Objective:

This study aims to characterize autoantibody-positive autoimmune cerebellar ataxia (ACA), identify factors associated with poor functional status, and assess functional outcomes using different metrics.

Background:

ACA commonly causes significant morbidity. Prognostic predictors may better inform timely and appropriate immunotherapy. Traditional functional outcome measures such as the modified Rankin Scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) may not adequately capture cerebellar symptom changes.

Design/Methods:

This retrospective cohort study included adults (> 18 years) treated for seropositive ACA at Massachusetts General Hospital or Brigham and Women’s Hospital (2004– 2025). Clinical characteristics, treatments, and outcomes were compared between paraneoplastic and non-paraneoplastic cohorts. The patient with an immune-related adverse event (irAE) after immune checkpoint inhibitor exposure was analyzed separately. Time to wheelchair dependence was estimated with the Kaplan–Meier method and compared using the log-rank test. Univariable Cox proportional hazards regression was used to identify predictors of wheelchair dependence. Functional outcomes were assessed using mRS, CASE, and Brief Ataxia Rating Scale (BARS).

Results:

19 seropositive ACA cases (median age 66 years; 68.4% female) were included. 11 (57.9%) were paraneoplastic, 7 (36.8%) were non-paraneoplastic, and 1 (5.3%) was irAE. All paraneoplastic patients were PCA1 autoantibody–positive; non-paraneoplastic cases had heterogeneous autoantibodies. Paraneoplastic patients were more often female (90.9% vs. 28.6%, p = 0.01), had worse functional outcomes by BARS at last follow-up (20 vs. 7, p < 0.01), and higher mortality (63.6% vs. 14.3%, p = 0.046). Acute symptom onset (< 2 weeks), paraneoplastic association, and PCA1 positivity were associated with wheelchair dependence. BARS appeared to monitor ACA symptoms more precisely than mRS or CASE.

Conclusions:

Non-paraneoplastic cases showed diverse anti-neuronal antibody profiles. Acute onset, paraneoplastic association, and PCA1 positivity were key predictors of severe functional decline. A cerebellar symptom–specific outcome measure such as BARS should be used to monitor ACA.