Modulation of specific components of sleep disturbances by simultaneous subthalamic and nigral stimulation in Parkinson's disease.

OBJECTIVE: To compare the effect of simultaneous deep brain stimulation of the subthalamic nucleus and substantia nigra pars reticulata (STN+SNr-DBS) to conventional subthalamic stimulation (STN-DBS) on sleep quality in Parkinson's disease (PD) patients. METHODS: The study was a single-center, randomized, double-blind, cross-over clinical trial to compare the effect of STN-DBS vs. combined STN+SNr-DBS on subjective measures of sleep quality. Fifteen PD patients (2 female, age 62.5 ± 6.7 years) suffering from moderate idiopathic PD (disease duration: 12.0 ± 5.0 years, Hoehn & Yahr stage: 2.2 ± 0.4 in the MED-ON & STN-DBS-ON condition, Hoehn & Yahr stage: 2.6 ± 0.8 in the MED-OFF condition preoperatively) participated in the study. Sleep quality was evaluated in both stimulation conditions using the PDSS-2 score as a self-rating questionnaire covering several aspects of sleep disturbances. RESULTS: PD patients showed mild-moderate sleep disturbances (STN-DBS: PDSS-2 score 17.0 ± 11.0; STN+SNr-DBS: 14.7 ± 9.5) with slight but not significant differences between both stimulation conditions. Considering the different subitems of the PDSS-2, combined STN+SNr stimulation was superior to conventional STN stimulation in improving restless legs symptoms (RLS) at night (STN-DBS = 1.9 ± 2.7 STN+SNr-DBS = 1.0 ± 1.8; W = -2.06, p = 0.039) and immobility at night (STN-DBS = 1.5 ± 1.4 STN+SNr-DBS = 0.6 ± 0.8; W = -2.041, p = 0.041). CONCLUSION: This study demonstrates the safety of STN+SNr-DBS compared to conventional STN-DBS on sleep in general with potential beneficial input on RLS symptoms and akinesia at night.

Prospective evaluation of Globus pallidus internus deep brain stimulation in Huntington's disease.

INTRODUCTION: Pharmacological treatment of chorea in Huntington's disease (HD) is often limited by poor efficacy or side effects. Pallidal deep brain stimulation (DBS) has been considered in these patients but experience is so far limited. METHODS: We prospectively evaluated the effects of bilateral DBS of the Globus pallidus internus (GPi) over one year in six severely affected HD patients with treatment refractory chorea in an advanced stage of the disease. Primary endpoint of the study was improvement in chorea. Additionally, we evaluated the effects of GPi DBS on the motor part of the Unified Huntington's Disease Rating Scale (UHDRS), bradykinesia, dystonia, functional impairment, psychiatric and cognitive symptoms. Side effects were systematically assessed. RESULTS: The chorea subscore was significantly reduced postoperatively (-47% six months, -40% twelve months postoperatively). The UHDRS total motor score was significantly reduced at six months postoperatively (- 17%) but the effect was not sustained twelve months after the operation (- 5%). Pallidal DBS did not improve other motor symptoms or functional impairment. There was no effect on psychiatric symptoms or cognition. A number of side effects were noted, especially spasticity in three of the patients. CONCLUSIONS: Pallidal DBS is a treatment option for HD patients with severe pharmacologically refractory chorea. Further studies are needed to define optimal candidates for this procedure.

Impact of Combined Subthalamic Nucleus and Substantia Nigra Stimulation on Neuropsychiatric Symptoms in Parkinson's Disease Patients.

The goal of the study was to compare the tolerability and the effects of conventional subthalamic nucleus (STN) and combined subthalamic nucleus and substantia nigra (STN+SNr) high-frequency stimulation in regard to neuropsychiatric symptoms in Parkinson's disease patients. In this single center, randomized, double-blind, cross-over clinical trial, twelve patients with advanced Parkinson's disease (1 female; age: 61.3 ± 7.3 years; disease duration: 12.3 ± 5.4 years; Hoehn and Yahr stage: 2.2 ± 0.39) were included. Apathy, fatigue, depression, and impulse control disorder were assessed using a comprehensive set of standardized rating scales and questionnaires such as the Lille Apathy Rating Scale (LARS), Modified Fatigue Impact Scale (MFIS), Becks Depression Inventory (BDI-I), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS), and Parkinson's Disease Questionnaire (PDQ-39). Three patients that were initially assigned to the STN+SNr stimulation mode withdrew from the study within the first week due to discomfort. Statistical comparison of data retrieved from patients who completed the study revealed no significant differences between both stimulation conditions in terms of mean scores of scales measuring apathy, fatigue, depression, impulse control disorder, and quality of life. Individual cases showed an improvement of apathy under combined STN+SNr stimulation. In general, combined STN+SNr stimulation seems to be safe in terms of neuropsychiatric side effects, although careful patient selection and monitoring in the short-term period after changing stimulation settings are recommended.

Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus.

Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory-motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing.

[The Neuroleptic Malignant Syndrome]. / Das maligne neuroleptische Syndrom (MNS)--Eine systematische Übersicht.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening medication-induced syndrome. Core symptoms are hyperthermia, diaphoresis, rigidity, impaired consciousness, and creatinine kinase elevation. Additionally, patients show vegetative dysregulation including blood pressure fluctuations. The purpose of this paper is to summarize current findings, to facilitate diagnostics and to distinguish NMS from other syndromes. METHODS: We performed a systematic review of the literature. We included scientific publications, books and guidelines. RESULTS: In this review we summarize the current diagnostic criteria, differential diagnosis, pathogenesis and therapeutic options. CONCLUSION: Clinical symptoms of NMS are heterogeneous and it is difficult to diagnose early states. Early interventions are important to ensure fast and complete recovery. Since NMS is a rare condition, publications on NMS-therapy are based on single-case reports, meta-analysis or expert opinions. Core symptoms should be considered: Exposure to dopamine-antagonists, hyperthermia, diaphoresis, rigidity, mental status alteration, creatinine kinase elevation, and vegetative dysregulation.

Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism.

OBJECTIVE: Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. METHODS: Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30 min and during 25/30 min of high-frequency GPi stimulation. RESULTS: While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231 ± 102% in comparison to baseline values), a decrease was observed in the GPe (22 ± 10%). Extracellular glutamate levels largely remained unchanged. CONCLUSIONS: Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs.

Subthalamic deep brain stimulation improves auditory sensory gating deficit in Parkinson's disease.

OBJECTIVE: While motor effects of dopaminergic medication and subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients are well explored, their effects on sensory processing are less well understood. Here, we studied the impact of levodopa and STN-DBS on auditory processing. METHODS: Rhythmic auditory stimulation (RAS) was presented at frequencies between 1 and 6Hz in a passive listening paradigm. High-density EEG-recordings were obtained before (levodopa ON/OFF) and 5months following STN-surgery (ON/OFF STN-DBS). We compared auditory evoked potentials (AEPs) elicited by RAS in 12 PD patients to those in age-matched controls. Tempo-dependent amplitude suppression of the auditory P1/N1-complex was used as an indicator of auditory gating. RESULTS: Parkinsonian patients showed significantly larger AEP-amplitudes (P1, N1) and longer AEP-latencies (N1) compared to controls. Neither interruption of dopaminergic medication nor of STN-DBS had an immediate effect on these AEPs. However, chronic STN-DBS had a significant effect on abnormal auditory gating characteristics of parkinsonian patients and restored a physiological P1/N1-amplitude attenuation profile in response to RAS with increasing stimulus rates. CONCLUSIONS: This differential treatment effect suggests a divergent mode of action of levodopa and STN-DBS on auditory processing. SIGNIFICANCE: STN-DBS may improve early attentive filtering processes of redundant auditory stimuli, possibly at the level of the frontal cortex.