Introduction: Primary small vessel CNS vasculitis is an increasingly recognized, devastating inflammatory brain disease in children. An elective brain biopsy is mandatory to confirm the diagnosis. However, no standardized evaluative approach for brain biopsies has been defined. The study aimed to develop and validate a histological scoring tool for the diagnosis of small vessel CNS vasculitis on brain biopsies.

Methods: A comprehensive, evaluative instrument was drafted and reviewed by 7 expert neuropathologists across Canada. The refined tool was applied to cases and epilepsy controls diagnosed at Sickkids, Toronto. Stains included Hematoxyllin & Eosin and immunohistochemistry for all immune cell subsets (CD3, 4, 8, 20 and 68). A consensus-meeting panel reviewed the results and finalized the tool for prospective validation.

Results: A total of 40 evaluations were included, 25 cases, 15 controls. Cortical inflammation was present in 68% of the cases vs. 24% of the controls (p=0.002) Perivascular small vessel inflammation was noted in 60% of cases vs. 20% of controls (P.04). Cortical vessel inflammation was predominantly T-cell mediated (79% CD3+, 96% CD8 +). White matter inflammation was present in 54% of cases vs. 3% of controls (p=0.01), correspondingly, white matter inflammation was primarily T-cell mediated (86% CD3+, 90% for CD8+), only 27% were CD20+. Myelin loss was rare in both cases and controls. Leptomeningeal inflammation was noted in 47% of cases and 45% of controls.

Conclusion: Canadian expert neuropathologists agreed on a consensus approach towards diagnosing small vessel CNS vasculitis including brain biopsy quality recommendations and a histological assessment tool.