Towards a histological diagnosis of childhood small vessel CNS vasculitis. (S35.003)

OBJECTIVE: To systematically review biopsies of Childhood primary small vessel CNS vasculitis (SVcPACNS) patients and inflammatory and epilepsy controls and to determine characteristic features defining the diagnosis of SVcPACNS.BACKGROUND: SVcPACNS is an increasingly recognized inflammatory brain disease with high morbidity and mortality mandating an elective brain biopsy to confirm the diagnosis.DESIGN/METHODS: A previously developed, standardized brain biopsy review instrument was applied to consecutive full thickness brain biopsies of pediatric cases and controls collected at a single center. Standardized stains including Hematoxyllin u0026 Eosin, histochemistry of immune cell subsets plus electron microscopy. Nine North American expert neuropathologists were blinded reviewed to the patient’s presentation, diagnosis and therapy. All biopsies were de-identified and scored independently by two reviewers. Univariate analyses compared variable between groups; correspondence analysis determined the multi-dimensional relationship of histological variables and patient diagnoses.RESULTS: A total of 31 brain biopsy specimens of children with SVcPACNS, 12 with epilepsy and 11 with non-vasculitic inflammatory brain disease controls were included. Correspondence analyses revealed distinct clusters of the three diagnoses based on dimensions of location of infiltrate and subtype/ severity of inflammation. Significant histological characteristics found to set apart SVcPACNS from controls included angiocentric (pu003c0.01) and/or perivascular infiltrates (p=0.04), evidence of endothelial cell activation (pu003c0.01) and inflammation in both grey and white matter (pu003c0.01). The infiltrate was found to be primarily T-cell mediated (CD3+ 86[percnt], CD8+ 90[percnt]) only 27[percnt] of SVcPACNS biopsies had evidence of B cells. Features reported in adult PACNS including granulomas, necrosis or fibrin deposits were absent in all biopsies. Leptomeningeal inflammation was non-diagnostic.CONCLUSIONS: Distinct histological features were identified on brain biopsies of SVcPACNS and may help define the disease. These were absent in biopsies of children with epilepsy and non-vasculitic inflammatory brain diseases and allow for the development of diagnostic criteria. Disclosure: Dr. Nabavi Nouri has nothing to disclose. Dr. Tyrrell has nothing to disclose. Dr. Twilt has nothing to disclose. Dr. Dropol has nothing to disclose. Dr. Sheikh has nothing to disclose. Dr. Benseler has nothing to disclose. Dr. Hawkins has nothing to disclose.