Neurology(R) neuroimmunology & neuroinflammationJournal Article
undefined Jul 2025
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.
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.
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], < 0.005). Most patients achieving remission continued maintenance therapy, with an overall relapse rate of 19%.
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.
S.P. Reddy was supported by the Fogarty International Center of the NIH under Award Number D43TW009343 and the University of California Global Health Institute. S.C. LaHue receives research support from the NIH National Institute on Aging (R03AG074035), Larry L. Hillblom Foundation, Doris Duke Foundation, UCSF Bakar Aging Research Institute, UCSF Pepper Center. Non-Funding Disclosures: S.C. LaHue receives speaker honoraria from American Academy of Neurology and Medscape. J.M. Gelfand receives research support to UCSF from Hoffman LaRoche and Vigil Neurosciences and consulting fees for Arialys and Ventyx Bio. The other authors report no relevant disclosures. Go to Neurology.org/NN for full disclosures.
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