Towards a histological diagnosis of childhood small vessel CNS vasculitis

• Published in: Pediatric rheumatology online journal 2024-12, Vol.22 (1), p.111-11, Article 111
• Main Authors: Nouri, Maryam Nabavi, Dropol, Anastasia, Tyrrell, Pascal N, Sheikh, Sheila, Twilt, Marinka, Michaud, Jean, Ellezam, Benjamin, Sarnat, Harvey B, Dunham, Christopher, Schutz, Peter W, Keith, Julia, Munoz, David G, Vinters, Harry V, Hawkins, Cynthia, Benseler, Susanne M
• Format: Article
• Language: English
• Subjects: Adolescent; Biopsy - methods; Brain - pathology; Brain biopsy; Child; Child, Preschool; cPACNS; Female; Humans; Inflammatory brain disease; Male; PACNS; Sv-cPACNS; Vasculitis, Central Nervous System - diagnosis; Vasculitis, Central Nervous System - pathology
• ISSN: 1546-0096; 1546-0096
• DOI: 10.1186/s12969-024-01053-4

Primary small vessel CNS vasculitis (sv-cPACNS) is a challenging inflammatory brain disease in children. Brain biopsy is mandatory to confirm the diagnosis. This study aims to develop and validate a histological scoring tool for diagnosing small vessel CNS vasculitis. A standardized brain biopsy scoring instrument was developed and applied to consecutive full-thickness brain biopsies of pediatric cases and controls at a single center. Stains included immunohistochemistry and Hematoxylin & Eosin. Nine North American neuropathologists, blinded to patients' presentation, diagnosis, and therapy, scored de-identified biopsies independently. A total of 31 brain biopsy specimens from children with sv-cPACNS, 11 with epilepsy, and 11 with non-vasculitic inflammatory brain disease controls were included. Angiocentric inflammation in the cortex or white matter increases the likelihood of sv-cPACNS, with odds ratios (ORs) of 3.231 (95CI: 0.914-11.420, p = 0.067) and 3.923 (95CI: 1.13-13.6, p = 0.031). Moderate to severe inflammation in these regions is associated with a higher probability of sv-cPACNS, with ORs of 5.56 (95CI: 1.02-29.47, p = 0.046) in the cortex and 6.76 (95CI: 1.26-36.11, p = 0.025) in white matter. CD3, CD4, CD8, and CD20 cells predominated the inflammatory infiltrate. Reactive endothelium was strongly associated with sv-cPACNS, with an OR of 8.93 (p = 0.001). Features reported in adult sv-PACNS, including granulomas, necrosis, or fibrin deposits, were absent in all biopsies. The presence of leptomeningeal inflammation in isolation was non-diagnostic. Distinct histological features were identified in sv-cPACNS biopsies, including moderate to severe angiocentric inflammatory infiltrates in the cortex or white matter, consisting of CD3, CD4, CD8, and CD20 cells, alongside reactive endothelium with specificity of 95%. In the first study of its kind proposing histological criteria for evaluating brain biopsies, we aim to precisely characterize the type and severity of the inflammatory response in patients with sv-cPACNS; this can enable consolidation of this population to assess outcomes and treatment methodologies comprehensively.