Inside the Heterogeneity of Primary CNS Vasculitis: A Single-Center 40-Year Experience

Primary CNS vasculitis (PCNSV) is a heterogeneous condition. This study examines a large cohort with long-term follow-up to identify potential disease subsets.

We retrospectively analyzed 216 patients with PCNSV (Mayo Clinic, 1983-2023), using standardized diagnostic criteria, classifying by vessel size, histopathology, and outcomes. Subsets and predictors of functional and therapeutic outcomes were evaluated.

Diagnosis was based on cerebral angiography in 142 patients and histologically confirmed in 74. Isolated small vessel involvement was positively associated with mass-lesion presentation (odds ratio [OR] 19.38, p = 0.02), meningeal-enhancing lesions (OR 39.10, p < 0.0001), elevated CSF protein (OR 4.04, p = 0.03), and β-amyloid vascular deposits (OR 23.43, p = 0.0001), but negatively with focal manifestations (OR 0.32, p = 0.04) and cerebral infarcts (OR 0.22, p = 0.003). Lymphocytic vasculitis was linked to younger age at diagnosis (p = 0.006), longer symptom-to-diagnosis interval (p = 0.05), more seizures (p = 0.04), and lower disability (p = 0.003) and mortality (p = 0.008). Necrotizing vasculitis was associated with intracranial hemorrhage (p = 0.008). Two or more relapses occurred in 12.7%, associated with histologic diagnosis (OR 3.15, p = 0.009) and inversely with gadolinium-enhanced lesions (OR 0.33, p = 0.01). Therapy response occurred in 82.9%, long-term remission in 23.6%. Cerebral infarcts, especially multiple, were associated with poor therapy response (OR 0.11, p = 0.03). Histologic diagnosis was inversely associated with long-term remission (OR 0.44, p = 0.03), whereas aspirin use was positively associated (OR 2.8, p = 0.002). A rapidly progressive course occurred in 13.4% of patients and was linked to increasing age (OR 1.34/10 years, p = 0.04), cognitive dysfunction (OR 5.59, p = 0.02), cerebral infarctions (OR 5.02, p = 0.004), and large vessel involvement (OR 3.51, p = 0.02). Gadolinium-enhanced lesions (OR 0.36, p = 0.04) and aspirin (OR 0.42, p = 0.08) were protective. Mortality (21.3%) was associated with older age (HR 1.42, p = 0.002), cognitive dysfunction (HR 3.93, p = 0.006), and cerebral infarctions (HR 1.94, p = 0.03).

PCNSV heterogeneity, driven by vessel size and histology, affects presentation and outcomes; our findings offer insights to improve diagnosis and treatment.