Discordance Between Patient-Reported Outcomes and Physician-Rated Motor Symptom Severity in Early-to-Middle-Stage Spinocerebellar Ataxia Type 3

Abstract

AbstractAssessment 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.