Health-related quality of life (Hr-QoL) scales provide crucial information on neurodegenerative disease progression, help improving patient care, and constitute a meaningful endpoint for therapeutic research. However, Hr-QoL progression is usually poorly documented, as for multiple system atrophy (MSA), a rare and rapidly progressing alpha-synucleinopathy. This work aimed to describe Hr-QoL progression during the natural course of MSA, explore disparities between patients, and identify informative items using a four-step statistical strategy.We leveraged the data of the French MSA cohort comprising annual assessments with the MSA-QoL questionnaire for more than 500 patients over up to 11 years. The four-step strategy (1) determined the subdimensions of Hr-QoL in MSA; (2) modelled the subdimension trajectories over time, accounting for the risk of death; (3) mapped the sequence of item impairments with disease stages; and (4) identified the most informative items specific to each disease stage.Among the 536 patients included, 50% were women and they were aged on average 65.1 years old at entry. Among them, 63.1% died during the follow-up. Four dimensions were identified. In addition to the original motor, nonmotor, and emotional domains, an oropharyngeal component was highlighted. While the motor and oropharyngeal domains deteriorated rapidly, the nonmotor and emotional aspects were already slightly to moderately impaired at cohort entry and deteriorated slowly over the course of the disease. Impairments were associated with sex, diagnosis subtype, and delay since symptom onset. Except for the emotional domain, each dimension was driven by key identified items.Hr-QoL is a multidimensional concept that deteriorates progressively over the course of MSA and brings essential knowledge for improving patient care. As exemplified with MSA, the thorough description of Hr-QoL using the 4-step original analysis can provide new perspectives on neurodegenerative diseases' management to ultimately deliver better support focused on the patient's perspective.

翻译：健康相关生活质量量表可提供神经退行性疾病进展的关键信息，有助于改善患者护理，并构成治疗研究中有意义的终点。然而，对于多系统萎缩这种罕见且快速进展的α-突触核蛋白病，其生活质量进展通常记录不足。本研究旨在描述多系统萎缩自然病程中的生活质量进展，探索患者间的差异，并通过四步统计策略识别信息量丰富的项目。我们利用了法国多系统萎缩队列的数据，该队列包含500多名患者长达11年的年度评估（采用MSA-QoL问卷）。四步策略包括：(1) 确定多系统萎缩中生活质量子维度；(2) 模拟子维度随时间变化的轨迹，同时考虑死亡风险；(3) 绘制项目损伤与疾病阶段的对应序列；(4) 识别各疾病阶段最具信息量的特定项目。在纳入的536名患者中，女性占50%，入组时平均年龄65.1岁，其中63.1%在随访期间死亡。共识别出四个维度：除原有的运动、非运动和情感领域外，还凸显出口咽部组件。运动和口咽部领域迅速恶化，而非运动和情感方面在队列入组时已呈现轻度至中度损伤，并在病程中缓慢恶化。损伤与性别、诊断亚型和症状发作延迟时间相关。除情感领域外，每个维度均由关键识别项目驱动。生活质量是多维概念，在多系统萎缩病程中逐步恶化，为改善患者护理提供重要知识。以多系统萎缩为例，通过四步原创分析对生活质量进行详尽描述，可为神经退行性疾病管理提供新视角，最终实现以患者视角为中心的更优支持。