H. Lundbeck A/S, Copenhagen, Denmark.
Department of Mathematical Sciences, University of Copenhagen, Copenhagen, Denmark.
Mov Disord. 2022 Aug;37(8):1719-1727. doi: 10.1002/mds.29077. Epub 2022 Jun 6.
Multiple system atrophy (MSA) is a rare and aggressive neurodegenerative disease that typically leads to death 6 to 10 years after symptom onset. The rapid evolution renders it crucial to understand the general disease progression and factors affecting the disease course.
The aims of this study were to develop a novel disease-progression model to estimate a population-level MSA progression trajectory and predict patient-specific continuous disease stages describing the degree of progress into the disease.
The disease-progression model estimated a population-level progression trajectory of subscales of the Unified MSA Rating Scale and the Unified Parkinson's Disease Rating Scale using patients in the European MSA natural history study. The predicted disease continuum was validated via multiple analyses based on reported anchor points, and the effect of MSA subtype on the rate of disease progression was evaluated.
The predicted disease continuum spanned approximately 6 years, with an estimated average duration of 51 months for a patient with global disability score 0 to reach the highest level of 4. The predicted continuous disease stages were shown to be correlated with time of symptom onset and predictive of survival time. MSA motor subtype was found to significantly affect disease progression, with MSA-parkinsonian (MSA-P) type patients having an accelerated rate of progression.
The proposed modeling framework introduces a new method of analyzing and interpreting the progression of MSA. It can provide new insights and opportunities for investigating covariate effects on the rate of progression and provide well-founded predictions of patient-level future progressions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
多系统萎缩（MSA）是一种罕见且侵袭性的神经退行性疾病，通常在症状出现后 6 至 10 年内导致死亡。其快速进展使得了解疾病的总体进展和影响疾病进程的因素至关重要。
本研究旨在开发一种新的疾病进展模型，以估计 MSA 人群水平的进展轨迹，并预测描述疾病进展程度的患者特定连续疾病阶段。
使用欧洲 MSA 自然史研究中的患者，使用统一 MSA 评分量表和统一帕金森病评分量表的亚量表来估计疾病进展模型的人群水平进展轨迹。通过基于报告的锚定点的多项分析验证预测的疾病连续体，并评估 MSA 亚型对疾病进展速度的影响。
预测的疾病连续体跨度约为 6 年，估计全球残疾评分 0 的患者达到最高 4 分的平均持续时间约为 51 个月。预测的连续疾病阶段与症状出现时间相关，并可预测生存时间。MSA 运动亚型显著影响疾病进展，MSA-帕金森型（MSA-P）患者的进展速度更快。
所提出的建模框架引入了一种分析和解释 MSA 进展的新方法。它可以为研究进展速度的协变量效应提供新的见解和机会，并为患者未来进展提供有充分依据的预测。© 2022 作者。运动障碍由 Wiley 期刊公司代表国际帕金森病和运动障碍协会出版。
