Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Experimental Psychology, Helmholtz Institute, Utrecht University, Utrecht, the Netherlands.
Cerebellum. 2021 Dec;20(6):887-895. doi: 10.1007/s12311-021-01252-9. Epub 2021 Mar 10.
Assessment of patient-reported outcome measures (PROMs) in spinocerebellar ataxias (SCAs) could provide valuable insights into self-perceived health status. Although they are considered additional endpoints in future clinical trials, determinants and interactions of different PROMs in early disease stages remain largely unknown. The aims of the present study were to evaluate health-related quality of life, depressive symptoms, fatigue, and physical activity in mildly to moderately affected SCA3 patients and to examine interrelations between these PROMs and objective disease severity indices. Twenty SCA3 patients and twenty healthy controls of comparable age and sex completed the EQ-5D-5L, Patient Health Questionnaire-9, Profile of Mood States, and International Physical Activity Questionnaire. Disease severity was quantified by the Scale for the Assessment and Rating of Ataxia (SARA) and Inventory of Non-Ataxia Signs (INAS). Mildly to moderately affected SCA3 patients reported lower quality of life (p = 0.049), more depressive symptoms (p = 0.028), and higher levels of fatigue (p = 0.001) than healthy controls. The amount of physical activity did not differ between both groups. Linear regression analyses revealed that quality of life was primarily determined by fatigue and not by ataxia severity, while physical activity was independently associated with SARA score and INAS count but not fatigue. Depressive symptoms were related to disease duration and fatigue but not to markers of motor disease progression. Taken together, decreased quality of life, increased levels of fatigue, and a higher number of depressive symptoms do not merely reflect motor impairment in early-to-middle-stage SCA3 patients. The observed discordance between patient-reported and clinician-based outcomes indicates that these measures genuinely evaluate distinct aspects of disease and emphasizes their complementariness in therapeutic trials. By contrast, the volume of self-reported physical activity is not associated with fatigue, reflects both ataxia severity and extracerebellar involvement, and could therefore represent a useful marker of motor impairment in a home setting.
评估脊髓小脑共济失调症（SCA）患者的患者报告结局测量（PROMs）可以提供对自我感知健康状况的宝贵见解。尽管它们被认为是未来临床试验中的附加终点，但不同 PROM 在疾病早期阶段的决定因素和相互作用在很大程度上仍然未知。本研究的目的是评估轻度至中度 SCA3 患者的健康相关生活质量、抑郁症状、疲劳和身体活动，并研究这些 PROM 与客观疾病严重程度指标之间的相互关系。20 名 SCA3 患者和 20 名年龄和性别相匹配的健康对照者完成了 EQ-5D-5L、患者健康问卷-9、情绪状态问卷和国际身体活动问卷。疾病严重程度通过共济失调评估和评分量表（SARA）和非共济失调体征量表（INAS）进行量化。与健康对照组相比，轻度至中度 SCA3 患者报告的生活质量较低（p=0.049）、抑郁症状较多（p=0.028）和疲劳程度较高（p=0.001）。两组之间的身体活动量没有差异。线性回归分析表明，生活质量主要由疲劳决定，而不是由共济失调严重程度决定，而身体活动与 SARA 评分和 INAS 计数独立相关，但与疲劳无关。抑郁症状与疾病持续时间和疲劳有关，但与运动疾病进展的标志物无关。综上所述，在早期至中期 SCA3 患者中，生活质量下降、疲劳程度增加和更多的抑郁症状不仅反映了运动障碍。观察到的患者报告和临床医生报告的结果之间的不匹配表明，这些措施真正评估了疾病的不同方面，并强调了它们在治疗试验中的互补性。相比之下，自我报告的身体活动量与疲劳无关，反映了共济失调的严重程度和小脑外参与，因此可以作为家庭环境中运动障碍的有用标志物。
