Fluctuations in Parkinson’s disease and personalized medicine: bridging the gap with the neuropsychiatric fluctuation scale

BackgroundNeuropsychiatric fluctuations (NpsyF) are frequent and disabling in people with Parkinson’s disease (PD). In OFF-medication, NpsyF entail minus neuropsychiatric symptoms (NPS) like anxiety, apathy, sadness, and fatigue. In ON-medication, NpsyF consist in plus NPS, such as high mood, hypomania, and hyperactivity. Accurate identification of these NpsyF is essential to optimize the overall PD management. Due to lack of punctual scales, the neuropsychiatric fluctuation scale (NFS) has been recently designed to assess NpsyF in real time. The NFS comprises 20 items with two subscores for plus and minus NPS, and a total score.ObjectiveTo evaluate the psychometric properties of the NFS in PD.MethodsPD patients with motor fluctuations and healthy controls (HC) were assessed. In PD patients, the NFS was administrated in both the ON-and OFF-medication conditions, together with the movement disorders society-unified Parkinson disease rating scale parts I–IV. Depression (Beck depression scale II), apathy (Starkstein apathy scale) and non-motor fluctuations items of the Ardouin scale of behaviour in PD (ASBPD OFF and ON items) were also assessed. NFS internal structure was evaluated with principal component analysis consistency (PCA) in both medication conditions in PD patients and before emotional induction in HC. NFS internal consistency was assessed using Cronbach’s alpha coefficient. NFS convergent and divergent validity was measured through correlations with BDI-II, Starktein, and ASBPD OFF and ON non motor items. Specificity was assessed comparing NFS global score between the HC and PD populations. Sensitivity was evaluated with t-student test comparing the ON-and the OFF-medication conditions for NFS global score and for minus and plus subscores.ResultsIn total, 101 consecutive PD patients and 181 HC were included. In PD patients and HC, PCA highlighted one component that explained 32–35 and 42% of the variance, respectively. Internal consistency was good for both the NFS-plus (alpha =0.88) and NFS-minus items (alpha =0.8). The NFS showed a good specifity for PD (p < 0.0001) and a good sensitivity to the medication condition (p < 0.0001).ConclusionThe satisfactory properties of the NFS support its use to assess acute neuropsychiatric fluctuations in PD patients, adding to available tools

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

International audienceBackground: 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. ICD were assessed using the Ardouin's Scale of Behaviors in PD (ASBPD), cognition using the Mattis scale, and PD symptoms using the UPDRS score. Treatment adjustments, DA withdrawal-associated symptoms, and ICDs social consequences were recorded.Results: 149 patients were included (78 cases and 71 controls), mean duration of follow-up was 4.4 ± 1 years. At baseline, psychiatric disorders were more common among BL-ICD + (42.3 vs 12.3% among BL-ICD-, p 50% DA doses (12.8 vs 1.4%, p = 0.019) or to withdraw DA (19.2 vs 5.6%, p = 0.025) was more frequently considered among BL-ICD+ . At follow-up, the prevalence of cognitive decline was lower among BL-ICD + (19.2 vs 37.1%, p = 0.025).Conclusion: ICDs were associated with increased psychiatric burden at baseline and better cognitive prognosis. Most patients were still showing ICDs at the follow-up visit, suggesting ICD to be considered as a chronic, neuropsychiatric disorder

Amantadine use in the French prospective NS-Park cohort

International audienceObjective: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD).Background: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres.Methods: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis).Results: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users.Conclusions: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs

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