Care of Late-Stage Parkinsonism: Resource Utilization of the Disease in Five European Countries.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease that leads to progressive disability. Cost studies have mainly explored the early stages of the disease, whereas late-stage patients are underrepresented. OBJECTIVE: The aim is to evaluate the resource utilization and costs of PD management in people with late-stage disease. METHODS: The Care of Late-Stage Parkinsonism (CLaSP) study collected economic data from patients with late-stage PD and their caregivers in five European countries (France, Germany, the Netherlands, UK, Sweden) in a range of different settings. Patients were eligible to be included if they were in Hoehn and Yahr stage >3 in the on state or Schwab and England stage at 50% or less. In total, 592 patients met the inclusion criteria and provided information on their resource utilization. Costs were calculated from a societal perspective for a 3-month period. A least absolute shrinkage and selection operator approach was utilized to identify the most influential independent variables for explaining and predicting costs. RESULTS: During the 3-month period, the costs were €20,573 (France), €19,959 (Germany), €18,319 (the Netherlands), €25,649 (Sweden), and €12,156 (UK). The main contributors across sites were formal care, hospitalization, and informal care. Gender, age, duration of the disease, Unified Parkinson's Disease Rating Scale 2, the EQ-5D-3L, and the Schwab and England Scale were identified as predictors of costs. CONCLUSION: Costs in this cohort of individuals with late-stage PD were substantially higher compared to previously published data on individuals living in earlier stages of the disease. Resource utilization in the individual sites differed in part considerably among these three parameters mentioned. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Phase 1 Randomized Trial of Specific Active α-Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy.

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disease with limited symptomatic treatment options. Aggregation of α-synuclein in oligodendrocytes is believed to be a central mechanism of the neurodegenerative process. PD01A and PD03A are 2 novel therapeutic vaccine candidates containing short peptides as antigenic moieties that are designed to induce a sustained antibody response, specifically targeting pathogenic assemblies of α-synuclein. The objectives of the current study were to evaluate primarily the safety and tolerability of PD01A and PD03A in patients with early MSA. Thirty patients (11 women) were randomized to receive 5 subcutaneous injections of either PD01A (n = 12), PD03A (n = 12), or placebo (n = 6) in this patient- and examiner-blinded, placebo-controlled, 52-week phase 1 clinical trial (ClinicalTrial.gov identifier: NCT02270489). Immunogenicity and clinical scores were assessed as secondary objectives. Twenty-nine patients reported a total of 595 treatment-emergent adverse events (mild or moderate, n = 555; severe, n = 40). Treatment-related adverse events included 190 injection-site reactions typically observed in vaccination trials with similar per-subject incidence in the treatment groups over time. Sustained IgG titers were observed in the PD01A-treated group, and 89% of treated patients developed a PD01-specific antibody response after receiving all injections. Induced antibodies displayed clear reactivity to the α-synuclein target epitope. Titers and antibody responder rate (58%) were lower in the PD03A-treated group. In conclusion, both PD01A and PD03A were safe and well tolerated. PD01A triggered a rapid and long-lasting antibody response that specifically targeted the α-synuclein epitope. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dopamine transporter imaging for the diagnosis of multiple system atrophy cerebellar type.

INTRODUCTION: The added value of dopamine transporter SPECT (DAT-SPECT) for the diagnosis of "possible" multiple system atrophy of the cerebellar type (MSA-C) remains unknown. METHODS: We reviewed retrospectively the charts of 128 consecutive patients with a clinical diagnosis of MSA-C who were seen between 2007 and 2016 at the French Reference Center for MSA. The main objective was to evaluate the proportion of patients for whom the diagnosis of "possible" MSA-C was made because of a positive DAT-SPECT. RESULTS: Seventy-eight MSA-C patients had at least one DAT-SPECT. Fifty-nine of them were considered for the final analysis. In these, 22 had "possible" MSA-C and 23 "probable" MSA-C before DAT-SPECT, while 14 did not reach diagnosis criteria at that time. In those with "possible" MSA-C, DAT-SPECT was positive in 64%. In patients with "probable" MSA-C, 83% showed nigrostriatal denervation. Six out of 14 (43%) received a diagnosis of "possible" MSA-C because of positive DAT-SPECT. These patients had mean disease duration of 2.3 years at the time of DAT-SPECT compared to 3.5 years of the entire cohort of MSA-C patients with DAT-SPECT. Of the eight remaining, one had positive DAT-SPECT but also pons atrophy on magnetic resonance imaging, and seven progressed to "probable" MSA based on clinical features. CONCLUSION: Our results suggest that DAT-SPECT significantly contributes to the diagnosis of "possible" MSA-C (43% of patients not reaching consensus diagnosis criteria before DAT-SPECT). DAT-SPECT seems especially useful in patients with shorter disease duration, while a negative result does not exclude a diagnosis of MSA.

Multiple System Atrophy - State of the Art.

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder that is characterized by a variable combination of parkinsonism, cerebellar impairment, and autonomic dysfunction. Some symptomatic treatments are available while neuroprotection or disease-modification remain unmet treatment needs. The pathologic hallmark is the accumulation of aggregated alpha-synuclein (α-syn) in oligodendrocytes forming glial cytoplasmic inclusions, which qualifies MSA as synucleinopathy together with Parkinson's disease and dementia with Lewy bodies. Despite progress in our understanding of the pathogenesis of MSA, the origin of α-syn aggregates in oligodendrocytes is still a matter of an ongoing debate. We critically review here studies published in the field over the past 5 years dealing with pathogenesis, genetics, clinical signs, biomarker for improving diagnostic accuracy, and treatment development.