[Intercultural adaptation of the PUKSoPC in German language : A scale for perceived control in patients with Parkinson's disease]. / Interkulturelle Adaptation der PUKSoPC in deutscher Sprache : Eine Skala zur gefühlten Kontrolle von Parkinson-Patientinnen und -Patienten.

BACKGROUND: The level of perceived control in people with Parkinson's disease plays a significant role in affecting their quality of life. Simpson et al. developed a scale of perceived control specific to Parkinson's disease called the Parkinson's UK Scale of Perceived Control (PUKSoPC). In this work, we present a cross-culturally adapted German translation of the original English version. METHODS: After receiving approval by the original authors, an internationally established procedure was used for cross-cultural adaptation. Firstly, the original English version was translated into German independently by two bilingual neuroscientists, who then agreed on a consensus version. This was tested on 10 people with Parkinson's disease and independently back translated into English by two different neuroscientists. After forming a consensus version, this English version was compared with the original version by all four translators. Differences between the versions resulted in modifications to the German translation so that the back translation matched the original as closely as possible. The final version was approved by two of the original authors and clinically tested on 50 people with Parkinson's disease. RESULTS: During the translation process, the four translators agreed on a culturally adapted German version of the PUKSoPC. Testing of the final version on 50 people with Parkinson's disease did not reveal any linguistic or content-related problems. CONCLUSION: The linguistically validated German version of the PUKSoPC presented in this paper is now freely available for measuring the levels of perceived control in people with Parkinson's disease to advance both research and clinical practice.

Beneficial effects of bilateral subthalamic stimulation on alexithymia in Parkinson's disease.

BACKGROUND AND PURPOSE: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL) and motor and non-motor symptoms in advanced Parkinson's disease (PD). However, its effect on alexithymia and its relationship to other neuropsychiatric symptoms and QoL in PD is unclear. METHODS: In this prospective, observational study of 39 patients with PD undergoing STN-DBS, we examined the Parkinson's Disease Questionnaire-8 (PDQ-8), 20-item Toronto Alexithymia Scale (TAS-20), Hospital Anxiety and Depression Scale (HADS), Self-Report Manic Inventory (SRMI), Apathy Evaluation Scale (AES), Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living, UPDRS motor examination and UPDRS complications (UPDRS-II/-III/-IV) and levodopa-equivalent daily dose (LEDD) pre-operatively and at 5-month follow-up. Outcome changes were tested with Wilcoxon signed-rank or paired t-test when parametric tests were applicable and corrected for multiple comparisons. The relationship between outcome changes was explored with bivariate correlations. Additionally, partial correlations between PDQ-8 and TAS-20 were computed controlling for HADS, SRMI and AES change scores. Predictor analyses for PDQ-8 improvement were calculated for all baseline parameters. RESULTS: The baseline prevalence of alexithymia was 17.9%. We observed significant beneficial effects of STN-DBS on PDQ-8, TAS-20, HADS, UPDRS-II, -III and -IV scores and significant LEDD reduction. The correlation between TAS-20 and PDQ-8 improvements remained significant after controlling for all other aforementioned outcomes. Predictor analyses for PDQ-8 improvement were significant for PDQ-8 and TAS-20. CONCLUSIONS: This is the first report of beneficial effects of STN-DBS on alexithymia. Alexithymia was significantly associated with QoL outcome independent of anxiety, depression, mania and apathy. Our study highlights the importance of alexithymia for holistic assessments of DBS outcomes.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Cognitive training in Parkinson's disease reduces cognitive decline in the long term.

BACKGROUND AND PURPOSE: Patients with Parkinson's disease (PD) are at high risk for cognitive dysfunction. Non-pharmacological interventions have attracted increasing interest for enhancing PD patients' cognitive functions. METHODS: One-year follow-up data (T2 ) of a randomized controlled trial evaluating two 6-week cognitive trainings - a structured (NEUROvitalis, NV) and an unstructured (mentally fit, MF) program - compared with a waiting list control group (CG) in non-demented PD patients (Hoehn and Yahr I-III) are presented. Forty-seven PD patients were examined at T2 . Effects on overall cognitive functions (Mini-Mental State Examination and DemTect) were compared between all groups with repeated measurement analyses of variance. A combined score of the percentage change value from baseline (T0 ) to T2 was calculated to identify patients who retained or improved their cognitive state (responders). The risk of developing mild cognitive impairment (MCI) was analyzed. RESULTS: Significant time × treatment effects on overall cognitive functions were found for both training groups, each compared separately to the CG (DemTect, P < 0.05). Nine patients (56.3%) of the NV group, seven (41.2%) of the MF group and three (21.4%) of the CG were responders. Comparing NV to CG the odds ratio was 4.7 [95% confidence interval (0.8; 33.3)], and comparing MF to CG it was 2.6 [95% confidence interval (0.4; 17.4)]. MCI risk for patients without prior MCI was 40.0% in CG, 18.2% in MF and 18.2% in NV. The odds ratio was 3 comparing NV to CG, MF to CG. DISCUSSION: This study gives evidence that cognitive training may be effective to prevent cognitive decline and onset of MCI in PD patients.

[Parkinson's disease: current standards in diagnostics and therapy]. / Morbus Parkinson: Aktuelle Standards in Diagnostik und Therapie.

Idiopathic Parkinson's disease is still a clinical diagnosis. However, modern imaging and nuclear techniques allow very early diagnosis and lead to higher security in the differential diagnosis between idiopathic Parkinson's disease and atypical Parkinson syndromes. At early stages of the disease, modification of disease progression and symptom control are key factors of the therapy. Continuous dopaminergic stimulation is even more important at later stages with first fluctuations. In stages where conservative medical options have been exhausted continuous pump therapies with Duodopa and apomorphine are attractive options. Deep brain stimulation in the subthalamic nucleus has turned out in the last years, especially in younger patients, to be a highly successful treatment option. Deep drain stimulation requires, however, a close preoperative work-up and individual consideration of potential effects and side effects.

[Long-term care of Parkinson patients with deep brain stimulation]. / Langzeitbehandlung von Parkinsonpatienten mit Tiefer Hirnstimulation.

For more than 15 years deep brain stimulation of the subthalamic nucleus and globus pallidus internus have become therapeutic options in advanced Parkinson's disease. The number of patients with long-term treatment is increasing steadily. This review focuses on issues of the long-term care of these Parkinson's patients, including differences of the available deep brain stimulation systems, recommendations for follow-up examinations, implications for medical diagnostics and therapies and an algorithm for symptom deterioration. Today, there is no profound evidence that deep brain stimulation prevents disease progression. However, symptomatic relief from motor symptoms is maintained during long-term follow-up and interruption of the therapy remains an exception.

[The dural arteriovenous fistula - an unimposing morphological correlate with imposing consequences]. / Die Durafistel - ein unscheinbares morphologisches Korrelat mit grossen Konsequenzen.

Dural arteriovenous fistulas (DAVFs) are abnormal arteriovenous shunts located within the dura mater representing approximately 10 - 15 % of all arteriovenous shunts in the central nervous system. The aetiology of spontaneous DAVFs remains to be elucidated. The symptoms associated with DAVFs can be highly variable and dependent upon the direction of the blood flow, the amount of arteriovenous shunting and the specific location of the fistula. Considering the diversity of clinical presentation in the setting of unremarkable imaging results, diagnosing a DAVF can be difficult. To avoid permanent neurological deficits due to DAVFs, it is important to consider the possibility of a DAVF whenever one encounters unclear neurological symptoms and to initiate appropriate diagnostic procedures including intraarterial DSA and MRI/MRA. The current DAVF classification accounts for the disparity of clinical symptoms, therapeutic/interventional implications as well as vital complications depending on each particular fistula subtype. While type I DAVFs drain anterogradely into a cerebral sinus and mainly cause functional deficits, the risk for severe intracerebral bleeding increases when DAVFs drain retrogradely (type II), or into cortical (types III and IV), perimedullar or radiculo-medullar veins (type V), respectively. In particular in the case of type IIb to V DAVFs, the appropriate treatment option is a complete fistula occlusion by transvenous embolization, transarterial glue or particulate embolization or surgery. In the following we systematically explain the differential anatomy underlying DAVFs and discuss possible symptoms and necessary diagnostic and therapeutic means. In that, we are seeking to increase attention for this rare, but clinically relevant neurological disease.

Directional DBS leads show large deviations from their intended implantation orientation.

OBJECTIVE: Lead orientation is a new degree of freedom with directional deep brain stimulation (DBS) leads. We investigated how prevalent deviations from the intended implantation direction are in a large patient cohort. METHODS: The Directional Orientation Detection (DiODe) algorithm to determine lead orientation from postoperative CT scans was implemented into the open-source Lead-DBS toolbox. Lead orientation was analyzed in 100 consecutive patients (198 leads). Different anatomical targets and intraoperative setups were compared. RESULTS: Deviations of up to 90° from the intended implantation direction were observed. Deviations of more than 30° were seen in 42% of the leads and deviations of more than 60° in about 11% of the leads. Deviations were independent from the neuroanatomical target and the stereotactic frame but increased depending on which microdrive was used. DISCUSSION: Our results indicate that large deviations from the intended implantation direction are a common phenomenon in directional leads. Postoperative determination of lead orientation is thus mandatory for investigating directional DBS.

Modulation of local field potential power of the subthalamic nucleus during isometric force generation in patients with Parkinson's disease.

Investigations of local field potentials of the subthalamic nucleus of patients with Parkinson's disease have provided evidence for pathologically exaggerated oscillatory beta-band activity (13-30 Hz) which is amenable to physiological modulation by, e.g., voluntary movement. Previous functional magnetic resonance imaging studies in healthy controls have provided evidence for an increase of subthalamic nucleus blood-oxygenation-level-dependant signal in incremental force generation tasks. However, the modulation of neuronal activity by force generation and its relationship to peripheral feedback remain to be elucidated. We hypothesised that beta-band activity in the subthalamic nucleus is modulated by incremental force generation. Subthalamic nucleus local field potentials were recorded intraoperatively in 13 patients with Parkinson's disease (37 recording sites) during rest and five incremental isometric force generation conditions of the arm with applied loads of 0-400 g (in 100-g increments). Repeated measures analysis of variance (ANOVA) revealed a modulation of local field potential (LFP) power in the upper beta-band (in 24-30 Hz; F(3.042)=4.693, p=0.036) and the gamma-band (in 70-76 Hz; F(4)=4.116, p=0.036). Granger-causality was computed with the squared partial directed coherence and showed no significant modulation during incremental isometric force generation. Our findings indicate that the upper beta- and gamma-band power of subthalamic nucleus local field potentials are modulated by the physiological task of force generation in patients with Parkinson's disease. This modulation seems to be not an effect of a modulation of peripheral feedback.

Discontinuities in slow finger movements in patients with Parkinson's disease.

Slow finger movements in healthy humans are characterized by discontinuous rhythmic changes in a low frequency band about 8 Hz. These pulsatile changes in velocity are thought to present the central output of an oscillatory cerebello-thalamo-cortical network in the same frequency. Hypothesizing that patients with Parkinson's disease (PD) in the dopaminergic OFF- and ON-condition show changes in the characteristics of discontinuities compared to healthy humans, we used a 3D-ultrasound device to measure slow finger movements of 16 patients with PD and 12 age-matched controls. We provide evidence that slow finger movements of patients with PD are characterized by discontinuities in acceleration, which are significantly slower in the OFF- but not in the ON-condition compared to healthy controls. Correlation analysis between clinical motor improvement after dopaminergic medication and changes of peak frequencies and peak power of discontinuities was not significant. We conclude that the oscillatory brain network of slow finger movements is affected in PD, presenting in a lower frequency in the OFF-condition. We suggest that one factor of the modulation of this network is a dopaminergic stimulation.

The tremor network targeted by successful VIM deep brain stimulation in humans.

OBJECTIVE: Deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM) is a treatment option in medically intractable tremor, such as essential tremor or tremor-dominant Parkinson disease (PD). Although functional studies demonstrated modulation of remote regions, the structural network supporting this is as yet unknown. In this observational study, we analyzed the network mediating clinical tremor modulation. METHODS: We studied 12 patients undergoing VIM stimulation for debilitating tremor. We initiated noninvasive diffusion tractography from tremor-suppressive VIM electrode contacts. Moreover, we tested for the contribution of primary motor projections in this structural correlate of a functional tremor network, comparing the connectivity of effective DBS contacts with those of adjacent, but clinically ineffective, stimulation sites. RESULTS: VIM stimulation resulted in decrease of tremor and improvement in quality of life. Tractography initiated from the effective stimulation site reconstructed a highly reproducible network of structural connectivity comprising motor cortical, subcortical, and cerebellar sites and the brainstem, forming the anatomic basis for remote effects of VIM stimulation. This network is congruent with functional imaging studies in humans and with thalamic projections found in the animal literature. Connectivity to the primary motor cortex seemed to play a key role in successful stimulation. CONCLUSIONS: Patients undergoing DBS provide a unique opportunity to assess an electrophysiologically defined seed region in human thalamus, a technique that is usually restricted to animal research. In the future, preoperative tractography could aid with stereotactic planning of individual subcortical target points for stimulation in tremor and in other disease entities.