PCNSV is a rare inflammatory vasculopathy of the brain and spinal cord. Its characterization of relapse risk remains poorly defined, particularly in biopsy-confirmed cohorts.

We retrospectively identified PCNSV cases at Mass General Brigham. Patients with non-supportive pathology or evidence of systemic vasculitis, malignancy, infection, or amyloid-β angiopathy were excluded. Relapse required new or worsening neurological symptoms with new MRI lesions. Asymptomatic radiographic progression also met criteria, whereas symptomatic episodes without radiographic change did not. Time-to-event analyses used Fine-Gray subdistribution hazard models with death as a competing risk. ARR were calculated overall and stratified into early (≤3 years) vs late (>3 years) periods and compared using incidence-rate ratios (IRR).

Twenty-six patients were followed for a mean of 8.1 years. Relapse occurred in 15 patients (57.7%); five had ≥2 relapses. Mean time to first relapse was 2.1 years (range 0.20–8.60). Cumulative incidence was highest within the first three years. ARR was greater early than late (IRR 7.15, p=0.004). In Fine-Gray models, histopathologic subtype and sex were not significantly associated with relapse. Cerebrospinal fluid status was associated with relapse risk (abnormal vs normal sHR 0.02, 95% CI 6.04×10^-4-6.74×10?¹, p=0.029), though it did not correspond to a significantly shorter time to relapse. Non-relapse patients had a shorter time to first treatment (p=0.02). Event plots showed most first relapses within three years and clustering of subsequent relapses within two years of the first.

In this biopsy-confirmed PCNSV cohort, more than half of patients relapsed, with risk concentrated in the first three years. Earlier treatment initiation was associated with lower relapse likelihood, while normal vs abnormal CSF predicted relapse. These findings support early vigilant surveillance and may inform strategies targeting early relapse prevention.