To investigate clinical and treatment-related factors associated with outcomes of Purkinje cell cytoplasmic antibody Type 1 (PCA1) paraneoplastic autoimmunity.

Factors associated with outcomes in this rare disorder are poorly understood.

We conducted a retrospective review of 54 patients with PCA1 paraneoplastic autoimmunity identified at two tertiary autoimmune neurology referral centers from July 2000 through June 2023. The primary outcome was time to death, and secondary outcomes included wheelchair dependence and modified Rankin Scale (mRS) ≥4 at last follow up. We used Cox regression for mortality and Firth penalized logistic regression for disability outcomes.

The median age at onset was 61 years (interquartile range [IQR] 52–67); 53 patients (98%) were female; 42 (78%) had breast or other gynecologic malignancies. Median follow-up was 39 months (IQR 15–69). Twenty-three patients (43%) died at a median of 32 months (IQR 14–63). At last follow-up, 39 (74%) were wheelchair-bound and 42 (78%) had mRS ≥4. Older age (adjusted hazard ratio [aHR] 2.50 per decade, 95% confidence interval [CI] 1.50–4.18, p<0.001) whereas cyclophosphamide use (aHR 0.33, 95%CI 0.12–0.93, p=0.036) were independently associated with lower mortality. For disability outcomes, CSF pleocytosis was independently associated with wheelchair dependence (adjusted odds ratio [aOR] 12.5, 95%CI 1.19–131.96, p=0.011). No factor was associated with mRS ≥4 at the last visit in multivariate analysis, and cancer type was not associated with any outcome.

Older age was associated with worse survival, while CSF pleocytosis was associated with severe disability, suggesting a potential role for cell-mediated inflammation in disease progression. Cyclophosphamide was associated with improved survival. These findings highlight potential prognostic markers and therapeutic signals in PCA1 paraneoplastic autoimmunity; however, validation in larger cohorts is warranted.