This review synthesizes evidence across five complementary biomarker domains, clinical, imaging, fluid, genetic, and digital, and judges their readiness for forecasting onset and progression. Clinical scales such as SARA capture genotype-specific trajectories but lose sensitivity at the extremes of the disease course. Volumetric, microstructural, and spectroscopic MRI and blood neurofilament light chain change before ataxia onset and predict subsequent decline, whereas repeat length and genetic modifiers set prior risk. Wearable-sensor gait and balance metrics detect change earlier than clinical scales and sharply reduce required sample sizes. We argue that no single modality satisfies every context of use, and that stage-specific, multimodal composites, integrated through harmonized international cohorts and machine learning, offer the most credible path to prognostic enrichment and to shorter, adequately powered, and preventive trials.
Wednesday, September 9, 2026
Predicting disease progression in progressive cerebellar ataxias: integrating clinical, imaging, fluid, genetic, and digital biomarkers
Hao Y and Hao X (2026) Predicting disease progression in progressive cerebellar ataxias: integrating clinical, imaging, fluid, genetic, and digital biomarkers. Front. Neurol. 17:1921210. doi: 10.3389/fneur.2026.1921210
