Biopsy-Confirmed Small Vessel Primary CNS Vasculitis: Clinical Features and Impact of Early Intensive Treatment on Remission.

BACKGROUND AND OBJECTIVES: This single-center retrospective cohort study sought to characterize the clinical spectrum of small vessel predominant primary CNS vasculitis (sv-PCNSV) and to investigate the impact of early intensive immunosuppressive therapy on remission. METHODS: We analyzed data of patients diagnosed with biopsy-proven sv-PCNSV at our institution between 2009 and 2023. "Early intensive treatment" (EIT) was defined by cyclophosphamide therapy within 3 months of immunosuppressive treatment initiation. Patients in the "escalation treatment" (ESC) group initially received glucocorticoids, either as monotherapy or in conjunction with azathioprine, mycophenolate mofetil, or methotrexate. RESULTS: Twenty-six patients (50% female) met the study criteria, including 7 with amyloid-beta-related angiitis (ABRA). The median age at onset was 55.5 years (range 20-82), and headache (76.9%) and altered mental status (61.5%) were common presenting symptoms. Neuroimaging commonly showed bihemispheric T2/FLAIR lesions (77%) and abnormal gadolinium enhancement (88.5%), but intracranial vascular irregularities indicating large or medium vessel involvement were rare (11.5%). Among patients with non-ABRA sv-PCNSV (n = 19), some demonstrated spinal cord involvement (15.8%) and others exhibited isolated unihemispheric disease (21.1%). Although CSF testing (n = 23) often demonstrated mild pleocytosis, a notable minority of patients (17.4%) had a normal CSF analysis. Six patients (23.1%) underwent repeat brain biopsy because of initial nondiagnostic findings. Remission was achieved in all patients in the EIT group (n = 12/12), in contrast to 78.6% of patients in the ESC group (n = 11/14). Time to remission was significantly shorter among patients in the EIT group compared with the ESC group (median 5 vs 19 months, hazard ratio = 0.24, 95% CI [0.10-0.63], p < 0.005). Most patients achieving remission continued maintenance therapy, with an overall relapse rate of 19%. DISCUSSION: This study highlights the considerable clinical heterogeneity in sv-PCNSV, a rare but serious condition. Early, aggressive treatment with cyclophosphamide is associated with a shorter time to remission, and further validation in prospective studies is warranted.