Leukoaraiosis does not impact motor outcomes in Parkinson’s patients post deep brain stimulation

Objectives: We sought to assess the impact of leukoaraiosis (LA) on motor outcomes in Parkinson disease (PD) patients undergoing DBS. We hypothesized that LA is associated with less improvement in motor function in PD patients post-DBS. Methods: We reviewed data of adult patients with PD treated with DBS in a single center between 2012 and 2021. Demographics, risk factors, medications, Hoehn and Yahr scale and Unified Parkinson’s Disease Rating Scale (UPDRS) Motor Score before and after DBS and severity of LA were collected. Simple linear regression (SLR) was used to determine variables of interest to include in the multiple linear regression (MLR). MLR was used to determine independent predictors of motor outcomes (UPDRS) post-DBS including LA as a continuous and dichotomized variable of interest. Results: A total of 90 patients were included in the analysis. Mean age was 65.7 years (±9.7), primarily male (69 %) with a high incidence of young onset PD (29 %), treated with carbidopa/levodopa combination (98 %) and with moderate severity of disease (Hoehn and Yahr Stage 2.0 [2.0, 2.5]). Moderate to severe leukoaraiosis was noted in 26 (32.5 %) patients. SLR revealed age, diabetes and disease severity as predictors of post-DBS motor UPDRS. In adjusted analysis, LA was not an independent predictor of motor outcomes post-DBS either as continuous (β = 0.20, p = 0.77) or dichotomized (β = −0.64; p = 0.77) variable. Conclusion: In conclusion, our data suggests that motor outcomes in Parkinson’s disease patients undergoing deep brain stimulation (DBS) are not impacted by pre-existing leukoaraiosis. Further studies are needed to validate our findings

A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA) : Rationale, Design, and Baseline Data

Altres ajuts: F. Hoffmann-La Roche Ltd.Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease. Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40-80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations. Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve). Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD. Trial Registration: NCT03100149