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Background: Movement disorders in Huntington's disease are often medically refractive. The aim of the trial was assessment of procedure safety of deep brain stimulation, equality of internal- and external-pallidal stimulation and efficacy followed-up for 6 months in a prospective pilot trial. Methods: In a controlled double-blind phase six patients (four chorea-dominant, two Westphal-variant) with predominant movement disorder were randomly assigned to either the sequence of 6-week internal- or 6-week external-pallidal stimulation, or vice versa, followed by further 3 months chronic pallidal stimulation at the target with best effectside- effect ratio. Primary endpoints were changes in the Unified Huntington's Disease Rating Scale motor-score, chorea subscore, and total motor-score 4 (blinded-video ratings), comparing internal- versus external-pallidal stimulation, and 6 months versus baseline. Secondary endpoints assessed scores on dystonia, hypokinesia, cognition, mood, functionality/disability, and quality-of-life. Results: Intention-to-treat analysis of all patients (n=3 in each treatment sequence): Both targets were equal in terms of efficacy. Chorea subscores decreased significantly over 6 months (-5.3 (60.2%), p=0.037). Effects on dystonia were not significant over the group due to it consisting of three responders (>50% improvement) and three non-responders. Westphal patients did not improve. Cognition was stable. Mood and some functionality/disability and quality-of-life scores improved significantly. Eight adverse events and two additional serious adverse events - mostly internal-pallidal stimulationrelated - resolved without sequalae. No procedure-related complications occurred. Conclusion: Pallidal deep brain stimulation was demonstrated to be a safe treatment option for the reduction of chorea in Huntington's disease. Their effects on chorea and dystonia and on quality-of-life should be examined in larger controlled trials. [ABSTRACT FROM AUTHOR]

Healthy aging is associated with decline in basic motor functioning and higher motor control. Here, we investigated age-related differences in the brain-wide functional connectivity (FC) pattern of the subthalamic nucleus (STN), which plays an important role in motor response control. As earlier studies revealed functional coupling between STN and basal ganglia, which both are known to influence the conservativeness of motor responses on a superordinate level, we tested the hypothesis that STN FC with the striatum becomes dysbalanced with age. To this end, we performed a seed-based resting-state analysis of fMRI data from 361 healthy adults (mean age: 41.8, age range: 18-85) using bilateral STN as the seed region of interest. Age was included as a covariate to identify regions showing age-related changes of FC with the STN seed. The analysis revealed positive FC of the STN with several previously described subcortical and cortical regions like the anterior cingulate and sensorimotor cortex, as well as not-yet reported regions including central and posterior insula. With increasing age, we observed reduced positive FC with caudate nucleus, thalamus, and insula as well as increased positive FC with sensorimotor cortex and putamen. Furthermore, an age-related reduction of negative FC was found with precuneus and posterior cingulate cortex.We suggest that this reduced de-coupling of brain areas involved in self-relevant but motor-unrelated cognitive processing (i.e. precuneus and posterior cingulate cortex) from the STN motor network may represent a potential mechanism behind the age-dependent decline in motor performance. At the same time, older adults appear to compensate for this decline by releasing superordinate motor control areas, in particular caudate nucleus and insula, from STN interference while increasing STN-mediated response control over lower level motor areas like sensorimotor cortex and putamen. [ABSTRACT FROM AUTHOR]

Akinesia, a cardinal symptom of Parkinson's disease, has been linked to abnormal activation in putamen and posterior medial frontal cortex (pMFC). However, little is known whether clinical severity of akinesia is linked to dysfunctional connectivity of these regions. Using a seed-based approach, we here investigated resting-state functional connectivity (RSFC) of putamen, pMFC and primary motor cortex (M1) in 60 patients with Parkinson's disease on regular medication and 72 healthy controls. We found that in patients putamen featured decreases of connectivity for a number of cortical and subcortical areas engaged in sensorimotor and cognitive processing. In contrast, the pMFC showed reduced connectivity with a more focal cortical network involved in higher-level motor-cognition. Finally, M1 featured a selective disruption of connectivity in a network specifically connected with M1. Correlating clinical impairment with connectivity changes revealed a relationship between akinesia and reduced RSFC between pMFC and left intraparietal lobule (IPL). Together, the present study demonstrated RSFC decreases in networks for motor initiation and execution in Parkinson's disease. Moreover, results suggest a relationship between pMFC-IPL decoupling and the manifestation of akinetic symptoms.

Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients' mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

Bimanual synchronization relies on the precisely coordinated interplay of both hands. It is assumed that during temporal bimanual coordination, timing signals controlling each hand might be integrated. Although a specific role of the cerebellum for this integration process has been suggested, its neural foundations are still poorly understood. Since dynamic interactions between spatially distributed neural activity are reflected in oscillatory neural coupling, the aim of the present study was to characterize the dynamic interplay between participating brain structures. More specifically, the study aimed at investigating whether any evidence for the integration of bilateral cerebellar hemispheres could be found. Seven right-handed subjects synchronized bimanual index finger-taps to a regular pacing signal. We recorded continuous neuromagnetic activity using a 122-channel whole-head neuromagnetometer and surface EMGs of the first dorsal interosseus (FDI) muscle of both hands. Coherence analysis revealed that an oscillatory network coupling at 8-12 Hz subserves task execution. The constituents are bilateral primary sensorimotor and premotor areas, posterior-parietal and primary auditory cortex, thalamus and cerebellum. Coupling occurred at different cortical and subcortical levels within and between both hemispheres. Coupling between primary sensorimotor and premotor areas was observed directly and indirectly via the thalamus. Coupling direction suggests that information was integrated within the left premotor cortex corroborating a specific role of the left premotor cortex for motor control in right-handers. Most importantly, our data indicate strong coupling between both cerebellar hemispheres substantiating the hypothesis that cerebellar signals might be integrated during task execution.

Unlabelled: We want to define the patterns of lymphatic drainage for primary melanoma to sentinel lymph nodes (SLNs) based on a large lymphoscintigraphic database. Preoperative lymphoscintigraphy was used to identify and classify SLN drainage basins and patterns of drainage., Methods: Lymphoscintigraphy using intradermally administered technetium-99m labeled sulfur colloid was performed on 400 consecutive patients with malignant melanoma to define lymphatic drainage channels and draining SLN basins before surgery. Primary tumor sites consisted of head and neck, upper extremity, trunk, and lower extremity. Different types of drainage patterns were classified and correlated with different anatomic sites., Results: SLN(s) were identified in over 98% of the patients, whereas lymphatic drainage channels were successfully identified in 90% of the patients. Drainage from the primary site to a single SLN through a single lymphatic channel (type IA) was seen in 186 of 400 patients (47%) as the most common type. In patients with a single SLN within a single basin (type I-V), the percentage of patients with primary lesions in the head and neck, upper extremity, trunk, and lower extremity regions were 61%, 79%, 55%, and 78%, respectively. In cases of multiple lymphatic channels (type VI-VII), the percentages of patients with primary lesions in the head and neck, upper extremity, trunk, and lower extremity regions were 24%, 8%, 36%, and 19%, respectively., Conclusion: Various drainage patterns were noted from primary melanomas in different anatomic sites. Preoperative lymphoscintigraphy is important in establishing the SLN basins for harvesting the SLN(s).