Non-motor subtypes in candidates for subthalamic deep brain stimulation for Parkinson's disease.

Introduction: Patients with Parkinson's Disease (PD) vary markedly in terms of non-motor symptoms (NMS) as the disease progresses. To improve PD management and clinical-trial assessment, we aimed to determine NMS endotypes in a cohort of patients with advanced PD.

Methods: We conducted an ancillary cluster analysis of the 2013-2018 cohort (n = 722) of PREDISTIM.

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.

A delphi consensus statement about French practical management of continuous apomorphine infusion in patients with Parkinson's disease and motor fluctuations.

Background: There are currently no consensus guidelines on how to progressively optimize treatment when initiating continuous subcutaneous apomorphine infusion (CSAI) in patients with Parkinson's disease (PwPD).

Aims: To provide practical guidelines on CSAI initiation in PwPD with motor fluctuations, with a focus on the target dose of apomorphine over time and subsequent adjustment of oral treatment according to the patient's characteristics.

Methods: A panel of French neurologists with extensive experience in treating patients with advanced Parkinson's disease used a modified Delphi approach to generate a knowledge synthesis on CSAI initiation according to patient characteristics.

Use and misuse of domperidone in patients living with Parkinson disease in France.

Context: After observing increased sudden death risk associated with domperidone use, the European Medicines Agency (EMA) imposed usage restrictions in 2014, limiting age (≤60 years), daily dose (≤30 mg/day), and duration (≤7 days). Nausea commonly occurs as an adverse effect of dopaminergic drugs in Parkinson's disease (PD) patients, with few alternative anti-emetic options. This study aimed to assess domperidone prescription patterns in French PD patients.

Therapeutic modalities of deferiprone in Parkinson's disease: SKY and EMBARK studies.

BackgroundReducing nigrostriatal iron overload reduces neuronal loss in Parkinson's disease (PD) models.ObjectiveExamine the safety and efficacy of deferiprone in reducing motor disability progression in dopaminergic-treated and treatment-naïve patients with early-stage PD.MethodsTwo phase II, multicenter studies, SKY and EMBARK, enrolled patients diagnosed with early PD (<3 years from screening).

Directional Subthalamic Deep Brain Stimulation Better Improves Gait and Balance Disorders in Parkinson's Disease Patients: A Randomized Controlled Study.

Objective: To investigate the effects of directional subthalamic deep brain stimulation (STN-dDBS) on gait and balance disorders, including freezing of gait (FOG), in patients with advanced Parkinson's disease (PD).

Methods: We included 10 participants who underwent STN-DBS and presented severe preoperative FOG, in a randomized, double-blind, crossover study. We used segmented DBS electrodes to investigate whether directing the predicted volume of tissue activated (VTA) to overlap the central STN preferentially improved gait and balance disorders compared to directional DBS applied in the more posterior STN (sensorimotor).

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.

Trial of Lixisenatide in Early Parkinson's Disease.

Background: Lixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in a mouse model of Parkinson's disease.

Methods: In this phase 2, double-blind, randomized, placebo-controlled trial, we assessed the effect of lixisenatide on the progression of motor disability in persons with Parkinson's disease. Participants in whom Parkinson's disease was diagnosed less than 3 years earlier, who were receiving a stable dose of medications to treat symptoms, and who did not have motor complications were randomly assigned in a 1:1 ratio to daily subcutaneous lixisenatide or placebo for 12 months, followed by a 2-month washout period.

The impact of subthalamic deep-brain stimulation in restoring motor symmetry in Parkinson's disease patients: a prospective study.

Background And Objectives: The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL).

Methods: Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort.

Parkinsonian central pain is linked to the connectivity of the nucleus accumbens and the anterior insula.

Pain is a frequent and disabling non-motor symptom of Parkinson's Disease (PD). Yet, no treatment to date can efficiently reduce this pain. This article investigates the brain functional connectivity of PD patients with central pain and the effects of levodopa and oxycodone on this connectivity.

ON/OFF non-motor evaluation: a new way to evaluate non-motor fluctuations in Parkinson's disease.

Background: NMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity of non-motor fluctuations (NMF) in Parkinson's disease (PD).

Prognosis of impulse control disorders in Parkinson's disease: a prospective controlled study.

Background: The long-term prognosis of impulsive compulsive disorders (ICD) remains poorly studied in Parkinson's disease (PD).

Objective: Evaluating the natural history of ICD and its impact on PD symptoms including cognition and treatment adjustments.

Materials And Methods: We assessed PD patients at baseline (BL) with (BL-ICD+) or without (BL-ICD-) ICD despite dopamine agonist (DA) exposure of > 300 mg levodopa-equivalent daily dose for > 12 months at baseline and after more than two years of follow-up.

Motivational and cognitive predictors of apathy after subthalamic nucleus stimulation in Parkinson's disease.

Postoperative apathy is a frequent symptom in Parkinson's disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: (i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering; and (ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and 1-year postoperative apathy in Parkinson's disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus.

Phenotype and imaging features associated with APP duplications.

Background: APP duplication is a rare genetic cause of Alzheimer disease and cerebral amyloid angiopathy (CAA). We aimed to evaluate the phenotypes of APP duplications carriers.

Methods: Clinical, radiological, and neuropathological features of 43 APP duplication carriers from 24 French families were retrospectively analyzed, and MRI features and cerebrospinal fluid (CSF) biomarkers were compared to 40 APP-negative CAA controls.

Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease.

Background: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone.

Objective: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments.

Methods: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS).

Can Dopamine Responsiveness Be Predicted in Parkinson's Disease Without an Acute Administration Test?

Background: Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson's disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources.

Objective: Our objective was to develop a predictive model combining clinical scores and imaging.

Heterogeneity of PD-MCI in Candidates to Subthalamic Deep Brain Stimulation: Associated Cortical and Subcortical Modifications.

Background: Parkinson's disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes.

Objective: To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS.

Cerebrospinal Fluid Profile of Tau, Phosphorylated Tau, Aβ42, and Aβ40 in Probable Cerebral Amyloid Angiopathy.

Background: There is no consensus regarding the diagnostic value of cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in cerebral amyloid angiopathy (CAA).

Objective: To describe the CSF levels of Aβ42, Aβ40, total protein Tau, and phosphorylated-Tau (p-Tau) in a large series of probable CAA patients and to compare with AD patients in order to identify a specific pattern in CAA but also to look for correlations with the neuroimaging profile.

Methods: We retrospectively included from 2 French centers probable CAA patients according to modified Boston criteria who underwent lumbar puncture (LP) with CSF AD biomarker quantifications.

Telemedicine in French Memory Clinics During the COVID-19 Pandemic.

This multicenter study was conducted in French memory clinics during the first COVID-2019 lockdown (March-May 2020). The objective was to evaluate the effect of a telemedicine consultation on treatment modification in dementia care. Among 874 patients who had a telemedicine consultation, 103 (10.

Personality Related to Quality-of-Life Improvement After Deep Brain Stimulation in Parkinson's Disease (PSYCHO-STIM II).

Background: Deep brain stimulation of the sub-thalamic nucleus (DBS-STN) reduces symptoms in Parkinson's disease (PD) patients with motor fluctuations. However, some patients may not feel ameliorated afterwards, despite an objective motor improvement. It is thus important to find new predictors of patients' quality of life (QoL) amelioration after DBS-STN.