Objective Rehabilitation is thought to reduce ataxia severity in individuals with hereditary cerebellar ataxia (HCA). This multicenter, randomized controlled superiority trial aimed to examine the efficacy of a 30‐week goal‐directed rehabilitation program compared with 30 weeks of standard care on function, ataxia, health‐related quality of life, and balance in individuals with an HCA. Methods Individuals with an autosomal dominant or recessive ataxia (aged ≥15 years) were enrolled at 5 sites in Australia. Participants were randomized (1:1) to receive rehabilitation (6 weeks of outpatient physiotherapy followed by a 24‐week home exercise program) (n = 39) or continued their usual activity (n = 37). The primary outcome measure was the motor domain of the Functional Independence Measure (mFIM) at 7 weeks. Secondary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the SF‐36v2, assessed at 7, 18, and 30 weeks. Outcome assessors were blinded to treatment allocation. Results Seventy‐one participants (rehabilitation, 37; standard‐care, 34) were included in the intention‐to‐treat analysis. At 7 weeks, mFIM (mean difference 2.26, 95% confidence interval [CI]: 0.26 to 4.26, p = 0.028) and SARA (−1.21, 95% CI: −2.32 to −0.11, p = 0.032) scores improved after rehabilitation compared with standard care. Compared with standard care, rehabilitation improved SARA scores at 30 weeks (mean difference −1.51, 95% CI: −2.76 to −0.27, p = 0.017), but not mFIM scores (1.74, 95% CI: −0.32 to 3.81, p = 0.098). Frequent adverse events in both groups were fatigue, pain, and falls. Interpretation Goal‐directed rehabilitation improved function at 7 weeks, with improvement in ataxia and health‐related quality of life maintained at 30 weeks in individuals with HCA, beyond that of standard care. ANN NEUROL 2024

Goal‐Directed Rehabilitation Versus Standard Care for Individuals with Hereditary Cerebellar Ataxia: A Multicenter, Single‐Blind, Randomized Controlled Superiority Trial