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Deep brain stimulation (DBS) of the internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (VIM) are established treatment options in primary dystonia and tremor syndromes and have been reported anecdotally to be efficacious in myoclonus-dystonia (MD). We investigated short- and long-term effects on motor function, cognition, affective state, and quality of life (QoL) of GPi- and VIM-DBS in MD. Ten MD-patients (nine epsilon-sarcoglycan-mutation-positive) were evaluated pre- and post-surgically following continuous bilateral GPi- and VIM-DBS at four time points: presurgical, 6, 12, and as a last follow-up at a mean of 62.3 months postsurgically, and in OFF-, GPi-, VIM-, and GPi-VIM-DBS conditions by validated motor [unified myoclonus rating scale (UMRS), TSUI Score, Burke-Fahn-Marsden dystonia rating scale (BFMDRS)], cognitive, affective, and QoL-scores. MD-symptoms significantly improved at 6 months post-surgery (UMRS: 61.5%, TSUI Score: 36.5%, BFMDRS: 47.3%). Beneficial effects were sustained at long-term evaluation post-surgery (UMRS: 65.5%, TSUI Score: 35.1%, BFMDRS: 48.2%). QoL was significantly ameliorated; affective status and cognition remained unchanged postsurgically irrespective of the stimulation conditions. No serious long-lasting stimulation-related adverse events (AEs) were observed. Both GPi- and VIM-DBS offer equally effective and safe treatment options for MD. With respect to fewer adverse, stimulation-induced events of GPi-DBS in comparison with VIM-DBS, GPi-DBS seems to be preferable. Combined GPi-VIM-DBS can be useful in cases of incapaciting myoclonus, refractory to GPi-DBS alone.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD), but its mechanism of action is unclear. Exaggerated oscillatory synchronization in the beta (13-30 Hz) frequency band has been associated with bradykinesia in patients with PD. Accordingly, we tested the hypothesis that the clinical benefit exerted by STN HFS is accompanied by suppression of local beta activity. To this end, we explored the after effects of STN HFS on the oscillatory local field potential (LFP) activity recorded from the STN immediately after the cessation of HFS in 11 PD patients. Only patients that demonstrated a temporary persistence of clinical benefit after cessation of HFS were analyzed. STN HFS led to a significant reduction in STN LFP beta activity for 12 s after the end of stimulation and a decrease in motor cortical-STN coherence in the beta band over the same time period. The reduction in LFP beta activity correlated with the movement amplitude during a simple motor task, so that a smaller amount of beta activity was associated with better task performance. These features were absent when power in the 5-12 Hz frequency band was considered. Our findings suggest that HFS may act by modulating pathological patterns of synchronized oscillations, specifically by reduction of pathological beta activity in PD.

As part of the first randomized, sham-stimulation controlled trial on deep brain stimulation (DBS) in primary segmental or generalized dystonia, health-related quality of life (HRQoL) was assessed by SF-36. After the 3-month sham-controlled phase, significant HRQoL improvement occurred only in the active-stimulation group. The open-label extension phase resulted in a significant improvement in all SF-36 domains following 6 months of neurostimulation. These results demonstrate a favorable impact of DBS on HRQoL in primary dystonia., (2007 Movement Disorder Society)

Background: Neurostimulation of the internal globus pallidus has been shown to be effective in reducing symptoms of primary dystonia. We compared this surgical treatment with sham stimulation in a randomized, controlled clinical trial., Methods: Forty patients with primary segmental or generalized dystonia received an implanted device for deep-brain stimulation and were randomly assigned to receive either neurostimulation or sham stimulation for 3 months. The primary end point was the change from baseline to 3 months in the severity of symptoms, according to the movement subscore on the Burke-Fahn-Marsden Dystonia Rating Scale (range, 0 to 120, with higher scores indicating greater impairment). Two investigators who were unaware of treatment status assessed the severity of dystonia by reviewing videotaped sessions. Subsequently, all patients received open-label neurostimulation; blinded assessment was repeated after 6 months of active treatment., Results: Three months after randomization, the change from baseline in the mean (+/-SD) movement score was significantly greater in the neurostimulation group (-15.8+/-14.1 points) than in the sham-stimulation group (-1.4+/-3.8 points, P<0.001). During the open-label extension period, this improvement was sustained among patients originally assigned to the neurostimulation group, and patients in the sham-stimulation group had a similar benefit when they switched to active treatment. The combined analysis of the entire cohort after 6 months of neurostimulation revealed substantial improvement in all movement symptoms (except speech and swallowing), the level of disability, and quality of life, as compared with baseline scores. A total of 22 adverse events occurred in 19 patients, including 4 infections at the stimulator site and 1 lead dislodgment. The most frequent adverse event was dysarthria., Conclusions: Bilateral pallidal neurostimulation for 3 months was more effective than sham stimulation in patients with primary generalized or segmental dystonia. (ClinicalTrials.gov number, NCT00142259 [ClinicalTrials.gov].)., (Copyright 2006 Massachusetts Medical Society.)

Background: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management., Methods: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III)., Results: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08)., Conclusions: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].)., (Copyright 2006 Massachusetts Medical Society.)

Depth recordings in patients with Parkinson's disease (PD) have demonstrated oscillatory activity in the gamma frequency (60-100 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesised to contribute to movement preparation, it is unclear to what extent these LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded LFPs and neuronal activity from microelectrodes inserted into the STN in PD patients during functional neurosurgery. Eight sides in seven patients out of 15 sides in 12 patients were identified that had peaks in the gamma band in spectra of LFPs. As microelectrodes descended towards STN, there was a pronounced increase in gamma frequency band LFP activity 1 mm above the line joining the anterior and posterior commissures and 2 mm above the microelectrode defined dorsal border of the STN. Gamma activity dropped again 3 mm below the microelectrode defined dorsal border of the STN. Spike-triggered averages of LFP activity suggested that the discharges of neurons in this region were locked to gamma oscillations in the LFP. Gamma band oscillations in the LFP are therefore likely to represent synchronous activity in populations of neurons in the upper STN and bordering zona incerta of patients with PD.

Excessive synchronisation of basal ganglia activity at frequencies < 30 Hz is a hallmark of the parkinsonian state, and may contribute to bradykinesia. Accordingly, we electrically stimulated chronically implanted subthalamic macroelectrodes in 10 Parkinson's disease patients, after overnight withdrawal of anti-parkinsonian medication. We compared the effects of stimulation at 0, 5, 10, 15, 20, 25, 30, and ca. 130 Hz by measuring kinesia time (KT) in a tapping task. Although the effects of direct stimulation were small, frequency-response curves demonstrated local peaks at 5-10 Hz and at 20-25 Hz, superimposed upon an overall tendency for KT to reduce with increasing stimulation frequency. This is consistent with the hypothesis that spontaneous activities in these bands might promote bradykinesia.

During the last few years, deep brain stimulation (DBS) of the subthalamic nucleus (STN) has emerged as a promising therapy, alleviating major motor symptoms of Parkinson's disease (PD). However, in times of growing budgetary limitations, medical decisions are no longer merely based on clinical efficacy, but also on cost-effectiveness. Here we assess treatment costs (i. e. costs for conservative pharmacological treatment and all in-patient admissions) of 46 PD patients for one year before and two years after STN-DBS. The present data show that total treatment costs were increased by 32% for the first year and decreased by 54% for the second year of STN-DBS in comparison with preoperative values while the Unified Parkinson's Disease Rating Scale (UPDRS III) was significantly improved. The increase for the first year after surgery was mainly due to the implantation of the STN electrodes and the stimulation device. Taken together, STNDBS pays off from the second year of stimulation while motor symptoms are significantly improved. The present study provides first data of an important number of patients on clinical effectiveness and expenses in relation to STNDBS.