The human thalamus orchestrates neocortical oscillations during NREM sleep.

A hallmark of non-rapid eye movement sleep is the coordinated interplay of slow oscillations (SOs) and sleep spindles. Traditionally, a cortico-thalamo-cortical loop is suggested to coordinate these rhythms: neocortically-generated SOs trigger spindles in the thalamus that are projected back to neocortex. Here, we used intrathalamic recordings from human epilepsy patients to test this canonical interplay. We show that SOs in the anterior thalamus precede neocortical SOs (peak -50 ms), whereas concurrently-recorded SOs in the mediodorsal thalamus are led by neocortical SOs (peak +50 ms). Sleep spindles, detected in both thalamic nuclei, preceded their neocortical counterparts (peak -100 ms) and were initiated during early phases of thalamic SOs. Our findings indicate an active role of the anterior thalamus in organizing sleep rhythms in the neocortex and highlight the functional diversity of thalamic nuclei in humans. The thalamic coordination of sleep oscillations could have broad implications for the mechanisms underlying memory consolidation.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part IV: deep brain stimulation.

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.

Microvascular decompression for trigeminal neuralgia in the elderly: efficacy and safety.

OBJECTIVE: The safety and efficacy of surgical microvascular decompression (MVD) in elderly patients with trigeminal neuralgia (TN) is controversially discussed in the literature. A widespread reluctance to expose this cohort to major intracranial surgery persists. Our aim was to compare the efficacy and safety between older and younger patients with TN. METHODS: In this cross-sectional study, 139 MVD procedures (103 patients < 70 and 36 patients ≥ 70) were included. Surgical fitness was assessed by the American Society of Anesthesiology (ASA) grade. The pain-free interval was evaluated using Kaplan-Meier analysis only in patients with a recent follow-up visit. Independent risk factors for recurrence in patients with a minimum 12-month follow-up were determined. RESULTS: Patients ≥ 70 showed a significantly higher number of comorbidities. Pain intensity, affection of trigeminal branches and symptom duration was similar between groups. No significant difference in treatment associated complications and permanent neurological deficits was shown. There was no treatment-related mortality. A tendency towards a lower recurrence rate in patients < 70 did not reach statistical significance (17.6% vs. 28.6%, P = 0.274). Pain-free interval was not different between both cohorts (78.7 vs. 73.5 months, P = 0.391). CONCLUSION: Despite a higher prevalence of comorbidities in elderly patients, complication rates and neurological deficits after MVD were comparable to younger patients. Rates of immediate and long-term pain relief compared favorably to previous studies and were similar between elderly and younger patients. These data endorse MVD as a safe and effective first-line surgical procedure for elderly patients with TN and neurovascular conflict on MRI.

What have we learned from 8 years of deep brain stimulation of the anterior thalamic nucleus? Experiences and insights of a single center.

OBJECTIVE: In the absence of a standard or guideline for the treatment of epilepsy patients with deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT), systematic single-center investigations are essential to establish effective approaches. Here, the authors report on the long-term results of one of the largest single-center ANT DBS cohorts. METHODS: The outcome data of 23 consecutive patients with transventricularly implanted electrodes were retrospectively analyzed with regard to adverse events, lead placement, stimulation-related side effects, and changes in seizure frequency. Depression and quality-of-life scores were collected in a subgroup of 9 patients. RESULTS: All but 2 patients initially underwent bilateral implantation, and 84.4% of all DBS leads were successfully located within the ANT. The mean follow-up time was 46.57 ± 23.20 months. A seizure reduction > 50% was documented in 73.9% of patients, and 34.6% achieved an Engel class I outcome. In 3 patients, clinical response was achieved by switching the electrode contact or changing from the monopolar to bipolar stimulation mode. Unilateral implantation seemed ineffective, whereas bilateral stimulation with successful ANT implantation only on one side led to a clinical response. Double stimulation with additional vagus nerve stimulation was safe. Changes in cycling mode or stimulation amplitude influenced therapy tolerability and, only to a lesser extent, seizure frequency. Side effects were rare and typically vanished by lowering the stimulation amplitude or changing the active electrode contact. Furthermore, depression and aspects of quality of life significantly improved with ANT DBS treatment. CONCLUSIONS: The transventricular approach as well as double stimulation proved safe. The anteroventral ANT appeared to be the most efficacious stimulation site. This systematic investigation with reluctant medication changes allowed for the development of a better idea of the association between parameter changes and outcome in ANT DBS patients, but larger samples are still needed to assess the potential of bipolar stimulation and distinct cycling frequencies. Furthermore, more multifaceted and objective assessments of treatment outcome are needed to fully assess the effects of ANT DBS treatment.

[Trigeminal neuralgia : Modern diagnostic workup and treatment]. / Trigeminusneuralgie : Moderne Diagnostik und Therapie.

The present article gives an update of relevant aspects in the diagnosis and therapy of trigeminal neuralgia from the neurological, neuroradiological and neurosurgical point of view. The diagnosis of trigeminal neuralgia is clinical, but high-quality imaging is mandatory to identify secondary causes and a neurovascular contact. New methods such as DTI (diffusion tensor imaging) allow a more differentiated assessment of the consequences of a vascular contact on the trigeminal nerve. Carbamazepine and oxcarbazepine continue to be first choice for the medical treatment, but have been supplemented by additional options such as pregabaline, lamotrigine, and onabotulinumtoxin A. In patients insufficiently responding to medical treatment, there are neurosurgical treatment options giving very good results. The best long-term results have been described for microvascular decompression, but percutaneous and radiosurgical treatments also are good options, especially in patients with an increased surgical risk profile, in secondary trigeminal neuralgia, and in case of recurrence after microvascular decompression.

Microstructural alterations in trigeminal neuralgia determined by diffusion tensor imaging are independent of symptom duration, severity, and type of neurovascular conflict.

OBJECTIVE: In this prospective study diffusion tensor imaging (DTI) was used to evaluate the influence of clinical and anatomical parameters on structural alterations within the fifth cranial nerve in patients with trigeminal neuralgia (TN) due to neurovascular compression. METHODS: Overall, 81 patients (40 men and 41 women; mean age 60 ± 5 years) with typical TN were included who underwent microsurgical decompression. Preoperative 3.0-T high-resolution MRI and DTI were analyzed in a blinded fashion. The respective fractional anisotropy (FA) and apparent diffusion coefficient values were compared with the clinical, imaging, and intraoperative data. This study was approved by the institutional review board, and written informed consent was obtained from all patients. RESULTS: DTI analyses revealed significantly lower FA values within the vulnerable zone of the affected trigeminal nerve compared with the contralateral side (p = 0.05). The DTI analyses also included 3 patients without clear evidence of neurovascular conflict on preoperative MRI. No differences were seen between arterial and venous compression. Lower FA values were found 5 months after symptom onset; however, no correlation was found with the duration of symptoms or severity of compression. CONCLUSIONS: DTI analysis allows the quantification of structural alterations, even in those patients without any discernible neurovascular contact on MRI. Moreover, our findings support the hypothesis that both the arteries and veins can cause structural alterations that lead to TN. These aspects can be useful for making treatment decisions.

Endotracheal Tube Electrodes to Assess Vocal Cord Motor Function During Surgery in the Cerebellopontine Angle.

BACKGROUND: The 10th cranial nerve (CN X) is at risk during surgery in the lower cerebellopontine angle (CPA). OBJECTIVE: To evaluate endotracheal surface electrodes for assessment of CN X motor function during CPA surgery. METHODS: Twenty patients were enrolled. Electrophysiological recordings were analyzed and retrospectively correlated with clinical, imaging, and intraoperative data. RESULTS: Recordings from endotracheal surface electrodes were reliable and eligible for analyses in 17 patients; in 3 patients, no surface electrode compound motor action potentials (CMAPs) could be obtained. Those patients with sufficient recordings underwent surgery in the CPA for tumors in 14 patients and for nontumor pathologies in 3 patients. In 12 patients, bipolar stimulation of motor rootlets in the CPA resulted in simultaneous CMAPs recorded from both surface electrodes and needle electrodes placed in the soft palate. Coactivation was particularly seen in patients with an intricate relationship between lower cranial nerves and tumor formations (n = 9/10). Amplitudes and latencies of vocal cord CMAPs showed high interindividual but low intraindividual variability. Parameters were not well correlated with the type of surgery (tumor vs nontumor surgery) and lower CN anatomy (displaced vs undisplaced). In 2 patients, vocal cord CMAPs were lost during tumor surgery, which was associated with postoperative dysphagia and hoarseness in 1 patient. CONCLUSION: Endotracheal surface electrodes allow identification of vocal cord motor rootlets in the CPA. Worsening of CMAP parameters might indicate functional impairment. These aspects support the use of endotracheal surface electrodes in selected patients in whom the vagus nerve might be at risk during CPA surgery.

Onset latency of segmental dystonia after deep brain stimulation cessation: a randomized, double-blind crossover trial.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus internus is an effective treatment for cervical dystonia (CD). Interestingly, the onset of initial DBS effects is significantly prolonged compared with that in other diseases, such as Parkinson's disease. The return of symptoms after cessation of DBS could be delayed as well, but this has not been studied systematically. METHODS: In patients who were treated for CD using DBS and had a good treatment effect, we compared interruption of DBS with sham-OFF in a randomized, double-blind crossover trial. RESULTS: We observed that dystonic features appeared within a few minutes at almost full intensity in all patients after the cessation of DBS. CONCLUSIONS: The almost immediate onset of dystonic features in our sample seems to exclude mechanisms with long time constants from the pathophysiology of dystonia. Thus, it is likely that, in these patients, an aberrant pattern of neural activity representing an inappropriate set point value for the position of the head is responsible for dystonia.

Connectivity patterns of pallidal DBS electrodes in focal dystonia: a diffusion tensor tractography study.

Deep brain stimulation (DBS) of the internal pallidal segment (GPi: globus pallidus internus) is gold standard treatment for medically intractable dystonia, but detailed knowledge of mechanisms of action is still not available. There is evidence that stimulation of ventral and dorsal GPi produces opposite motor effects. The aim of this study was to analyse connectivity profiles of ventral and dorsal GPi. Probabilistic tractography was initiated from DBS electrode contacts in 8 patients with focal dystonia and connectivity patterns compared. We found a considerable difference in anterior-posterior distribution of fibres along the mesial cortical sensorimotor areas between the ventral and dorsal GPi connectivity. This finding of distinct GPi connectivity profiles further confirms the clinical evidence that the ventral and dorsal GPi belong to different functional and anatomic motor subsystems. Their involvement could play an important role in promoting clinical DBS effects in dystonia.

Functional outcome and quality of life in Tourette's syndrome after deep brain stimulation of the posteroventrolateral globus pallidus internus: long-term follow-up.

OBJECTIVES: Deep brain stimulation (DBS) for Tourette's syndrome (TS) in various targets has been in the focus for some years. However, there are hardly any data on "psychosocial" outcome after DBS for TS. The aim of the present study therefore was to focus on the functional outcome and "psychosocial changes" in TS patients after DBS. METHODS: Six patients with treatment-refractory TS underwent GPi-DBS. The Yale Global Tic Severity Scale (YGTSS) was used to evaluate symptomatic outcome. Psychosocial changes were assessed applying the Global Assessment of Functioning Scale (GAF) and the Gilles-de-la-Tourette-Syndrome Quality-of-Life scale (GTS-QOL) with additionally documenting psychosocial changes. Follow-up ranged between 12 and 72 months. RESULTS: In all symptomatic responders (4 of 6) we found a significant functional improvement (mean GAF increasing from 53.75 (± 7.5) pre-operatively to 83.75 (± 7.5) at last follow-up) along with a positive correlation with the course of GTS-QOL (R(2) = 0.62). CONCLUSIONS: Treatment success should not only be assessed with the classic "tic-scales", but also with the GAF and GTS-QOL. Although improvement of tics seems to be positively correlated with improved functional outcome, symptomatic improvement may lead to unexpected major psychosocial changes - which both the patient and the clinicians in charge - should be prepared for.

A portable system for quantitative assessment of parkinsonian rigidity.

Rigidity is one of the primary symptoms of Parkinson's disease. Passive flexion and extension of the elbow is used to assess rigidity in this study. An examiner flexes and extends the subject's elbow joint through a rigidity assessment cuff attached around the wrist. Each assessment lasts for 10 seconds. Two force sensor boxes and an inertial measurement unit are used to measure the applied force and the state of the elbow movement. Elastic and viscous values will be obtained through a least squares estimation with all the data. 9 healthy subjects were tested with this system in two experimental conditions: 1) normal state (relaxed); 2) imitated rigidity state. Also the subjects were performed the assessment task with different frequencies and elbow movement ranges. The imitated rigidity action increases viscosity and elasticity. The effect sizes (Cohen's d) of the viscosity and elasticity between normal state and imitated state are 1.61 and 1.36 respectively, which means the difference is significant. Thus, this system can detect the on-off fluctuations of parkinsonian rigidity. Both wrist movement angle and frequency have small effect on the viscosity, but have elevated effect on the elasticity.

Early cranioplasty may improve outcome in neurological patients with decompressive craniectomy.

PRIMARY OBJECTIVE: Decompressive craniectomy is an effective therapy to relieve intractable intracranial hypertension following acute brain injury. However, little is known about the optimal timing for cranioplasties in the sub-acute phase. The objective of the present study was to analyse the effect of cranioplasty timing on neurological outcomes. RESEARCH DESIGN: Single-centre observational study. METHODS AND PROCEDURES: One hundred and forty-seven consecutive patients with decompressive craniectomy and cranioplasty during the course of inpatient neurorehabilitation were identified by means of a retrospective hospital database search. This database contains the following prospectively-entered weekly scores: Barthel-Index (BI), Functional Independence Measure (FIM) and Coma Remission Scale (CRS). Additional clinical data were taken retrospectively from patient charts. Regression analysis was used to identify factors that influenced the end-of-rehabilitation outcome. MAIN OUTCOMES AND RESULTS: Patients with shorter delays to cranioplasty (<86 days) had a better functional outcome than patients with longer delays of >85 days (60 ± 29.5 versus 25 ± 24.1 BI points; p < 0.01, respectively). Age, pre-operative BI and CRS scores were additional independent outcome factors. Complication rates were not different between early and late cranioplasty groups. CONCLUSIONS: Patients with decompressive craniectomy for management of intracranial hypertension may benefit from early cranioplasty.

Movement kinematic after deep brain stimulation associated microlesions.

BACKGROUNDS: Deep brain stimulation is widely used for the treatment of movement disorders such as Parkinson's disease and dystonia. After the implantation of electrodes an immediate improvement of clinical symptoms has been described. It is unclear, whether movement kinematics are also changed by this 'microlesion effect'. METHODS: To gain further insight into these mechanisms, we studied arm, hand and finger movements preoperatively and immediately after the implantation of deep brain stimulation electrodes in patients with Parkinson's disease and dystonia. RESULTS: After implantation and without stimulation there was a clear reduction of clinical symptoms in both groups, as has been described previously. However, movement velocity was affected differently. Parkinsonian patients showed increased movement velocity postoperatively, whereas dystonic patients were significantly slower after electrode implantation. CONCLUSIONS: Lesioning and stimulation of these structures have the same beneficial clinical effects. Furthermore we suggest that globus pallidus internum lesions act by inhibiting a system which mainly acts upon muscular tone and limb posture whereas subthalamic stimulation or lesion causes a more unspecific disinhibition of movements.

Evidence of a non-motor microlesion effect following deep brain surgery: a case report.

We report the case of a patient who developed acute transient psychosis after implantation, but not activation of pallidal deep brain electrodes for generalised dystonia. Psychotic symptoms coincided temporally with postoperative motor improvement induced by the microlesion effect after electode implantation. This finding suggests that the microlesion effect may not be confined to motor improvement, but also comprises non-motor symptoms. In our case, affection of adjacent dopaminergic fibres of passages has to be assumed.

Long-term results of electroconvulsive therapy in severe Gilles de la Tourette syndrome.

To avoid chronic distress and increasing social isolation, patients with severe, medication-resistant Gilles de la Tourette syndrome (GTS) require treatment alternatives. Electroconvulsive therapy (ECT) is such an alternative treatment, which, however, is rarely mentioned in the literature: a Pubmed search revealed only 7 reports on GTS and ECT, and there were no long-term data on continuously applied maintenance ECT in GTS. This report is the first to document a 5-year-long, full remission from severe GTS after long-term ECT.

Early globus pallidus internus stimulation in pediatric patients with generalized primary dystonia: long-term efficacy and safety.

Primary generalized dystonia presents mainly at a young age and commonly is severely disabling. The authors report the long-term follow-up (mean, 73 months; range, 50-101 months) of 5 pediatric patients (mean age at surgery 13 years; range, 8-16 years) undergoing globus pallidus internus deep brain stimulation. Mean improvement in the Burke-Fahn-Marsden movement score was 67.4% (range, 47.0%-87.5%), 75.4% (range, 61.5%-91.7%), and 83.5% (range, 72.0%-93.3%) at 3 months, 12 months, and long-term follow-up (>36 months), respectively. Hardware problems (electrode dislocation/breakage of extension cable, and imminent perforation of extension cable) were observed in 2 patients (operative revision without sequelae). Except for mild dysarthria in 2 patients, no other therapy-related morbidity was observed. The authors found globus pallidus internus stimulation to offer a very effective and safe therapy in pediatric patients with primary dystonia. Early neurosurgical intervention seems to be crucial to prevent irreversible impairment of motor function.

Bilateral pallidal stimulation in children and adolescents with primary generalized dystonia--report of six patients and literature-based analysis of predictive outcomes variables.

INTRODUCTION: Primary generalized dystonia is a rare movement disorder. Medical treatment rarely relieves symptoms. The aim of this study was to investigate the efficacy and safety of bilateral pallidal stimulation in 6 children and adolescents with primary generalized dystonia. In addition, we strived to find predictors for treatment outcome by review and analysis of previously published studies. METHODS: Six patients with primary generalized dystonia underwent chronic bilateral stimulation of the globus pallidus internus. A PubMed and MEDLINE search was performed in order to identify children and adolescents who underwent deep brain stimulation for primary generalized dystonia. The primary efficacy endpoint was the relative change of the Burke-Fahn-Marsden-Dystonia-Rating-Scale (movement score) after surgery. RESULTS: Forty-four patients were found to meet the inclusion criteria. The mean age at onset of the disease was 7.8+/-2.8years and the mean age at surgery was 14.2+/-3.5years. The mean Burke-Fahn-Marsden-Dystonia-Rating-Scale (movement score) was 56.9+/-22.7 before surgery and 23.7+/-23.2 at a mean follow up of 13.0+/-4.8months (p<0.001). The improvement in the DYT1-positive group was significantly higher compared to the DYT1-negative group (77%+/-24% and 44%+/-30%, respectively, p<0.001). A positive correlation between the movement score before and after surgery was found in both the DYT1-positive and DYT1-negative cohort (rs=0.624, p<0.001 and rs=0.734, p<0.001, respectively). CONCLUSION: DBS is an effective treatment in children and adolescents with primary generalized dystonia. Predictive factors for a better treatment outcome are DYT1-positive status and minor motor impairment before surgery.