A totally data-driven whole-brain multimodal pipeline for the discrimination of Parkinson's disease, multiple system atrophy and healthy control.

Parkinson's Disease (PD) and Multiple System Atrophy (MSA) are two parkinsonian syndromes that share many symptoms, albeit having very different prognosis. Although previous studies have proposed multimodal MRI protocols combined with multivariate analysis to discriminate between these two populations and healthy controls, studies combining all MRI indexes relevant for these disorders (i.e. grey matter volume, fractional anisotropy, mean diffusivity, iron deposition, brain activity at rest and brain connectivity) with a completely data-driven voxelwise analysis for discrimination are still lacking. In this study, we used such a complete MRI protocol and adapted a fully-data driven analysis pipeline to discriminate between these populations and a healthy controls (HC) group. The pipeline combined several feature selection and reduction steps to obtain interpretable models with a low number of discriminant features that can shed light onto the brain pathology of PD and MSA. Using this pipeline, we could discriminate between PD and HC (best accuracy = 0.78), MSA and HC (best accuracy = 0.94) and PD and MSA (best accuracy = 0.88). Moreover, we showed that indexes derived from resting-state fMRI alone could discriminate between PD and HC, while mean diffusivity in the cerebellum and the putamen alone could discriminate between MSA and HC. On the other hand, a more diverse set of indexes derived by multiple modalities was needed to discriminate between the two disorders. We showed that our pipeline was able to discriminate between distinct pathological populations while delivering sparse model that could be used to better understand the neural underpinning of the pathologies.

Effect of ropinirole on sleep onset: a randomized, placebo-controlled study in healthy volunteers.

Somnolence and "sleep attacks" have been reported as an adverse effect of several antiparkinsonian drugs. The authors document, in a placebo-controlled, randomized, double-blind, crossover study performed in 20 healthy volunteers, using the Multiple System Latency Test (MSLT) as primary outcome, that ropinirole reduces time to sleep onset in humans. Ropinirole therapy was not associated with daytime episodes of rapid eyes movement (REM) sleep.

Sleep disruption, daytime somnolence and 'sleep attacks' in Parkinson's disease: a clinical survey in PD patients and age-matched healthy volunteers.

Recent case reports of 'sleep attacks' (SA) in patients with Parkinson's disease (PD) generated concerns about drug-induced daytime somnolence in this population. However, there are nearly no comparative data on sleep and vigilance problems between PD patients and normal controls. We performed a cross-sectional survey in PD patients and age-matched controls using a structured questionnaire on PD history, treatments, co-morbidity, activities of daily living, habits, exercise, sleep pattern, driving, pre-existing nocturnal problems, daytime somnolence, episodes of SA and the circumstances in which such episodes occurred. Daytime somnolence was also measured with the Epworth Sleepiness Scale (ESS) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). 176 PD patients and 174 controls were included. The same proportion of PD patients (27%) and controls (32%) reported episodes of SA, but these were more frequent in PD patients and occurred more frequently during situations requiring attention (10.8% vs. 1.7%, p<10(-3)). More PD patients had abnormal daytime somnolence (ESS) and poor sleeping quality (PSQI). The most consistent factor associated with SA was the duration of levodopa therapy and the predictive value of an abnormal ESS score was rather poor (40.7%). Abnormal daytime somnolence and poor sleep quality at night are more frequent in PD patients than in normals. However, SA are reported in both groups, although less frequently in the normals during activities that requires attention.

Sleep attacks and Parkinson's disease treatment.

Three patients with Parkinson's disease had so-called sleep attacks at the wheel while taking bromocryptine, lisuride pergolide, or piribedil. We believe that all dopamine agonists can induce sleep attacks.

Transmission of group II heteronymous pathways is enhanced in rigid lower limb of de novo patients with Parkinson's disease.

A potent heteronymous excitation of quadriceps motoneurones via common peroneal group II afferents has recently been demonstrated in normal subjects. The aim of this study was to investigate whether this group II excitation contributes to rigidity in Parkinson's disease. The early and late facilitations of the quadriceps H reflex elicited by a conditioning volley to the common peroneal nerve (CPN) at twice motor threshold, attributed to non-monosynaptic group I and group II excitations, respectively, were investigated. The comparison was drawn between results obtained in 20 "de novo" patients with Parkinson's disease (hemiparkinsonian, 17; bilateral, three) and 20 age-matched normal subjects. There was no statistically significant effect of "group" (patients/controls), "duration", "global severity" [Unified Parkinson's Disease Rating Scale (UPDRS)] or "side" (unilaterally versus bilaterally affected) factors on either group I or group II facilitations. To further the analysis, the factors of status (affected or non-affected limb), akinesia (lower limb akinesia score) and rigidity (lower limb rigidity score) were entered in a general linear model to explain the variations of the quadriceps H reflex facilitation. Rigidity was the only factor useful in predicting the value of the group II facilitation of the quadriceps H reflex (P < 0.007). Group I and group II facilitation was then compared between the rigid, non-rigid and control lower limbs [multivariate analysis of variance (MANOVA)]. Results are represented as mean +/- SEM (standard error of the mean). Group II facilitation was enhanced in the rigid lower limb of unilaterally affected patients (153.2 +/- 7% of control H reflex) compared with non-rigid lower limbs (124 +/- 4% of control H reflex; P < 0.007) or control lower limbs (126.1 +/- 4.1%; P < 0.01). There was no difference between the non-rigid lower limbs of the unilaterally affected patients and the control lower limbs, but a difference was observed between the rigid lower limbs of unilaterally less affected and bilaterally more affected patients (153.2 +/- 7% and 123.8 +/- 7.5% of control H reflex, respectively; P < 0.04). These results suggest a facilitation of the transmission in the interneuronal pathway activated by group II afferents in rigid lower limb of de novo hemiparkinsonian patients, probably resulting from a change in their descending monoaminergic inhibitory control.

Clozapine improves dyskinesias in Parkinson disease: a double-blind, placebo-controlled study.

OBJECTIVE: To investigate the efficacy and safety of clozapine in the treatment of levodopa-induced dyskinesias (LID) in patients with severe Parkinson disease (PD). METHODS: Fifty patients were randomized to treatment in this 10-week, double-blind, parallel-group, placebo-controlled, multicenter trial. The principal measure of outcome was the diurnal change in the "on" time with LID assessed using a self-evaluation of the motor performance fluctuations performed every 2 weeks. An acute levodopa challenge was also performed at the beginning and end of the study. RESULTS: A reduction in the duration of "on" periods with LID was noted in favor of the clozapine group at the end of the study (placebo group day 0: 4.54 +/- 0.53 hours, end: 5.28 +/- 0.70 hours; clozapine group day 0: 5.68 +/- 0.66 hours, end: 3.98 +/- 0.57 hours; p = 0.003). The mean clozapine dosage was 39.4 +/- 4.5 (SEM) mg/day. The maximal LID score at rest during the levodopa challenge was significantly decreased under clozapine treatment, with a variation from day 0 to day 70 in the placebo group of +0.15 +/- 1.01 and in the clozapine group of -2.22 +/- 0.52 (p < 0.05). Five patients receiving clozapine and seven receiving placebo discontinued on account of adverse events. Among them, three patients in the clozapine group developed eosinophilia, which rapidly resolved after withdrawal of the drug. CONCLUSION: Clozapine is effective in the treatment of levodopa-induced dyskinesias in severe PD.