CO:12:1 | Inside the Heterogeneity of Primary Central Nervous System Vasculitis: A single-centre 40-year experience

Carlo Salvarani¹, Gene G Hunder², Caterina Giannini², Teresa Jh Christianson², Robert D Brown² | ¹Azienda USL-IRCCS di Reggio Emilia e UNIMORE Reggio Emilia, Italy; ²Mayo Clinic Rochester, USA

Background. Primary CNS vasculitis (PCNSV) is a heterogeneous condition with varying presentations and outcomes. This study examines a relatively large cohort of patients with PCNSV to identify potential distinct disease subsets.

Methods. We retrospectively analyzed 216 consecutive PCNSV patients evaluated at a single -centre from 1983 to 2023. Diagnosis was based on uniform radiological and pathological criteria, with comprehensive clinical data and long-term follow-up. Patients were categorized by vessel size, histopathological pattern, and outcomes. We assessed subset characteristics and predictors of functional and therapeutic outcomes.

Results. Diagnosis was based on cerebral angiography in 142 patients, including 31 with negative biopsies. Vasculitis was histologically confirmed in 74 cases. Isolated small vessel involvement was positively associated with tumor-like presentation (OR 19.38, p = 0.02), gadolinium-enhanced (OR 21.16, p < 0.0001) and meningeal enhancing lesions (OR 39.10, p < 0.0001) on MRI, elevated CSF protein (>70 mg/dL) (OR 4.04, p = 0.03), and beta-amyloid vascular deposits (OR 23.43, p = 0.0001). Focal manifestations (OR 0.32, p = 0.04) and cerebral infarcts (OR 0.22, p = 0.003) were negatively associated. Patients with lymphocytic vasculitis were younger at diagnosis (p = 0.006), had a longer symptom-to-diagnosis interval (p = 0.05), more seizures (p = 0.04), and lower disability (p = 0.003) and mortality (p = 0.008) rates. Necrotizing vasculitis was associated with intracranial hemorrhage (p = 0.008). 12.7% of patients had two or more relapses, positively associated with angiographic diagnosis (OR 3.15, p = 0.009) and negatively with gadolinium-enhanced lesions (OR 0.33, p = 0.01). Therapy response and long-term remission were seen in 82.9% and 23.6% of patients. Cerebral infarcts (OR 0.27, p = 0.004), especialy multiple (OR 0.11, p = 0.03), were negatively associated with therapy response, while angiographic diagnosis (OR 2.2, p = 0.03) and aspirin therapy (OR 2.8, p = 0.002) were positively associated with long-term remission. A rapidly progressive course occurred in 13.4% of patients, and was associated with increasing age (per 10 years) (OR 1.34, 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 (parenchymal or meningeal) (OR 0.36, p = 0.04) and aspirin therapy (OR 0.42, p = 0.08) were negatively associated. Mortality (21.3%) was associated with increasing age (HR 1.42, p = 0.002), cognitive dysfunction (HR 3.93, p = 0.006), and cerebral infarctions (HR 1.94, p = 0.03).

Conclusions. PCNSV is a heterogeneous disorder, with vessel size of PCNSV involvement and the histological pattern detected on biopsy impacting presentation and outcomes.