Background/Purpose: Primary central nervous system vasculitis (CNS-V) is vasculitis confined to the brain, spinal cord and meninges. It is a rare condition with unknown pathogenesis. Brain biopsy is the gold standard for the diagnosis of CNS-V, which histologically is marked by transmural inflammation of small and medium-sized leptomeningeal and parenchymal arterial vessels. This study aimed to analyze in depth other histopathologic features that may better distinguish CNS-V from other non-CNS-V conditions.

Methods: We identified patients who had brain biopsy and who were enrolled in the prospective CNS Vasculopathy Bioregistry at the Cleveland Clinic between 2012 and 2019. Registry participants are enrolled in both outpatient and inpatient settings based on differential diagnosis of CNS-V or a mimic of its symptoms. Out of 33 patients included, 19 were diagnosed with CNS-V according to (Calabrese and Mallek, 1988). Fourteen patients had uncertain diagnosis or diagnosis not consistent with CNS-V. Pathology reports were analyzed looking for documented  inflammatory cell types (T cells, B cells, macrophages, reactive astrocytes, plasma cells, and giant cells) and other histological features (granuloma/epithelioid histiocytes, necrotizing vasculitis, infection, neuronal loss, myelin loss, and amyloid deposits), each categorized by the presence (‘yes/no’) of cell type or histological feature, abundance (‘scant’ or ‘abundant’), confirmation by staining (‘yes/no’), and localization (‘transmural’ or ‘perivascular’).

Results: Our cohort consisted of mostly white (~90%), male (≥50%) and middle-aged (48.6±15.8 years; age at biopsy) individuals who had undergone 1.15±0.44 biopsies. Both CNS-V and non-CNS-V cases had the right side (53% and 64%) and frontal lobe (35% and 29%) as the most affected sites. Patients with diagnosis of CNS-V were more likely to have vascular wall infiltration by T cells (33% vs 10%), B cells (20% vs 10%), macrophages (18% vs 0%), and reactive astrocytes (22% vs 0%), and more prevalence of necrotizing vasculitis (11.8% vs 0%). Perivascular distribution was conversely lower in CNS-V than non-CNS-V, noted in 42% vs 70% for T cells, 40% vs 60% for B cells, and 18% vs 20% for macrophages.

Conclusion: In this retrospective study, we took a broad approach of comparing brain biopsies of patients with or without CNS-V to identify histopathological features that may be unique or more predictive of CNS-V. Intramural infiltration of inflammatory cells was more specific to the diagnosis of CNS-V than findings of perivascular inflammatory process. The presence of perivascular inflammation is nonspecific and is more common in non-CNS-V specimens.  

Reference: Calabrese, L.H. and Mallek, J.A. (1988) Primary angiitis of the central nervous system. Report of 8 new cases, review of the literature, and proposal for diagnostic criteria. Medicine (Baltimore) 67, 20–39

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identifying-patterns-of-histopathologic-presentation-in-cns-vasculitis/