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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.

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.

In 2011 the European Society for the Study of Tourette Syndrome (ESSTS) published its first European clinical guidelines for the treatment of Tourette Syndrome (TS) with part IV on deep brain stimulation (DBS). Here, we present a revised version of these guidelines with updated recommendations based on the current literature covering the last decade as well as a survey among ESSTS experts. Currently, data from the International Tourette DBS Registry and Database, two meta-analyses, and eight randomized controlled trials (RCTs) are available. Interpretation of outcomes is limited by small sample sizes and short follow-up periods. Compared to open uncontrolled case studies, RCTs report less favorable outcomes with conflicting results. This could be related to several different aspects including methodological issues, but also substantial placebo effects. These guidelines, therefore, not only present currently available data from open and controlled studies, but also include expert knowledge. Although the overall database has increased in size since 2011, definite conclusions regarding the efficacy and tolerability of DBS in TS are still open to debate. Therefore, we continue to consider DBS for TS as an experimental treatment that should be used only in carefully selected, severely affected and otherwise treatment-resistant patients.

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.

Background: Chronic tinnitus can have an immense impact on quality of life. Despite recent treatment advances, many tinnitus patients remain refractory to them. Preclinical and clinical evidence suggest that deep brain stimulation (DBS) is as a promising treatment to suppress tinnitus. The thalamic medial geniculate body (MGB) takes a key position in the tinnitus network, shows pathophysiological hallmarks of tinnitus, and is readily accessible using stereotaxy. This study will evaluate the safety and therapeutic effects of DBS in the MGB in severe tinnitus sufferers.Methods: Bilateral DBS of the MGB will be applied in six patients with severe and refractory tinnitus. A double-blinded, randomized 2x2 crossover design (stimulation ON and OFF) will be applied, followed by a period of six months open label follow-up. The primary focus is to assess safety and feasibility (acceptability). Secondary outcomes assess a potential treatment effect and include tinnitus severity measured by the Tinnitus Functional Index (TFI), tinnitus loudness and distress, hearing, cognitive and psychological functions, quality of life, and neurophysiological characteristics. Discussion: Whilst carefully balancing risks and benefits and taking ethical considerations into account, this study explores the safety and feasibility of DBS in severe refractory tinnitus, by extensive assessment of clinical and neurophysiological outcome measures. Additionally, important insights in the underlying mechanism of tinnitus and hearing function might be revealed. Trial registration: ClinicalTrials.gov NCT03976908 (June 6, 2019)

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.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) has become a routine treatment of advanced Parkinson's disease (PD). DBS surgery is commonly performed under local anesthesia (LA) to obtain reliable microelectrode recordings. However, procedural sedation and/or analgesia (PSA) is often desirable to improve patient comfort. The impact of PSA in addition to LA on outcome is largely unknown. Therefore, we performed an observational study to assess the effect of PSA compared to LA alone during STN DBS surgery on outcome in PD patients.METHODS: Seventy PD patients (22 under LA, 48 under LA + PSA) scheduled for STN DBS implantation were included. Dexmedetomidine, clonidine or remifentanil were used for PSA. The primary outcome was the change in Movement Disorders Society Unified Parkinson's Disease Rating Score III (MDS-UPDRS III) and levodopa equivalent daily dosage (LEDD) between baseline, one month before surgery, and twelve months postoperatively. Secondary outcome measures were motor function during activities of daily living (MDS-UPDRS II), cognitive alterations and surgical adverse events. Postoperative assessment was conducted in "on" stimulation and "on" medication conditions.RESULTS: At twelve months follow-up, UPDRS III and UPDRS II scores in "on" medication conditions were similar between the LA and PSA groups. The two groups showed a similar LEDD reduction and an equivalent decline in executive function measured by the Stroop Color-Word Test, Trail Making Test-B, and verbal fluency. The incidence of perioperative and postoperative adverse events was similar between groups.CONCLUSION: This study demonstrates that PSA during STN DBS implantation surgery in PD patients was not associated with differences in motor and non-motor outcome after twelve months compared with LA only.

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.

Glioblastoma (GBM) is the most malignant primary brain tumor for which no curative treatment options exist. Non-invasive qualitative (Visually Accessible Rembrandt Images (VASARI)) and quantitative (radiomics) imaging features to predict prognosis and clinically relevant markers for GBM patients are needed to guide clinicians. A retrospective analysis of GBM patients in two neuro-oncology centers was conducted. The multimodal Cox-regression model to predict overall survival (OS) was developed using clinical features with VASARI and radiomics features in isocitrate dehydrogenase (IDH)-wild type GBM. Predictive models for IDH-mutation, 06-methylguanine-DNA-methyltransferase (MGMT)-methylation and epidermal growth factor receptor (EGFR) amplification using imaging features were developed using machine learning. The performance of the prognostic model improved upon addition of clinical, VASARI and radiomics features, for which the combined model performed best. This could be reproduced after external validation (C-index 0.711 95% CI 0.64–0.78) and used to stratify Kaplan–Meijer curves in two survival groups (p-value &lt, 0.001). The predictive models performed significantly in the external validation for EGFR amplification (area-under-the-curve (AUC) 0.707, 95% CI 0.582–8.25) and MGMT-methylation (AUC 0.667, 95% CI 0.522–0.82) but not for IDH-mutation (AUC 0.695, 95% CI 0.436–0.927). The integrated clinical and imaging prognostic model was shown to be robust and of potential clinical relevance. The prediction of molecular markers showed promising results in the training set but could not be validated after external validation in a clinically relevant manner. Overall, these results show the potential of combining clinical features with imaging features for prognostic and predictive models in GBM, but further optimization and larger prospective studies are warranted.

This is a unique case describing hydrocephalus to be the primary presenting symptom of neurosarcoidosis. A 49-year-old woman with previous ischemic cerebral events presented with a gait disorder, urinary incontinence and cognitive impairment. Imaging showed obstructive hydrocephalus, progressive white matter abnormalities and basal leptomeningeal enhancement. Further diagnostics suggested sarcoidosis.

Background and aim: Deep brain stimulation (DBS) is an effective treatment for patients with severe therapy-resistant obsessive-compulsive disorder (OCD). After initiating DBS many patients still require medication and/or behavioral therapy to deal with persisting symptoms and habitual behaviors. The clinical practice of administering postoperative cognitive behavioral therapy (CBT) varies widely, and there are no clinical guidelines for this add-on therapy. The aim of this review is to assess the efficacy, timing and procedural aspects of postoperative CBT in OCD patients treated with DBS. Method: Systematic review of literature. Results: The search yielded 5 original studies, one case series and three reviews. Only two clinical trials have explicitly focused on the effectiveness of CBT added to DBS in patients with therapy-resistant OCD. These two studies both showed effectiveness of CBT. However, they had a distinctly different design, very small sample sizes and different ways of administering the therapy. Therefore, no firm conclusions can be drawn or recommendations made for administering CBT after DBS for therapy-resistant OCD. Conclusion: The effectiveness, timing and procedural aspects of CBT added to DBS in therapy-resistant OCD have hardly been studied. Preliminary evidence indicates that CBT has an added effect in OCD patients being treated with DBS. Since the overall treatment effect is the combined result of DBS, medication and CBT, future trials should be designed in such a way that they allow quantification of the effects of these add-on therapies in OCD patients treated with DBS. Only in this way information can be gathered that contributes to the development of an algorithm and clinical guidelines for concomittant therapies to optimize treatment effects in OCD patients being treated with DBS.

Tourette syndrome (TS) is a complex childhood-onset neuropsychiatric disorder characterized by multiple motor tics, plus one or more vocal tics, lasting longer than 1 year. The prevalence of TS in childhood is estimated at 0.3–0.9%, and overall TS has a favorable prognosis. About one third of children with TS will experience a significant decrease in tics during adolescence, and another third of children will become completely tic free. Yet a small proportion of patients do not experience this remission. There is no cure for TS, and treatment aims to reduce or alleviate tics and other comorbid symptoms. Behavioral therapy and pharmacological treatment may provide relief, but some patients remain refractory or experience unbearable side effects. For those patients, deep brain stimulation (DBS) can be considered. The first TS patient was treated with DBS of the thalamus in 1999; since then, approximately 270 patients have been operated. A key factor in attaining optimal results from this surgery is target selection, a topic still under debate due to the complex clinical profile presented by TS patients. Nine separate brain areas have been targeted so far: the medial part of the thalamus (three different areas), the internal globus pallidus (GPi) (anterior and posterior part), the external globus pallidus (GPe), the nucleus accumbens (NA), the anterior limb of the internal capsule (ALIC), and the subthalamic nucleus (STN). Interfering with DBS at the level of one of the main output or relay stations of the basal ganglia seems to result in clinical benefits in refractory TS patients. Overall, DBS results in a significant short-term improvement of 53% on the Yale Global Tic Severity Scale (YGTSS) on all targets. The degree of tic improvement appears to be most robust for the thalamic and the GPi targets. Further research should provide more clarity in selection of the optimal stimulation target, stimulation parameters, and the effectiveness of this treatment.

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.

Deep brain stimulation is invasive and used in selected patients with intractable Tourette Syndrome. The anaesthetic technique of first choice during implantation of the electrodes is an awake technique with local anaesthetics and conscious sedation. The anaesthetic management can be challenging, especially in Tourette Syndrome patients due to sudden movements. The anaesthetic goal is to have a comfortable patient during the procedure with minimal influence of pharmacological agents on microelectrode recordings. Here, we describe our experience with the use of an intravenous dexmedetomidine infusion during deep brain stimulation in a patient with Tourette Syndrome. We discuss the effects on the microelectrode recordings and clinical testing. Finally, we describe the advantages of dexmedetomidine as a sedative agent in Tourette Syndrome patients during deep brain stimulation and the pharmacological effects of dexmedetomidine on the basal ganglia.

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.

Item does not contain fulltext OBJECTIVES: The use of 7 Tesla (T) magnetic resonance imaging (MRI) has recently shown great potential for high-resolution soft-tissue neuroimaging and visualization of microvascularization in glioblastoma (GBM). We have designed a clinical trial to explore the value of 7 T MRI in radiation treatment of GBM. For this aim we performed a preparatory study to investigate the technical feasibility of incorporating 7 T MR images into the neurosurgical navigation and radiotherapy treatment planning (RTP) systems via qualitative and quantitative assessment of the image quality. MATERIALS AND METHODS: The MR images were acquired with a Siemens Magnetom 7 T whole-body scanner and a Nova Medical 32-channel head coil. The 7 T MRI pulse sequences included magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE), T2-SPACE, SPACE-FLAIR and gradient echo sequences (GRE). A pilot study with three healthy volunteers and an anthropomorphic 3D phantom was used to assess image quality and geometrical image accuracy. RESULTS: The MRI scans were well tolerated by the volunteers. Susceptibility artefacts were observed in both the cortex and subcortical white matter at close proximity to air-tissue interfaces. Regional loss of signal and contrast could be minimized by the use of dielectric pads. Image transfer and processing did not degrade image quality. The system-related spatial uncertainty of geometrical distortion-corrected MP2RAGE pulse sequences was

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.

Brain metastases (BM) frequently occur in non-small cell lung cancer (NSCLC) patients. Most patients with BM have a limited life expectancy, measured in months. Selected patients may experience a very long progression-free survival, for example, patients with a targetable driver mutation. Traditionally, whole-brain radiotherapy (WBRT) has been the cornerstone of the treatment, but its indication is a matter of debate. A randomized trial has shown that for patients with a poor prognosis, WBRT does not add quality of life (QoL) nor survival over the best supportive care. In recent decades, stereotactic radiosurgery (SRS) has become an attractive non-invasive treatment for patients with BM. Only the BM is irradiated to an ablative dose, sparing healthy brain tissue. Intracranial recurrence rates decrease when WBRT is administered following SRS or resection but does not improve overall survival and comes at the expense of neurocognitive function and QoL. The downside of SRS compared with WBRT is a risk of radionecrosis (RN) and a higher risk of developing new BM during follow-up. Currently, SRS is an established treatment for patients with a maximum of four BM. Several promising strategies are currently being investigated to further improve the indication and outcome of SRS for patients with BM: the effectivity and safety of SRS in patients with more than four BM, combining SRS with systemic therapy such as targeted agents or immunotherapy, shared decision-making with SRS as a treatment option, and individualized isotoxic dose prescription to mitigate the risk of RN and further enhance local control probability of SRS. This review discusses the current indications of SRS and future directions of treatment for patients with BM of NSCLC with focus on the value of SRS.

Contains fulltext : 191178.pdf (Publisher’s version ) (Open Access) Glioblastoma is the most aggressive adult primary brain tumor which is incurable despite intensive multimodal treatment. Inter- and intratumoral heterogeneity poses one of the biggest barriers in the diagnosis and treatment of glioblastoma, causing differences in treatment response and outcome. Noninvasive prognostic and predictive tests are highly needed to complement the current armamentarium. Noninvasive testing of glioblastoma uses multiple techniques that can capture the heterogeneity of glioblastoma. This set of diagnostic approaches comprises advanced MRI techniques, nuclear imaging, liquid biopsy, and new integrated approaches including radiogenomics and radiomics. New treatment options such as agents targeted at driver oncogenes and immunotherapy are currently being developed, but benefit for glioblastoma patients still has to be demonstrated. Understanding and unraveling tumor heterogeneity and microenvironment can help to create a treatment regime that is patient-tailored to these specific tumor characteristics. Improved noninvasive tests are crucial to this success. This review discusses multiple diagnostic approaches and their effect on predicting and monitoring treatment response in glioblastoma.

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

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.

Background Treatment of glioblastoma (GBM) xenografts with chloroquine (CQ) has been shown to inhibit autophagy, thereby reducing the hypoxic fraction and sensitizing tumours to radiation. Preclinical evidence shows that EGFRvIII+ GBM may benefit most from CQ because of autophagy dependency. This study explores the safety, pharmacokinetics and maximum tolerated dose (MTD) of CQ in combination with radiotherapy (RT) and concurrent daily temozolomide (TMZ) in patients with a newly diagnosed GBM. Methods This study is a single-centre, open label, dose-finding phase I trial (3 + 3 design). Patients received oral CQ once daily one week before the course of concurrent chemoradiation (TMZ 75 mg/m2/day) until the end of RT. Toxicity was scored according to the CTCAE 4.0. Molecular markers were identified on paraffin embedded tissue. Results Thirteen patients were included in the study (n = 6:200mg, n = 3:300mg, n = 4:400mg CQ). Tumour characteristics: 7/13 MGMT promotor hypermethylation, 12/13 IDH wildtype, 0/13 1p/19q co-deletion and 7/13 EGFRvIII expression. A total of 44 adverse events possibly/likely related to CQ were registered. Serious adverse events are presented in Table. In the 400mg cohort 2 patients developed ECG QTc prolongation and 1 patient developed irreversible blurred vision. Three patients developed grade III nausea/vomiting (n = 2 300mg, n = 1 200mg) resulting in cessation of TMZ or delay of adjuvant TMZ cycles. Median overall survival is 8,1 months for EGFRvIII – and 13,4 months for EGFRvIII + patients; with 7 patients currently still alive at a median follow-up of 9 months (range 2 – 21). Table: 425P . Serious adverse events grade I - V - Adverse events possibly/likely related to chloroquine are presented with an *. Toxicity Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Blurred Vision* 1 Confusion 1 Electrocardiogram (ECG) QT corrected interval prolonged* 1 1 Fall (trauma capitis)* 1 Hypercalcemia 1 Nausea/vomiting* 3 3 Seizure 1 Thromboembolic event 1 1 Conclusions A daily dose of 200mg CQ was established as the MTD when combined with RT and concurrent TMZ for newly diagnosed GBM. Favorable tolerability and extensive pre-clinical evidence on anti-tumour activity support further clinical phase II and III studies. Clinical trial identification The study was approved by the Medical Review Ethics Committee Maastricht UMC+: #NL52723.068.15/METC153051. (NCT02378532). Legal entity responsible for the study The authors. Funding Stichting StopHersentumoren. Disclosure All authors have declared no conflicts of interest.

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.

Meningiomas are the most common type of primary central nervous system tumors. Approximately, 80% of meningiomas are classified by the World Health Organization (WHO) as grade I, and 20% of these tumors are grade II and III, considered high-grade meningiomas (HGMs). Clinical control of HGMs, as well as meningiomas that relapse after surgery, and radiation therapy is difficult, and novel therapeutic approaches are necessary. However, traditional chemotherapies, interferons, hormonal therapies, and other targeted therapies have so far failed to provide clinical benefit. During the last several years, next generation sequencing has dissected the genetic heterogeneity of meningioma and enriched our knowledge about distinct oncogenic pathways driving different subtypes of meningiomas, opening up a door to new personalized targeted therapies. Molecular classification of meningioma allows a new design of clinical trials that assign patients to corresponding targeted agents based on the tumor genetic subtypes. In this review, we will shed light on emerging medical treatments of meningiomas with a particular focus on the new targets identified with genomic sequencing that have led to clinical trials testing novel compounds. Moreover, we present recent development of patient-derived preclinical models that provide platforms for assessing targeted therapies as well as strategies with novel mechanism of action such as oncolytic viruses.

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.

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 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.

In 1999 deep brain stimulation was introduced as a new therapeutic option for patients with intractable Tourette syndrome. Tourette syndrome is a neurodegenerative disorder characterized by tics and associated behavioural disorders, with typical onset in early childhood. In most patients, the symptoms decrease spontaneously when adulthood is reached, or can be treated with behavioural therapy or medication. Only a small proportion of patients are candidates for surgical treatment. About 70–80 Tourette syndrome patients having received deep brain stimulation have been described in the literature. A diversity of targets have been used, mainly located at the level of the medial part of the thalamus, in the globus pallidus interna (anteromedial limbic and posteroventrolateral motor part), the globus pallidus externa, and the internal capsule/nucleus accumbens. Because of the small number of patients, there is a strong need for multicentre, double-blind trials with standard protocols.

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.

Publisher Summary This chapter focuses on the use of deep brain stimulation (DBS) for treating tourette's syndrome (TS). TS is a chronic complex neuropsychiatric disorder characterized most prominently by tics. Tics are sudden, rapid, recurrent, nonrhythmic, stereotyped muscle contractions (motor tics), or sounds produced by moving air through the nose, mouth, or throat (vocal tics). They may be abrupt in onset, fast and brief, or may be slow and sustained. The motor patterns of tics may involve individual muscles or small groups of muscles with discrete contractions (simple tics) like eye blinking, nose-twitching, sniffing or grunting. Complex tics involve a larger number of muscles acting in a coordinated pattern to produce complicated movements that may resemble purposeful voluntary movements. Complex tics include head shaking, scratching, throwing, touching or uttering short phrases. Tics increase with stress and decrease with relaxation or when the individual is engaged in acts that require selective attention. DBS was first introduced as a new surgical technique for the treatment of intractable TS in 1999. The TS patients considered for DBS should comprise only very severe cases who have received careful trials of standard therapies without adequate benefit. It is of paramount importance that the exact location of the DBS electrode and in particular the contact providing the greatest efficacy is precisely determined and that all positive and negative effects are meticulously described. The most commonly used scale for tic rating is the Yale Global Tic Severity Scale (YGTSS). The tics should be rated on video by two independent investigators. Ideally, the patient and investigator should be blinded to the status of the stimulation. A careful psychiatric and neuropsychological evaluation should be performed at regular intervals.

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.