Directional electrodes in deep brain stimulation: Results of a survey by the European Association of Neurosurgical Societies (EANS).

Introduction: Directional Leads (dLeads) represent a new technical tool in Deep Brain Stimulation (DBS), and a rapidly growing population of patients receive dLeads. Research question: The European Association of Neurosurgical Societies(EANS) functional neurosurgery Task Force on dLeads conducted a survey of DBS specialists in Europe to evaluate their use, applications, advantages, and disadvantages. Material and methods: EANS functional neurosurgery and European Society for Stereotactic and Functional Neurosurgery (ESSFN) members were asked to complete an online survey with 50 multiple-choice and open questions on their use of dLeads in clinical practice. Results: Forty-nine respondents from 16 countries participated in the survey (n = 38 neurosurgeons, n = 8 neurologists, n = 3 DBS nurses). Five had not used dLeads. All users reported that dLeads provided an advantage (n = 23 minor, n = 21 major). Most surgeons (n = 35) stated that trajectory planning does not differ when implanting dLeads or conventional leads. Most respondents selected dLeads for the ability to optimize stimulation parameters (n = 41). However, the majority (n = 24), regarded time-consuming programming as the main disadvantage of this technology. Innovations that were highly valued by most participants included full 3T MRI compatibility, remote programming, and closed loop technology. Discussion and conclusion: Directional leads are widely used by European DBS specialists. Despite challenges with programming time, users report that dLeads have had a positive impact and maintain an optimistic view of future technological advances.

The Diagnostic Value of Ultrasound of the Rectus Femoris for the diagnosis of Sarcopenia in adults: A systematic review.

BACKGROUND & AIM: Sarcopenia is defined as a loss of muscle mass and function, which can be caused by normal ageing or factors such as physical inactivity. Severe health consequences caused by sarcopenia highlight the need for early identification. Computed Tomography (CT) imaging, often mentioned as the gold standard due to its accuracy, is costly and not routinely performed in daily clinical care. Ultrasound of the rectus femoris, however, is low in costs and easily accessible. The aim is to present the current and most recent literature regarding the diagnostic value of ultrasound measurements of the rectus femoris for the diagnosis of sarcopenia in adults. METHODS: The databases PubMed and Web of Science were used to search for studies comparing ultrasound of the rectus femoris with a reference test to diagnose sarcopenia in adults. The quality of the final eligible studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies, version 2, tool (QUADAS-2). RESULTS: Six studies were included in this systematic review. The muscle thickness and cross-sectional area of the rectus femoris were assessed and compared with the reference tests CT, Dual-Energy X-ray Absorptiometry (DXA), and Bioelectrical Impedance Analysis (BIA). Half of the studies had a low risk of bias on all QUADAS-2 domains. Three studies reported statistical significant outcomes and diagnostic values ranging from 60 to 81% sensitivity and 51 to 94% specificity. CONCLUSIONS: Ultrasound of the rectus femoris muscle to diagnose sarcopenia has been shown to be a promising method in multiple clinical populations. However, there were some limitations such as a high methodological heterogeneity. Future research should develop standardized protocols and determine clear cut-off values to allow for a better implementation of ultrasound in clinical practice.

Myasthenia gravis after glioblastoma resection: paraneoplastic syndrome or coincidence? A unique case report and review of the literature.

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.

The complement system in glioblastoma multiforme.

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.

Ethics of Deep Brain Stimulation in Adolescent Patients with Refractory Tourette Syndrome: a Systematic Review and Two Case Discussions.

INTRODUCTION: Tourette Syndrome (TS) is a childhood onset disorder characterized by vocal and motor tics and often remits spontaneously during adolescence. For treatment refractory patients, Deep Brain Stimulation (DBS) may be considered. METHODS AND RESULTS: We discuss ethical problems encountered in two adolescent TS patients treated with DBS and systematically review the literature on the topic. Following surgery one patient experienced side effects without sufficient therapeutic effects and the stimulator was turned off. After a second series of behavioural treatment, he experienced a tic reduction of more than 50%. The second patient went through a period of behavioural disturbances that interfered with optimal programming, but eventually experienced a 70% tic reduction. Sixteen DBS surgeries in adolescent TS patients have been reported, none of which pays attention to ethical aspects. DISCUSSION: Specific ethical issues arise in adolescent TS patients undergoing DBS relating both to clinical practice as well as to research. Attention should be paid to selecting patients fairly, thorough examination and weighing of risks and benefits, protecting the health of children and adolescents receiving DBS, special issues concerning patient's autonomy, and the normative impact of quality of life. In research, registration of all TS cases in a central database covering a range of standardized information will facilitate further development of DBS for this indication. CONCLUSION: Clinical practice should be accompanied by ongoing ethical reflection, preferably covering not only theoretical thought but providing also insights in the views and perspectives of those concerned, that is patients, family members and professionals.

Deep brain stimulation of the subthalamic nucleus in obsessive-compulsive disorder: Neuroanatomical and pathophysiological considerations.

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 δ-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.

The International Deep Brain Stimulation Registry and Database for Gilles de la Tourette Syndrome: How Does It Work?

Tourette Syndrome (TS) is a neuropsychiatric disease characterized by a combination of motor and vocal tics. Deep brain stimulation (DBS), already widely utilized for Parkinson's disease and other movement disorders, is an emerging therapy for select and severe cases of TS that are resistant to medication and behavioral therapy. Over the last two decades, DBS has been used experimentally to manage severe TS cases. The results of case reports and small case series have been variable but in general positive. The reported interventions have, however, been variable, and there remain non-standardized selection criteria, various brain targets, differences in hardware, as well as variability in the programming parameters utilized. DBS centers perform only a handful of TS DBS cases each year, making large-scale outcomes difficult to study and to interpret. These limitations, coupled with the variable effect of surgery, and the overall small numbers of TS patients with DBS worldwide, have delayed regulatory agency approval (e.g., FDA and equivalent agencies around the world). The Tourette Association of America, in response to the worldwide need for a more organized and collaborative effort, launched an international TS DBS registry and database. The main goal of the project has been to share data, uncover best practices, improve outcomes, and to provide critical information to regulatory agencies. The international registry and database has improved the communication and collaboration among TS DBS centers worldwide. In this paper we will review some of the key operation details for the international TS DBS database and registry.

Deep Brain Stimulation of the internal globus pallidus in refractory Tourette Syndrome.

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.

Tic related local field potentials in the thalamus and the effect of deep brain stimulation in Tourette syndrome: Report of three cases.

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 1-8Hz 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.

Deep brain stimulation in movement disorders. The applications reconsidered.

In this study the role of DBS in advanced Parkinson disease (PD) is re-evaluated and new indications in the field of movement disorders are explored. The authors performed unilateral pallidal stimulation in 26 patients with advanced PD. At long-term follow-up review, the motor effect is unsatisfying. The authors conclude that unilateral pallidal stimulation is not a favourable treatment option for patients with advanced PD. Bilateral subthalamic nucleus stimulation was performed in twenty patients with advanced PD. After a minimum follow-up of 4 years, there was still a significant improvement in motor function and functional performance in all patients. One side-effect of the stimulation was however rather concerning: four patients presented with stimulation-induced hypomanic to manic characteristics. Bilateral subthalamic stimulation was performed in four patients with multiple system atrophy-parkinsonism. At long-term follow-up, the patients fared better with than without stimulation. The authors finally present a completely new indication for DBS: Tourette syndrome (TS). They review the literature on surgical procedures performed in TS, all of which consisted of making lesions. Three TS patients are presented on which bilateral thalamic stimulation was performed. At long-term follow-up, all major tics had disappeared, as well as associated behavioral disturbances.

Management of hardware infections following deep brain stimulation.

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.

Thalamus and penile erection.

Penile erection is a complex neurovascular event. The neuronal system involved is often divided into a spinal (generator) and supraspinal (controller) network. Little is known about the supraspinal control. The recent finding of changes in penile erection following deep brain stimulation of the thalamus in two patients has raised the question as to what extent the thalamus is involved in erectile function. The thalamus has generally been regarded as a group of relay nuclei that served as a 'gate' for sexual information from the spinal cord towards higher centres. Recent evidence, however, suggests a more integrated regulatory function. Our review of the literature from 1960 until 2003 revealed 13 reports describing original data (preclinical and clinical). Various thalamic regions, varying from the midline thalamus to the posterior thalamus, have been reported to be activated during erection. The majority of the reports, however, showed that mainly the mediodorsal (MD) nucleus and the centromedian-parafascicular nucleus (Cm-Pf complex) are involved in penile erection. MD is the second largest nuclear aggregation located within the medial part of the thalamus. Anatomically, the MD is closely related to the Cm-Pf complex. The Cm-Pf complex is one of the most important relay stations in which the anterolateral spinothalamic pathway is further processed. This pathway is thought to transmit peripheral sexual sensations. On the whole, the present data on the role of the thalamus in erection are far from complete and future experiments are required to delineate its involvement.