Classification of GBA1 variants and their impact on Parkinson's disease: an in silico score analysis.

Bi-allelic pathogenic GBA1 variants cause Gaucher disease (GD), whereas certain heterozygous missense variants increase the risk of Parkinson's disease (PD), although the underlying mechanisms are unclear. Here, we classified GBA1 missense variants using predictive and structural scores, and analysed their associations with enzyme activity, Saposin C (SapC) interaction and PD progression in 639 patients with heterozygous GBA1 variants from five cohorts. Principal component analysis (PCA) identified two components: PC1, associated with reduced β-glucocerebosidase activity, the GD clinical severity classification, younger age at PD diagnosis, and faster cognitive and motor decline; and PC2, associated with surface-exposed, flexible regions involved in SapC interactions, younger age at PD diagnosis, and slightly with motor decline.

Exploring the link between personality dimensions and non-motor fluctuations in Parkinson's disease.

BackgroundParkinson's disease (PD) patients on dopaminergic drugs may experience non-motor fluctuations (NMFs) which are often heterogeneous and respond variably to treatments.ObjectiveWe evaluated if personality was associated to NMFs and could modulate the NMFs responsiveness to dopaminergic medication and deep brain stimulation of the sub-thalamic nucleus (STN-DBS).MethodsFrom the PREDISTIM cohort, personality dimensions of 235 PD patients were assessed by the Temperament and Character Inventory (TCI) before STN-DBS (V0).

Motor and Non-motor Complications Following Different Early Therapies in Parkinson's Disease: Longitudinal Analysis of Real-Life Clinical and Therapeutic Data from the French NS-PARK Cohort.

Background: Levodopa, dopamine agonists (DA) and monoamine oxidase inhibitors (MAOI) are all approved first-line therapies for Parkinson's disease (PD), as monotherapy or in combination. Data on their use in the early management of patients with PD in real-life are lacking. Our objective was to assess the impact of early therapeutic strategies on the development of motor and neuropsychiatric complications using a nationwide PD cohort.

Sleep Deprivation in Healthy Males Increases Muscle Afferents, Impairing Motor Preparation and Reducing Endurance.

Purpose: Sleep deprivation (SD) reduces time to task failure during endurance exercises. The aim of our work was to study the effect of acute SD on the endurance of a skeletal hand muscle and to investigate cortical motor drive to muscle and perception of effort.

Methods: Origin of the early exhaustion after SD might be insufficient cortical motor drive to muscle or motor inhibition because of excessive perception of effort.

Oxycodone or Higher Dose of Levodopa for the Treatment of Parkinsonian Central Pain: OXYDOPA Trial.

Background: Among the different types of pain related to Parkinson's disease (PD), parkinsonian central pain (PCP) is the most disabling.

Objectives: We investigated the analgesic efficacy of two therapeutic strategies (opioid with oxycodone- prolonged-release (PR) and higher dose of levodopa/benserazide) compared with placebo in patients with PCP.

Methods: OXYDOPA was a randomized, double-blind, double-dummy, placebo-controlled, multicenter parallel-group trial run at 15 centers within the French NS-Park network.

Environment-dependent behavioral traits and experiential factors shape addiction vulnerability.

The transition from controlled drug use to drug addiction depends on an interaction between a vulnerable individual, their environment and a drug. Here we tested the hypothesis that conditions under which individuals live influence behavioral vulnerability traits and experiential factors operating in the drug taking environment to determine the vulnerability to addiction. The role of behavioral vulnerability traits in mediating the influence of housing conditions on the tendency to acquire cocaine self-administration was characterized in 48 rats housed in either an enriched (EE) or a standard (SE) environment.

Personality Dimensions Are Associated with Quality of Life in Fluctuating Parkinson's Disease Patients (PSYCHO-STIM).

Background: Parkinson's disease (PD) negatively affects patients' Quality of Life (QoL) which depends on both objective criteria such as physical health and subjective ones such as worries and norms according to personal believes. Therefore, QoL could be also associated to personality dimensions in chronic neurological diseases such as PD.

Objective: Our objective was thus to study the potential association between personality dimensions and QoL in PD patients with motor fluctuations before Deep Brain Stimulation of the Sub-Thalamic Nucleus (DBS-STN).

Anterior pallidal deep brain stimulation for Tourette's syndrome: a randomised, double-blind, controlled trial.

Background: Deep brain stimulation (DBS) has been proposed to treat patients with severe Tourette's syndrome, and open-label trials and two small double-blind trials have tested DBS of the posterior and the anterior internal globus pallidus (aGPi). We aimed to specifically assess the efficacy of aGPi DBS for severe Tourette's syndrome.

Methods: In this randomised, double-blind, controlled trial, we recruited patients aged 18-60 years with severe and medically refractory Tourette's syndrome from eight hospitals specialised in movement disorders in France.

Multi-facetted impulsivity following nigral degeneration and dopamine replacement therapy.

Impulse control disorders (ICDs) are debilitating side effects of dopamine replacement therapy (DRT) in Parkinson's disease (PD) that severely affect the quality of life of patients. While DRT, the pattern and extent of neurodegeneration, and prodromic factors of vulnerability (e.g.

Atomoxetine decreases vulnerability to develop compulsivity in high impulsive rats.

Background: The factors contributing to the development and severity of obsessive-compulsive spectrum disorders such as obsessive-compulsive disorder, Tourette's syndrome, pathological gambling, and addictions remain poorly understood, limiting the development of therapeutic and preventive strategies. Recent evidence indicates that impulse-control deficits may contribute to the severity of compulsivity in several of these disorders. This suggests that impulsivity may be a transnosological endophenotype of vulnerability to compulsivity.