Grasping the big picture: impact analysis of screening tools for timely referral for device-aided therapies.

Several screening tools are available to assist general neurologists in the timely identification of patients with advanced Parkinson's disease (PD) who may be eligible for referral for a device-aided therapy (DAT). However, it should be noted that not all of these clinical decision rules have been developed and validated in a thorough and consistent manner. Furthermore, only a limited number of head-to-head comparisons have been performed. Available studies suggest that D-DATS has a higher positive predictive value and higher specificity than the 5-2-1 criteria, while the sensitivity of both screening tools is similar. However, unanswered questions remain regarding the validity of the decision rules, such as whether the diagnostic performance measures from validation studies are generalizable to other populations. Ultimately, the question is whether a screening tool will effectively and efficiently improve the quality of life of patients with PD. To address this key question, an impact analysis should be performed. The authors intend to set up a multinational cluster randomised controlled trial to compare the D-DATS and 5-2-1 criteria on the downstream consequences of implementing these screening tools, with a particular focus on the impact on disability and quality of life.

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.

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.

Phase-coherence classification: A new wavelet-based method to separate local field potentials into local (in)coherent and volume-conducted components.

BACKGROUND: Local field potentials (LFP) reflect the integrated electrophysiological activity of large neuron populations and may thus reflect the dynamics of spatially and functionally different networks. NEW METHOD: We introduce the wavelet-based phase-coherence classification (PCC), which separates LFP into volume-conducted, local incoherent and local coherent components. It allows to compute power spectral densities for each component associated with local or remote electrophysiological activity. RESULTS: We use synthetic time series to estimate optimal parameters for the application to LFP from within the subthalamic nucleus of eight Parkinson patients. With PCC we identify multiple local tremor clusters and quantify the relative power of local and volume-conducted components. We analyze the electrophysiological response to an apomorphine injection during rest and hold. Here we show medication-induced significant decrease of incoherent activity in the low beta band and increase of coherent activity in the high beta band. On medication significant movement-induced changes occur in the high beta band of the local coherent signal. It increases during isometric hold tasks and decreases during phasic wrist movement. COMPARISON WITH EXISTING METHODS: The power spectra of local PCC components is compared to bipolar recordings. In contrast to bipolar recordings PCC can distinguish local incoherent and coherent signals. We further compare our results with classification based on the imaginary part of coherency and the weighted phase lag index. CONCLUSIONS: The low and high beta band are more susceptible to medication- and movement-related changes reflected by incoherent and local coherent activity, respectively. PCC components may thus reflect functionally different networks.

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.