.  The surgery traditionally has involved stereotactic techniques refined with microelectrode (MER) mapping and stimulation of the target.  These techniques may require multiple trajectory passes through the brain prior to final implantation of the leads.  There is evidence that the number of trajectories may increase the risk of hemorrhage.    Interventional-mri guided (iMRI) DBS is a new technique that allows real-time image guided implantation of the electrodes without MER or stimulation, limiting the number of passes through the brain.

Material/Methods

50 patients underwent iMRI guided implantation of DBS electrodes for Parkinson’s disease since September of 2011.   There were 23 female and 27 male patients.  Mean age was 67.8.  (SD 7.14)  Mean years with PD prior to surgery was 9.77 years (SD 5.73).  All patients underwent DBS implantation with the ClearPoint technique using a diagnostic MR scanner.  11 were implanted using a Siemens Symphony 1.5 T scanner, and 39 were implanted using a Siemens AERA 1.5T scanner. All had bilateral implants with 47 having had the STN as the target and 3 the GPi.

Results

100 leads were implanted via MRI guided technique.  For six leads, a second trajectory was performed for improved accuracy.  Our overall mean error in accuracy was 0.56 mm on the left and 0.63 mm on the right without the corrective trajectory.  With the correction our overall error was 0.56 mm on the left and 0.53 mm on the right.  We had an average of 1.06 passes for 100 DBS implants.  This compared to an average of 1.69 brain passes in our cohort of MER guided patients. (P<.005)

Conclusions

iMRI guided DBS implantation allows implantation of leads with reduced number of brain penetrations.  This may reduce the risk of surgical related hemorrhages compared to traditional MER guided surgery.

Background: For safe DBS planning an accurate visualization and localization of vessels is mandatory. Contrast enhanced (ce) MRI depicts both arteries and veins. Computed tomography angiography (CTA) detects arteries with high geometric accuracy. We routinely combine both modalities for DBS planning. In this study we analyzed the number and location of vessels visible in ceMRI and CTA in each trajectory.

Materials and Methods: A total of 222 trajectories in a consecutive series of 113 patients who underwent DBS operations from March 2014 to February 2017 were included. In all patients a preoperative T1-weighted 3D ceMRI sequence, a CTA and a postoperative native CT scan were available. In all 222 trajectories the number of veins and arteries in a 5 mm diameter around the planned trajectory was counted in both modalities (T1w-3D-ceMRI and CTA). If a vessel was visible in both modalities the distance was measured.

Results: A total of 371 vessels were counted in a total of 222 trajectories. 240 vessels (65%) were visible in both modalities. In 134 vessels we detected a difference of the vessel’s location with an average distance of 1.24 mm (SD 0.58). 81 vessels (22%) were visible only in ceMRI, 50 vessels (13%) only in CTA. We had a total of 4 bleedings in 3 patients (1.8% per lead) of which 1 was symptomatic (0.45%). All of them were implants into the subthalamic nucleus, one with a posterior approach. In all but one we performed microelectrode recording.

Conclusion: The majority of vessels were visible in both modalities. However, in more than half of these cases the location was not identical. Here, the location in CTA can be regarded as ground truth. Moreover, both CTA and ceMRI depicted vessels not seen in the other imaging modality. We therefore assume that the combination of both imaging modalities for DBS planning increases the chance to detect vessels along the planned trajectories, thus reducing the risk of intracranial bleeding. This assumption is supported by our low bleeding rate of 1.8%.

Objective:

Since a few years rechargeable pacemaker technology is available in deep brain stimulation. This technical innovation becomes more and more important in clinical practice, particularly for patients with a need for high energy delivery. Unforeseen handling issues, however, may compromise its use in certain patients.

Methods:

Over a period of ten years, 360 patients underwent deep brain stimulation for various indications. Rechargeable pacemakers are increasingly used upon replacement after battery depletion. Despite meticulous screening for suitability, we had to switch battery to non-rechargeable technology because of unforeseen technical difficulties in two patients.

Results:

A 73-year-old man with a high cognitive performance with Parkinson's disease, underwent bilateral deep brain stimulation in the internal globus pallidus. Pulse generators were replaced because of battery depletion in 2-year intervals. At the time of third replacement, it was decided to use rechargeable technology because of the relatively frequent need of pacemaker replacements. Two years later the patient requested to remove the pacemaker and reimplant a non-rechargeable once more because of increasing problems with handling of the recharger and inconvenience with the daily monitoring of the battery level.

A 62-year-old woman underwent bilateral deep brain stimulation in the nucleus accumbens for alcohol addiction. She needed biennial pacemaker replacements, the pacemaker was replaced against a rechargeable device at the time of the second replacement. Two years later system malfunction was detected with fracture of the extension cable secondary to twiddler's syndrome. The patient for the main part had had increased difficulties recharging the battery.

Conclusions:

Rechargeable pacemakers undoubtedly are a step forward in providing standard of care medical treatment. Many patients stand to benefit from rechargeable technology, smaller devices and fewer replacement operations. However, with new technology we also have new requirements concerning technical capabilities and compliance. Although removal of a rechargeable device before end of service of the battery and replacement with a non-rechargeable pacemaker poses an undue economic burden, it may be the only solution under certain circumstances to guarantee the benefit of chronic stimulation.

Objective:

Dystonic storm is a rare but life threatening condition. DBS or radiofrequency lesioning have been used in severe cases, however, there is no agreement on the optimal target. Patients who had already previous basal ganglia surgery pose a particular challenge with limited treatment options available.

Methods:

An 11-year-old boy with pallidal DBS for treatment of DYT-6 positive generalized dystonia since 2 years developed severe dystonic storm. After implantation of DBS electrodes at age 9 his condition had improved for more than 2 years. Upon the occurrence of dystonic storm, re-programing of DBS could not ameliorate the severe status dystonicus. Only sedation with high dose benzodiazepines, baclofen, gabapentin and trihexyphenidyl resulted in transient improvement.

Results:

The BMFDR motor score on admission was 138. MRI imaging showed positioning of the DBS electrodes in the globus pallidus internus (GPi), however, more lateral and posterior than at the usual target. It was decided to reimplant the GPi electrodes and to implant thalamic Vim electrodes in addition. Early postoperatively this resulted in marked and immediate improvement of dystonic storm (BMFDRS 100,5). At 12-month follow-up, there was remarkable benefit and the patient could walk and attend school without medication.

Conclusion:

Dystonic storm may develop despite periods of beneficial response to pallidal DBS for several years. If electrodes are no optimally placed in the posteroventral lateral GPi, repositioning should be considered, which might not only abate status dystonicus, but also provide lasting benefits.

Mounting the stereotactic frame is one of the most crucial steps in deep brain stimulation surgeries. In the routine clinical practice, we aim to mount the frame as symmetrical as possible parallel to the Reid’s line. However, in several cases the frame is mounted asymmetrical, often due to patient-related reasons. In this study, we addressed the question whether this influences the accuracy of stereotactic electrode implantation, and if yes, to which extent. A citrullus lanatus was used for this study. Symmetric and asymmetric mounting of the frame was performed and CT and MR images were obtained. Three different stereotactic software packages were used to analyze the results. In addition, manual calculations were performed. We have found that an asymmetrically mounted frame (deviated, tilted or rotated) does not affect the accuracy in the medio-lateral axis (X coordinate) or the antero-posterior axis (Y coordinate). However, it can lead to a clinically relevant error in the supero-inferior axis (Z coordinate). These results suggest that asymmetrical frame mounting can lead to stereotactic inaccuracy.  

Background: The non-elective surgical revision of deep brain stimulation (DBS) patients is a growing concern amongst neurosurgeons. Scarce literature is available concerning the surgical management of DBS complications, particularly the non-infectious kind and there are no globally accepted guidelines on how to handle these complications. Furthermore, both the epidemiology and surgical management provided in each case vary greatly and are therefore worthy of study.

Methods: Retrospective cohort study of patients submitted to DBS surgery between 2006 and 2016 at our centre. The demographics - gender, age - and clinical variables - disease, the reason for non-elective re-intervention, and the performed surgical technique - were analysed.

Results: 195 patients were included (119 males; 76 females). The majority suffered from Parkinson’s disease (PD)–166 (85.1%) versus 25(12.8%) with Dystonia (DYST) and 2 (1%) with Essential Tremor (ET) and 2 (1%) with Tourette Syndrome. 18 non-elective surgical interventions were performed– 9% of treated patients (88.9% DP–16 patients and 11.1% DYST–2 patients). In this subgroup, 8 patients had an infection (44.4%), 1 had a central nervous system infection, 5 presented with hardware exposure and 4 displayed a foreign body reaction. An initial system-preserving technique (non-removal of the entire system) was used for every patient as a first line treatment. Only 3 patients (16.7%) required a second surgery for removal of the entire system, of which 2 presented with an infection of the subclavian IPG pouch and 1 with hardware exposure. Neither PD, nor DYST were related with an increased risk for non-programmed surgical intervention (p-value=0.596).

Conclusions: Even though entire system removal has been the consensual approach to DBS-related complications, this data supports that a system-preserving technique is of high-value and should be taken into consideration whilst planning for a surgical revision of patients presenting with these complications.

Objective: Subthalamic nucleus (STN) is a widely used anatomical target in deep brain stimulation (DBS) surgery. Highly precise targeting the STN in Parkinson’s disease is vital. Furthermore, the length of the STN passed by the final electrode is desired to be as possible as long to achieve more stimulation combinations and flexibility in further programming. For these reasons, we questioned the relation between different stereotactic approach angles and clinical parameters in our series of STN DBS surgeries.

Methods: The DBS database of Maastricht University Medical Center Neurosurgery Department between 2005 and 2015 was retrospectively analyzed. Patient demographics, preoperative and postoperative UPDRS-III (Unified Parkinson Disease Rating Scale) scores, levodopa equivalent doses (LED), intraoperative microelectrode recording (MER) data and sagittal and coronal stereotactic angles were documented. 94 STNs of 51 patients met the criteria and were included into study. Effects of stereotactic angles were analyzed statistically.

Results: Twenty-two patients were females and 29 were males. Mean electrophysiological STN length was calculated 4.7 mm ±1.5SD (0.5-7.5). The mean sagittal angle of approach was 57.2° ±10.3SD (34.2-83.9) and the coronal angle was 24.8° ±5.7SD (11.6-52.0). A mean 44.3% decrease was found between preoperative and postoperative med-off UPDRS-III scores. Postoperative analysis for levodopa doses showed a mean 50.9% decrease in postoperative LED. Two tailed correlation analysis between groups showed a positive correlation between the length of electrophysiological motor STN and postoperative percentage of the LED decrease. Correlation analyses performed between groups also showed a negative correlation between sagittal angle and percentage of UPDRS-III decrease. Another significant negative correlation was also found between the sagittal angle and STN length.

Conclusion: Our study showed that a lower sagittal trajectory angle (around 50°) is correlated with a longer electrophysiological STN and better improvement in postoperative UPDRS score. However, the coronal angle did not affect the clinical and electrophysiological parameters. Another interesting finding was that a longer intraoperative STN recording was related to a lower postoperative LED. Thus, we may speculate that a patient with longer STN recording may require less dopaminergic medication postoperatively.    

Objective: Camptocormia is a disabling syndrome characterized by forward flexion that can be an idiopathic or associated with numerous diseases like movement disorders, especially Parkinson's disease (PD). Treatment options are usually futile and L-dopa shows little or no effect. Posture improvement could be expected in bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) or subthalamic nucleus (STN) in PD patients with camptocormia. Outcome results are inconsistent, especially for STN. The aim of this study was to determine the efficacy of bilateral STN DBS in alleviating the degree of camptocormia in two PD patients.

Patients and methods: Two patients (67 year old female and a 66 year old male) suffering from PD in the last ten years and more were subjected to bilateral STN DBS procedure. The positions of electrodes were verified with a postoperative magnetic resonance imaging. The results were objectivized by measuring thoracolumbar flexion angle before and after operation and using all recommended scales for the international survey of DBS.

Results: The degree of forward flexion of the spine has substantially decreased and the quality of life, motor symptoms and functioning improved in both patients. 

Conclusion: STN DBS should be considered as a potential treatment option for PD patients with camptocormia. Further analysis is needed to conclude what PD patients are candidates for bilateral STN or GPi stimulation in the treatment of camptocormia.

Introduction
Deep brain stimulation (DBS) is used for the treatment of movement disorders in Parkinson’s disease (PD) and the standard targets are globus Pallidus interna (GPi) and subthalamic nucleus (STN)[1]. DBS can improve the psychiatric symptoms by altering the tonic activity of subcortical circuits but the exact mechanism is still remains unclear[2]. In STN stimulation some transient manias, or hallucinations complications reported, but these complications usually occurred after onset of STN stimulation. We want to share our two patient’s experiences who developed agitated psychosis and hallucinations complications, immediately after bilateral STN DBS implantation but before stimulation on.
Material & Method
The patient’s ages were 48 and 51 years old they had no prior psychiatric history. They were underwent to operations without prior medication interruption. Three guide cannulas were passed first on left and later on right. On each side and microelectrode recording (MER) was recorded from 5.0 mm above to 2.0 mm below the target. In two patients during the right side MER, hallucinations and meaningless speech developed. The patients were took quickly to the computerized tomography (CT) after the macrostimulation and skin closure. CT scans did not reveal any abnormality. The first patient underwent to operation theatre again for implantable pulse generator implantation and after the operation he was taken to intensive care unit (ICU). The pulse generator implantation of the second patient was made after 7 days. The second patients’ agitation and hallucination complications was ceased only 3 or 4 hours after and he didn't remember anything. However, complications of the first patient prolonged approximately 6 or 7 days.
Discussion
Both patients DBS leads were placed within STN and substantia nigra (SN). Injury of SN (esp. in young patients) may lead to excess dopamine release (Particularly when medication is on). The injury on ventral STN and SN especially in young patients may associated with limbic side effects.
Conclusion
There are a lot of report about psychosis as a consequence of electrical STN stimulation, but the report about to arise directly from injury of STN and surrounding structures by a DBS lead is limited. Immediately anesthesia after the delirium symptoms may be questioned therefore the second part of the surgery may be postponed.

Introduction

Surgical site infections are a problematic complication in deep brain stimulation, with estimates ranging as high as 10%.  Application of vancomycin powder to the surgical bed prior to closure has shown positive results in instrumented spine surgery.  To assess its impact in reducing infections in deep brain stimulation (DBS) surgery, we compared a prospective cohort of patients undergoing DBS lead and generator placements using vancomycin powder with a retrospective cohort off patients that did not receive vancomycin powder. 

 Methods

A total of 450 DBS cases were included between April 2015 and December 2016 (215 cases without vancomycin powder, analyzed retrospectively and 235 cases, analyzed prospectively with vancomycin powder) with a minimum of three month follow-up. Operations included all DBS lead insertions, extension wire and pulse generator implantations and generator exchanges. A surgical site infection was defined as culture positive evidence of infection that necessitated antibiotic therapy and/or removal of hardware, including superficial wound infections. Infection rates were recorded and compared.

Results

Infections were noted in 5/215 (2.3%) of the pre-vancomycin powder group compared to only 1/235 (0.4%) in the vancomycin powder group. The sole infection in the vancomycin powder group consisted of a patient who presented with gross infection of the left chest generator necessitating removal of the entire system.  Culture data tested positive for methicillin-sensitive S. aureus and was successfully treated with a prolonged course of intravenous antibiotics.

Conclusion

The use of vancomycin powder in DBS surgery appears to be a safe and feasible protocol to decrease surgical site infections without increasing the risk of antibiotic resistant organisms.  Larger prospective randomized trials are necessary to determine vancomycin powders ability to significantly reduced the infection rate in DBS surgery.

Abstract:

Introduction: Deep brain stimulation (DBS) has been applied to treat various neurological disorders and to record from different brain regions. The effects of electrical stimulation of different brain parts on cardiovascular physiology have been investigated in several reports. Here in, we review brain stimulation effects on cardiovascular function.

Methods: A systematic review of the English literature using PubMed search. Brain targets resulted in clinical cardiovascular effects with DBS were included. Cortical stimulation was excluded. The stimulated targets were classified based on anatomical location and type of cardiovascular effect.

Results: Intraoperative electrical stimulation of Subthalamic nucleus (STN) showed heart rate (HR) increment in several studies, particularly dorsal stimulation of STN in contrast to ventral. Globus pallidus internus (GPi) stimulation evoked a paradoxical arousal reaction resulted in transient increase in blood pressure (BP). Moreover, amygdaloid nucleus and nucleus accumbens (NAc) DBS showed an increase in both HR and BP. Hypothalamic stimulation varied with the site of stimulation. Posterior hypothalamic area showed no change in HR or BP, whereas Ventroposterior Hypothalamus and Posteriomedial hypothalamus showed an increase in both.  In regards to periaqueductal gray matter/periventricular gray matter (PAG/PVG) DBS, decrement in BP was noted with stimulation of the ventral part and an increment with dorsal stimulation.

Conclusion: STN is the most studied target. Other targets that showed positive cardiovascular effect include amygdala, NAc, hypothalamus and PVG/PAG. Stimulating the GPi, per se, does not appear to have any positive effects. In addition to various neurological disorders, DBS could be used in the future to treat disorders related to the cardiovascular system.

Introduction

The electric field (EF) around the active deep brain stimulation (DBS) contact is of interest for optimizing the therapeutic effect. We have previously developed a method for simulation and visualization of the EF. The aim of the project is to improve the software for quick and user friendly simulations.  

Methods

The ELMA software for brain model creation has been improved by adding quick ROI selection and transformation to an electrical conductivity map based on tissue classification through multiple slices of the preoperative MRI. These data are used as input for Comsol Multiphysics simulations of the EF. Two points along the position of the lead, as seen in the postoperative images, are used for correct placement in the brain model. Multiple DBS lead models are pre-programmed. The active contact and amplitude are user-selected.

Results

After a simulation the result is visualized with a user defined isolevel or isosurface superimposed on the patients preoperative MRI. An example is shown in Fig. 1. The 3389 lead is places in zona inserta (Zi) and contact 1 activated with 2 and 4 V respectively. An isolevel of 0.2 V/mm is used corresponding to a ~ 3-4 µm axon diameter when using a pulse length of 60 µs. More examples will be presented at the meeting.

Conclusion

The software for patient-specific simulations of EF around DBS electrodes has been improved for quicker simulations and more DBS leads. As a next step user friendly Apps will be implemented.

Purpose: Previously deep brain stimulation revision due to misplaced leads from targets were reported previously. However, the importance of trajectory angle is not well known. Anteriorly slanted low ring angled trajectories may be farther from sensory-motor subthalamic nucleus and closer to corticospinal tracts with lower outcomes and side-effects.

Materials and methods: Among 200 patients treated by deep brain stimulation from March 2013 to Dec 2016 in the Asan Medical Center by one neurosurgeon and one neurologist (J.K. Lee and C.S. Lee), subthalamic lead reposition cases were collected. Patients with ring angles < 55° were defined as having low ring angle trajectory. We defined trajectory revision as the ring angle change ≥ 15°. Patient’s global impression (PGI) were scored postoperatively. For a subgroup of four referred patients with six leads we could collect ring angles of all operated cohort by a surgeon. The ring angles of these patients were compared to patients indicated for revisions.

Results: Leads were repositioned in nine patients of 15 electrodes. Intervals between the initial lead insertions and revisions ranged from 1 to 157 months (median: 38 months). Before revision, patients improved by 24±19 % (0 – 55 %) in UPDRS part III motor scores. All patients indicated for revision showed various side effects and suboptimal outcomes.

Five of fifteen leads (33 %) indicated for revisions had low ring angles, < 55°. In seven of fifteen leads (47 %), ring angles were increased ≥ 15°. Patients improved in PGI (patients’ global impression of improvement) scores by 1.2±1.5. Patients with either target or trajectory revisions showed improvements in PGI scores except one patient with PGI score -1.

For all subthalamic 40 leads operated by surgeon A, mean ring angles were 55±8°. Revised leads previously operated by surgeon A had 47±7°, significantly lower than the all surgery patients by the surgeon A (p = 0.02) in Mann-Whitney U test.

Conclusion: We show that low ring angled trajectory may be associated with suboptimal outcome which are indicated for revisions. A subgroup of patients who had suboptimal outcomes had low ring angles. Previously, only target revisions were reported for DBS. Low ring angled trajectory which can be closer to corticospinal tracts and farther from sensory-motor STN may be a potential target of DBS revision.

Objectives: Conventional deep brain stimulation (DBS) leads stimulate brain targets in a nondirectional fashion, whereas directional DBS leads with segmented electrodes allow for more flexibility in shaping the stimulation field. The latter may be used to optimize therapeutic efficacy and reduce stimulation-related side-effects. A computational model was used to evaluate directional neural activation in the subthalamic nucleus (STN) resulting from stimulation with the Infinity^TM DBS lead (Abbott, Plano, TX).

Methods: A two-stage computational model of STN-DBS was used to analyze neural activation generated with the Infinity directional lead (1.5 mm spacing, 1-3-3-1 configuration). The first stage involved using a finite element analysis (FEA) model to calculate electrical potentials generated in the brain with cathodic monopolar DBS (1.5 mA, 90 µs). The FEA model incorporated a multimodal, imaging-based detailed anatomical (MIDA) model of the human head, and the DBS lead was placed with contact 1 at the ventral STN boundary and surrounded by a 0.5mm thick encapsulation layer. In the second stage, electrical potentials from the FEA model were coupled to biophysical cellular models of 1,000 STN projection neurons with realistic morphological and electrophysiological characteristics. Volume of tissue activation (VTA) was compared between nondirectional (segments 2A-C) and unidirectional (segment 2A) DBS. The extent of directionality was calculated as the percentage of VTA volume on the side of the lead with segment 2A.

Results: VTAs were distinct for nondirectional and unidirectional DBS (Figure). At 1.5 mA amplitude, the VTA volume was larger with unidirectional stimulation (4.29 mm³) than nondirectional stimulation (3.85 mm³). Additionally, the extent of directionality was greater for unidirectional stimulation (93%) compared to nondirectional stimulation (56%).

Conclusion: An anatomically-precise computational model of STN-DBS demonstrated that unidirectional stimulation increases directionality in the region of neural activation and produces a larger VTA volume at a given stimulation amplitude, compared to nondirectional stimulation. Clinically, these results indicate that directional DBS leads may be used to increase the therapeutic window by providing a customized stimulation field focused only on targeted brain regions, and may increase battery life by reducing the stimulation amplitude required to activate a given volume of tissue [Rebelo NANS 2017].

Imaging techniques have revealed that several cortical brain regions like the prefrontal cortex, the anterior cingulate cortex, and the posterior parietal cortex are involved in the maintenance of cognitive flexibility. However, the role of basal ganglia in the ability to switch between several concepts remains unknown. To address this issue we recorded local field potentials from the nucleus subthalamicus (STN) while participants performed a task that required executive processes like planning and set shifting. Seven patients with Parkinson disease that underwent STN deep brain stimulation have been included in the study. The patients performed a computerized version of the Wisconsin Card Sorting Test. The participants were required to match the cards according to three possible matching rules (color, shape and number). After the sorting choice was made, a feedback ‘switch’ or ‘repeat’ indicated that the rule had to be changed or repeated respectively. Integration cue is the first repeat cue following a shift cue. The results show that the amplitudes of the integration cue are larger than those of the repeat cue. Integration condition induced oscillatory changes with the highest power in the theta band in comparison to the repeat condition. Moreover, there is a significant late higher activation of beta band for the integration trials. In conclusion, there are broadband oscillatory changes in the STN during executive processes. STN appears to be involved in shifting cognitive sets and modulating responses.

Deep brain stimulation (DBS) is an effective therapy for Parkinson's disease and dystonia, as well as some other evolving indications. This therapy has been utilized since 1990 in many centers across the world, and in many countries and cities more than one center is providing this therapy. Yet, many large parts of the developing world still miss such therapy due to numerous strategic and economic issues. Establishing a new center in a developing country faces unique challenges and dilemmas for the responsible team.

We established the DBS surgery program in Shiraz in 2014, as the second center in Iran with a population of over 80 million people countrywide. Shiraz is one of the major cities located in the Southeast of the country, and is the major referral medical center for most of the Southern provinces, covering one fourth of the whole population.

We started DBS surgery in Shiraz with the support of the new national health reform program since 2014. Loyalty to the team work principles and provision of enough international exposure and training to the whole team were essential considerations in our experience. Major changes have occurred in the team, technique, hardware, programming, and financial supply since the beginning, which are thoroughly discussed in this presentation. 

Background

Even though the clinicians as well as the patients have an idea of when it is time to exchange the neuro-stimulator (NS) due to reduced battery capacity, it is not always the exchange is done before depletion due to various reasons. Due to changes in the management of scheduled NS exchange 16% of the patients had total DBS treatment arrest due to battery depletion before exchange. 

Aim 

Investigate consequences of DBS treatment arrest due to depleted NS batteries in terms of reoccurrence of symptoms and time to recovery after exchange and which actions that were  taken while waiting for surgery. 

Method  

The patient records for the 23 out of the 25 whom during the years 2015 and 2016 had battery depletion before the exchange of NS were reviewed.  Diagnosis, target(s) consequences (hospital care, increased home care, symptoms etc.), reason (hospital or patient delay) time between decreased battery capacity and battery depletion, DBS settings and time until recovery.  

Result 

In most patients the hospital delay were the major reason for depletion. The majority (n=13) had Parkinson’s disease (PD), followed by essential tremor (n=7) and dystonia (n=3). All patents had bilateral electrodes, 11 of them had bilateral NS. DBS targets were Thalamus VIM, STN and GPi. The time between battery depletion and exchange 0 to 57 days and during this time 3 patients were hospitalized (or nursing home). In PD the medication was increased especially in those with one dual channel NS. All patients’ their movement disorder symptoms were perceived as worsened. Family members or care givers needed to help/support in everyday activities.  

None of the patients had a life-threatening condition and all perceived good DBS effects (may be not as good as before depletion) after the DBS has been optimally programmed (1-6 mth postop).

Conclusion 

Battery depletion had severe impact on the patients and their families’ everyday life due to severe movement disorder symptoms, furthermore it also increased the healthcare needed especially in patients with PD pre- as well as postoperative. Thus, it is really worthwhile minimizing time without DBS treatment due to battery depletion and it is better to exchange NS sooner than later and create routines for calling nursing care homes for report of residual battery capacity.  

Introduction: Infection is estimated to affect 5-15% of DBS implantation cases. IPG infections are more common than intracerebral infections, but likely these figures have been underreported. Device-related infections are most often associated with Staph aureus, but other pathogens may be encountered. Especially as the volume of DBS procedures increases, we anticipate unusual infectious complications. We review a single center's experience with DBS-related infections.

Methods: A retrospective review of all DBS-related procedures performed by a single surgeon was performed. Both new system implantations, generator exchanges and other procedures were cataloged, and not was made of any infection that required further surgical treatment for infections. A survey of the pathogen involved was performed and antibiotic susceptibilities noted. Patient outcomes are summarized.

Results: IPG site infections occurred more often than extension site or intracranial infections. While Staphylococcus aureus was the most common pathogen in this series, other notable pathogens included other Staphylococcus species, Enterebacter cloacae, Klebsiella pneumoniae, and Candida parapsilosis. These unusual cases are discussed in detail.

Conclusion:While infectious complications of DBS are uncommon, the incidence of infection and the range of pathogens should be appreciated.

Background and Purpose: Automatic segmentation methods are gaining relevancy in image-based targeting of neural structures. In order to evaluate the feasibility of such approaches we retrospectively analyzed the concordance of MR-imaging based automatic segmentation of the Subthalamic Nucleus (STN) and intraoperatively recorded mircoelectrode recordings (MER).

 Methods: The data of ten patients STN-implanted with 20 DBS electrodes for the treatment of PD (9) and dystonia (1) were processed using Brainlab Elements Anatomical Mapping segmentation of the STN – with two volumetric T1 (with and without contrast) and volumetric T2 images as input. The stereotactic CT was co-registered with that imaging and the stereotactic coordinates for these cases originally planned using ELEKTA Surgiplan were imported, so that the actually surgically executed trajectories could be overlaid onto the segmentation. Records of the electrophysiology (MER, measured in 0.5 mm steps) along the central trajectory were analyzed with respect to distance of noted STN entry and STN exit to the segmented STN boundary (40 distances).

 Results: In none of the patients did the independently pre-planned trajectory miss the subsequently segmented STN - indicating a good overlap of the trajectory planning concept employed in our center and the automatic segmentations. Along those trajectories the electrophysiological STN entry deviated (median) 1,6 mm (n=20, min=0, max=4,5) and the STN exit deviated 0,7 mm (n=20, min=0, max=3,9) from the segmented STN boundary. In 8 instances the STN entry showed electrophysiologicaly deeper (closer to target) than the segmented boundary (12 instances STN entry was recorded higher than the boundary), in 2 instances the STN exit showed electrophysiologicaly higher (still within than the STN boundary) and in 18 instances deeper, respectively.

 Conclusions: In the trajectories analyzed with intraoperative MER, the electrophysiological borders of the STN and the borders of the automatically segmented STN in the MRIs had a high level of concordance. To further characterize this observation, we are currently analyzing a larger patient cohort and factoring in recordings from alternate tracks. If this trend is confirmed, automatic three-dimensional segmentation of the STN is an exciting method to visualize patient anatomy for neurosurgeons and neurologists.

The Wake Up Time Evaluation After Subthalamic Nucleus Deep Brain Stimulation Surgery – Pilot Study

Introduction

Deep brain stimulation surgery (DBSS) is the treatment modality for medical refractory movement disorders especially Parkinson's disease (PD), essential tremor and dystonia. The Subthalamic Nucleus (STN) and the Globus Pallidus Internus are accepted effective areas for PD.

DBSS could be separate in two parts. The first part is the placement of the electrode(s) and the second part is the implantation of impulse generator.

Several reports suggested that the first part of the operation should be make awake because to verify that the test stimulation of the electrode improves the patient's symptoms with minimal side-effects. The second part of the surgery could be made by cervical regional anesthesia or under general anesthesia.

The management of the patients after the general anesthesia is important and it continues until the patient has returned to their physiological preoperative state. Especially in PD the postoperative management is important because the PD patients are more sensitive to sedatives and are prone to hypoventilation. The Aldrete scoring system (ASS) is the most widely used scoring system to clinically assess the status of the patients about recovering from anesthesia. The maximum score of the ASS is 10 and the minimum is 2 and when the ASS reached up to nine the patients assume as returned to their physiological preoperative state and could be sent from postoperative care unit.

Material Method

6 patients were presented with PD that were undergone STN DBSS reviewed. The first part of the surgery was made under local anesthesia and the second part of the surgery was made under general anesthesia. The time interval from the extubating time to reach up score 9 according to ASS has been calculated (Wake up time).

Results

The minimum and maximum wake up time has been found 13 minutes and 15 minutes respectively and the mean wake up time has been found 14,2 minutes.

Discussion and Conclusion

There are a few reports in the literature about the recovering time from anesthesia after DBSS. Our aim to evaluate and compare the recovering time of DBSS with other surgeries. The number of patients are insufficient because our study is a pilot study and it is still continue.

Introduction: Subthalamic nucleus (STN) and globus pallidus (GPi) targets for deep brain stimulation (DBS) can be defined by reference to atlas coordinates or direct visualisation of the target on MRI. The aim of this study was to evaluate the difference between atlas-based targeting and direct MRI guided targeting. Methods: We reviewed prospectively collected records of adult patients who underwent DBS surgery from 2007 to 2016. MRI guided targeting was used to implant 206 STN electrodes and 62 GPi electrodes in 139 patients with Parkinson disease or dystonia. Surgery was performed using a Leksell G frame and targeting performed on 2mm thick T2 weighted MRI (for STN) and proton density (for GPi) scans acquired preoperatively. The Cartesian STN and GPi coordinates were normalised to the AC-PC plane and compared with atlas coordinates. Atlas STN coordinates were 12mm lateral (x), 2mm posterior (y) and 4 mm ventral (z); atlas GPi coordinates were 22mm lateral (x), 2 mm anterior (y), and 4 mm ventral (z) in relation to the AC– PC plane (y=distance from midpoint of AC-PC line). Results: The directly targeted coordinates (mean, SD, range) for STN were: x (9.9 ± 1.1 (7.1 – 13.2)), y (-0.8 ± 1.1 (-4.2 – 2)), z (-4.7 ± 0.59 (-5.9 - -1.5)) and for GPi were: x (22.3 ± 2.0 (17.8 – 26.1)), y (-0.2 ± 2.1 (-4.5 – 3.4)), z (-4.3 ± 0.8 (-6.1 – -2.3)). The mean of the directly visualised STN was 2.1mm more medial (4.9 to -1.2, p < 0.0001), 0.2mm more anterior (-2.2 to -6, p < 0.0001) and 0.7mm more ventral (-1.9 to 2.5, p < 0.0001) than the atlas target. The mean of the directly visualised GPi target was 0.3mm (-4.2 to 4.1) more medial (not significant) 2.2mm (-6.5 to 1.4, p < 0.001) more posterior and 0.3mm (-2.1 to 1.7, p=0.009) more ventral than atlas coordinates. Conclusions: MRI guided direct targeting may be more accurate than atlas based targeting due to individual variations in anatomy. 

Background:Alterations in iron homeostasis can participate in development of Parkinson disease (PD) due to accumulation of iron in the substantia nigra. Blood serum concentration of labile iron, transferrin and ferritin play important role in transfer of peripheral iron into the brain. Deep brain stimulation (DBS) is an established and effective method of treatment of motor symptoms in PD. DBS delivers a constant low, electrical current to a small region of the brain through implanted electrodes.  The aim of this study was to evaluate changes in iron metabolism in PD patients after DBS. Methods:Examined group consisted of 18 patients with PD: 13 patients who underwent unilateral implantation of electrode in subthalamic nucleus (STN), 4 patients who underwent bilateral implantation of electrodes into the STN , and 1 who underwent unilateral thalamotomy, 3 patients with dystonia : 1 with unilateral GPi electrode implantation , 1 with bilateral GPi electrode implantation and 1 with pallidotomy, Another 1 patient with essential tremor who underwent thalamotomy.Iron, ferritin and transferrin blood levels were assessed before and at least 12 hours after the commencement of DBS or the day after surgery.Results: The reduction of iron concentration after the electric stimulation was significant from 13,8 umol/l before to 7,7 umol/l on stimulation. After stimulation a significant rise of ferritin (from 146 ng/ml before to 181,3 ng/ml after)(p=0,023), significant reduction of transferrin concentration from 2,4 to 2,1 g/l (p=0,001) and reduction of transferrin saturation from 24,6% to 13,3% (p=0,001) were observed.In group of patients who underwent thalamotomy or pallidotomy there were no statistically significant differences in iron concentrations (17,4umol/l  and 13,3umol/l; p=0,46 ), ferritin levels ( 168ng/l and 197ng/l p=0,7), transferrin levels before and after surgery (2,41g/l and 2,41g/l  p=1,0) and transferrin saturation (29,8% and 22,7% p=0,54).Conclusions:Alterations in iron metabolism can be seen after surgeries with implantation of neurostimulators and further with electric DBS, but are not observed after lesion surgeries without postoperative electric stimulation. Findings of this study indicate that DBS by delivering electric current, alternates the iron metabolism in PD patients. It could suggest that DBS not only improves motor symptoms, but may also influence on pathogenesis of this disease, which is associated with proper iron homeostasis.

The direct antidyskinetic effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson’s disease (PD) patients with levodopa-induced dyskinesia (LID) is provided by involvement of the white matter above the STN into the stimulation. For this purpose bipolar stimulation or monopolar two-contact stimulation with active contacts within the aforementioned structures is performed.

We observed the direct relief of LID as well as appropriate antiparkinsonian effect by monopolar stimulation by one contact located on the boundary of anterodorsal STN and the area above the STN.

Materials and Methods: A 60-year-old woman with 6-year history of akinetic-rigid PD with on-of motor fluctuations and severe peak-dose dyskinesia (levodopa equivalent dose = 1580 mg/day) underwent bilateral STN-DBS procedure according to the standard stereotactic coordinates. Postoperative CT-MRI fusion demonstrated mild proximal dislocation of both electrodes in such a way that the most distal contacts were located on the boundary of anterodorsal STN and the white matter above the STN. The patient underwent monopolar stimulation using both most distal contacts (130 Hz, 60 msec, 2,5V). There was no adverse effects.  The levodopa dosage was unchanged perioperatively.

Results: During the follow up pre-existing choreiform LID transformed into akathisia and after the first month of stimulation the complete control of LID was observed. Almost complete control of OFF-state motor symptoms and motor fluctuations was achieved. The patient’s quality of life improved significantly. After two months of follow up the daily levodopa equivalent dose was gradually reduced to 300 mg/day.

Conclusions: Monopolar one-contact stimulation on the boundary of anterodorsal STN and the area above the STN was observed to induce direct relief of LID as well as appropriate antiparkinsonian effect.

Introduction: In this study we analyze the electrode–brain interface (EBI) in the globus pallidus internus (GPI) and the estimated electrical field density geometry and radial extension required to induce an internal capsule and optic tract clinical response.

Methods: A total of 184 electrode contacts implanted in the GPI were analyzed. The anatomical distance between the center of each contact and the optic tract and internal capsule was measured on the magnetic resonance image (MRI). Monopolar electrical stimulation was applied to elicit a clinical response from the internal capsule and optic tract. The threshold-distance data for the estimated electrical field ET (V/mm).

Results: Five contacts were excluded due to relatively high impedance. The mean distance between the distal contact and optic tract was 1.84 mm, and the mean distance from the electrodes’ nearest contacts to the internal capsule was 3.4 mm. DBS stimulation parameters were at 60 us, 130 Hz, and monopolar mode. The clinical response threshold was 0.8 V/mm for optic tract and 1.2 V/mm for the internal capsule. The overall estimated isolevel of the electrical field that activated a clinical response around each contact was 2.4 mm at 1 volt stimulation.

Conclusion: This study revealed the extent of electrical field delivered from a cylindrical electrode contact. Utilizing an electrode with multiple small contacts to steer the electrical field toward the target can minimize the unintended stimulation side effects.

Study’s Objectives:

To determine the long-term levodopa equivalent dose (LED) drug reduction following deep brain stimulation (DBS) of subthalamic nucleus (STN) in Parkinson’s patients.

Methods Used:

Retrospective observational study of 106 Parkinson’s disease (PD) patients who underwent bilateral STN stimulation between October 2002 and December 2014.

Variables recorded included age, sex, first symptom, date of diagnosis of PD, duration of diagnosis at operation date, last clinical follow up. Also, the voltage, rate and pulse width of DBS in last clinical follow up were recorded.

Medications at both preoperative and last clinical follow up were recorded and total LED dose in milligrams were calculated using Parkinson’s disease measurement calculator.

 Results:

Of the 106 patients, 70 were male and 36 were female.

The average preoperative total LED  was 1352.13 mg and the post operative total LED was 618.86mg.

The average percentage of drug reduction post DBS was 48.25 % at the last clinic follow up .The median period of follow up post DBS was 45.5 months ( 3.7 years, Range = 9.8 months (0.8 years ) -154 months ( 12.7 years).

Using Spearman’s Correlation coefficients, there was a negligible correlation between the percentage reduction in LED and the duration of follow up (rho=-0.01, p=0.93) and also between the post-operative LED and duration of follow-up (rho=0.004, p=0.97). This implies that both the percentage reduction in LED and post-operative LED are maintained over time.

Also, noted was a weak , but non-significant positive correlation between the duration of diagnosis and the percentage of drug reduction (rho=0.17,p=0.139) implying that patients with longstanding disease had a greater percentage reduction in LED at the final follow up but statistically not significant.

Conclusion:

Our study confirms that LED reduction does not change significantly in the long term for patient with STN DBS which suggests that DBS may have a protective neuro-modulatory effect.

Bilateral deep brain stimulation (DBS) of the thalamic Vim nucleus has been accepted as the standard treatment for essential tremor (ET), but results are limited by side effects such as speech impairment, ataxia and stimulation tolerance in long term¹; in extreme cases reoperation may be required². More recently, stimulation of the caudal Zona Incerta (cZI)³ emerged as a promising target for tremor control, aiming the ascending cerebello-rubro-thalamic fibers with encouraging results. We proposed bilateral implantation of 8-contact-electrodes aligning the VIM and the cZI in the same trajectory, offering multiple stimulation targets with no additional risk for the patient. The index case of refractory ET treated with bilateral double target DBS is presented here. A 65-year-old man diagnosed with ET for 49 years referred progressive functional impairment especially in the last 5 years. Action tremor was quite disabling, particularly when trying to perform simple daily tasks, such as grabbing a cup, using a fork or shaving. Stigmatizing tremor also compromised his professional activity as salesman. He scored 37/144 in Fahn-Tolosa-Marin Tremor Rating Scale (FTMRS) even receiving propranolol 40mg/day and primidone 700 mg/day limited by side effects. Bilateral DBS was proposed as a treatment option for the tremor, which was performed using 8-contact leads. The stereotactic planning included the Vim and the cZI in one straight trajectory in each side according to the anatomy of the region. As a single trajectory was performed in each side, no additional risk for the patient was taken. In the first 6 weeks, the therapeutic window (130Hz and 60µs) was tested in each of the contacts. Satisfactory tremor control was achieved with monopolar stimulation in upper contacts (Vim) and also in lower ones (cZI), with different profiles of adverse effects. Since the tremor control was outstanding and no significant side effects were observed at the level of cZi (monopolar stimulation in contact 3 as the cathode), we kept this as therapeutic stimulation for 10 months. The patient experienced close to full tremor control most of the time and we observed 86% improvement in global scores in FTMRS (5/144). Tremor amplitude in the dominant hand was also assessed by accelerometry (Lift Pulse Software - Lift Labs, USA) with 92,3% improvement when compared to no stimulation. Studies comprising more cases can determine which level of this complex region is best for tremor control.

Background: Deep Brain Stimulation(DBS) has been traditionaly implanted with non rechargeable battery.Some groups argue that the implantation of the rechargeable battery is associated wiht difficulty to learn to handle it,pain in the moment of recharghing it and the much greater cost of the system.Nevertheless,the implantation of rechargeable battery since the electrodes are implanted for the first time,or in the replacement of the previous non rechargeable battery is increasing in some centers like ours.

Objective:To report clinical follow-up in 87 patients who underwent DBS with rechargeable battery.Criteria inclusion,follow up and satisfaction survey.

Methods:  87 patients between 13 and 77 years old,56% female,in a period of time between December 2012-February 2017 and follow up between 1-50 months,underwent DBS mainly for movements disorders,but also for psychiatric,epilepsy and pain illness. Based on diagnosis and calculating duration of the battery, relation between chest wall thickness and battery size and cost of the device to long term, patients received rechargeable battery most of them since the electrodes were implanted for the first time, but also as a second stage changing previous non rechargable battery.  Surgeries were performed with Leksell frame,Surgiplan software,3TMRI,microrecording,macrostimulation,all of it with awake patient in most of the cases.Sedation or general anesthesia was used for the battery implantation,all in one stage procedure.Satisfaction survey was applied focusing on the learning process to handle the battery,efficiency in the use of the battery,damages presented in the recharging device and side effect such as pain. 

Results:All patients are adequately recharching the battery,55% by themselves,and the others by close relatives or caregivers. 87% learned to handle it within the first week,11% within the first month and 2% within the 3 first months after surgery.4% has had the battery at 0 charge one time.72% has full communication expressed in 8 cubes in black.5% have damaged part of the rechargeable system that was repaired in a timely manner. 15% have had minor pain or discomfort any time after surgery and 6% when they were charged.  The most frequent areas of pain were:subclavicular area,right neck and shoulder.

Conclusions: DBS with rechargeable battery is easy to handle with minor damages in the system per se and manegeable pain. Long term it is less expensive. More cases and longer follow up should be carried out.   

Introduction:

Diffusion tensor imaging (DTI) is widely used in neurological and neuropsychiatric diseases, such as Parkinson’s disease (PD). We intended to evaluate the effectiveness of white matter tract based spatial statistics (TBSS) generated from DTI in patients with PD in detecting differences in patient motor response to deep brain stimulation (DBS).

Methods:

Six subjects with advanced PD from 55-66 years old were scanned for DTI protocol under anesthesia in a 3.0T Philips Achieva MR scanner before surgery. Motor scores (UPDRS-III) were collected before and after DBS (mean follow-up 5.9 months). The group was divided into two cohorts: patients with improvement in UPDRS-III after DBS; and patients without improvement in UPDRs-III after DBS. 

The diffusion volumes were first corrected for eddy current distortions and motion artifacts. Diffusion tensor maps were computed from the pre-processed DTI volumes for each subject on a voxel-by-voxel basis using FSL FDT diffusion toolbox. Various DTI indices such as fractional anisotropy (FA), mean diffusivity (MD), and diffusion traces along main Cartesian axes (L1, L2, L3) were generated. To generate TBSS, all FA maps were aligned MNI space and FA skeletonisation was then applied to all FA images with a threshold of 0.2 set to only constrain analysis to highly anisotropic white matter tissue. Also, TBSS were applied to the none FA images (MD, L1, L2 and L3).  

Results:

Significant differences were identified between ‘responders’ and ‘nonresponders’. In summary, FA shows high number of white matter skeleton voxels (4.23%) altered significantly between two groups of PD patients compared to the other DTI maps. Compared to the patients with low UPDRS-III score, FA shows significant increase in patients with higher UPDRS-III score or responders and diffusion trace along z direction shows significant decreases in patients with lower UPDRS-III score or nonresponders.

Conclusion:

The results suggest that many regions of white matter pathology were altered differently and show the variability of DTI parameters related to the neuropathology of the PD patients. While the focus has generally been on the motor component of the cortico-basal ganglia-thalamo-cortical circuit, diffuse changes affecting the associative and limbic components may also play a role in DBS response. While studying all brain networks is not feasible, TBSS has potential to serve as an screening tool to identify regions of interest.  

Objectives: Deep brain stimulation (DBS) is a recommended option for the treatment of movement disorders in well-selected patients. Both rechargeable and non-rechargeable devices are available; one of the advantages of a rechargeable DBS device may lie in the avoidance of costs for battery replacements and associated risks and hospitalisations. The objective of this study was to evaluate the economic impact of using a rechargeable DBS device over a non-rechargeable device in patients treated for either Parkinson’s Disease (PD) or Dystonia.

Methods: An economic model (Markov Model) was built to follow a group of dystonia and PD DBS patients over time comparing two scenarios, one assuming a rechargeable and one assuming a non-rechargeable device, for first implant and replacements. The model captures patients’ replacement surgeries, hospitalisations, adverse events and deaths. Data for the model were sourced from the Medtronic product surveillance registry (PSR; patient characteristics, adverse events and consequences associated with implant and replacement surgeries) and non-rechargeable device longevity data from Medtronic performance registry based modelling analyses. For the rechargeable device longevity, current longevity (9 years) and a hypothetical longevity scenario (15 years) were tested. Clinical expert advice was used to inform model assumptions. Costs were estimated from a UK health care perspective. Sensitivity analyses were undertaken to test for parameter uncertainty, including time horizon. 

Results: Results of the base case analysis (16 year time horizon) show:For PD,an average of 3.68 battery replacements in the non-rechargeable vs 0.62 in the rechargeable group; for Dystonia, 5.08 and 0.74 replacements in the non-rechargeable vs the rechargeable group(15-year hypothetical device longevity). Over 16 years,the model suggests cost savings of £15,564 (PD) and £27,954 (Dystonia) using the 9 year device longevity, and £20,418 and £32,060, respectively, for a 15-year hypothetical device longevity. Sensitivity analyses showed that over a patient’s life time, cost savings were £28,450(PD) and £65,413(dystonia)(15-year hypothetical device longevity).

Conclusion: The use of a rechargeable DBS device in this model is cost saving in the long-term compared to a non-rechargeable device. Prolonging rechargeable device life to 15 years is predicted to reduce DBS treatment costs and would thus improve DBS therapy cost-effectiveness, for both PD and dystonia. 

Objectives

There is now a significant body of published literature reporting the outcomes from Deep Brain Stimulation (DBS) for major depression (MDD). To explore patient characteristics, we constructed a patient-level registry based on reported studies between 2005 and 2017.

Method

Studies published reporting outcomes from DBS for MDD between 2005 and 2017 were included. All study types were included if patient outcomes were reported. Duplicate reporting was flagged so that reports of outcomes from the same patients could be excluded.

Results

The registry currently contains data for 234 patients from 25 studies. Of these, 171 patients from 17 published studies were unique. Patients who received DBS for indications other than MDD were excluded (N=11).

The median number of participants in included studies was 7 (range 1 – 30). The mean ± SD duration of follow-up was 12.8 ± 5.4 months; and 41.1% of studies reported follow-up of less than one year. Countries with the most DBS electrode implantations were: USA (40.4%); Canada (29.3%); and Netherlands (14.6%).

Gender breakdown was: males (41.5%); females (58.5%); unreported (19.5%). The mean age of onset was 27.2 ± 7.1 years and the average age of surgery was 48.8 ± 4.9 years. The average duration of the current depressive episode was 8.7 ± 2.2 years.

The most common targets for DBS were: CG25 (43.9%); VC/VS (25.7%); and ALIC (14.6%). Other targets made up 15.8% of cases.

The mean baseline HRSD-17 score was 24.4 ± 3.5, indicating symptoms in the severe range. However, 32.1% of patients had baseline scores in the ‘moderate’ range. The no. of failed antidepressant trials was unreported in 56.1% of cases. Most (67.3%) had previously had ECT, but 6.4% had not. This was unreported for 26.3%.

Comorbidity was poorly reported. Axis I comorbidity is not reported in 84.2% of cases. Although personality disorder is reported in 5.9%, it is unreported in 70.2% of cases.

The overall response rate was 40.4%, but 53.2% did not respond. The response status was not known in 6.4% of patients.

Conclusion

Inconsistent reporting of baseline patient characteristics means that there is uncertainty about comparability of DBS patients to ablative neurosurgical patients in terms of severity.

It is still unclear what the optimum target is and further work is required to determine this. Patient characteristics remain poorly reported and this limits generalisability to patients for whom neurosurgery may be considered.

Objectives Interpersonal dysfunction is a core component of depressive illness but is poorly studied or understood. Here, we report profiles of interpersonal functioning in 16 patients undergoing anterior cingulotomy (ACING) for chronic depression and compare them with 42 patients undergoing a specific psychological therapy developed for chronic depression.

Method The 64-item Inventory of Interpersonal Problems (IIP-64) is a self-report measure of difficulties that people encounter in their interpersonal relationships. The IIP-64 assesses interpersonal problems in eight specific domains of interpersonal functioning. The Total T-score reflects the overall burden of difficulties. Sixteen patients undergoing ACING completed the IIP-64 at baseline and 12-months following surgery. This group was compared to 42 patients with chronic depression who underwent a course of psychological therapy (CBASP). The outcome measure in both groups was change on the 17-item Hamilton Rating Scale for Depression (HRSD-17). Response was defined as ≥50% improvement from baseline score.  We compared changes in scores on the IIP-64 in relation to changes in symptom burden and response to both treatments. Total T-scores post-treatment were compared between responders and non-responders for both groups. Finally, we attempted to relate change in depressive symptoms to changes in interpersonal functioning.

Results Sixteen individuals (M:F - 1:15) underwent ACING. The mean ± SD age was 48.9 ± 8.3 years. The mean ± SD baseline HRSD-17 score was 28.6 ± 4.9.

Forty-two patients (M:F ratio 9:33) received CBASP. The mean ± age was 51.0 ± 9.8 years. The mean ± SD baseline HRSD-17 score was 20.5 ± 4.7.

In the ACING group, 7 (43.8%) were responders. In the CBASP treated group, 13 (31.0%) were responders.

In all responders, there was a statistically-significant correlation between change in HRSD-17 score and change in IIP-64 total score: ACING (Pearson’s r=0.896, P=0.006); CBASP (Pearson’s r=0.599, P=0.03).

Conclusion

Following both neurosurgery and psychological therapy, responders showed changes in interpersonal functioning that were not seen in non-responders. In responders, there was a relationship between change in symptoms and change in interpersonal functioning.

There was no evidence of deterioration in interpersonal functioning following ACING; even in non-responders.

It is likely that improvements in interpersonal functioning are mediated by a common factor – improvement in depressive symptoms.

Objectives

Care planning is an important component of the pathway for individuals undergoing neurosurgical treatment for depression. All patients have prolonged histories of ill health and are typically embedded within complex networks of care and support. We developed audit criteria to assess whether our care planning was consistent with WSSFN Consensus Guidance (Nuttin et al, 2014). Here we describe the operationalisation of this process.

Method

We designed a care-planning audit tool focusing on eight key domains: multi-disciplinary involvement; immediate post-op period; focus of treatment; engagement with patient; collaboration between neurosurgical service and local services; consistency of follow-up; adherence to care plan; and frequency of contact. These domains reflect the care planning of both our service and the patient’s locality mental health services.

Pre-operative care plans and adherence at 12-month follow-up were rated for 27 anterior cingulotomy patients and 5 Vagus Nerve Stimulation patients. We compared two time periods: 1999-2008 (21 procedures); 2010-2015 (15 procedures) to examine changes over time. We also compared scores between procedures.

Results

Highest scores were seen in the ‘consistency of follow-up’ domain, which reflected consistency in key healthcare personnel. Next highest scores were in the ‘frequency’ domain, indicating that patients were seen regularly in the 12-months following surgery. Lowest scores were seen in the ‘adherence to care plan’ and ‘immediate post-op period’.

Scores on ‘adherence to care plan’ reduced a little over time, whilst the domains that showed improvement were: ‘immediate post-op period; and ‘focus of treatment’. Scores for ACING patients were higher than scores for VNS.

These findings suggest that there are consistent challenges relating to care planning but that more structured approaches by neurosurgical services may help to overcome these difficulties.

Conclusion

Care planning is vital and has the potential to impact upon patient outcomes. Whilst neurosurgical services may not be able to control all aspects of care provided by other services, we clearly have a role in establishing explicit, realistic, and collaborative care plans for patients undergoing neurosurgery. We are now developing standards for care planning that we can use in discussions with local services when planning care for patients undergoing psychiatric neurosurgery. We will audit against these new standards in the future.

Background: Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to incur rapid anti-depressant effects (Schlaepfer et al., 2013, Fenoy et al., 2016). Diplopia is a side effect often experienced when programming. We sought to identify modulated fiber tracts associated with diplopia so they can be avoided and targeting improved.

Methods: 6 patients were implanted with electrodes targeting their individually mapped MFB. Optimal parameters resulting in anti-depressant effect were 1+2-3-, 130 Hz, 60 µs, 3-4V; stimulation of electrode contact 0 resulted in diplopia in every patient at 1V. The volume of tissue activated (VTA) was estimated using cathodal contact parameters; this was used as the seed region in deterministic fiber tracking to identify modulated fiber tracts.

Results: Use of contact 0 as a seed region revealed modulated tracts that were in proximity to atlas-defined oculomotor fibers. These tracts were consistently ventral and dissociable from those correlated with anti-depressant effect. Both sets of modulated fibers traversed the targeted MFB region. Mean coordinate of contact 0 was (5, -2.5, -9); contact 2 was (5.2, -0.5, -5).

Conclusion: Modulated fibers that incurred diplopia were consistently ventral to those producing anti-depressant effect. More rostral targeting within the MFB region is preferable. It is unlikely that current steering would improve side effect avoidance with Z as the critical dimension.

                              Matabolic Brain Networks in Parkinson’s Disease Patients with Depression Symptom Based on ¹⁸F-FDG PET Imaging

Objectives: Parkinson’s disease (PD), characterized by loss of dopamine neurons in the substantia nigra (SN) and the subsequent deficiency in striatal dopaminergic system, is the second most common  neurodegenerative disorder with a frequent comorbid symptom of depression. Drawing the brain metabolic pattern of PD may help to target the core biological and psychological features of the psychiatric comorbidity and to the diagnosis and recovery criteria. In this study, we use ¹⁸F-FDG PET to show brain metabolic network for Parkinson’s Disease-associated depression.

Methods: Glucose metabolism in 21patients and 17 age-matched healthy controls were studied using ¹⁸F-FDG PET. SPM was used to compare brain metabolism in PD patients with depression with that in healthy controls.

Results: The SPM (statistical parametric mapping ) analysis showed hypermetabolism in the putamen (bilateral), the globus pallidus (bilateral), lentiform nucleus (bilateral) and striatum compared with the controls ( P＜0.01 ). PD patients with depression had bilateral area of hypometabolism in the frontal lobe, temperal lobe and parahippocampal gyrus compared with healthy controls. (P＜0.01).  

Conclusion: The changes in brain glucose metabolism illustrated the brain metabolic pattern in PD patients with depression. Furthermore, the pattern went accordance with the severity of depression. The regions with altered metabolism could interconnected to form a network and integrate information related to depression in PD patients. Our study may provide information for targeting the potential candidate brain regions for understanding the pathophysiology of depression in PD patients and assessing the severity of the illness.

Keywords: PET , Parkinson’s Disease, depression, functional imaging , glucose metabolism    

Depression is a common disorder and comprises the leading cause of disability worldwide. Within the limbic circuitry passing through the medial forebrain bundle (MFB), the mesolimbic pathway is particularly implicated in the pathophysiology of depression, since it is associated with reward, aversive learning, social behavior, and addictive behavior. It is known that, in rodents, specific dopaminergic cells from the ventral tegmental area (VTA) project to the medial shell of the nucleus accumbens (NAc). Furthermore, appetitive motivation for rewards and fearful motivation toward threats are organized in circuits arranged in an environment-dependent keyboard fashion in the NAc medial shell. However, if and how this circuitry is altered in depression is not yet understood.

In order to detect electrophysiological signatures associated with a depressive phenotype, we recorded local field potentials (LFP) in the VTA and NAc medial shell of control (Sprague-Dawley) and Flinders Sensitive Line (FSL) rats using stereotactically inserted bipolar concentric electrodes. Recordings were performed at several time points in vivo, during free behavior, both while the rats were in their usual home environment and in a stressful environment. Correct electrode placement was evaluated through histological analysis.

The data is currently being analyzed using time-frequency domain and connectivity analysis techniques in MATLAB and will be presented at the meeting. Between-group and within-group comparisons are being performed for both home environment and stressful environment conditions. Early assessment suggests differences across the groups in the VTA and NAc power spectra and connectivity measurements, differences which are accentuated in the stressful environment.

The data point towards altered electrophysiological activity in a rodent model of depression in neural structures associated with major depressive disorder and provides guidance to future studies that will integrate LFP recordings with electrical and optogenetic stimulation of the MFB in the FSL rat.

Major Depression is a common, multifactorial psychiatric disease with heterogeneous symptoms, including anhedonia and reduced motivation. These symptoms are associated with the dysfunction of the limbic circuitry in the brain. The dopaminergic neurons of this circuitry are involved in reward and motivation, and targeted for the treatment of depression. Modulation of these neurons by antidepressant medication or the pathways with Deep Brain Stimulation can reverse a depression-like phenotype in rodents. Nevertheless, mechanisms of the disease and the therapeutic effects of stimulation are not understood.

In this study, we used optogenetic stimulation of the medial forebrain bundle (MFB) as a treatment attempt in a rodent model of depression, the Flinder’s Sensitive Line (FSL) rat. The FSL rat has been bred selectively for more than 25 years and shows a depressive-like phenotype due to decreased BDNF levels, decreased 5-HT synthesis, hyperactive HPA-axis and more.

FSL rats with an intact dopamine system (DA+) were compared with rats that received a bilateral 6-OHDA lesion of the Nucleus accumbens (DA-), depleting the reward circuitry. The effect of the stimulation in depleted vs. intact animals was investigated in freely moving rats in a number of behavioral tests. Animals of the stimulation groups received 30 min of light stimulation directly prior to each behavior test. The behavior was tested using the sucrose preference test, forced swim test, social interaction test, open field test, ultrasonic vocalization and activity measurements, induced by amphetamine or stimulation.

Results show an increase in amphetamine-induced activity in both groups, but the effect is much less prominent in the DA- groups, confirming the partial lesion. Activity is also enhanced by stimulation of the MFB. Stimulation increased the track length in the open field in all groups, but the track length in the center zone was only increased in the DA+ group. Besides, stimulation of the MFB enhanced social interactions in the DA+ group.

The increased activity due to stimulation of the MFB and the observed exploratory behavior of the rats indicate a robust SEEKING (enhanced drive) response, thus an activation of the brain reward circuitry. Extended track length in the center zone of the open field and increased social interactions only in the stimulated DA+ group point towards an important role of the dopaminergic part of the limbic system in possible treatments for Major Depression.

Background: Deep brain stimulation of globus pallidus internus (GPi-DBS) has proved efficient in primary dystonia and some secondary dystonias. However, 15% to 20% of dystonia patients underwent GPi-DBS respond to this therapy insufficiently. Exploration of alternative DBS target is important to provide further treatment. We have performed stimulation or ablation of thalamic Vo nucleus for focal hand dystonia and some generalized dystonia, in addition to GPi-DBS. Here, we report the clinical featrures of patient with dystonia underwent GPi-DBS and Vo-DBS/ablation.

Subject and Method: A total of 46 patients with dystonia underwent DBS from 2003 to 2014 at Tokushima University Hospital. All patients were assessed every one to three months after surgery. Motor symptoms of dystonia were assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS).

Results: Forty-four patients underwent only GPi-DBS (GPi group) and six patients underwent GPi-DBS followed by thalamic Vo surgery (GPi+Vo group). The improvement ratio of BFMDRS after surgery was 54% in the GPi group, and 67% in the GPi+Vo group. In the GPi+Vo group, four of six were focal hand dystonia (FHD), and two of six were primary generalized dystonia (DYT-6 and sporadic dystonia).

Discussion: In 2005 and 2006, two multicenter randomized controlled trial proved GPi-DBS has the efficacy in primary generalized/segmental dystonia. However, recent reports revealed the presence of the poor responders to GPi-DBS by limitation of therapy due to the stimulation related side effect, and by a pathogenetic reason such as DYT-6 positive. Although it is known that thalamic Vo-DBS is effective for FHD, in our case, DYT-6 dystonia also well responded to Vo-DBS. Recently, the genesis of dystonia has been suggested to be associated with altered activities, not only of the basal ganglia, but also of the cerebellum. In the Vo-complex nucleus, the Voa is largely associated with the pallido-thalamic pathway while the Vop is with the cerebello-thalamic pathway.¹⁶ This indicates that unlike GPi-DBS, Vo-complex stimulation has the potential to modulate the activities of not only the pallidal pathway but also the cerebellar pathway at the thalamus level. We suggest that the thalamic Vo-complex nucleus could serve as an alternative target for some generalized dystonia with a relation to the cerebello-thalamic pathway as well as FHD.

Introduction:

Medical treatment of dystonia is very complex and sometimes unsuccessful. Surgical treatment like thalamotomy, pallidotomy and Deep brain stimulation (DBS) can be beneficial for the patients.

Methods

Two cases of dystonia have been treated surgically in Annapurna Neurological Institute and Allied Sciences in last two years. First case is a case of 47 years old lady with tardive dystonia who underwent bilateral GPi(Globus Pallidus Interna) pallidotomy under local anesthesia. Her preoperative Burke-Fahn-Marsden Dystonia rating score(BFMDRS) was 36/123. There was no postoperative complications and her postoperative BFMDRS was 1/123. There was no recurrence in two years follow up period.

Second case is a 48 years old male with primary dystonia involving the neck and trunk muscles. His preoperative BFMDRS score was 42/123. He neither responded to medical treatment nor to botulism toxins. He also underwent bilateral GPi Pallidotomy under local anesthesia. His postoperative BFMDRS score was 2/123. This patient developed mild dysarthia after surgery and it is improving with time. There is no recurrence of symptoms in nine months follow up period.

The standard functional targets were used. Then fusion of MRI( 3 Tesla Philips) and CT (1 slice Siemens) stereotaxy( with ZD Fisher frame) was used and it was reconfirmed with the inbuilt Schaltenbrant Atlas. Total eight lesions were made in each side with 70 degree centigrade for 40 second each using Cosman Radiofrequency (RF) generator  and the lesioning probe was 1 mm in diameter with 2 mm exposed tip. Continuous monitoring of motor symptoms and visual symptoms were done during the surgery

Result

The patients’ dystonia improved in terms of BFMDRS score and there were no major postoperative complications.

Conclusion

Patients with dystonia can benefit from bilateral GPi pallidotomy but GPi DBS is also an alternate option for affordable patients.

Objective: To introduce the botulinum toxin injecton technique on the periocular area for the treatment of hemifacial spasm and report the treatment results.

Materials and Methods : Thirteen sessions with five patients were performed with botulinum toxin therapy injected to the periocular area. Botulinum toxin was injected at four sites on the affected side at a dose of 2.5 unit botulinum toxin per site.
Results: All treated patients had symjptom improvement. The degree of improvement measured on the visual analogue scale was 89.3%, and the average duration of the effect was 6.3 months. One patient had ptosis after his third session.

Conclusion: Botulinum toxin therapy is effective for the treatment of hemifacial spasm. Our patients were satisfied with the treatment results. Ptosis is the most common complication reported in the literature, but it can be avoided by preventing the spread of neurotoxin after the injection and avoiding inadvertent injections.

Secondary dystonia is  extremely disabling affecting the quality of life of the individual as well as the caretaker. Multiple treatment options  are aimed at improving physical ability. Treatment options for generalised, hemi-dystonia or segmental dystonia are limited. Lesioning and /or Deep Brain Stimulation have become the treatment of choice for primary dystonia. The results in secondary dystonia are  variable. We share our experience  of patients with secondary dystonia including,  clinical details, technical difficulties, complications and outcomes.

Materials

Nineteen patients with secondary dystonia were analysed.

The clinical picture varied from inability to swallow, breathing difficulties, inabilty to sit, oromandibular dystonia, truncal dystonia and deformities.  

 The patients were evaluated with standardised rating scales and treatment planned in consultation with the team. 

Patients underwent either lesioning or Deep Brain stimulation. The targets were either in the globus pallidus interna and thalamus, decided after team discussion.  

Quality of life and outcomes were analysed.

Results

The clinical improvement in secondary dystonia is not as good as in primary dystonia. The quality of life improved in segmental dystonia  and in some cases of generalised dystonia. Generalised dystonia secondary to hypoxic ischemic damage  did not show any significant improvement.

Conclusion

Clinical outcomes  are variable in secondary dystonia  though not as rewarding as in primary dystonia. 

Objective: In the literature data of deep brain stimulation for post stroke dystonia are rare, particularly for long-term outcome. Due to disappointing benefits after single target stimulation multiple targets are discussed.

Methods: We report one patient with a dystonic-jerky-unsteady-hand-syndrome, who presented with hyperkinetic movements of the right arm. MRI showed small explaining lesion in the left ventroposterior thalamus and additional small lesions in the cerebellum. Due to failure of noninvasive therapies we have planned the unilateral stimulation of the left VOA and supplementary the GPI in standby. The surgery was performed using stereotactic MRI and multiple trajectories for micro recording and macro stimulation under local anaesthesia in 2008.

Results: Intraoperative we found good thalamic activity on the trajectory of the VOA. A good reduction of the symptoms was shown under macro stimulation without relevant side effects. Owing to the impressive effect the GPI-stimulation wasn’t performed. Under permanent stimulation improvement with complete reduction of tremor and dystonic movements was achieved from first day of stimulation and meanwhile in the nine year follow-up. No adapting of stimulation parameters was necessary. Patient is absolute independent in every day´s life and ongoing on work.

Conclusion: We conclude that the deep brain stimulation of the VOA could be an effective method for the long-term treatment of post stroke tremor and dystonia with outstanding economic importance. 

Objective: Deep brain stimulation (DBS) has been shown to be efficacious in the treatment of primary dystonia (idiopathic and inherited dystonia). There is less experience in, however, secondary dystonia (acquired dystonia). Since patients with secondary dystonia, who are often more disabled, may be more vulnerable to postoperative complications we aimed to investigate the 30-day morbidity in a large cohort of patients with secondary dystonia operated over a period of 19 years.

Methods: From 1997 until 2016, a total of 49 patients (27 women and 22 men; mean age 43,5 years (range 13-77)) with secondary dystonia underwent DBS with electrodes implanted either in the thalamic Nucl. ventralis intermedius (Vim) or the posteroventral lateral globus pallidus internus (GPi). Most frequent cause of for dystonia was cerebral palsy in 17 patients.

Results: There were no intraoperative complications or complications in the early postoperative period related to surgery. The electrode location was corrected in 2 instances. Two patients developed a wound infection, one patient had a subdural hematoma and subcutaneous collection of cerebrospinal fluid (CSF). Three weeks after DBS the subdural hematoma and CSF resolved.

Conclusion: The 30-day morbidity rate in DBS for secondary dystonia is comparable to that in primary dystonia. DBS surgery may be offered to patients with secondary dystonia without concerns about higher morbidity.

Objective: Pallidal deep brain stimulation (DBS) has been established as a treatment option in patients with medically refractory dystonia. Mohr-Tranebjaerg syndrome (MTS) or Dystonia-Deafness-Syndrome is a rare genetic disorder characterized by deafness, dystonia and neurological abnormalities like impaired vision, dementia and cortical blindness. So far little is known about the efficacy of DBS in MTS.

Methods: A 44-year- old man with a history of generalized dystonia, deafness, visual blindness, ataxia and tremor was diagnosed with MTS which was confirmed by genetic analysis. He underwent bilateral stereotactic implantation of DBS electrodes in the posteroventral lateral globus pallidus internus (GPi). Electrode location was confirmed by postoperative stereotactic CT.

Results: Bilateral pallidal stimulation yielded modest improvement of dystonia at 6-months follow-up. During the next four months there was an increase of tremor and ataxia. The initial benefit was lost within the next two years. Extensive reprogramming did not yield additional improvement. After three years of chronic stimulation it was decided to switch off the pacemaker because of loss of efficacy.

Conclusions: It is important to check for the genetic background in patients with unusual clinical symptoms. As opposed to inherited isolated dystonia, patients with MTS may achieve little benefit from pallidal DBS.

Introduction: Dystonic Storm (DS) is a life-threatening complication of dystonia characterized by sudden and persistent episodes of dystonic movements that become increasingly frequent and severe, requiring urgent hospital admission, leading to respiratory, metabolic and bulbar complications^1,2. Pharmacologic treatment has been the mainstay management, however, many refractory patients will still require further treatments. Deep brain stimulation (DBS) of bilateral globus pallidus internus (GPi) is an interesting therapeutic strategy that has been used for dystonia and now it has been proposed to be used for DS.Case series: We describe 5 cases (Two pediatric and three adults) with DS, admitted to our institution, that required emergent placement of a bilateral GPi DBS to control their symptoms (Table 1.). Dystonia etiology was identified as secondary in two of them (cerebral palsy with dyskinetic predominance), other case with a genetic syndrome, and two cases continue in studies for primary genetic causes. All five patients coursed with dystonic movements of different body regions including neck, extremities and trunk that interfered with ambulation. Severity was measured with the UDRS scale. Precipitating factors were identified in two cases (superior airway infection and electrode dislocation). Pharmacologic therapy wasn’t effective in any of the cases and ICU admission was necessary before surgery. Before discharge, symptomatic relief (diminution of dystonic movements and resolution of abnormal postures) was achieved in all five patients in a mean period of 6,6 days (1,6 days adults, 14 days pediatric).Discussion: DS treatment is challenging. As reported by Fassano et al. in 89 cases of DS, pharmacological therapy was used as first line treatment in 82.4% of cases, ceasing DS only in 9 cases (10.1%), while surgery [either DBS (13 cases) or ablations] was used in the 30.2% of cases being effective in the 33.7% of these events¹. In our case series, pharmacologic therapy wasn’t sufficient to abort DS and DBS placement in bilateral GPi was effective for symptoms control.Conclusions: GPi DBS can be a suitable, versatile, reversible and adequate therapy of DS. Further research is needed to establish adequate criteria in respect of the proper moment of implantation, initial and follow-up parameters configuration changes as well as concomitant pharmacological therapy.

Introduction:Deep brain stimulation (DBS) devices may be used for refractory dystonia, which do not respond to medical management⁴.Despite it is not widely used, this surgery is becoming a more common practice because it can be safely performed as a last resort. This is one of the few reported cases of SD in a child with a DBS previously implanted.Case Presentation:A 10-year-old boy with a previous history of perinatal kernicterus and mixed cerebral palsy, developed progressive dystonic symptoms over the course of a year.He began to have markedly cervical and trunk spasms; extension of upper right limb appeared, which lead to dystonic posture.Furthermore, he was developmentally disabled and progressed to becoming wheelchair bound. At age 5, bilateral DBS electrodes were placed into the Globus Pallidus Internus (GPi). The patient was admitted to our pediatric emergency department with feeding problems and worsening of dystonic movements in the upper limbs and a painful opisthotonic posture. UDRS scale was 42. CT-scan-findings revealed bilateral electrode displacement of 2.5mm from both GPi.Three days following admission, he underwent bilateral replacement of GPi DBS, with a new system. Targeting the nucleus was made using direct technique, because of important discrepancy between coordinates, functional brain atlas and kid's brain.   Subsequently, stimulation was titrated to an amplitude of 2.0mAmp, a pulse width of 100mcseg and a frequency of 130Hz, afterwards he was transferred to the ICU.The patient improved completely on POD-7 and was discharged home on POD-21.Discussion:SD is a life-threatening-condition usually related to metabolic disturbances, surgery, infections or changes in medication³.In our case, we believe that migration of the electrodes triggered a SD. A European cohort reported 2,3 % cases of electrodes displacement, with 4,6% of the cases associated to dystonic status². Several causes have been theorized to explain electrodes upward migration. Brain shift, steady growth of the patient, dystonic movements of the head and neck and surgical errors are the most common causes involved¹. Dislocation of the device causes gradual loss of stimulation efficacy.Conclusion: DBS electrodes displacement is a rare condition which neurosurgeons seldom see.Despite its infrequency, it must be considered in cases of worsening dystonic movements, with prior successful DBS implantation, especially in the pediatric population.

Background:

Secondary dystonia are the syndromes that have dystonic symptoms due to brain insult which can be associated with neonatal encephalopathy syndromes, trauma, vascular injury, infections, demyelinations, or hereditary disorders associated with neurodegenerative process. The disability inflected by dystonia encouraged the development of many neurosurgical procedures in order to improve the quality of life of these patients.

The aim of this study was to compare the outcomes of different Neuroablative and modulation techniques in treatment of secondary dystonia.

Patients and methods

This is a prospective study included 80 patients suffering from intractable secondary dystonia. Ablative techniques included the brain lesioning procedure and combined anterior and posterior lumbar rhizotomy (CAPR). Modulation techniques were deep brain stimulation (DBS). Patients with generalized dystonia were included in either of the brain lesioning or the deep brain stimulation, and patients with predominant affection of both lower limbs were included in the (CAPR) group.

Assessment measures included the evaluation of the muscle tone, range of motion, and the Burke-Fahn-Marsden dystonia rating scale through a follow up period of one year.

Results

Muscle tone was significantly reduced in the ablative techniques, but the changes in the DBS group were not significant. The range of motion improved in all groups; the changes were significant in the ablative techniques but were not significant in the DBS group. The BFMDRS showed improvement in all groups, the changes were significant in all groups except the DBS group.

Conclusion

Both neuroablative and neuromodulation techniques have the beneficial impact on secondary dystonias especially with stationary neurological pathologies with no significant statistical difference between both techniques.

While the neuromodulation techniques had the advantages of being adjustable, titratable, reversible, and can be performed bilaterally.

Paroxysmal nonkinesigenic dyskinesia  (PNKD) is a rare inherited movement disorder characterized by sudden episodes of dystonia, chorea, ballism or a combination of these, precipitated by several stimuli but not by movements or physical effort. We report a 19 year-old man with treatment-refractory PNKD since the age of 4 with daily severe episodes of generalized dystonia who displayed a successful outcome 6 months after bilateral globus pallidus internus (GPi) deep brain stimulation (DBS). Baseline severity and improvement in motor function was evaluated using the UDRS for his constant dystonic features and during the paroxysmal events. Two 3387- Medtronic electrodes were implanted under microrecording and semi-macrostimulation with patient awake, and connected to an ACTIVA RC pulse generator.  The stimulation was turned ON three weeks after the implant. At 6-months follow-up with stimulation On, fixed dystonia severity reduced 43% in the UDRS score from preoperatory baseline (50 vs. 28). The total UDRS score during the paroxysmal generalized dystonic events at baseline was 86, with severe compromise of larynx muscles as the main medical concern due to choking and aphonia. These events disappeared during the immediate weeks after the implant of the electrodes; they came back at the end of week 3. After 2 weeks of turning the stimulation On, the severity of the paroxysmal dystonic episodes reduced 46.5% (86 vs 53.5%) with a progressive reduction in their frequency until the total disappearance of the paroxysmal events after 4 months On- stimulation. No major adverse effects were recorded. Bilateral GPi- DBS resulted in a complete control of the paroxysmal dystonia events, including the severe axial features, with no neurological complications. 

Myoclonus- dystonia (MD) is a severe movement disorder with a negative functional impact due to its severity and poor pharmacological response. Bilateral deep brain stimulation (DBS) has been used to treat MD patients, targeting the GPi, the Vim or both targets simultaneously. No reports of radiofrequency lesions have been described in recent literature due to the limitations of a unilateral approach. We present a case of a right-handed 19 year-old girl, with severe hereditary myoclonus dystonia who had simultaneous left-side Vim thalamotomy (VimTh) and posteroventral pallidotomy (PVP), who showed a significant benefit in postoperatory functional scores. Motor improvements were evaluated with rest/action and total subscores of the Unified Myoclonus Rating Scale (UMRS), functional improvements with the patient questionnaire and functional test subscores of the UMRS, Dystonia severity was evaluated with the Unified Dystonia Rating Scale (UDRS), preoperatively and 6 months after surgery.  At 6-months follow-up, myoclonus improved 60% in the total UMRS score. The motor improvement in the right limbs using rest and action subscores was 98%, with no benefit observed in the left side limbs. Functional improvement was highlighted by the right side benefit obtained, with a 74% improvement in the overall functional tests, and a 94% improvement if the left hand spiral score was drawn out of the sum. The patient perception of improvement was 92% according to the patient questionnaire subscore of the UMRS. The severity of dystonia reduced 38% according to the total UDRS; the subscore for right shoulders, hip and limbs displayed a more significant improvement with a 79% severity reduction, with no benefits observed in left side hemi-body.  No major adverse effects were recorded. Improvements are consistent with those reported in DBS cases. We did not find any limitations in functional benefits with this unilateral procedure, since the largest improvement was directed towards the dominant side of the patient. The combined approach of VimTh and PVP allowed us to reach a better control not only in the dystonic features but also in the severity of the myoclonus with no neurological complications. Unilateral and simultaneous radiofrequency Vim thalamotomy and posteroventral pallidotomy are safe and highly effective in patients with MD, with a profound positive impact in motor severity and functional scores when aimed at the dominant side.

Objective: To evaluate pallidal oscillation in secondary dystonia following a head injury. Methods: The patient was an 18-year-old male. At the age of 15, he suffered a left brain contusion due to a traffic accident.  At the age of 17, he experienced forced opening of the mouth while sitting (upright position), chewing, and speaking. He was able to drink with a straw, but was unable to chew or speak. We diagnosed him with secondary dystonia induced by movement. Bilateral pallidal deep brain stimulation (DBS) was performed under general anesthesia. Bilateral local field potentials (LFPs) and EEG over the sensorimotor areas in the resting state were recorded from four bilateral contacts of the DBS electrodes 1week after the operation. Contacts 0 and 1were located in the internal pallidum (GPi), and Contacts 2 and 3 were in the external pallidum (GPe). LFPs were calculated for the three bipolar contact pairs of DBS electrodes. Power spectra of 2-35Hz were identified as sub-frequency bands and defined as follows: 2-4Hz (delta), 5-7Hz (theta), 8-13Hz (alpha), and 14-35Hz (beta). Results: (1) Oscillatory activities: Spectral peaks of the delta band in the GPi, GPe, and motor cortex (MCx) were more prominent than those of the theta, alpha, and beta bands. The delta power was increased more on the right than on the left. (2) Functional coupling between the GPe and GPi: The coherences between the GPe and GPi in the delta and theta bands were stronger on the right than on the left. (3) Functional coupling between the ipsilateral MCx and GPe or GPi: On the left, no prominent coherence in the four bands was observed between the MCx and GPi or GPe. However, on the right, the delta band in the GPi was strongly coherent with the MCx, and the theta band in the GPe was also coherent with the MCx. Conclusion: The left brain was affected, but the right brain was not. The left and right oscillatory activities were quite different. The delta power increased in the right GPi and GPe, and was functionally coupled with the MCx. DBS treatment using monopolar stimulation with contact 0 bilaterally was very effective. The phenomenon of oscillatory activities in the non-affected GP may be similar to the functional compensation that occurs in patients with chronic stroke.

Sensory abnormalities are increasingly being recognized as an accompanying symptom in patients with dystonia. The aim of this study was to investigate whether sensory abnormalities could be related to age or the distribution of motor symptoms in patients with idiopathic and hereditary dystonia. For this purpose we recruited 20 dystonic patients from which 8 had generalized dystonia, 7 cervical dystonia and 5 segmental dystonia with arm/hand involvement. The patients with arm/hand involvement were divided into two subgroups: younger than 40 years (6 patients) and older than 40 years (7 patients). All patients with cervical dystonia were older than 40 years. We used Quantitative Sensory Testing (QST) at the back of the hand in all patients and at the shoulder in patients with cervical dystonia. The main finding on the hand QST was impaired dynamic mechanical allodynia (DMA) and thermal sensory limen (TSL). The other impairments were characteristic of the subgroups. The alterations were present on the clinically more and less affected side, but more pronounced on the side more affected with dystonia. Patients with cervical dystonia showed a reduced hot detection threshold (HDT) and CDT, enhanced TSL and DMA at the back of the hand, whereas the shoulder QST only revealed increased CPT and DMA. In summary, QST clearly shows distinct sensory abnormalities in patients with idiopathic and hereditary dystonia, which partly varied with age and which may also manifest in body regions without evident dystonia.

Objective  To investigate over 10-years efficacy of the subthalamic nucleus-deep brain stimulation(STN-DBS) on primary dystonia.Methods All patients are selected from the group consisting of 13 primary dystonia patients receiving bilateral STN-DBS implantation treatment from May 2002 to November 2006.All patients were evaluated with the Burke–Fahn–Marsden dystonia rating scale (BFMDRS) and 36-item short form (SF-36) before surgery and at 1 month, 1 year and then over 10 years later postoperatively,follow-up time ranged from 10 to 15 years (mean: 12.7±1.8 years).Results All patients with bilateral STN DBS experienced a remarkable long-term and stability improvement after STN-DBS stimulation. The mean increase in movement score of the BFMDRS was 60%, 82%, and 84% after 1 month, 1 year and at least 10 years later stimulation. The quality of life (SF-36 questionnaire) significantly improved with 1 month stimulation (P<0.001), the improvement progressed within 1 year (P<0.05), and then kept stable . Adverse events included misplacement of the electrode,wire breakage and exclusive reaction. Conclusion  This over 10-years follow-up study confirms the benificial effect of STN DBS in primary dystonia,significantly improving motor symptoms and quality of life,long-term efficacy and stability. 

Background and purpose: Dystonia, with variety of its clinical forms is a multidisciplinary challenge for physicians. Author presents a group of patients with various dystonia types treated with subthalamic (STN) or pallidal (GPi) deep brain stimulation (DBS).

Materials and methods:  42 patients (20 male, 22 female) age from 6 to 64  (mean 31,4) affected by dystonia were treated with DBS. 16 patients diagnosed with idiopathic general dystonia, 14 NBIA- related general dystonia, 5 hemidystonia, 3 torcicollis, 2 DYT-1- related general dystonia,  1 myoclonic dystonia and 1 oromandibular dystonia. The patients were evaluated with the Fahn-Marsden Scale (FMS), Unified Dystonia Rating Scale (UDRS), Global Dystonia Scale (GDS) and torticollis patients were evaluated with Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) before treatment and 6, 12 and 24 moths after the procedure. The permanent electrodes were implanted  to GPi in 31 cases or to STN in 9 patients or GPi and STN in 2 patients. The target was identified with direct and indirect method. Intrasurgical macrostimulation and microrecording were used for neurophysiological evaluation of the target.

Results: No serious morbidity or mortality were noticed in the group.  Local chest hematoma was reported at the region, where internal pulse generator was implanted. Best results were achieved among patients with with DYT-1 related general dystonia (mean 91%) and oromandibular dystonia (84%). The poorest results were noted at the PKAN group (mean 41%).  Mean improvement of 72% was achieved in all groups.

Bilateral posteroventral Pallidotomy in the management of post-anoxic generalized dystonia

Dystonia is the third most common movement disorder after tremors and Parkinson’s disease, that significantly renders the functionality of an individual and hence the society. Secondary post-anoxic generalized dystonia isn’t uncommon in developing countries with lack of effective perinatal care and facilities. Our aim is to clinically assess the role of bilateral pallidotomy on seven patients with post-anoxic generalized dystonia.    

Method:

This study is done on a retrospective manner on seven patients (3 males- 4 females), with age range from (8- 29) diagnosed with post-anoxic generalized dystonia, who received Bilateral posteroventral Pallidotomy, aiming to lessen the severity of the dystonia.  Guided by a peri-operative clinical assessment and scaling with Burke–Fahn–Marsden dystonia rating scale. All patients had a post operative MRI to confirm pallidotomy lesion site.

Results:

The seven patients had a noticeable improvement on BFM score and the severity of the dystonia after one month follow up, but for one patient who had an associated contracture and scoliosis that rendered his clinical improvement.

 where the BFM score mean pre-operative 53.57, with a standard deviation 20.13, while post operative BFM score mean was 42.5 with standard deviation 20.31 ( p value= 0.007) , thus there is a 20.75% reduction in the mean BFM score.

Conclusion:

Bilateral posteroventral Pallidotomy is considered a safe and effective line of management in generalized dystonia especially secondary dystonia. None the less it doesn’t carry the drawbacks of other alternative managements as in DBS, like hardware hazards, from infection or dislocation, or its long term maintenance and high costs. By highlighting the efficacy of pallidotomy and studying more patients and with applying our data to more comparative studies, that will lead us to more understanding to the most suitable option for each patient.

Introduction: Hemidystonia is a neurological condition caused by plastic changes developed after an injury to cortical-thalamic-spinal pathways, usually secondary to different causes. In the past various cases series have shown encouraging results of lesions in various targets for the treatment secondary dystonia. More recently reports applied DBS showing no better results. Currently, there no standardized treatment for this condition. 

Objectives: We present preliminary results of an open trial comparing best medical treatment (oral medication and botulin toxin) with unilateral single lesion of the posterior zona incerta.

Material and Methods: Fourteen patients entered the study. All patients had baseline evaluation (BL) with dystonia (FMDS) and quality of life rating scales (SF-36) at 1, 3 and 6 months after BL evaluation. Patients had the choice either surgery or best medical treatment. Six patients accepted the surgical procedure while 7 were followed under medical treatment for at least 180 days. 

Results: Patients under medical treatment presented FMDS average score of 30.4±8 and 6.3%, 18% and 18% improvement at 1, 3 and 6 months respectively. Patients operated had FMDS average score of 33.6±7.6 and 34.5%, 43.8%, 37% in in 1, 3 and 6 months respectively in FMDS (ANOVA + Bonferroni post-test p< 0.05). The operated patients revealed average of 75,6% improvement in the subscore of functional capacity of SF-36, while the medically treated patients revealed average 8,5%. The operated group had 65,6% improvement in pain subscore while the medically treated patients had 17,3%. 

Conclusion: Despite the limited number of patients and relatively short follow up, the preliminary results revealed that surgical treatment was significantly better than best medical treatment for patients with hemidystonia. Further trials should be performed to confirm the results in long term.

BACKGROUND                                      

The exploration of the insula in pre-surgical evaluation of epilepsy is considered to be associated with a high vascular risk resulting in an incomplete exploration of the insular cortex.

OBJECTIVE

We report a retrospective observational study of insular exploration using stereoelectroencephalography (sEEG) with transopercular and parasagittal oblique intracerebral electrodes from January 2008 to January 2015. The first purpose of this study was to evaluate the surgical risks of insular cortex sEEG exploration. The second purpose was to define the ability of placing intracerebral contacts in the whole insular cortex.

METHODS

Ninety-nine patients underwent 108 magnetic resonance imaging (MRI)-guided stereotactic implantations of intracerebral electrodes in the context of pre-operative assessment of drug-resistant epilepsy, including at least one electrode placed in the insular cortex. On post-operative computed tomography (CT) images co-registered with MRI, followed by MRI segmentation and application of a transformation matrix, intracerebral contact coordinates of the insular electrodes’ contacts were anatomically localized in the Talairach space. Finally, dispersion and clustering analysis was performed.

RESULTS

There was no morbidity, in particular hemorrhagic complications, or mortality related to insular electrodes. Statistical comparison of intracerebral contact positions demonstrated that whole insula exploration is possible on the left and right sides. In addition, the clustering analysis showed the homogeneous distribution of the electrodes within the insular cortex.

CONCLUSION

In the pre-surgical evaluation of drug-resistant epilepsy, the insular cortex can be explored safely and comprehensively using transopercular sEEG electrodes. Parasagittal oblique trajectories may also be associated to achieve an optimal exploration.

Aim: Investigation of the long-term efficiency in clinical treatment and social function improvements of the MRI-guided stereotactic bilateral anterior capsulotomy in chronic epileptic patients with psychiatric comorbidity .

Methods: 15 patients with psychiatric comorbidity in epilepsy who underwent the capsulotomy were included . The treatment effects were evaluated with Positive and Negative syndrome scale (PANSS), Barratt impulsiveness scale (BIS-11-C), Buss-Perry scale (BPS) and Social Disability Screening Scale.

Results: Evaluations were performed at baseline,1 week , 6 months and 1 year after surgery . There was an improvement based on the statistical analysis for Positive Symptom(21.07±7.17vs11.40±3.43vs9.20±2.14vs8.29±1.86);Negative Symptom(26.60±5.79vs17.00±3.51vs13.07±4.40vs11.67±4.82);Barratt no-planning impulsiveness Scale(29.00±5.96vs10.67±4.95vs9.17±3.86vs8.50±3.64);Barratt Cognitive impulsiveness Scale(32.33±6.97vs11.33±3.76vs7.67±3.59vs7.14±4.14 );Barratt Motor impulsiveness Scale(51.50±9.81vs27.83±4.71vs6.16±4.99vs5.18±4.75);Buss-Perry Scale(78.07±7.96vs61.40±6.13vs51.47±8.69vs48.73±10.03);Scocial disability screening Scale(12.53±3.67vs7.80±2.98vs5.60±3.48vs5.14±3.61).

Conclusion: MRI-Guided Stereotactic Bilateral Anterior Capsulotomy could improve the positive symptom such as aggressive behavior disorder(ABD) and impulsive behavior disorder(IBD) ,the negative symptom such as depression, and the compliance of other treatments, also further reconstitute their social function for the epilepitic patients with psychiatric comorbidity. 

Background Anterior thalamic Nuclei (ANT) stimulation has been proven effective in controlling epilepsy in many studies, but its mechanisms remain unclear. Objective To study the neuroprotective effects of ANT stimulation on epileptic monkeys. Methods Eight male rhesus monkeys were randomly assigned to a stimulation group (n=3), a sham-stimulation group (n=3) and a control group (n=2). DBS devices were implanted into the left ANT of monkeys from the stimulation and sham-stimulation groups. Kainic acid was injected into the left hippocampi of monkeys from the stimulation and sham-stimulation groups, and saline of the same amount was injected in the control monkeys. Chronic ANT stimulation was administered in the stimulation monkeys. All animals were continuously video-monitored for epileptic seizures in the following 6 months. Immunohistochemical stainings were performed to determine the pathological alterations. Results The monthly seizure frequency was 45.7% lower in the stimulation group than in the sham-stimulation group. The amount of survival neurons of the stimulation group was significantly higher than that of the sham-stimulation group. The gliosis was also lower in the stimulation group. Conclusions Chronic ANT stimulation can reduce the hippocampal injury and gliosis, which may be an important mechanism of ANT stimulation on the temporal epilepsy.

Management of hypothalamic hamartoma (HH) with intractable gelastic epilepsy remains challenging. We performed robotic (ROSA) guided radiofrequency ablation for the treatment of HH with intractable gelastic epilepsy in a child of 6 months age. During the surgery, intracranial depth electrode implanted to the hamartoma to identify the ictal onset. Planning for surgery was performed under ROSA assistance with MRI guided targeting and radiofrequency ablation of the hypothalamic hamartoma was performed to achieve disconnection effects. No intraoperative complications occurred. The present study was primarily aimed at verifying the feasibility of using robotic guided radiofrequency disconnection technique in terms of safety, short surgical duration in younger patients to prevent further secondary epileptogenesis from hypothalamic hamartomas.

Introduction: The super-refractory status epilepticus (SRSE), defined as a seizure that persist for more than 24 hours after the intravenous anesthetic pharmacological treatment, is associated with high morbidity and mortality.  The maximum medical treatment fails in >30% of cases, in which discharge control can be achieved by neurosurgical procedures.

Objective: To report the application of neurosurgical treatment in patients with SRSE, both in pediatric and adults patients.

Methods: We present 5 cases of SRSE with hemispheric syndromes, without focal expansive lesions. All of them received maximum pharmacological treatment that included continuous infusion of propofol and / or midazolam, without seizure control. They were undergone surgically through disconnection or resection techniques.
- Patient 1: Female, 21 years old; left fronto-temporal dysplasia and maturational delay. EEG: left frontal acute seizure evolved to status epilepticus. Left hemispherotomy was performed. Seizure-free since surgery (07/07/13).
- Patient 2: Female, 18 years old;  Parry-Romberg Syndrome. Left hemispherotomy was performed 36 days after admission. She developed hydrocephalus; requiring ventriculoperitoneal shunt. Seizure-free since surgery (05/21/14).
- Patient 3: Female, 8 years old; focal refractory epilepsy. EEG: refractory status epilepticus. Right temporal lobectomy is performed, improvement of epileptic seizure was obtained. She persisted with complex partial seizures every 2 months, controlled with pharmacological treatment.
- Patient 4: Female, 21 year old; Rasmussen encephalitis. EEG: refractory status epilepticus. Right hemispherotomy was performed. Seizure-free since surgery (03/06/15).
- Patient 5: Male, 4 months old; right hemimegalencephaly, associated with predominantly fronto-parietal pachygyria. EEG compatible with right hemi-hypsarrhythmia preceding refractory status epilepticus. Left hemispherotomy was performed (08/02/17). Seizure-free since the 9th postoperative day.

Outcomes: 4 of the 5 patients undergoing surgery were completely free of seizures and one persisted with medically managed seizures.

Conclusion: Management of SRSE is a challenge in clinical practice. The literature on therapeutic options after the maximum medical treatment is scarce. This encouraging experience proposes surgery as an effective measure in SRSE with non-expansive focal lesions in which pharmacological treatment has failed.

Introduction: Epilepsy surgery is a valid option for patients with refractory epilepsy, which constitute approximately 30% of the total of cases. Epileptic syndromes without structural lesions or bilateral or multiple foci are candidates for non-resective techniques, among which Neuromodulation as one of the most modern forms of emerging treatment.

Methods: In our experience in palliative surgery of epilepsy through neuromodulation, two patients have been implanted. The electrodes was bilaterally placed in orthogonal transventricular direction towards the anterosuperior portion of the anterior thalamic nucleus. The first case was a 45-year-old man with a history of monoxide poisoning who evolved at 3 years with refractory generalized seizures. MRI showed bilateral temporomesial sclerosis. VEEG showed bitemporal discharges without lateralization. 8 bilateral deep electrodes were implanted with stereotactic guidance in wich a bitemporal origin was observed. Resective surgery was contraindicated and DBS was implanted. The second patient was a 21-year-old man, with a history of 8 years of epilepsy with falls and tonic clonic seizure several times per day. Pharmacological treatment obtained just only an initial improvement, without sustained control of seizures. It was studied by MRI, VEEG and PET, without being able to determine indications of laterality of the epileptogenic focus. Finally, SEEG was performed using 15 deep electrodes, which showed bifronto-temporal foci. Based on the results obtained DBS was indicated.

Outcomes: Both DBS system implanted has been switched on, achieving a significant reduction of the seizures in the medium and short term, respectively. Longer follow-up time is necessary to give definitive results. The patients tolerated very well the procedure without intraprocedural neither post-surgical complications.

Conclusion: In view of the results obtained and the perspectives of our center, we plan to continue developing this type of treatment in an interdisciplinary way. In our experience, DBS of the anterior thalamus nucleus for refractory epilepsy is a safe form of treatment for the patient. The international literature demonstrated its effectiveness in the control of the amount of crisis and duration of the same, which projects us to develop this technique at the level of the worldwide reference groups.

Objectives: A controversy exist in interpretating the postoperative EEG driving response (DR) an indicator of electrode placement within the thalamic nucleus in the deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) for refractory epilepsy.

Materials and Methods: We retrospectively investigated the relation between postoperative EEG DR and the location of electrodes (n=11) in 6 patients who underwent ANT DBS for refractory epilepsy. (Table 1)

Results: A cerebral synchronizing, EEG DR (Fig.1) was observed in 10 electrodes, however, 9 of 11 electrodes were found to be located within ANT. Among the 2 electrodes missed ANT, DR was observed in one, misplaced electrode facing the anterior surface of ANT within the third ventricle (Fig. 2a). The other misplaced electrode without DR elicitation showed a DR after repositioning of the electrode (Fig. 2b).

Conclusions: A diagnostic significance of DR as an indirect evidence of electrode within thalamic nuclei is limited. If DR is not elicicited, it should be regarded as a misplacement. Even if DR is elicited, it should not be interpreted as a sound indicator of proper electrode placement within the thalamus. Therefore, a sophisticated, postoperative imaging study is warranted in every case of ANT DBS.

Introduction Optogenetics is a combination of optical and genetic methods used to control the activity of specific populations of cells using light with high temporal and spatial resolution. Our aim was to reproduce kindling phenomenon using optogenetics.

Method Transgenic rats expressing light-sensitive protein, channelrhodopsin-2 (ChR2), on neuronal membrane were used. ChR2 is activated with blue light and has permeability of cations. We developed an observation facility where EEG and behaviors could be monitored 24hr/day for days with plastic optical fibers implanted into the hippocampus in freely moving animals. Short burst of optical stimuli was given once per hour, 12 times a day, for 4 days.

Results Short burst of optical stimuli activated the neurons and oscillatory hyperexcitation wave  sustained for a short period, which presented afterdischarges on EEG with minimal behavioral changes. The duration of afterdischarges progressively increased with each trial, and behavioral seizures also aggravated. Finally, generalized seizures were frequently induced, which meant that kindling phenomenon occurred. Surprisingly, when additional neuronal stimulation were added, the hyperexcitation began to be suppressed and simultaneous activation of astrocytes were observed. This suppressive effect was revealed to be the result of homeostatic increase in adenosine.

Conclusion We proved that kindling phenomenon could occur evenby selective activation of neurons using optogenetics. Futhermore, we succeeded to identify the innate suppression mechanism towards neuronal excitation.

Introduction

The orientation in the intracranial space remains a neurosurgical challenge and transition from slices to three-dimensional (3D) imaging makes surgeon closer to the reality. New developments in magnetic resonance imaging (MRI) and the release of free softwares as 3DSlicer, Freesurfer and FSL improved dramatically the quality of 3D reconstruction. Our aim to present the possibilities of 3D cortico-vascular and stereotactic electroencephalography (SEEG) reconstructions using common MRI sequences and free softwares.

Material and Methods

This study has included fifty-five consecutive epilepsy patients operated on during the period between January 2015 and December 2016. All patients underwent 1.5 T preoperative MRI and DICOM data postprocessing using FSL, Freesurfer and 3DSlicer. Intraoperative neuronavigation was performed in 40 patients and SEEG was performed in 15 patients using postprocessed images and raw data.

Results

Three-dimensional  reconstruction improve preoperative planning and intraoperative orientation especially in extratemporal epilepsy patients where the sulcal pattern is more complex and tailored SEEG implantations and cortical resctions are needed.

 Conclusions

Postprocessing of raw MRI and CT DICOM sets could provide useful preoperative and intraoperative information.

Background and purpose: Previously, automatic detectors for electrocorticography pathologic low (LFAs) and high-frequency activities (HFAs) were trained based on expert’s manual classification results. We introduce a new optimization method, reinforcement machine learning based on the resective epilepsy surgery seizure outcome, to improve the automatic detector for interictal pathologic activities in neocortical epilepsy (NE).
Methods: We analyzed electrocorticographies from 39 patients with medically intractable NE. We separately analyzed 38 frequency-bins from 0.9 to 600 Hz to sort out bands related with seizure outcome. An automatic detector using four kinds of thresholds of low and high amplitude, duration and number was used. The two different interictal electrocorticography dataset was selected containing epileptiform activities. In the first, training dataset, the automatic detector was trained to best differentiate the seizure-free group from the not-seizure-group based on ranks of resection percentages of detected activities using genetic algorithm. This fitness function is identical to the one-tailed U of the Mann-Whitney U test on the premise that resection percentages of the detected activities should be higher in the seizure-free group. We tested 70,000 threshold combinations in the training and found 6,000 optimized automatic detectors which can significantly differentiate seizure outcome groups (p < 0.05). These optimized automatic detectors were retested in the second validation dataset. Then, we also measured resection percentage differences of detected activities between seizure outcome groups (Dif-R) to evaluate detector performances and compare with literature.
Results: There were 16 seizure-free (41%) patients. The mean follow-up duration was 21 ± 11 months (13 to 44 months). Automatic detectors found significantly seizure outcome related activities in 2.3 – 30 Hz, 75 and 90 Hz and 155 – 555 Hz in the validation dataset. Dif-R of LFAs were median 16.5 % and the maximum 81 % in 4 Hz and median 32 % and the maximum 63 % in 5.8 Hz in the validation dataset. Dif-R of HFAs were median 53 % and the maximum 57 % in 223 Hz.
Conclusion: Using the reinforcement machine learning from seizure outcome, we could achieve Dif-Rs much higher than the best manual and automatic detections of HFAs in literature (17 to 27 %). Thus, we suggest this method would be useful for improving detector performance with minimal human intervention.

Background  In this study, we attempted to establish the ictal HFOs network to figure out how focal HFOs generated from an epileptogenic cortex spread out and synchronize across large areas of cortex.

Methods We applied the network topology measures to 20 seizures observed in 5 patients from their SEEG signals. We measured inter-electrode cross-coefficient between all pairs of electrodes for each 1 second window. By constructing the HFOs network, the topology was analyzed by network measures such as the density and the components.

Results By using the SEEG to explore the dynamic topologies of cortical and subcortical HFOs networks, we found the HFOs network synchronization and ripple energy increase during seizure progression.

Conclusion The improvement of spatiotemporal resolution established by SEEG and HFOs’ network helped us to recognize and analyze the epileptic seizures. Consistent topologies changes implied the common epileptogenic pattern in temporal lobe epilepsy.

Purpose:

Epilepsy surgery for focal cortical dysplasia (FCD) often requires multiple non-invasive as well as invasive pre-surgical evaluations and innovative surgical strategies. There is limited data regarding surgical management of people with chronic drug resistant epilepsy (DRE) & FCD among the low and middle-income countries (LAMIC) including India.

Method:

Presurgical evaluation, surgical strategy and outcome of 53 people who underwent resective surgery for DRE with FCD between January 2008 and November 2016 were analyzed. Blumcke et.al 2011 classification was used for histo-pathological categorization. Engel classification was used for defining seizure outcome. The surgical outcome was correlated with preoperative clinical, VEEG, MRI, invasive monitoring, surgical findings as well as histopathology and QOLIE- 89 scores.

Results:

This cohort consists of 19 cases evaluated retrospectively and 34 cases prospectively. Age of onset ranged from 1 to 43 years (mean 9.28yrs; SD 7.25). Duration of epilepsy ranged from 1-39 years (mean 11.68; SD 8.99). The following regional distribution was found; Temporal-31 (Language-13), Frontal-9 (Motor Cortex- 5), Parietal-5 (Sensory Cortex-4), Occipital-3 and multilobar-5. Forty seven percent of the cases had FCD in the right hemisphere and 53% had FCD in the left hemisphere. Invasive monitoring was performed for identification of the epileptogenic zone (EZ) as well as eloquent cortex in 7 and intra-operative electro-corticography (ECoG) was used in 32 cases. Histopathology revealed the following distribution; FCD Ia-5, Ib- 2, Ic-4, IIa-6, IIb-10, IIIa-20, IIIb -3, IIId-3. Overall outcome of Engel’s class Ia was 61.3 %. Pre- operative QOLIE-89 score was 26.33-40.17 (mean 33.69, SD 4.35) and post-operative score was 59.21-89.79(mean 73.81; SD 8.29; p=0.04).

Conclusions:

Surgical management of people with DRE and FCD is possible in countries with limited resources. Meticulous pre-surgical evaluation to localize epileptogenic zone and complete resection of the focus and lesion can lead to cure or control of epilepsy and improvement in QOL was observed along with seizure-free outcome. The  author will present several illustrative  cases with videos of the surgical strategy. The resected tissue is a gold-mine and can be subjected to proteomic, genomic and metabolomic evaluation through international research collaboration. 

Polymicrogyria（PMG）is a highly heterogeneous malformation of cortical development. 60% to 85% of patients with PMG have epilepsy which could be partially or generalized and even catastrophic. We present two cases of unilateral PMG with partial seizure pattern refractory to medication treated by resective surgery with/without intracranial electroencephalogram (IEEG) at our center.

The presurgical evaluation methods included medical history assessment, neurological examination, magnetic resonance imaging (MRI), video- electroencephalogram (VEEG) monitoring with surface electrodes and stereotactic intracranial electrodes, and neuropsychological assessments. The surgical results, pathological diagnosis and follow-up data are analyzed.

The first patient (27 years old male, seizure begin at 4) has seizure onset with aura of dizziness and without functional deficit. MRI showed right hemisphere PMG mainly on frontal and parietal lobe. Ictal VEEG revealed right hemisphere epileptiform activity mainly on the posterior part. Stereotactic IEEG and functional mapping was performed followed with restricted resection of the part of the parietal PMG. (Fig.1)  There was no neurological deficit and neuropsychological deterioration after surgery. And after 2 years of follow-up only 2 seizures was reported. The second patient(16 years old female, seizure begin at 2) has seizure onset with aura of right hand paresthesia and she has right hand paralysis. MRI showed small left hemisphere with PMG. Ictal VEEG revealed left hemisphere epileptiform activity. Because of her poor family, direct resection of the parietal PMG posterior to the central sulcus was performed. (Fig.2) There wasn't new neurological deficit and neuropsychological deterioration after surgery. She is seizure free till now which is 2.5 years after surgery. The pathological diagnosis revealed heterotopia and fusion of the molecular layer and deep underlying complex sulcal branching in both patients.

Schizencephaly(SZ) and PMG are malformations arising due to defects in postmigrational development of neurons. They are in the same pathological spectrum. This two cases showed that epileptogenic zone are mainly around the cleft in the area of PMG though the cleft are not connect with ventricle. And the pathological results showed the heterotopia in both patients. PMG may have different epileptogenic potential and our two cases showed that cortical cleft with heterotopia may highly facilitate to epileptogenesis. 

Introduction: The number of procedures for treatment of refractory epilepsy boomed after the introduction of MRI in clinical practice. MRI was able to identify new brain pathology and adequately document the traditional ones. We studied the pathological findings over time of 982 patients submitted to surgery over the last 10 years.

Methods: 982 patients submitted to resective surgery for refractory epilepsy from 2006 to 2015 were studied. Their type of resection and the more frequent pathological findings were plotted over time.

Results: At the first year of the studied series (10 years ago), there were 43 mesial temporal sclerosis patients (MTS), 16 with cortical dysplasia, 25 with brain tumors, 8 with vascular pathology, 4 with Rasmussen syndrome, 2 with Sturge-Weber, 6 with HHE and 10 patients with no detectable lesion. During the last studied year (2015), there were 12 patients with MTS, 20 with cortical dysplasia, 27 with tumors, 10 with vascular pathology, 1 with Sturge-Weber, 5 with HHE, and 25 had no detectable lesion; there was no patient with Rasmussen syndrome. Overall, there was a progressive decrease in the number of patients with MTS, and in increment of patients with no detectable pathology. The number of procedures per year remained stable (ranging from 82 to 110). Rasmussen patients are now seen only sporadically.

Discussion: It appears that the pathological spectrum found in epilepsy surgery patients has been changing over the last decade. We are doing more non-lesional cases (in whom we could expect a worse outcome compared to lesional cases), and less MTS patients. The number of patients with brain tumors, vascular pathology and cortical dysplasia remained stable. Rasmussen syndrome patients are now rare; on the other hand, we have seen a significant increase in auto-immune encephalitis. Contrary to Rasmussen patients, patients with auto-immune encephalitis usually have bilateral lesions and are not surgical candidates.

Introduction. Although different Authors report the efficacy of VNS in paediatric population, only few papers focused on the so-called “best responders” (patients showing > 80% seizure reduction).

Materials and methods. Among all the paediatric cases operated upon in our centre, we focused on best responders, i. e. the children showing a decrease >80% in seizure rate.

Results. Between 2007 and 2015, 32 patients were implanted during paediatric age for drug-resistant epilepsies. 17 patients (58.6%) presented a decrease of the seizure rate > 80%. 3/17 patients became seizures free.The prevalence of the best responders did not differ significantly at 6 (50%), 12 (50%) and 24 months (55%). 12/32 patients underwent the scale PedsQl 4.0 to assess the health-related quality of life (HRQOL). Comparing the best-responders to all the other patients, we obtained a significant correlation in the following sub-items: alertness (p-values 0,010), concentration (p-value 0.032), memory (p-value 0.046), communication skills (p-value 0.005) and adaptive behaviour (p-value 0.010). Comparing various clinical features to the outcome, we found that only the etiology of epilepsy correlated with best outcome: the patients suffering from structural-metabolic epilepsies showed a p-value = 0.022; 4 patients presented with Tuberous Sclerosis Complex, becoming in 2/4 seizures free. Finally, comparing the age at the implant and the outcomes, youngests (<7 years) correlate with best results (Spearman i. + 0.425): 84.6% presented with decrease of the seizure rate >80% and 3 patients (23%) are currently seizure free.

Conclusions. In our experience, 58.6% of our patients presented a reduction > 80% of the seizures rate and at present 3/32 are seizures free. We suggest that the earlier the implant the better the outcome and that structural epilepsies, like TSC or large cortical dysplasias, obtained a best response when conpared to genetic or unknown aethiology epilepsies.

Objectives: We aim at describing the surgical approaches for the implantation of perisylvian depth electrodes in patients with drug-resistant epilepsy. Based on a retrospective analysis of functional mapping using electrical stimulation in a population of patients, we aim at providing guidelines for targeting specific functional areas.

Methods: In a population of 8 patients undergoing presurgical evaluation for drug-resistant epilepsy, we have implanted depth electrodes that are targeting the insular-opercular areas using three main approaches: a) orthogonal trans-opercular; b) parasagittal oblique anterior; c) parasagittal oblique posterior. Functional mapping using 50 Hz electrical stimulation is performed, and the results are co-registered across patients using FreeSurfer and Matlab scripts to provide combined insular-opercular functional maps.

Results: Perisylvian implantations (Fig 1a, patient 8) have been performed without complications, including parasagittal oblique trajectories (Fig. 1b). A number of 142 clinical symptoms evoked by electrical stimulation were co-registered across patients to create functional maps. Some symptoms showed a spatial segregation, as illustrated in the cortical surface reconstruction (Fig. 1c) and the inflated version (Fig. 1d).

Conclusions: Targeting perisylvian structures using approaches guided by the functional maps contributes to the success of the SEEG investigations.

Introduction: Stereotactic laser amygdalohippocampotomy (SLAH), performed with laser interstitial thermal therapy, is a recent addition to the minimally invasive alternatives to open epilepsy surgery. Several studies have demonstrated that stereotactic ablative procedures are capable of achieving short term outcomes in the range of traditional surgical resections. Despite the considerable advantages minimally invasive approaches offer to patients, they may be associated with additional costs related to disposable charges, but which may be counter-balanced by decreased length of stay and case acuity. We therefore undertook a short-term economic evaluation of SLAH in comparison to open epilepsy surgery.

Methods: 45 encounters were reviewed including the 15 most recent of 3 groups: SLAH cases using the ClearPoint^® intraoperative-MRI system, SLAH cases using the CRW^® stereotactic frame, and open surgery cases. One-way MANOVA determined differences for Total Cost among groups and between open surgery and combined SLAH procedures. Costs were stratified by category. Significant multivariate effects were defined at alpha=0.05. Bonferroni alpha correction defined significant univariate effects(p<0.0038).

Results: Significant differences were found for Total Costs (F[2,38]=10.48, p=0.0002), OR/Anesthesia Time (F[2,38]=54.90, p<0.0001), Hospitalization, Medication and Test Costs (all p<0.0001). On average, open surgery cost $15,488 (95% Bonferroni CI: $3,996 , $26,980) more than minimally invasive methods, which were not significantly different from each other. Open surgery costs associated with OR/Anesthesia Time and Hospitalization costs were also significantly different from comparators, with average excess costs of $8,672 ($5,387 , $11,956) and $11,189 ($7,338 , $15,041) respectively. There was no significant difference in procedure-related costs (p=0.04), or patient payment estimates (p=0.23).

Conclusion: Relative to open surgery, minimally invasive approaches offer measurable reductions in cost. Hospitalization costs account for the majority of the difference in cost, related to a mean 7-day increase in length of stay among open surgery patients. With no difference in payment estimates, it is unlikely that these findings are attributable to variations in billing or healthcare payer practices. In addition to other advantages such as decreased discomfort, stereotactic laser amygdalohippocampotomy (SLAH) is an economically sound alternative to open epilepsy surgery.

Newer techniques are evolving to perform surgeries for refractory epilepsy.

Focus is being laid on the making the surgery less invasive  with good outcomes and reduced rate of complications.

Disconnection procedures are  popular  with it’s aim at tissue preservation and lesser long term complications.

Disconnection procedures need better understanding of the ventricular and  white matter anatomy.

Tissue viability and eloquent area preservation when feasible  are the main aims of disconnection procedures.Though hemispheric disconnection is now established form of surgical treatment for epilepsy of hemispheric origin, the decision making in lobar epilepsy, scar epilepsy and epilepsy of deeper origin is pathology dependent.

Motor preservation is one of the main concerns in lobar disconnections. The decision making is largely dependent on surgeon’s comfort and pathology.

Available data does not provide the guidelines to make the decision between resection and disconnection procedures for lobar epilepsy. 

We  analyse long-term seizure freedom, complication rates of the reported disconnection procedures.

An attempt is also made to provide some guidelines for use of resection or disconnection procedures.

BACKGROUND

Destructive surgery offers the chance of cure in refractory epilepsy patients. Radiofrequency thermocoagulation (RF-TC) is a minimally invasive technique that allows for the creation of small lesions through stereotactic intracranial EEG (sEEG) electrodes, potentially allowing patients to avoid open epilepsy surgery.

METHODS

From 2014-2016, 7 patients with refractory focal epilepsy underwent sEEG and were treated with RF-TC after localization of seizures and related eloquent cortices. Electrode contacts involved in seizure onset and early spread were ablated using a radiofrequency lesion-generator system (Cosman Medical Inc., Burlington, MA, USA). In patients with seizure foci in eloquent cortex, neurologic function was tested after each increase in power. EEG was recorded before and after ablation. Brain MRI was performed within 24h to determine lesion extent. Postoperative seizure outcomes and neurologic deficits were assessed.

RESULTS

Seven patients between 32-63 years (4 female, 3 male) were treated. Six patients were lesional (3 cortical dysplasias; 1 stroke; 1 cystic lesion; 1 encephalomalacia); one was non-lesional. All underwent sEEG using a median of 9 (range 6-19) 10-contact depth electrodes; one patient also had 4 subdural strip electrodes. Onsets were left frontal (3), right frontal (1), left parietal (1), left temporal (1), and posterior cingulate (1). All patients underwent RF-TC during awake sEEG monitoring, either at the bedside (3) or in the operating theatre (4). Current was delivered stepwise from 1.5 to 6 Watt for up to 60 seconds. A median of 16 (range 5-28) contacts were ablated. Cortices underlying two strip electrode contacts were also ablated in 1 patient. Re-ablation was performed in 2 patients in subsequent hours or days that had continued epileptiform discharges post-ablation. Lesion size was inadequate on MRI in 1 patient, who then immediately underwent stereotactic laser interstitial thermal ablation under anesthesia along two existing electrode trajectories. Five of 7 pts were free of disabling seizures at a median of 12 (range 4-30) months postop. There were no permanent neurologic deficits.

CONCLUSIONS

RF-TC is a safe, minimally invasive treatment option for patients with refractory focal epilepsy. Though 71% of our patients were free from disabling seizures and avoided craniotomies with sEEG-guided RF-TC alone, longer follow-up and larger series are needed to confirm the efficacy of the procedure. 

RATIONALE

Corpus callosotomy (CC) is a surgical disconnection to treat generalized and atonic seizures in refractory epilepsy patients. While minimally invasive MRI-guided stereotactic laser ablation is a safe, effective alternative for refractory focal epilepsy, stereotactic laser corpus callosotomy (SLCC) is less defined. We compare outcomes of 4 patients who underwent SLCC to 4 patients who underwent open CC.

METHODS

At surgery, patients in the SLCC and CC groups were a median 32.5 (range 20-47) and 32 (range 26-39) y old, respectively.  All but 1 SLCC patient had vagus nerve stimulators, 1 in each group had prior temporal lobe surgery, and all but 1 were male. All 4 SLCC patients had atonic seizures and diagnoses of Lennox Gastaut syndrome (LGS); 3 underwent anterior 2/3 SLCC; of which 1 had additional ablation (posterior 1/3 SLCC) 1 m later for continued seizures. A 4th SLCC patient that had prior incomplete CC had worse atonic seizures after mesial temporal lobe ablation for mesial temporal sclerosis and had completion SLCC (genu and splenium) 8 m later.  Two CC patients had focal seizures with frequent generalization; 2 had LGS with atonic seizures; all underwent anterior 2/3 CC.

RESULTS

Acute hospital stays in the SLCC and CC groups were median 3.5(range 2-9) and 13 (range 3-21) d, respectively. Total hospitalization stays in SLCC and CC groups were median 11(range 2-31) and 21(range 10-35)d, respectively, including subsequent inpatient rehab stays and a readmission in 1 CC patient for seizures. One patient in each group had an intracranial hemorrhage; 1 in each group had supplementary motor area syndrome. Two SLCC patients had persistent deficits (mild hemiparesis; incontinence); 1 CC patient had persistent abulia. With median postop follow-up of 9 m(range 6-16 m) and 5 y(range 9 m–9 y), atonic seizures ceased in all SLCC, but only 1 CC patient, respectively. Generalized seizures decreased by >50% in all patients except 1 SLCC patient. All SLCC patients had  >50% decrease in absence seizures. Absence and focal seizures were unchanged in 3 of 4 CC patients. Two SLCC patients were seizure free; no open CC patients were seizure free.

CONCLUSIONS

Minimally invasive MRI guided SLCC is a safe, effective alternative to open CC. Patients undergoing SLCC had comparable rates of postop complications but shorter hospital and rehab stays. Seizure outcomes appear favorable after SLCC, but larger groups, longer follow up, and improved patient matching are required.

Introduction

Vagus nerve stimulation (VNS) is one of the main surgical options for refractory epilepsy both in adult and pediatric population. The authors present here their surgical experience on the first series of patients with drug-resistant epilepsy operated for VNS in Romania and discuss how to adapt the surgical technique to individual anatomical variations of the vagus nerve and its relationship with common carotid artery and internal jugular vein.

Patients and methods

We included in this series 300 patients with refractory epilepsy operated for VNS in Neurosurgery Clinic, "Bagdasar-Arseni" Clinical Hospital, between October 2012 and February 2017. In all cases we used the latest VNS generator model (103). For all patients we used a left latero-cervical approach. The medium follow-up period was 11 months and the minimum follow-up period was one month.

Results and Discussions

There were 63 children and 237 adults in our series. The gender distribution was 147 females and 153 males. The average period of hospitalization was 4,8 days. There were no deaths in our series. There was a single case of left vocal cord paresis which remitted at two months follow-up. Postoperative hoarseness was noticed in 26 patients (8,6%) and disphagia in 19 patients (6,3%). The anatomical variations observed by the authors include: a vertical orientation of the great vessels with the internal jugular vein located superiorly, common carotid artery located inferiorly and the vagus nerve in intermediate position (compared with normal "horizontal" orientation with jugular vein located laterally and common carotid artery located medially), and a greater size of the internal jugular vein. When we met both anatomical variants in the same individual (observed in 29 patients - 9,6%), the vagus nerve dissection became more difficult and the risk of the vascular injury increased, because the vagus nerve was practically covered by a voluminous internal jugular vein. Surgical technique should be addapted in this situation and includes a carefully dissection of the internal jugular vein with the mobilization and rotation of the vein in order to gain a proper access to the vagus nerve.

Conclusions

VNS is a safe and efficient surgical procedure with a short hospitalization period and minimum postoperative complications. Adapting the surgical technique to individual anatomical variants makes the intraoperative and postoperative complications related to VNS procedure to become very rare events.

Purpose: Gamma Knife radiosurgery (GKS) has been proposed as an alternative therapeutic option for patients with intractable glossopharyngeal neuralgia (GPN) who are poor candidates for microvascular decompression surgery. The role of GKS for GPN remains controversial, and only a few cases have been reported.

Materials and METHODS: Forty-three patients with intractable idiopathic GPN have been surgically treated. Among them, five patients (3 males, 2 females; mean age 75 [range 50–80] years) were treated with Gamma Knife radiosurgery (Model C, Elekta Instruments AB, Sweden) because of serious medical problems or advanced age. The maximum target dose ranged from 50 to 85 Gray (Gy) was delivered using a single 4-mm collimator. The target for GPN was either the cisternal segment of the glossopharyngeal nerve (n=3) or the glossopharyngeal meatus (GPM) (n=2). The three patients with primary GPN treated with a dose ≥80 Gy, regardless of the target. The other two patients were treated with prescribed doses of 50–75 Gy, because both the trigeminal nerve and GPM were needed to be targeted to treat trigeminal neuralgia simultaneously. The pre- and post-GKS pain outcomes were evaluated using the visual analog scale with the Barrow Neurological Institute pain intensity scoring system.

RESULTS: The mean follow-up was 40.8 (range 2–75) months. The three patients with primary GPN treated with a dose ≥80 Gy had good pain relief (Class II-III), regardless of the target. Despite some improvement, pain relief was unsatisfactory in the other two patients (class IV). No GKS-associated complications were observed in any patient.

CONCLUSIONS: GKS appears to be a safe therapeutic modality for medically refractory GPN in selected patients.

Microvascular decompression (MVD) is considered as the first line therapeutic option for glossopharyngeal neuralgia (GPN). Gamma Knife radiosurgery (GKS) has been proposed as an alternative therapeutic option for the selected patients with intractable GPN. The objective of this study was to compare surgical outcomes of GPN between MVD and GKS.

Forty-three patients (24 males, 19 females; mean age 55.8 [range 32–80] years) with intractable idiopathic GPN were surgically treated from 1996 to 2016. MVD was chosen as the first line therapeutic option in 38 patients and was performed with the transposition technique (26 cases, 68.4%) and the interposition technique (12 cases, 31.6%).

Five patients (3 males, 2 females; mean age 75 [range 50–80] years) were treated by GKS because of serious medical problems or advanced age. The maximum target dose was 50-85 Gray (Gy), delivered using a single 4-mm collimator. The target for GPN was either the cisternal segment of the glossopharyngeal nerve (n=3) or the glossopharyngeal meatus (GPM) (n=2). Three patients were treated with ≥80 Gy. The other two patients were treated with reduced doses of 50–75 Gy, as the trigeminal nerve was targeted to treat concurrent trigeminal neuralgia. The pre- and post-GKS pain outcomes were evaluated using the Barrow Neurological Institute (BNI) pain intensity scoring system.

The average follow-up durations in patients treated with MVD and GKS were 55.97 months (range 3-251 months) and 41.5 months (range 3-75 months). Among 38 patients treated with MVD, 30 patients became pain free immediate post-operatively and maintained in BNI grade I state (78.9%). Among the 32 patients treated with MVD who were followed up for ≥ 1 year, 31 good pain relief (BNI grade I-II, 96.8%). Neuralgic pain recurred in one patient; however, the pain was less frequent and less severe than that observed preoperatively. Cranial nerve impairments developed in 4 cases, but resolved in the following months. A permanent decrease in hearing occurred in one patient.

Among the five patients treated by GKS, the three patients with a dose ≥80 Gy had good pain relief (Class II- III). Despite some improvement, pain relief was unsatisfactory in the other two patients (class III-IV). No GKS-associated complications were observed in any patient.

The results suggest that MVD is the treatment of choice for medically intractable GPN. GKS appears to be a safe therapeutic modality for medically refractory GPN in selected patients.

INTRODUCTION

Motor cortical stimulation (MCS) is a tool to   treat intractable chronic neuropathic central pain mainly in patients operated for trigeminal pain. If the MCS can ameliorates dysesthesias and/or allodynia very few cases of sensory loss improvement have been reported. We describe two patients with partial recovery  of painful trigeminal second branch sensory loss.

CLINICAL CASES

These two females 38 and 52 years-old underwent percutaneous trigeminal thermocoagulation respectively 2 and 5 years before the admission to our Department for  typical trigeminal neuralgia. After these procedures a neuropathic pain in trigeminal second branch developed. Medical therapies were ineffective to treat the pain so a Motor Cortex Stimulation  was carried out using a 16 poles paddle connected to a  implantable multiple source generator. The surgical technique used to implant the device consisted in the use of neuronavigation and of  intraoperative neurophysiological registration to find the somatotopic motor cortex  area  of  the face.

RESULTS

The pain one month after surgey decreases of 40%. Two month after MCS implant, the patients reported improvement of  tactile sensitivity of second branch  trigeminal sensory loss.

DISCUSSION

The mechanisms leading to sensory restoration is unclear. One hypothesis could report  that the sensory impairment, maintained by central mechanisms has been reversed by MCS, leading to the sensory restoration.

Objective: To determine the postoperative outcome, recurrence and prognostic factors of MVD in patients with primary trigeminal neuralgia (TGN) operated at the General Hospital of Mexico.

Material and Methods. The study included 70 patients with diagnosis of primary trigeminal neuralgia with a follow-up of 10 years. A Kaplan-Meier survival analysis was generated at 1 and 10 years of follow-up for the study of recurrence. We assessed pain using the Visual Analog Pain Scale (VAPS) before and after MVD. The results were analyzed using a Mann-Whitney test with a significant p <0.05.
Prognostic variables were patient age, sex, affected segments of the trigeminal nerve, and conflicting blood vessel in relation to recurrence.

Results. The mean age of the patients was 35 years. 49 patients (70%) were female and 21 patients (30%) were male. The involvement of the ophthalmic branch (V1) was diagnosed in 17 patients (24.28%), mandibular branch (V3) in 17 patients (24.28%) and maxillary branch (V2) and mandibular branch (V3) in 36 patients (51.42%). 72% of the patients had affection on the right side of the face (n=50). All patients had an arterial neurovascular conflict. The conflicting artery was the Superior Cerebellar Artery (SUCA) in 97.14% (n = 68) and later the Anteroinferior Cerebellar Artery (AICA) in 2.85% (n = 2). According to Kaplan-Meier analysis, the success rate (defined as pain-free patients without any medication) was 96% at 1 year and estimated to be 84.24% after 10 years of follow-up. Immediate relief from pain occurred in all patients. None of the following patient-related factors played any significant role in prognosis: sex, patient age, affected segments of the trigeminal nerve, and conflicting blood vessel in relation to recurrence. Permanent hypoesthesia and motor function of the trigeminal nerve was intact in all patients. No other complication was found.

Conclusion. MVD offers patients affected by TGN due to vascular compression a long-lasting cure in 96% of the cases at 1 year and estimated to be 84.24% after 10 years of follow-up. MVD is a safe and effective management option for TGN with neurovascular conflict.

Visualization of implanted intracranial electrodes in three-dimensional space provides valuable information for surgeons in planning resection in epilepsy surgery. Many studies published various coregistration methods for accurately visualizing intracranial electrodes. From a clinician’s point of view, coregesitration method should be easy to learn and fast to apply, especially in hospitals with limited human resources. We introduce simple coregistration method using two open source imaging programs (Freesurfer and Slicer) with acceptable accuracy and beautiful three-dimensional visualization. Seven consecutive patients with intractable drug-resistant epilepsy were included in this study. Subdural grids, strips and depth electrodes were inserted as needed.  All patients underwent thin sliced preoperative MRI (3T, 0.9 mm thin-sliced T1 MPRAGE) and postoperative 2 mm thin-sliced CT scan. Freesurfer program was used for three-dimensional cortical reconstruction. Because this process generally takes several hours, it was prepared before the day before surgery. Reconstructed three dimensional images could be used as a reference for planning subdural electrode placement as well. Slicer program was used for coregistratimg postoperative CT and preoperative MRI or reconstructed cortical images by Freesurfer. A built-in registration module(BRAINS) with Rigid and Affine registration phases were used. In case of subdural or strip electrodes, electrode localization of postoperative CT over reconstructed cortical surfaces using markers. Linear transformation was needed when there was a brain shifting. Coregistration of depth electrodes were easier because of the minimal brain shifting. Required time for each coregistration process was less than 10 minutes. The accuracy of results was verified during the second surgery, which was satisfactory. We concluded that this method is easy and fast with acceptable accuracy for usual epilepsy surgery with intracranial electrode placement. 

Objectives: Following a non-infectious DBS hardware erosion, the standard practice is to explant the device and re-implant after sufficient healing. This leads to significant hospital costs and a temporary cessation of therapeutic stimulation. In the published literature, erosion complications are typically lumped together within the category of infectious complications. In this study, we investigated if we can differentiate non-infectious erosions from infectious wound dehiscence and determine if erosions could be managed without explantation.

Methods: n=3 patients presented to our clinic with implantable neural stimulator (INS) erosions in their chest. Standard microbiology tests ruled out erosions of infectious etiology. Figure 1 is a typical presentation of a non-infectious INS erosion. Wound debridement was performed with hydrogen peroxide (HP) and the wounds were primarily revised without hardware explantation. Patients were followed-up a minimum of six months post-operatively. Clinical images were documented to demonstrate progress of wound healing.

Results: n=2 subjects were able to keep their DBS hardware and there was no cessation of therapeutic stimulation. The third patient presented two months later with an onbvious infection requiring explantation. Figure 1 demonstrates the erosion preoperatively and six months post-operatively of one of the successful cases. An analysis of hardware and hospital associated costs saved per case was approximately $50,000 USD. We present a detailed algorithm to manage hardware-related complications in DBS.

Conclusion: The application of HP during wound debridement and revision for non-infectious INS and scalp erosions can be used as a hardware-saving procedure. Details of the procedure are provided for practical purposes. We expect this hardware-saving procedure is applicable to not only DBS practitioners, but also those using Spinal Cord Stimulation, Motor Cortex Stimulation, and experimental neurostimulator devices.

AIM: to analyze the clinical and urodynamic results as well as the complications from SARS (sacral anterior root stimulator) extradural implantation in the treatment of patients with spinal cord injury (SCI) associated with neurogenic detrusor overactivity (NDO). Materials and methods: Descriptive study of the results obtained in a single center from 6 patients diagnosed SCI with NDO and implanted since 2012. RESULTS: All patients were male, aged 38 ±10 years, and suffered a traumatic complete spinal cord lesion. The average time of evolution was 84 months (48-108). 83% of the patients showed ASIA A classification, 83% located at dorsal level. Symptomatic recurrent urinary infection (more than three per year) rate before SARS was 100%, and 0% after the procedure (p<0,69). Before SARS all patients suffered urinary incontinence due to overactive detrusor, and after SARS 100% of the patients gained control and achieved a bladder capacity greater than 300 ml. Preoperative autonomic dysreflexia rate was 66% and afterwards only 5% (p<0,07). All patients achieved an effective voiding, with residual post-voiding volume lower than 50ml and stopped using catheters. 66% of the patients used the device for erectile function and 88% of the cases use for bowel function. Infection rate has been 0%. Failure of the device was seen in three patients but only in the external controller, all of them where solved without surgery. Conclusion Since 2012, our group has been carrying out SARS implants in selected patients using the extradural technique with good clinical and urodynamic results, in terms of improvement of urinary incontinence, infection rate, erectile and bowel function in patients with NDO due to SCI. It proves to be a safe procedure when carried out in an interdisciplinary team.

Introduction
Transcranial magnetic stimulation (TMS) can induce speech arrest at 25 Hz repetitive TMS used  for brain mapping in a population of epileptic patients scheduled for epilepsy surgery (Pascual-Leone1991) . It is based on reversible temporal brain tissue lesion principle. There are date suggesting that speech arrest could offer information not only on dominant hemisphere but on spatial Brocca area localization in the brain (Jennum).  
Method
A total of 72 patients were evaluated for epilepsy surgery. An innovative Neuro MSD device was used for TMS studies. The maximum TMS output of this device is in the range of 0 to 4 Tesla (for iron core). The figure eight shaped stimulation coil and an iron   cone shaped core were used for focalization. Motor threshold is the intensity of stimulation needed to induce contraction in thumb. This intensity was used to block Brocca area activity in digit span. Different word picture association tasks were used.
Results
None of our patients presented postoperative permanent language deficits.  
We found that TMS not even block speech but elicit misjudgment of word picture association. It was categorized as wrong, late, slow or absent. Wernike area was more difficult to localize, but we found that there are different patterns depending on stimulus timing before, during and short after naming tasks which are presented.   
Discussions
Temporary lesions is comparable to current stimulation or Wada test and is obtained by TMS noninvasively. This is helpful during dominant hemisphere resection for epilepsy or other lesions. TMS blocks speech in most of subjects but not in all. Head motor primary area is mainly involved in speech arrest but real motor aphasia is rear and bilateral speech control is found mostly in reeducated left handed subjects.
Conclusion
TMS is a noninvasive method of modulating cortex and is proper for study of language in humans. It can give information on hemispheric dominance a motor area localization. Standardized study could provide important insights on the organization of this function not explained by evolution theory.

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Background and Study Aims: The purpose of the present study is to compare the characteristics, i.e. efficacy, duration and hospital stay, of a frameless fiducial-less brain biopsy method with those of the standard frame-based stereotactic technique. Material and Methods: In the present prospective cohort study were enrolled 56 adult patients: 1) for whom no conclusive diagnosis could be settled in a noninvasive manner; and 2a) who also had lesions involving deeply seated and eloquent areas, or multifocal lesions, or lesions for which the probable diagnosis is a contraindication for craniotomy, or 2b) were poor candidates for open craniotomy (over 80 years old or serious comorbidities that were considered contraindications for open craniotomy). 28 patients were operated on with each method. Regarding the frameless biopsy technique, we used a navigation system (StealthStation® S7™) without fiducials in combination with the Navigus trajectory guide. Concerning the frame-based stereotactic method we used the Cosman-Roberts-Wells (CRW) frame and a planning software (FrameLink™ Stereotactic Planning Software). Results:  Failure of diagnosis was recorded in 4 cases (14.3%) of the frame-based method group and 3 cases (10.7%) of the frameless fiducial-less method group, in spite of the accurate targeting, without a statistically significant difference (p= 1.0). The mean duration of the overall procedure was 111.3min for the frame-based method and 79.1min for the frameless method, a statistically significant difference (p= 0.001). Concerning neurologic morbidity, new abnormal findings in the postoperative head CT scan (p= 1.0) and postoperative hospital stay (p= 0.66) the two methods did not differ significantly. The smallest maximal diameter of a lesion successfully targeted, acquiring samples which led to a diagnosis, was 15mm for both groups. Conclusions: The above frameless fiducial-less brain biopsy method was shown to be equally efficacious and safe, compared with the standard stereotactic frame-based technique, in terms of diagnostic yield, neurologic complications, and new findings in the postoperative head CT scan. Moreover, the frameless method was associated with a shorter duration of the overall procedure and of the respective preparatory steps; however with similar duration of the operation only and similar time spent inside the operating room overall. Finally, the length of postoperative hospitalization did not differ significantly too.

Introduction: Migraine is a highly prevalent disease and often refractory to medical therapy. ONS has been shown to
provide pain relief in patients with refractory primary headache disorders. It is also less invasive than other surgical
approaches; however, drawbacks have been reported, including technical issues with implantable components and
lack of efficacy of the treatment. The mobility of the head-neck region causes patient discomfort at the implantation
sites, when conventional straight wire SCS leads are used in ONS. We therefore investigated a new flexible, body
compliant SCS lead and system for its suitability in ONS in a series of patients for efficacy, complications and overall
outcome.
Materials/Methods: We hereby present a series of 27 patients suffering from chronic migraine (CM) (ICH criteria),
who underwent ONS lead implantation (12 contact leads bilaterally, Algovita, Algostim). Prior to implantation, all
patients received unsuccessfully conservative and surgical therapies, including antidepressants, occipital nerve
blocks, opioids and botulinum toxin injections. Using a midline incision at C1-2, two 12 contact leads were placed
subcutaneously and positioned under fluoroscopy bilaterally at the level of C1, respectively. Leads were tunneled and
the generator was placed in an all-in-one procedure under general anesthesia.
Results: At three months follow-up, a reduction in headache days in 16 out of 27 patients (26.5 to 20.4 days) was
observed, corresponding to a pain relief (9.9/7.0 on the VAS). Ten (10) patients reported a pain reduction of more than
30%, one (1) patient did not benefit so far (3 months postop). Decrease in pain led to an improvement in functional
capacity of the patient during the 3 months follow-up post implantation. (6-months results will be included at the time
of presentation). One failure occurred due to skin erosion of the lead tip during initial placement with concomitant
dislocation; a successful revision was performed. Frequent problems with stimulator rechargement could be solved in
all cases. No other complications, side effects or reports on patients discomfort were noted.
Discussion: There is an ongoing debate about optimal implant technique, indications and outcome measurement of
ONS. By using a new 20% stretchable implantable lead, mechanical complications can be reduced. Due to delayed
effect of the treatment we used an all-in-one approach with an outcome follow-up of 3-6 months.

[OBJECTIVE] MR-guided focused ultrasound therapy (MRgFUS) for medication-refractory essential tremor (ET) was introduced as a clinical trial in Japan in 2013. Accuracy is certainly important in the stereotactic neurosurgery, and even in MRgFUS, it is important that a lesion is created accurately in the target. Therefore, we examined the positional error and the volume of the lesion created with MRgFUS comparing with radiofrequency lesioning (RF).
[SUBJECT and METHOD] We compared 10 cases treated with MRgFUS for refractory medication-refractory ET after June 2014 (group A) with 7 cases treated by RF for dystonia (Group B), regarding the positional error between the target and the center of the lesion, and the volume. Exablate Neuro® was used for MRgFUS. Elekta Stereotactic System® was used for RF to create a lesion at 70℃ for 60 seconds after the test coagulation at 60℃ for 30 seconds with 2 * 2 mm an uninsulated tip. We measured the positional error by measuring it between the target and the center of the lesion, and the volume of the lesion by vertical * horizontal * height / 2, and we compared them statistically.
[RESULTS] The positional error of the lesion was 1.06 ± 0.44mm in group A and 3.47 ± 1.73 mm in group B, which was significantly smaller in group A (p = 0.007). The volume of the lesion was 62.1 ± 26.1mm³ in group A and 126.2 ± 66.4mm³ in group B, which was significantly smaller in group A (p = 0.018).
[CONCLUSION] MRgFUS has a smaller positional error than RF, and it is possible to create a lesion with higher accuracy.

Background and Objectives: Lesch-Nyhan Disease (LND) is extremely rare inherited disorder of purine salvage metabolism, clinically manifesting hyperuricaemia, compulsive self-injurious behavior, and extrapyramidal motor disorder. Various symptoms of LND is treated with pharmacological treatment such as antispastic drugs, antipsychoics, anti-parkinsonian drugs and dietary supplements, whereas their abnormal posturing or involuntary movement is difficult to control. Here we report a case of LND treated by intrathecal baclofen therapy (ITB), and discuss its role on their symptoms. Case report: A 22 year-old male genetically diagnosed as LND was referred to our clinic for his intermittent dyskinesia and hypertonic posturing. His abnormal posturing has been treated with oral haloperidol, diazepam and dantrolene as well as botulinum toxin A injection, but their efficacy was not satisfactory. The patient’s family wished to undergo  ITB. After the confirmation of the effect of intrathecal administration of baclofen on relief of his abnormal posturing, permanent implantation of infusion system was conducted under general anesthesia. Soon after operation, baclofen was administered with the dose of 28 ug/day, which sufficiently improved the score of Unified Dystonia Rating Scale from 40 to 19. Surface EMG study suggested his abnormal posture might be caused by dystonia, which improved after ITB. No adverse effects of ITB occurred so far. Conclusion: Intrathecal administration of baclofen with relatively low dose is effective for relief of motor symptoms in LND, at least for a short-term follow-up period. Abnormal posturing seen in LND seems to be dystonia, in which ITB could be of therapeutic value.

Background: The objective of this study was to elucidate the predictive factors for early distant brain failure in
patients with brain metastases of non-small-cell lung cancer (NSCLC) who were treated with gamma knife
radiosurgery (GKRS) without previous whole-brain radiotherapy (WBRT) or surgery.

Materials and Methods: We retrospectively reviewed clinical and imaging data of 459 patients with brain
metastases of NSCLC who underwent GKRS from June 2008 to December 2013. The primary end-point was
early distant brain failure, defined as the detection of newly developed metastatic lesions on magnetic resonance
imaging (MRI) 3 months after GKRS. Factors such as tumor pathology subtype, concurrent systemic
chemotherapy, epidermal growth factor receptor (EGFR) mutation status, use of EGFR tyrosine kinase
inhibitors (TKIs), systemic disease status, presence of a metastatic lesion only in delayed MRI, and volume and
number of metastases were analyzed.

Results: There were no statistically significant differences with respect to pathologic subtype, concurrent
systemic chemotherapy, EGFR mutation, and early distant brain failure. Patients treated with EGFR-TKIs (p =
0.004), with a stable systemic disease status (p = 0.028) and 3 or fewer brain lesions (p = 0.000) experienced a
significantly lower incidence of early distant brain failure.

Conclusion: This study suggests that GKRS alone could be considered for patients treated with EGFR-TKIs
who have a stable systemic disease status and 3 or fewer brain lesions. WBRT should be considered for other
patients.

Background: Awake craniotomy allows for intraoperative cortical mapping and functional testing during the resection of brain tumors that involve an eloquent region of the brain. However, most current awake craniotomy techniques require a rigid fixation of the skull that can cause discomfort to the patient during the awake phase of the surgery. Furthermore, airway management during different stages of surgery is complicated, and can cause unnecessary stress on both the surgeon and staff. We have developed a simple protocol for craniotomy under general anesthesia, with subsequent "wake-up" testing, which maximizes both patient and operative team comfort, leading to optimal outcomes.

Objective: To discuss the protocol that we have developed at the Stony Brook University Hospital. Neurosurgical and anesthetic techniques along with two example cases involving motor and language mapping will be discussed in detail.

Methods: Patients were positioned in a supine (for frontal craniotomy) or a lateral position (for temporal craniotomy). We used the frameless Brainlab™ skull-mounted array for stereotactic navigation. Rigid fixation of the skull was avoided. General anesthesia was used during the “asleep” phase of the surgery, with airways established by a laryngeal mask airway (LMA) or endotracheal (ET) tube. Following removal of the bone flap and opening of the dura, patients were woken up, and the LMA or ET tube was removed. Cortical mapping was performed to establish a safe entry zone for tumor removal. While the tumors were being removed, we continued motor examination and casual conversation with the patient to ensure safety. Completion of resection was confirmed with intraoperative ultrasound and microscope examination. Patients were lightly sedated during the remaining phase of the surgery until skin closure.

Results: No patient exhibited any neurological deficits or adverse anesthesia outcomes during the postoperative period. Gross total excision was achieved in the patient that underwent language mapping. In the patient that underwent motor mapping, resection was halted as a result of the patient developing hand weakness intraoperatively, which resolved immediately.

Conclusion: The protocol developed at Stony Brook University avoids rigid skull fixation and simplifies airway management, helping to maximize patient and physician comfort while allowing for successful tumor resection.

Objectives: A specialist multidisciplinary approach and lifelong follow-up is required for patients undergoing Deep Brain Stimulation (DBS). Access can be a challenge for remote communities or small nation states where the population cannot support such specialised services for the relatively small numbers of patients. Malta has a population of just under 450 000. The number of patients likely to benefit from DBS was envisaged to be around 5 to 10 per year. The purpose of this study was to determine the outcome of a cross border collaboration between specialist services in London and a tertiary centre in Malta.

Methods: Between 2011 and 2015, the total number of patients undergoing deep brain stimulation was 35. Of these, 29 patients received bilateral subthalamic nucleus (STN) DBS for Parkinson’s Disease. Surgery was performed using a Leksell G-frame under general anaesthesia using an MRI-guided and MRI-verified approach. Pre-operative motor function was compared with one year post-operative motor function assessments in 26 patients. Pre-operative and post-operative quality of life assessment was also completed in 24 patients.

Results: The demographics of the 26 patients were: 16 M; age 60 ± 9, range 32-70; disease duration 8.8 ± 2.7. There was a statistically significant improvement in off-medication Unified Parkinson’s Disease Rating Scale (UPDRS) III motor function (41.7%), reduction in Levodopa Equivalent Dose (LED) (30.6%) and improvement in quality of life as measured by the Parkinson’s Disease Questionnaire (PDQ-39) (52.3%). Sub analysis of the PDQ-39 dimensions showed significant improvement in all dimensions except communication, with greatest benefit for activities of daily living (ADLs) (72.4%) and stigma (66.3%). Surgical adverse events were transient with no permanent sequelae. Patients receiving DBS to targets other than the STN and for different indications also benefitted from the procedure.

Conclusion: This audit demonstrates the successful delivery of specialist services through cross border collaboration with achievement of expected results in terms of therapeutic benefit to patients. This positive outcome was contingent on the political desire to introduce and support the service and the close collaboration between specialists in both centres.

Objectives : DBS is effective for movement disorder, pain, psychiatric disorders, etc. Sometimes, in Dystonia patient and parkinsonian-dystonia patient developed DBS lead fracture.

Material and methods : We operated over 500 DBS and SCS, MCS operations during last 15 years. Among 6 patients developed DBS lead fractures. Disease entity consisted with 5 parkinsonism patients, 1 dystonia patient. 1)Among 1 parkinsonian 43-year-male patient devloped Rt DBS lead extension line fracture after 4 DBS operation. IPG showed battery was gone. We changed into new IPG and extension line. 2) 56-year-male patient operated STN DBS surgery in other hospital. 2 year later, Rt DBS impetance was bad, we checked radiography of skull and lead extension line fracture was suspected. In operation view, we checked lead extension line fracture and changed into new one. 3) 61-year-female patient operated Gpi- DBS surgery in other hospital. 3 years later, IPG connecting extension line fracture was developed and changed into new extension line.

Results : 4) 65-year-male patient operated STN- DBS surgery in other hospital. 3 years later, IPG connecting extension line fracture was developed and changed into new extension line 5) 27-year-male dystonia patient operated Gpi- DBS surgery . 5years later, DBS lead connecting proximal extension line fracture was developed and changed into new extension line 6) 58-year-male Parkinsonism patient operated STN- DBS surgery . 5years later, DBS lead connecting proximal extension line fracture was developed and changed into new extension line . DBS lead fracture site is 4 IPG connecting extension line , 2 DBS lead connecting proximal extension line.

Conclusion  : DBS is safe and effective treatment for intractable movement disorder patients. If patient's symptom is aggravated after DBS surgery and should check radiography of skull and, chest but rarely developed lead fracture in dystonia or parkinsonism patients.

Subthalamic nuclei (STN) deep brain stimulation (DBS) has become a widely accepted treatment modality in relieving tremor and rigidity for Parkinson’s disease. Usually, if the DBS lead is accurately and properly placed in the STN, tremor and rigidity will attenuate almost instantly after DBS is turned on. Recently, we began to notice a “delayed response” phenomenon in STN DBS surgeries, in which case the intraoperative STN test stimulation failed to show its expected effects whereas the stimulation in the ward did. We identified 6 patients who demonstrated definite delayed responses to STN DBS in a 3-year period. The clinical data of these patients were collected and analyzed. Our findings remind us that if the MER is perfect but test stimulation fails, we should consider the possibility of the STN delayed response phenomenon, which may help us out from missing a good target and changing targets aimlessly.

Objective : We investigated the clinical outcome and location of active contacts in chronic caudal zona incerta (cZI) deep brain stimulation (DBS) in the treatment of tremor-dominant movement disorders.

Methods : To evaluate the efficacy of cZI DBS on tremor in patients with essential tremor (ET) and Parkinson’s  disease (PD), assessment using the subscores of essential tremor rating scale (ETRS) and part III (motor) subscores of the unified Parkinson’s disease rating scale (UPDRS) was performed at 12 month postoperatively. The changes in the severity of tremor was measured as percent (%) tremor reduction. To determine the location of active contacts, 10 leads in 9 patients with cZI DBS were inevestigated.

Results : The scores of item 5 and 6 (contralateral tremor) of the ETRS decreased by 76.5 % (8.38 ± 2.26 to 2.13 ± 1.89, p<0.01, paired t test) and those of items 11-15 (contralateral hand function) improved by 72.6 % at postoperative 12 month (14.50 ± 4.21 to 4.38 ± 3.25, p<0.01, paired t test). The degree of improvement in PD was 81.9 % in items 20-21 (contralateral tremor), 50% in item 22 (contralateral rigidity), and 81.5 % in items 23-26 (contralateral bradykinesia). The head tremor improved by 83.3% in item 4 (from 6 to 1) with bilateral cZI stimulation. Three patient experience dysphasia. However, no permanent speech disturbance was observed. The mean intensity of stimulation at postoperative 12 month did not differ from that in early postoperative period, indicating stimulation tolerance was not significant during chronic cZI stimulation.

Conclusion : Chronic cZI stimulation is a safe and effective means in the treatment of tremor-dominant movement disorders. 

Background and objectives: Established targets of deep brain stimulation (DBS) in Parkinson disease (PD) are the subthalamic nucleus (STN) or globus pallidus internus (GPi). An early comparative study revealed the superiority of STN DBS in improvement of motor score in the medication-off period and reduction of dopaminergic medication. Consequently, the STN has been the most common target of DBS for PD for a long time. However, a current randomized comparative study reevaluated the potential of GPi DBS, and revealed that GPi DBS improved motor functions similarly to STN DBS with less psychiatric or cognitive deficit after surgery. Therefore, we selected the target in each patient based on the characteristics of these targets and the number of cases with GPi DBS was increasing. However, we had some patients who suffered from freezing of gait despite improvement of cardinal PD symptoms and dyskinesia/dystonia after GPi DBS. We report cases with freezing of gait after GPi DBS.

Methods: We retrospectively reviewed 77 patients who underwent bilateral DBS for PD between 2012 and 2015. Among them, twelve patients (16%) underwent GPi DBS. The reason for selecting GPi was severe dyskinesia or dystonia with low dose medications (8 cases) and/or a high risk of neuropsychological or psychiatric complications such as high aged patients or patients with mild cognitive decline (7 cases).

Results: GPi DBS significantly improved motor function, fluctuation, and dyskinesia/dystonia as well as STN DBS. On the other hand, 5 patients (42%) showed apparent deterioration of freezing of gait after GPi DBS. We tried increasing of dopaminergic medication or readjustment of stimulation parameters using interleaving mode for these patients. However, sufficient improvement of gait problem was not obtained.

Conclusions: GPi DBS is effective in improving cardinal motor symptoms and dyskinesia/dystonia in PD. However, vigilance is needed, because significant incidence of freezing of gait occurs after GPi DBS. We discuss about the mechanism and treatments for this problem.

a.          Objective

Deep brain stimulation is an established treatment in movement disorders. Holmes tremor following unilateral cerebellar brain lesions is rare and deep brain stimulation in these cases is always an individual decision. To reassess results of our surgical indications we compiled our cases related to the published literature for this special indication.

b.          Methods

We report on our five patient case series with post lesion Holmes tremor, their indications, lesion positions, target points, stimulation parameters and overall outcome after deep brain stimulation between the years 2002 - 2014. In all patients conservative medical treatment failed or showed no significant improvement in the patients’ overall quality of life. In addition we reviewed the published literature showing numerous case series but no randomized studies yet.

c.              Results

Unilateral deep brain surgery was initiated in all five patients. We targeted the contralateral Nucleus ventralis intermedius (VIM). Intraoperative four out of five patients had significant symptom improvement, but one patient tremor was tested intraoperative and showed no significant effect with testing over 10 trajectories, therefore no electrode was implanted. From the beginning of stimulation a significant reduction of target symptoms appeared with up to complete disappearance and improvement of quality of life. This effect was ongoing until now with a medium follow up of 36 months.

d.              Conclusion

In consent with published data deep brain stimulation for Holmes tremor can reduce the symptoms up to complete disappearance and improve the overall quality of life of patients. Since therapy may fail individual diagnosis should be strictly analyzed and maybe MRI-techniques like fibertracking could help to clarify the individual anatomy.

OBJECTIVE

To report four cases of a rare disorder, GAD (+) Stiff Person Syndrome (SPS), treated with Intrathecal baclofen therapy.

BACKGROUND

Stiff person syndrome is a rare disorder of unclear etiology characterized by progressive rigidity and stiffness resulting in postural deformities. Stiff-Person syndro