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Purpose Reduced temporal muscle thickness (TMT) has recently been postulated as a prognostic imaging marker and an objective tool to assess patients frailty in glioblastoma. Our aim is to investigate the correlation of TMT and systemic muscle loss to confirm that TMT is an adequate surrogate marker of sarcopenia in newly diagnosed glioblastoma patients. Methods TMT was assessed on preoperative MR-images and skeletal muscle area (SMA) was assessed at the third lumbar vertebra on preoperative abdominal CT-scans. Previous published TMT sex-specific cut-off values were used to classify patients as ‘patient at risk of sarcopenia’ or ‘patient with normal muscle status’. Correlation between TMT and SMA was assessed using Spearman’s rank correlation coefficient. Results Sixteen percent of the 245 included patients were identified as at risk of sarcopenia. The mean SMA of glioblastoma patients at risk of sarcopenia (124.3 cm2, SD 30.8 cm2) was significantly lower than the mean SMA of patients with normal muscle status (146.3 cm2, SD 31.1 cm2, P P < .001), and a strong association in the patients at risk of sarcopenia (Spearman’s rho 0.678, P Conclusion Our results confirm the use of TMT as a surrogate marker of total body skeletal muscle mass in glioblastoma, especially in frail patients at risk of sarcopenia. TMT can be used to identify patients with muscle loss early in the disease process, which enables the implementation of adequate intervention strategies.

Paraneoplastic neurological syndromes (PNS) can manifest with every type of malignancy. A well-known syndrome is myasthenia gravis (MG) in combination with thymomas. No association between primary brain tumors and neuromuscular disorders has been described. Here, we present a case of a 65-year-old patient who developed MG, following an uncomplicated, gross-total resection of a glioblastoma. To our knowledge, this is the first case describing the onset of MG during the early postoperative phase after glioblastoma resection. Current criteria of PNS are insufficient when the neurological syndrome is diagnosed at the time of a malignancy or shortly thereafter and should be revisited.

Introduction Obsessive-compulsive disorder (OCD) is among the most disabling chronic psychiatric disorders and has a significant negative impact on multiple domains of quality of life. Deep brain stimulation (DBS) is a treatment option for severe therapy-resistant OCD.Objective To provide a detailed clinical description and treatment outcome analysis in a cohort of eight refractory OCD patients receiving ventral capsule/ventral striatum (VC/VS) stimulation with the intention to validate discriminating fiber bundles previously associated with clinical response.Materials and Methods The primary outcome measure (the Yale-Brown Obsessive Compulsive Scale [Y-BOCS]) and secondary outcomes depressive symptoms, anxiety, and quality of life were retrospectively analyzed. DBS leads were warped into standard stereotactic space. A normative connectome was used to identify the neural network associated with clinical outcome.Results With a median stimulation duration of 26 months, patients exhibited a mean Y-BOCS reduction of 10.5 resulting in a response rate of 63%. Modulation of a fiber bundle traversing the anterior limb of the internal capsule (ALIC) was associated with Y-BOCS reduction. This fiber bundle connected the frontal regions to the subthalamic nucleus (STN) and was functionally identified as the hyperdirect pathway of the basal ganglia circuitry.Conclusion Our findings show that in VC/VS stimulation, the neural network associated with clinical outcome shows overlap with that of previously described for other targets namely the anterior limb of the internal capsula, the nucleus accumbens, or the STN, which supports the evolvement from the concept of an optimal gray matter target to conceiving the target as part of a symptom modulating network.

BACKGROUND: In our experience, we encountered more blood vessels during deep brain stimulation (DBS) surgeries in epilepsy. In this study, we have quantified and compared the cerebral vascularization in epilepsy, Parkinson's Disease (PD) and Obsessive-Compulsive Disorder (OCD).METHODS: A retrospective observational study in 15 epilepsy and 15 PD patients was performed. The amount, location and size of blood vessels within 5 millimeter (mm) of all DBS electrode trajectories (n=120) for both targets (anterior nucleus of the thalamus: ANT and subthalamic nucleus: STN) in both patient groups were quantified and compared on a Medtronic workstation. Additionally, blood vessels in the trajectories (n=120) of another group of 15 PD (STN) and 15 OCD (Ventral Capsule-Ventral Striatum, VC-VS) patients were quantified and compared (trajectories n=120), also to the first group. Statistical analyses were performed with SPSS version 27.0 (descriptive statistics, independent samples T-tests, Mann Whitney U tests, ANOVA test and post-hoc Tukey test). A P-value < 0.05 was considered statistically significant.RESULTS: Our results showed a significant greater amount of cerebral blood vessels in epilepsy patients (10 SD ± 4) compared to PD (PD1 6 SD ± 1 and PD2 5 SD ± 3) and OCD (5 SD ± 1) with P CONCLUSIONS: Our results show that the brain of epilepsy patients seems to be more vascularized compared to PD and OCD patients. This can make the surgical planning for DBS more challenging and the use of multiple trajectories limited.

Contains fulltext : 288348.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Neuropsychological assessment contributes to DBS treatment in several ways: it monitors the cognitive safety of the treatment, identifies beneficial or detrimental cognitive side effects, and it could aid to explain variability in treatment outcome, and possibly the treatment's working mechanism(s). BACKGROUND: This systematic review assessed the cognitive safety of DBS for OCD and explored whether changes in cognitive function may help explain its working mechanism(s). MATERIALS AND METHODS: EMBASE, PubMed/Medline, Psycinfo, and the Cochrane Library were systematically searched for studies reporting cognitive outcomes following DBS for OCD. Searches were completed in November 2020. Included studies were appraised for study design and quality according to National Heart, Lung, and Blood Institute (NHLBI) quality assessment tools. RESULTS: Five randomized controlled trials and ten observational studies comprising a total of 178 patients were analyzed collectively. Variable outcomes of DBS were observed in the domains of attention, memory, executive functioning, and in particular, cognitive flexibility. CONCLUSION: Although individual studies generally do not report cognitive deterioration after DBS for OCD, the variability of study designs and the multitude of cognitive measures used precluded a meta-analysis to confirm its safety and recognition of a cognitive pattern through which the efficacy of DBS for OCD might be explained. In the future, prospective studies should preferably include a standardized neuropsychological assessment battery specifically addressing executive functioning and have a longer-term follow-up in order to demonstrate the cognitive safety of the procedure. Such prospective and more uniform data collection may also contribute to our understanding of the working mechanisms of DBS in OCD.

Background: Deep brain stimulation (DBS) is an accepted treatment for patients with medication-resistant Tourette syndrome (TS). Sedation is commonly required during electrode implantation to attenuate anxiety, pain, and severe tics. Anesthetic agents potentially impair the quality of microelectrode recordings (MER). Little is known about the effect of these anesthetics on MER in patients with TS. We describe our experience with different sedative regimens on MER and tic severity in patients with TS. Methods: The clinical records of all TS patients who underwent DBS surgery between 2010 and 2018 were reviewed. Demographic data, stimulation targets, anesthetic agents, perioperative complications, and MER from each hemisphere were collected and analyzed. Single-unit activity was identified by filtering spiking activity from broadband MER data and principal component analysis with K-means clustering. Vocal and motor tics which caused artifacts in the MER data were manually selected using visual and auditory inspection. Results: Six patients underwent bilateral DBS electrode implantation. In all patients, the target was the anterior internal globus pallidus. Patient comfort and hemodynamic and respiratory stability were maintained with conscious sedation with one or more of the following anesthetic drugs: propofol, midazolam, remifentanil, clonidine, and dexmedetomidine. Good quality MER and clinical testing were obtained in 9 hemispheres of 6 patients. In 3 patients, MER quality was poor on one side. Conclusion: Cautiously applied sedative drugs can provide patient comfort, hemodynamic and respiratory stability, and suppress severe tics, with minimal interference with MER.

Despite the use of first-choice anti-epileptic drugs and satisfactory seizure outcome rates after resective epilepsy surgery, a considerable percentage of patients do not become seizure free. ANT-DBS may provide for an alternative treatment option in these patients. This literature review discusses the rationale, mechanism of action, clinical efficacy, safety, and tolerability of ANT-DBS in drug-resistant epilepsy patients. A review using systematic methods of the available literature was performed using relevant databases including Medline, Embase, and the Cochrane Library pertaining to the different aspects ANT-DBS. ANT-DBS for drug-resistant epilepsy is a safe, effective and well-tolerated therapy, where a special emphasis must be given to monitoring and neuropsychological assessment of both depression and memory function. Three patterns of seizure control by ANT-DBS are recognized, of which a delayed stimulation effect may account for an improved long-term response rate. ANT-DBS remotely modulates neuronal network excitability through overriding pathological electrical activity, decrease neuronal cell loss, through immune response inhibition or modulation of neuronal energy metabolism. ANT-DBS is an efficacious treatment modality, even when curative procedures or lesser invasive neuromodulative techniques failed. When compared to VNS, ANT-DBS shows slightly superior treatment response, which urges for direct comparative trials. Based on the available evidence ANT-DBS and VNS therapies are currently both superior compared to non-invasive neuromodulation techniques such as t-VNS and rTMS. Additional in-vivo research is necessary in order to gain more insight into the mechanism of action of ANT-DBS in localization-related epilepsy which will allow for treatment optimization. Randomized clinical studies in search of the optimal target in well-defined epilepsy patient populations, will ultimately allow for optimal patient stratification when applying DBS for drug-resistant patients with epilepsy.

Introduction For decisions on glioblastoma surgery, the risk of complications and decline in performance is decisive. In this study, we determine the rate of complications and performance decline after resections and biopsies in a national quality registry, their risk factors and the risk-standardized variation between institutions. Methods Data from all 3288 adults with first-time glioblastoma surgery at 13 hospitals were obtained from a prospective population-based Quality Registry Neuro Surgery in the Netherlands between 2013 and 2017. Patients were stratified by biopsies and resections. Complications were categorized as Clavien-Dindo grades II and higher. Performance decline was considered a deterioration of more than 10 Karnofsky points at 6 weeks. Risk factors were evaluated in multivariable logistic regression analysis. Patient-specific expected and observed complications and performance declines were summarized for institutions and analyzed in funnel plots. Results For 2271 resections, the overall complication rate was 20 % and 16 % declined in performance. For 1017 biopsies, the overall complication rate was 11 % and 30 % declined in performance. Patient-related characteristics were significant risk factors for complications and performance decline, i.e. higher age, lower baseline Karnofsky, higher ASA classification, and the surgical procedure. Hospital characteristics, i.e. case volume, university affiliation and biopsy percentage, were not. In three institutes the observed complication rate was significantly less than expected. In one institute significantly more performance declines were observed than expected, and in one institute significantly less. Conclusions Patient characteristics, but not case volume, were risk factors for complications and performance decline after glioblastoma surgery. After risk-standardization, hospitals varied in complications and performance declines.

Objective Thalamic deep brain stimulation (DBS) is effective in reducing tics in patients with refractory Tourette syndrome at the short-term. Here, we report on the long-term outcome. Materials and Methods Seven patients underwent bilateral DBS between 2001 and 2008. The target was the centromedian nucleus, substantia periventricularis and nucleus ventro-oralis internus cross point of the thalamus. The effect on tics and side effects were evaluated with a variable follow-up duration of 12 to 78 months. Results Patient 1 and 2 showed good tic improvements of 81.6% (60 months) and 50% (36 months), respectively. However, side effects like reducing levels of energy and visual disturbances increased. In patient 1, the target was changed to the anterior part of the internal pallidum and patient 2 switched the stimulator permanently off. Patient 3 experiences still satisfying results with a tic improvement of 88.9% (78 months). Patient 4 and 7 showed minor tic improvements of 34% (16 months) and 9% (60 months), respectively. In both patients side effects became more severe and the target was changed to the anterior part of the internal pallidum. Patient 5 showed a tic improvement of 27.5% (12 months) and went abroad for stimulation of the external globus pallidus. Patient 6 developed cerebellar atrophy. He experienced several nonstimulation related side effects and turned the stimulator off. Conclusions There seems to be an increasing disbalance of therapeutic effects and side effects at long-term follow-up, often leading to either switching the stimulator off or new surgery with a different neuro-anatomic target.

Evers, Silvia MAA/0000-0003-1026-570X; Tonge, Mehmet/0000-0002-0106-9363; Kubben, Pieter/0000-0002-8059-523X; Wetzelaer, Pim/0000-0002-7450-0046 WOS: 000450653000012 PubMed: 29465741 AIM: To investigate the costs of treating the infection with antibiotics only with the risk of surgery when unsuccessful versus immediate removal followed by re-implantation in patients with deep brain stimulation (DBS) hardware infection. MATERIAL and METHODS: We calculated the costs of the different strategies through a standard costing procedure. A decision model has been applied to establish the average treatment cost per patient representative for a clinical setting where both strategies are employed. Subsequently, a sensitivity analysis has been performed to assess the influence of clinical assumptions regarding the effectiveness of antibiotics treatment on average treatment costs. RESULTS: The costs of treating a case of DBS hardware infection with immediate internal pulse generator (IPG) replacement surgery were (sic)29,301 compared to (sic)9499 for successful antibiotic treatment. For antibiotic treatment followed by IPG replacement surgery the total costs were (sic)38,741. Antibiotic treatment alone was successful in 44% (4/9) of the included cases of DBS infection, resulting in average treatment costs per patient of (sic)26,745. Trying to resolve DBS hardware infections initially with antibiotics reduced treatment costs by 12.1%. CONCLUSION: Treatment with antibiotics with the risk of a later removal when unsuccessful was a more valuable strategy in terms of costs when compared to immediate surgical intervention in cases of hardware-related infections in DBS surgeries.

Background: Tourette syndrome is a hyperkinetic neurodevelopmental disorder characterized by tics. Objective: Assess the neuronal changes in the associative/limbic GP associated with Tourette syndrome. Methods: Neurophysiological recordings were performed from the anterior (associative/limbic) GPe and GPi of 8 awake patients during DBS electrode implantation surgeries. Results: The baseline firing rate of the neurons was low in a state-dependent manner in both segments of the GP. Tic-dependent transient rate changes were found in the activity of individual neurons of both segments around the time of the tic. Neither oscillatory activity of individual neurons nor correlations in their interactions were observed. Conclusions: The results demonstrate the involvement of the associative/limbic pathway in the underlying pathophysiology of Tourette syndrome and point to tonic and phasic modulations of basal ganglia output as a key mechanisms underlying the abnormal state of the disorder and the expression of individual tics, respectively. © 2017 International Parkinson and Movement Disorder Society

Deep brain stimulation of the anterior nucleus of the thalamus is an effective treatment for patients with refractory epilepsy who do not respond sufficiently to medical therapy. Optimal therapeutic effects of deep brain stimulation probably depend on accurate positioning of the stimulating electrodes. Microelectrode recordings show bursty firing neurons in the anterior nucleus of the thalamus region, which confirms the anatomical target determined by the surgeon. Deep brain stimulation electrodes in epilepsy patients are implanted under general anesthesia. The type and depth of anesthesia might interfere with microelectrode ecordings. Here, we describe our experience of a patient who underwent deep brain stimulation surgery under general anesthesia with sevoflurane, a volatile anesthetic, and its effect on the microelectrode recordings. Keywords: Thalamus, Deep brain stimulation, Sevoflurane

INTRODUCTION Tumor heterogeneity poses one of the major limitations in improving the treatment for glioblastoma (GBM), which calls for new clinically relevant predictive models. This study aims to investigate non-invasive diagnostic methods, including patient characteristics and qualitative imaging analysis as a prognostic classifier and predictor for druggable oncogenes. METHODS We performed a retrospective analysis on 143 GBM patients (discovery cohort). Diagnostic MRIs were re-analyzed for qualitative imaging features (VASARI features). DNA was extracted from formalin-fixed, paraffin-embedded GBM tissue of the discovery cohort for next-generation sequencing (Ion Torrent Cancer Hotspot panel v2Plus), TERT-promoter mutation and MGMT-methylation analysis. Multivariable regression analysis was used to determine the prognostic and predictive value of VASARI features. RESULTS Of the 143 patients, median age was 61.4 years (range 15.5–84.6) with a median overall survival of 12 months (range 0–142). We observed IDH1 R132H mutation in 8.5%, MGMT-promotor methylation in 26.1%, TERT-promotor mutation (C250T;C228T) in 69.5%, EGFR mutation in 20.3% and EGFR amplification in 37.5% of all patients. A set of eight VASARI features was identified to be associated with overall survival (p< 0.001), which is currently being validated in an external dataset (n= 184). Interestingly, VASARI features appeared to be associated with IDH1-mutation (four features, p=0.004), TERT-promotor mutation (five features, p-value < 0.001), EGFR mutation (five features, p-value < 0.001) and EGFR amplification (seven features, p-value < 0.001) but not with MGMT-methylation (two features, p-value=0.054). Additional cancer hotspots are currently being analyzed and internal validation is ongoing. CONCLUSION AND FUTURE PERSPECTIVES We propose an integrated prognostic classifier comprising MRI features, also associated with GBM-specific molecular alterations. Additionally, quantitative MRI radiomics features are being extracted from the discovery and validation set and incorporated in the prognostic classifier. Subsequently, radiomics and VASARI features will be correlated to intratumoral heterogeneity, assessed by tissue micro-array analysis of the discovery cohort.

Background: Frame mounting is considered one of the most critical steps in stereotactic neurosurgery. In routine clinical practice, the aim is to mount the frame as symmetrical as possible, parallel to Reid’s line. However, sometimes, the frame is mounted asymmetrically often due to patient-related reasons. Methods: In this study, we addressed the question whether an asymmetrically mounted frame influences the accuracy of stereotactic electrode implantation. A Citrullus lanatus was used for this study. After a magnetic resonance imaging scan, symmetric and asymmetric mounting of the frame, which could occur in clinical scenarios, was performed with computed tomography (CT). Three different stereotactic software packages were used to analyze the results. In addition, manual calculations were performed by two different observers. Results: Our results show that an asymmetrically mounted frame (deviated, tilted, or rotated) does not affect the accuracy in the mediolateral axis (X-coordinate) or the anteroposterior axis (Y-coordinate). However, it can lead to a clinically relevant error in the superoinferior axis (Z-coordinate). This error was largest with manual calculations. Conclusion: These results suggest that asymmetrical frame mounting can lead to stereotactic inaccuracy in the superoinferior axis (Z coordinate).

Highlights • Neurosurgeons are stable in STN targeting regardless of MRI field strength. • Neurosurgeons are stable in STN targeting regardless of MRI contrast. • The targeted STN electrode location is more ventral using 3 T versus 7 T scans., Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective surgical treatment for Parkinson’s disease (PD). Side-effects may, however, be induced when the DBS lead is placed suboptimally. Currently, lower field magnetic resonance imaging (MRI) at 1.5 or 3 Tesla (T) is used for targeting. Ultra-high-field MRI (7 T and above) can obtain superior anatomical information and might therefore be better suited for targeting. This study aims to test whether optimized 7 T imaging protocols result in less variable targeting of the STN for DBS compared to clinically utilized 3 T images. Three DBS-experienced neurosurgeons determined the optimal STN DBS target site on three repetitions of 3 T-T2, 7 T-T2*, 7 T-R2* and 7 T-QSM images for five PD patients. The distance in millimetres between the three repetitive coordinates was used as an index of targeting variability and was compared between field strength, MRI contrast and repetition with a Bayesian ANOVA. Further, the target coordinates were registered to MNI space, and anatomical coordinates were compared between field strength, MRI contrast and repetition using a Bayesian ANOVA. The results indicate that the neurosurgeons are stable in selecting the DBS target site across MRI field strength, MRI contrast and repetitions. The analysis of the coordinates in MNI space however revealed that the actual selected location of the electrode is seemingly more ventral when using the 3 T scan compared to the 7 T scans.

Objective: Deep Brain Stimulation in psychiatric disorders is becoming an increasingly performed surgery. At present, seven different targets have been stimulated in Tourette Syndrome, including the internal globus pallidus. We describe the effects on tics and comorbid behavioral disorders of Deep Brain Stimulation of the anterior internal globus pallidus in five patients with refractory Tourette Syndrome. Methods: This study was performed as an open label study with follow-up assessment between 12 and 38 months. Patients were evaluated twice, one month before surgery and at long-term follow-up. Primary outcome was tic severity, assessed by several scales. Secondary outcomes were comorbid behavioral disorders, mood and cognition. The final position of the active contacts of the implanted electrodes was investigated and side effects were reported. Results: Three males and two females were included with a mean age of 41.6 years (SD 9.7). The total post-operative score on the Yale Global Tic Severity Scale was significantly lower than the pre-operative score (42.2 +/- 4.8 versus 12.8 +/- 3.8, P=0.043). There was also a significant reduction on the modified Rush Video-Based Tic Rating Scale (13.0 +/- 2.0 versus 7.0 +/- 1.6, P=0.041) and in the total number of video-rated tics (259.6 +/- 107.3 versus 49.6 +/- 24.8, P=0.043). No significant difference on the secondary outcomes was found, however, there was an improvement on an individual level for obsessive-compulsive behavior. The final position of the active contacts was variable in our sample and no relationship between position and stimulation effects could be established. Conclusion: Our study suggests that Deep Brain Stimulation of the anterior internal globus pallidus is effective in reducing tic severity, and possibly also obsessive-compulsive behavior, in refractory Tourette patients without serious adverse events or side-effects.

Background: Evaluating the effect of treatment of tremor is mostly performed with clinical rating scales. Mobile applications facilitate a more rapid, objective, and quantitative evaluation of treatment effect. Existing mobile apps do not offer raw data access, which limits algorithm development. Objective: To develop a novel open-source mobile app for tremor quantification. Methods: TREMOR12 is an open-source mobile app that samples acceleration, rotation, rotation speed, and gravity, each in 3 axes and time-stamped in a frequency up to 100 Hz. The raw measurement data can be exported as a comma-separated value file for further analysis in the TREMOR12P data processing module. The app was evaluated with 3 patients suffering from essential tremor, who were between 55 and 71 years of age. Results: This proof-of-concept study shows that the TREMOR12 app is able to detect and register tremor characteristics such as acceleration, rotation, rotation speed, and gravity in a simple and nonburdensome way. The app is compatible with current regulatory oversight by the European Union (MEDDEV regulations) and the Food and Drug Administration (FDA) guidance on mobile medical applications. Conclusion: TREMOR12 offers low-cost tremor quantification for research purposes and algorithm development, and may help to improve treatment evaluation.

The human complement system is represents the main effector arm of innate immunity and its ambivalent function in cancer has been subject of ongoing dispute. Glioma stem-like cells (GSC) residing in specific niches within glioblastomas (GBM) are capable of self-renewal and tumor proliferation. Recent data are indicative of the influence of the complement system on the maintenance of these cells. It appears that the role of the complement system in glial tumorigenesis, particularly its influence on GSC niches and GSC maintenance, is significant and warrants further exploration for therapeutic interventions.

IMPORTANCE Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. OBJECTIVE To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. DESIGN, SETTING, AND PARTICIPANTS The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide. EXPOSURES Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]). MAINOUTCOMES AND MEASURES Scores on the Yale Global Tic Severity Scale and adverse events. RESULTS The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P

Objective: Three patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded.Methods: Event related potentials and event related spectral perturbations of EEG and LFP, event related cross-coherences between EEG/LFP and LFP/LFP were analyzed. As time locking events, the tic onsets were used. Spontaneous tics were compared to voluntary tic mimicking. The effect of tic suppression and DBS on thalamic LFPs was evaluated.Results: All three patients showed time-locked and prior to onset of spontaneous motor tics thalamic synchronization and thalamo-cortical cross-coherence. Also in three patients, not time-locked to motor tics, increased intra-thalamic coherences in the 1-8 Hz frequency band were found. In one patient it was demonstrated that voluntary mimicked tics were preceded by premotor cortical and thalamic potentials. In this patient unilateral thalamic DBS contralaterally decreased the background thalamic activity.Conclusions: The present study in three cases with TS shows that spontaneous tics in TS are preceded by repetitive coherent thalamo-cortical discharges, indicating that preceding a tic the basal ganglia circuits are "charged up", ultimately leading to a motor tic.Significance: Thalamic LFP recording may lead to more insight in underlying pathophysiological mechanisms in TS. (c) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Deep brain stimulation (DBS) may improve disabling tics in severely affected medication and behaviorally resistant Tourette syndrome (TS). Here we review all reported cases of TS DBS and provide updated recommendations for selection, assessment, and management of potential TS DBS cases based on the literature and implantation experience. Candidates should have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) diagnosis of TS with severe motor and vocal tics, which despite exhaustive medical and behavioral treatment trials result in significant impairment. Deep brain stimulation should be offered to patients only by experienced DBS centers after evaluation by a multidisciplinary team. Rigorous preoperative and postoperative outcome measures of tics and associated comorbidities should be used. Tics and comorbid neuropsychiatric conditions should be optimally treated per current expert standards, and tics should be the major cause of disability. Psychogenic tics, embellishment, and malingering should be recognized and addressed. We have removed the previously suggested 25-year-old age limit, with the specification that a multidisciplinary team approach for screening is employed. A local ethics committee or institutional review board should be consulted for consideration of cases involving persons younger than 18 years of age, as well as in cases with urgent indications. Tourette syndrome patients represent a unique and complex population, and studies reveal a higher risk for post-DBS complications. Successes and failures have been reported for multiple brain targets; however, the optimal surgical approach remains unknown. Tourette syndrome DBS, though still evolving, is a promising approach for a subset of medication refractory and severely affected patients.

Question Evaluating the effect of treatment of tremor is mostly performed with clinical rating scales. Mobile applications facilitate a more rapid, objective and quantitative evaluation of treatment effect. Existing mobile apps do not offer raw data access which limits algorithm development. Our objective is to develop a novel open-source mobile app for tremor quantification. Methods TREMOR12 is an open source mobile app that samples acceleration, rotation, rotation speed and gravity, each in 3 axes and time-stamped in a frequency up to 100Hz. The raw measurement data can be exported as a comma-separated value (CSV) file for further analysis in the TREMOR12P data processing module. The app was tested on five healthy volunteers (2 male, 3 female) aged between 22 and 41 years of age. Results This proof-of-concept study shows that the TREMOR12 app is able to detect and register tremor characteristics such as acceleration, rotation, rotation speed and gravity in a simple and non-burdensome way. The app is compatible with current regulatory oversight by the European Union (MEDDEV regulations) and the Food and Drug Administration (FDA) guidance on mobile medical applications. Conclusions TREMOR12 offers low-cost tremor quantification for research purposes and algorithm development, and may help to improve treatment evaluation.

Background:To report our experience of infections in deep brain stimulation (DBS) surgeries comparing shaving versus no shaving of cranial hair. Nonshaving is strongly preferred by patients due to aesthetic and psychological factors.Methods:This study is a prospective follow-up of the infection rate in 43 nonshaven DBS cases between April 2014 and December 2015 compared to our former infection rate with shaving in our center. Minimum follow-up was 6 months. All patients, except 7 epilepsy patients, received implantation of the electrodes together with the extension cables and internal pulse generator in one session.Results:In 43 nonshaven patients, a total of 81 electrodes were implanted or revised with a mean follow-up of 16 months. One patient (2.32%) developed an infection of the implanted DBS-hardware and was treated with antibiotics.Conclusion:In our experience nonshaving of cranial hair in DBS surgery does not lead to more infections when compared to shaving. We have changed our protocol to nonshaving based on these findings.Keywords: Complication, deep brain stimulation, infection, shaving

Kubben, Pieter/0000-0002-8059-523X WOS: 000435231900023 PubMed: 28770553 AIM: Deep brain stimulation (DBS) surgeries are multi-faceted and the various steps are interconnected. Since its first implementation, the method of DBS surgery has undergone changes. We have encountered several expected and also non-expected perioperative technical complications in the past seventeen years. Here, we describe the stereotactic frame, stereotactic localizer and planning station related complications and how we have managed them as much as possible. MATERIAL and METHODS: This study is a retrospective qualitative analysis of the documented technical events encountered during DBS surgeries from 1999 onwards. We have collected these events from a cohort of approximately 921 DBS electrodes implantations from the centers of the authors. RESULTS: Stereotactic frame related complications included movement related fixation problems, head anatomy related problems, and lack of maintenance related issues. Localizer related complications were compatibility issues of the stereotactic localizer and planning station, field of view effect on fiducials, air bubbles in localizers using liquid solutions, and disengaged localizer effect. Planning station related complications included image fusion failures and cerebrospinal fluid signal effect on image fusion. CONCLUSION: The road to success in DBS therapy passes through the ability to cope with surgical and technical complications. Each step is unconditionally connected to the other, and detection of the problems that can be encountered in advance and preparations for these negative conditions are the key to success for the group responsible for executing the therapy. We are still learning from these events and advance our surgical approaches.

PURPOSE: To measure between-hospital variation in risk-standardized survival outcome after glioblastoma surgery and to explore the association between survival and hospital characteristics in conjunction with patient-related risk factors. METHODS: Data of 2,409 adults with first-time glioblastoma surgery at 14 hospitals were obtained from a comprehensive, prospective population-based Quality Registry for Neurological Surgery in the Netherlands between 2011 and 2014. We compared the observed survival with patient-specific risk-standardized expected early (30-day) mortality and expected late (2-year) survival, based on patient age, performance status, and year of treatment. Summarized outcomes per hospital were analyzed in funnel plots. Hospital characteristics were analyzed in logistic regression and Cox proportional hazards models. RESULTS: Overall 30-day mortality was 5.2% and overall 2-year survival was 13.5%. Median overall survival varied between 4.8 and 14.9 months among hospitals, and biopsy percentages ranged between 16% and 73%. One hospital had lower than expected early mortality, and four hospitals had lower than expected late survival. Higher hospital volume was related with lower early mortality (P=0.031). A 10% increase in volume was associated with 3.9% relative decrease in early mortality, but not with overall survival. Patient-related risk factors (lower age; better performance; more recent years of treatment) were significantly associated with longer overall survival. Of the hospital characteristics, longer overall survival was associated with lower biopsy percentage (HR: 2.09, 1.34–3.26, P=0.001), and not with academic setting (HR: 0.951, 0.858–1.05), nor with hospital volume (HR: 0.954, 0.866–1.05). CONCLUSION: Hospitals vary more in late survival than early mortality after glioblastoma surgery. Widely varying biopsy percentages indicate treatment variation. Patient-related factors have a stronger association with overall survival than hospital-related factors.

Obsessive-compulsive disorder (OCD) is among the most disabling chronic psychiatric disorders and has a significant negative impact on multiple domains of quality of life. For patients suffering from severe refractory OCD, deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been applied. Reviewing the literature of the last years we believe that through its central position within the cortico-basal ganglia-thalamocortical circuits, the STN has a coordinating role in decision-making and action-selection mechanisms. Dysfunctional information-processing at the level of the STN is responsible for some of the core symptoms of OCD. Research confirms an electrophysiological dysfunction in the associative and limbic (non-motor) parts of the STN. Compared to Parkinson's disease patients, STN neurons in OCD exhibit a lower firing rate, less frequent but longer bursts, increased burst activity in the anterior ventromedial area, an asymmetrical left-sided burst distribution, and a predominant oscillatory activity in the 5-band. Moreover, there is direct evidence for the involvement of the STN in both checking behavior and OCD symptoms, which are both related to changes in electrophysiological activity in the non-motor STN. Through a combination of mechanisms, DBS of the STN seems to interrupt the disturbed information-processing, leading to a normalization of connectivity within the cortico-basal ganglia-thalamocortical circuits and consequently to a reduction in symptoms. In conclusion, based on the STN's strategic position within cortico-basal ganglia-thalamocortical circuits and its involvement in action-selection mechanisms that are responsible for some of the core symptoms of OCD, the STN is a mechanism-based target for DBS in OCD.

Tonge, Mehmet/0000-0002-0106-9363 WOS: 000387302000014 PubMed: 27337232 AIM: High frequency stimulation of the subthalamic nucleus (STN) is nowadays a widely performed surgery for patients with Parkinson's disease (PD). The field has witnessed a shift from indirect targeting to direct targeting. The question arises whether this change has influenced the final electrode position in STN deep brain stimulation surgery. To address this question, we compared the final electrode positions in atlas-based and magnetic resonance-based targeting methods in our series. MATERIAL and METHODS: We performed a database review of the surgeries performed in three affiliated centers. RESULTS: We have found that with the shift to direct imaging, three key changes have taken place. The first is that the number of microelectrode recording trajectories has decreased by approximately 1 microelectrode. Secondly, the central trajectory has been chosen as the final position in more patients, and the third change is that direct targeting has improved the laterality of the targeting significantly. CONCLUSION: Direct targeting has changed routine clinical practice, thereby further refining the surgical approach.

Kubben, Pieter/0000-0002-8059-523X; Tonge, Mehmet/0000-0002-0106-9363 WOS: 000366223600033 PubMed: 26513430 Objectives: Deep brain stimulation is nowadays a frequently performed surgery in patients with movement disorders, intractable epilepsy, and severe psychiatric disorders. The most feared complication of this surgery is an intracerebral hemorrhage due to the electrode placement, either for intraoperative electrophysiology (microelectrode recording) and/or implantation of the final electrode (macroelectrode). Here, we have investigated the risk of developing an intracerebral hemorrhage in our cohort of deep brain stimulation patients over a period of 15 years. Patients and methods: We have collected demographic data and analyzed the effect of performing surgery with single-electrode versus multiple electrode guided DBS. The effect of using single-dose versus double-dose contrast enhanced MRI to visualize vessels for the electrode trajectory planning has been investigated as well. Results: We have found that the overall calculated risk of an intracerebral hemorrhage in our series was 1.81% per patient, 0.3% per recording electrode and 0.23% per brain insertion. While three out of four patients recovered without neurological deficits, there was one mortality in a patient with cardiovascular comorbidities. Statistical comparisons between the groups of single-electrode versus multiple electrode guided surgery and single-dose gadolinium versus double-dose contrast enhanced MRI revealed no significant differences. In addition, there was no meaningful correlation between the age at surgery and the risk of bleeding. Conclusion: We have found that the risk of developing an intracerebral hemorrhage due to deep brain stimulation surgery is low. The clinical course of the patients with an intracerebral hemorrhage was generally favorable. (C) 2015 Elsevier B.V. All rights reserved.

Deep brain stimulation of the thalamus has been proposed as a therapeutic option in patients with Tourette syndrome who are refractory to pharmacological and psychotherapeutic treatment. Patients with intractable Tourette syndrome were invited to take part in a double-blind randomized cross-over trial assessing the efficacy and safety of stimulation of the centromedian nucleus - substantia periventricularis - nucleus ventro-oralis internus crosspoint in the thalamus. After surgery, the patients were randomly assigned to 3 months stimulation followed by 3 months OFF stimulation (Group A) or vice versa (Group B). The cross-over period was followed by 6 months ON stimulation. Assessments were performed prior to surgery and at 3, 6 months and 1 year after surgery. The primary outcome was a change in tic severity as measured by the Yale Global Tic Severity Scale and the secondary outcome was a change in associated behavioural disorders and mood. Possible cognitive side effects were studied during stimulation ON at 1 year postoperatively. Interim analysis was performed on a sample of six male patients with only one patient randomized to Group B. Tic severity during ON stimulation was significantly lower than during OFF stimulation, with substantial improvement (37%) on the Yale Global Tic Severity Scale (mean 41.1 +/- 5.4 versus 25.6 +/- 12.8, P = 0.046). The effect of stimulation 1 year after surgery was sustained with significant improvement (49%) on the Yale Global Tic Severity Scale (mean 42.2 +/- 3.1 versus 21.5 +/- 11.1, P = 0.028) when compared with preoperative assessments. Secondary outcome measures did not show any effect at a group level, either between ON and OFF stimulation or between preoperative assessment and that at 1 year postoperatively. Cognitive re-assessment at 1 year after surgery showed that patients needed more time to complete the Stroop Colour Word Card test. This test measures selective attention and response inhibition. Serious adverse events included one small haemorrhage ventral to the tip of the electrode, one infection of the pulse generator, subjective gaze disturbances and reduction of energy levels in all patients. The present preliminary findings suggest that stimulation of the centromedian nucleus - substantia periventricularis - nucleus ventro-oralis internus crosspoint may reduce tic severity in refractory Tourette syndrome, but there is the risk of adverse effects related to oculomotor function and energy levels. Further randomized controlled trials on other targets are urgently needed since the search for the optimal one is still ongoing.

Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst psychiatric disorders, with a current worldwide prevalence of 5–10% of the general population and up to 20–25% for the lifetime period. Historical perspective Nowadays, conventional treatment includes psychotherapy and pharmacotherapy; however, more than 60% of the treated patients respond unsatisfactorily, and almost one fifth becomes refractory to these therapies at long-term follow-up. Nonpharmacological techniques Growing social incapacity and economic burdens make the medical community strive for better therapies, with fewer complications. Various nonpharmacological techniques like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, lesion surgery, and deep brain stimulation have been developed for this purpose. Discussion We reviewed the literature from the beginning of the twentieth century until July 2009 and described the early clinical effects and main reported complications of these methods.

Background The ventral intermediate nucleus (VIM) is the most commonly used target for deep brain stimulation (DBS) in patients with essential tremor (ET). Recent evidence suggests that the posterior subthalamic area (PSA) might be a better target for tremor reduction. We compared the outcome of VIM DBS with PSA DBS in our cohort of patients. Methods Overall, 19 ET patients with bilateral DBS were included in this retrospective study, with a total of 38 electrodes (12 located in the VIM, 12 in the PSA, and 14 in an intermediate area). The outcome was measured using the essential tremor rating scale (ETRS), the glass scale and the quality of life in essential tremor questionnaire (QUEST). Results Unilateral tremor-scores with items 5-6 (tremor of the upper extremity), 8-9 (tremor of the lower extremity), and 11-14 (hand function) from the ETRS showed a 63% tremor reduction in the VIM group, 47% tremor reduction in the PSA group, and 67% tremor reduction in the intermediate group after a mean follow-up of 1.6 years. After a mean follow-up of 5.8 years, there was a tremor reduction of 50%, 34%, and 45%, respectively. In our series, side effects such as dysarthria (75%), ataxia and disequilibrium (40%), and paraesthesia (15%) were assessed. Conclusions All aforementioned anatomical target areas are effective in reducing tremor, although no superior reduction was found with PSA stimulation. Because of intraindividual differences between left and right hemisphere regarding the stimulated anatomical target, no conclusions can be drawn regarding differences in side effects.

Tourette’s Syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics, often associated with behavioral disorders. Symptoms often disappear before or during adulthood. The pathophysiology of TS is still a matter of considerable debate. Current knowledge of cortico—basal ganglia—thalamocortical circuits provide explanations for the beneficial effects of deep brain stimulation (DBS) on tics. When conservative treatment fails in patients with severe TS, DBS may be a therapeutic option. In 1999, thalamic DBS was introduced for intractable TS. Since then, multiple targets have been used in a small number of patients, including the globus pallidus pars interna and the nucleus accumbens. Inclusion and exclusion criteria have been formulated to identify good candidates for DBS.

In this report, we describe the effects of bilateral thalamic stimulation in one patient and of bilateral pallidal stimulation in another patient. Both patients suffered from intractable Tourette's syndrome (TS). Any conservative treatment had failed or had been stopped because of unbearable side effects in the 2 patients. In both cases, there was no comorbidity except for associated behavioral symptoms (compulsions). Electrodes were implanted at the level of the medial part of the thalamus (centromedian nucleus, the substantia periventricularis, and the nucleus ventro-oralis internus) in one patient and in the posteroventral part of the globus pallidus internus (GPi) in the other patient. In both cases, deep brain stimulation (DBS) resulted in a substantial reduction of tics and compulsions. These data show that bilateral DBS of the thalamus as well as of the GPi can have a good effect on tics and behavioral symptoms in patients suffering from intractable TS. (C) 2006 Movement Disorder Society.

Objective. To report our experience on hardware-related infections following deep brain stimulation (DBS). Methods. The present article presents the retrospective clinical notes review of gained in a two-centre, single-surgeon study experience of 108 consecutive DBS cases between 1996 and 2002. In all patients the minimum follow-up was six months. One hundred and eight patients received an intracerebral electrode implantation and 106 underwent internalization. Results. In total 178 electrodes were implanted with a mean follow-up of 42.6 months and a cumulative follow-up of 367.7 patient-years. Four patients (3.8%) developed an infection related to the DBS-hardware and all were initially treated with antibiotics. Two patients eventually required additional surgical treatment. Conclusion. Infections due to DBS-hardware can result in considerable levels of morbidity. In certain cases antibiotic therapy may be adequate. In others, surgical intervention to externalise the electrodes may be necessary. In our experience, there was never a need to remove the electrodes.

Introduction: Patients with medically refractory epilepsy treated with deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) vary highly in their therapy response. Proper positioning of the DBS lead is crucial to maximize efficacy and minimize side effects. For a correct implantation, the ANT is anatomically located using pre-operative 3T MRI and perioperative microelectrode recordings (MER). Neurons in the ANT have highly variable, yet characteristic patterns of firing in bursts. During DBS lead implantation, we noted differences among patients’ characteristic burst patterns along the electrode trajectory. In this study, we investigate whether electrophysiological characteristics of the target region could predict therapy response to DBS and could thus be used to improve ANT targeting during DBS surgery. Objectives: To determine whether perioperative neurophysiological characteristics relate to therapy response in DBS for patients with medically refractory epilepsy. Patients and methods: We included ten consecutive epilepsy patients planned for DBS surgery at Maastricht University Medical Center. All patients were diagnosed with medically refractory epilepsy and had incapacitating seizures. Patients failed trials of at least two reasonably tolerated and adequately chosen antiepileptic drug schedules. Using pre-operative 3T MRI, we planned an extraventricular approach to target. The ANT was defined as a grey matter structure at the top of the mamillothalamic tract. Along this trajectory, we performed stereotactic single cell MERs. The anatomical location of the recordings were verified using preoperative 3T MR images. We compared characteristics of the neural signals at different depths along the trajectory between DBS responders and non-responders. Responders were defined as patients with a seizure frequency reduction of more than 50% at one year follow-up. Results: Using MER data from 19 electrode trajectories of ten patients (one unilateral and nine bilateral trajectories), we found high-amplitude neuronal bursts around the target area or ANT. Responders to DBS (n = 5) had higher normalized mean firing rates and mean burst rates near the target area compared to non-responders (n = 5), with a clearer delineation between the target region and surroundings. Electrode trajectories and lead localization did not differ between responders and non-responders. Conclusion: Single cell firing patterns in the ANT relate to therapy response in DBS for patients with medically refractory epilepsy. Analysis of single cell firing patterns using MER may guide targeting or contribute to predicting therapy response to ANT DBS. Further exploration into the use of electrophysiological recordings is warranted to improve targeting or predict outcome in DBS for epilepsy patients.

BACKGROUND: Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD.CASE DESCRIPTION: We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects.CONCLUSIONS: Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS.

BACKGROUND: In the 2016 update of the World Health Organization Classification of Tumors of the central nervous system, phenotypic and genotypic parameters are integrated in diffuse low-grade glioma (LGG) tumor classification. Implementation of this combined phenotypic-genotypic characterization identifies prognostic relevant subgroups.CASE DESCRIPTION: We report a case of a 67-year-old patient with an LGG that showed molecular characteristics similar to glioblastoma multiforme (GBM). After gross total tumor resection, the patient received combination therapy (radiotherapy and chemotherapy) according to high-grade glioma treatment protocol.CONCLUSION: The introduction of molecular parameters to the classification of LGG will add a level of objectivity, which will yield biological homogeneous subclasses. Consequently, this will influence patient counseling and clinical decision making regarding treatment protocols.

Background: Since the introduction of subthalamic nucleus deep brain stimulation (STN DBS), many clinical studies have shown that this therapy is safe and effective in the short and medium term. Only little is known about long-term results. Objectives: To provide an analysis of motor and cognitive outcome 10 years after STN DBS. Methods: In this observational cohort study, we report on the motor and cognitive outcome in a cohort of 26 Parkinson's disease patients who were prospectively followed up for 10 years after STN DBS surgery. Results: In the early post-operative phase, improvement in the Unified Parkinson's Disease Rating Scale (UPDRS) III (10.6, p < 0.01) and IV (2.5, p < 0.01) was seen as well as a 32% reduction in levodopa equivalent dose (p < 0.01). After 5 years, a worsening of the motor performance was observed. The worsening of motor performance was mainly due to a deterioration in bradykinesia (12.4 ± 4.6, p < 0.05) and axial symptoms (6.9 ± 2.8, p < 0.01). Memory function seemed to improve in the short term, but there was a significant decline between 1 and 5 years after surgery (p < 0.01). Mood remained relatively stable during follow-up, and one third of the patients showed impulsive behaviour after surgery. Conclusions: The motor performance of patients showed deterioration over time, due to an increase in bradykinesia and axial symptoms.

Introduction Thalamic deep brain stimulation is effective in reducing tics in patients with severe Tourette syndrome at the short-term. Here, we report on the long-term outcome. Methods Seven patients with refractory Tourette syndrome were referred to the Maastricht University Medical Centre and underwent bilateral thalamic deep brain stimulation between 2001 and 2008. The target was the centromedian nucleus-substantia periventricularis-nucleus ventro-oralis internus cross point of the thalamus. During the visits to the outpatient clinic, effects on tics, side-effects and stimulations parameters were evaluated. The follow-up duration varied between 12 to 78 months. Results Patient 1 showed an improvement on tics of 81.6% after 60 months, but due to higher voltage stimulation after some years needed to suppress the tics, side-effects became more severe and the target was changed to the anterior part of the internal pallidum. Patient 2 showed a tic improvement of 50% after 36 months, but due to increasing side-effects, he switched the stimulator permanently off. In patient 3 the stimulator is still active and showed satisfying results with an improvement on tics of 88.9% after 78 months. Patient 4 experienced a tic improvement of 34% after 16 months. However, side-effects became more severe, and when the whole system had to be removed due to a persisting hardware infection after six years, the target was changed to the anterior part of the internal pallidum. Patient 5 showed a minor tic improvement of 27.5% after 12 months. He was unsatisfied and went to abroad for stimulation of the external globus pallidus. Patient 6 developed cerebral atrophy due to a neurodegenerative disease and experienced several non-stimulation related side-effects. His tic improvement was 34% on the YGTSS after 26 months and he decided to turn the stimulator off. The positive effect on tics in patient 7 decreased over time until an improvement of only 9% at 60 months of follow-up. The target was changed to the anterior part of the internal pallidum. Conclusion Thalamic deep brain stimulation in patients with severe Tourette syndrome is effective in reducing tics, at least at the short-term. At the long-term only in one patient the stimulator is still active, in three patients the target was changed to the anterior part of the internal pallidum due to side-effects and three were unsatisfied and turned off their stimulator. There seems to be an increasing disbalance of effects versus side effects leading to either switching off the stimulator or re-surgery changing the target. These clinical cases reflect the strong heterogeneity of the disease, with serious comorbity, interfering with effects and side-effects of deep brain stimulation.

Introduction Patients with severe Tourette syndrome are potential candidates for deep brain stimulation (DBS). We have shown that bilateral thalamic as well as pallidal stimulation can be effective in reducing the severity of motor and vocal tics. However, one of the challenges is the anesthetic approach in this type of surgery. During surgery there is an ’awake’ and an ’asleep’ phase. In the ’awake’ phase, anesthesia has three goals. First, to reduce the intraoperative tics to avoid the dislocation of the stereotactic frame. Second, adequate level of consciousness to allow intraoperative testing of stimulation effects. Third, avoid interference with the single-unit electrophysiological recordings. To date there is no consensus on how to reach these goals. In this study, we report our own experience in the past 15 years. In the ‘asleep’ phase there is the internalization of the extension leads and pulsgenerator. Methods From 1999 to 2015 surgery was performed in 15 patients (12 males and 3 females) with severe Tourette syndrome. Eight patients were operated in the thalamic target (cross point of the centromedian nucleus-substantia periventricularis-nucleus ventro-oralis internus) and 7 in the pallidal target (the anteromedial part of the internal globus pallidus). During the procedure different short-acting anesthetic regimens were used. In the ’awake’ phase we used a combination of propofol and remifentanil, remifentanil and clonidine, and remifentanil as a single anesthetic. In the asleep phase all patients were intubated and received a combination of propofol and remifentanil. Results With our awake-asleep anesthetic protocols, none of the patients experienced dislocation of the stereotactic frame during surgery. In the awake phase, all patients were cooperative and neuropsychological testing was possible. Moreover, stimulation related side effects could be screened. We obtained adequate single-unit recordings from the thalamic and pallidal neurons. Conclusion Tailored anesthetic techniques with low-dose sedation make it possible to achieve adequate tic reduction in the ‘awake’ phase, allowing intraoperative clinical testing, and obtain good neurophysiological recordings.

Introduction Patients with severe treatment resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial limbic part of the subthalamic nucleus (STN) and the ventral capsule/ventral striatum (VC/VS) are among the most commonly used targets. Objective To report a side effect of anteromedial STN-DBS in an OCD patient that has not been described before. Method Case report. Results A 49-year old female patient with a 30-year history of treatment-resistant obsessive-compulsive disorder was indicated for anteromedial STN-DBS. Correct target identification was done using electrophysiological recordings preoperatively and confirmed with CT scanning post-operatively. Already after the first days of STN stimulation, there was a clear mood-enhancing effect. However, the patient developed compulsive behavior towards the operation wounds (scratching and itching), which may have been the cause of a subsequent hardware infection. The infection resolved after surgery and antibiotic therapy. In the outpatient period, the programming was limited by the fact that STN-DBS caused motor symptoms at voltages above circa 2.5 V. These consisted of bilateral hyperkinesia and dyskinesias, as well as sudden large amplitude choreatic movements of the arms and legs. With lower stimulation amplitude (and 90 ms and 130 Hz) there was no effect on compulsions. Due to this programming limitation, we decided to re-operate and target the VC/VS, with the deepest electrode contact point in the area of the nucleus accumbens. After programming, the patient now experiences a substantial reduction (50%) of the key symptoms and obtained an acceptable quality of life. Conclusion In this 49-year old patient with OCD, anteromedial STN-DBS induced hyperkinetic movements in the lower extremities that limited the programming possibilities. Choreatic movements and (contralateral) hemiballismus have since long been associated with damage to the subthalamic nucleus ( Hawley and Weiner, 2012) , and have been described as a side-effect of STN-DBS in Parkinson’s disease ( Baizabal-Carvalla and Jankovic, 2016) . However, the emergence of such motor symptoms as a side-effect of STN-DBS in OCD has to our knowledge not been described before. Reimplantation to the VC/VS successfully overcame this limitation and resulted in adequate therapeutic response.

Tourette syndrome is a chronic neuropsychiatric disorder characterized by motor and vocal tics. In the majority of cases, tics are associated by behavioral disorders such as obsessive-compulsive behavior. First symptoms typically appear in early childhood. Mostly symptoms disappear when adulthood is reached. Treatment options consist of behavioral therapy and medication. In refractory cases, surgery may be an option. In the past, several attempts have been made to treat therapy-refractory patients through neurosurgical ablative procedures. In 1999, deep brain stimulation was introduced as a novel treatment option for patients with intractable Tourette syndrome. Up until now, five brain areas have been used or suggested as potential target areas for deep brain stimulation in Tourette syndrome. In the majority of the published cases, there is a clear effect on tics but most studies consist of only a limited number of patients. A strict patient selection is absolutely mandatory. There is a need for double-blinded multicenter trials with inclusion of more patients.

International audience; ABSTRACT Objective: Thalamic deep brain stimulation for intractable Tourette Syndrome has been introduced in 1999 by Vandewalle et al. In this follow-up study we report on the long-term (6 and 10 years) outcome in terms of tic reduction, cognition and mood and side-effects of medial thalamic DBS in two previously described Tourette patients. Methods: We compared the outcome of two patients at 6 and 10 years after surgery with their preoperative status and after 8 months and 5 years of treatment, respectively. Standardized video recordings were scored by three independent investigators. Both patients underwent (neuro)psychological assessment at all time points of follow-up. Results: Tic improvement observed at 5 years in patient 1 (90.1%) was maintained at 10 years (92.6%). In patient 2 the tic improvement at 8 months (82%) was slightly decreased at 6 years (78%). During follow-up, case 1 revealed no changes in cognition, but case 2 showed a decrease in verbal fluency and learning which was in line with his subjective reports. Case 2 showed a slight decrease in depression but overall psychopathology was still high at 6 years after surgery with an increase in anger and aggression together with difficulties in social adaptation. Besides temporary hardware related complications no distressing adverse effects were observed. Conclusion: Bilateral thalamic stimulation may provide sustained tic benefit after at least 6 years but overall improvement is not obvious. To maximize overall outcome attention is needed for postoperative psychosocial adaptation, already prior to surgery.

Addiction or substance dependence is a psychiatric disorder that affects many individuals in the general population. Different theories concerning the neurobiological aspects of addiction have been proposed. Special attention has been paid to models concerning dysregulation of the reward circuit and the inhibitory control system within the cortico-basal ganglia-thalamocortical pathways. In the past, attempts have been made to treat patients suffering from addiction by performing psychosurgery. Lesions were created in specific brain regions that were believed to be dysfunctional in addiction. Procedures such as cingulotomy, hypothalamotomy, and resection of the substantia innominata and the nucleus accumbens have been described as a treatment for severe addictive disorders. Deep brain stimulation, a neurosurgical treatment that has been proven to be a safe alternative for lesions in the treatment of movement disorders, has more recently been proposed as treatments for severe psychiatric conditions such as treatment-refractory obsessive-compulsive disorder and depression. With the expanding knowledge of the neurobiology of addiction, deep brain stimulation could be a future option in the treatment arsenal of addiction.

OBJECTIVE: We describe a patient who developed a vertical gaze paralysis after deep brain stimulation performed for intractable Tourette syndrome due to a small deep bleeding in the upper mesencephalon. CLINICAL PRESENTATION: A 39-year-old man underwent thalamic deep brain stimulation for intractable Tourette syndrome. Immediately postoperatively, he had diplopia and dizziness. The neurological examination revealed vertical gaze palsy with preserved vertical oculocephalic movements. A postoperative computed tomography scan revealed a discrete high-density lesion across the midline at the distal end of the left electrode. This area corresponds with the pretectal area, including the rostral interstitial nucleus of the medial longitudinal fasciculus, with sparing of the oculomotor and rubral nuclei. INTERVENTION: Six months postoperatively, maximal upward and downward smooth pursuit eye movements were achieved. Upward saccadic velocities were still reduced by 20 to 25 degrees. CONCLUSION: This case report describes a complication that might demand special attention during the planning of thalamic deep brain stimulation for the treatment of Tourette syndrome. Examination of both horizontal and vertical eye movements during deep brain stimulation surgery is recommended.