Clinical and neuropathological features of brain biopsies in 13 children diagnosed with angiography-negative, small vessel primary central nervous system angiitis (SVcPACNS) were characterized in a prospective cohort study at the Hospital for Sick Children, University of Toronto, Canada. Diagnosis was based on Calabrese criteria: 1) an acquired neurological deficit, 2) angiographic or histological evidence of cPACNS, and 3) no evidence of systemic vasculitides. Sites for lesional biopsies were identified by MRI. Nonlesional biopsies were sampled from the nondominant frontal lobe. The definition of SV vasculitis used for diagnosis of cPACNS required all of the following: 1) at least 2 layers of lymphocytes around vessel walls, 2) prominent endothelial cells in vessel walls, 3) neuronophagia, 4) parenchymal edema, and 5) no alternate diagnosis. Probable SVcPACNS required criteria (2) through (5). Patient ages ranged from 5 to 17 years. Presenting features included seizures (85%), headache (62%), and cognitive decline (54%). Elevated ESR and C-reactive protein, elevated CSF pressure and protein level, and moderate pleocytosis were frequent laboratory findings. EEG abnormalities included diffuse slowing and focal epileptiform discharges. MRI showed abnormalities attributable to cPACNS in 11 patients; 2 (15%) patients showed no evidence of vasculitis. Brain biopsy confirmed SVcPACNS diagnosis in 11 patients showing intramural lymphocytic infiltrate. Six nonlesional biopsies were also diagnostic. Lack of histological features correlated with delayed biopsy, prior steroids, or inadequate specimens.

Children presenting with new onset severe headaches, seizures, or cognitive decline should be considered for the diagnosis of SVcPACNS and brain biopsy. The biopsy should be collected before prolonged treatment with steroids. Histological features consistent with SVcPACNS include lymphocytic intramural inflammatory infiltrate, surrounding gliosis, and reactive endothelial cells. Absence of intramural infiltrate does not rule out the diagnosis and treatment with immunosuppression. [1]

COMMENT. PACNS is an immune-mediated, acquired inflammatory disease involving either small or large CNS blood vessels. In children, the disease may present acutely with seizures and refractory status epilepticus, subacutely with focal neurological deficits, or chronically with headaches and cognitive decline. In an editorial, Hunder GG and Brown RD Jr of the Mayo Clinic, Rochester, MN, and Salvarani C of Italy question whether childhood PACNS is a single disease entity [2]. They report 8 adult cases with similar findings to those in children, except in adults, focal neurological abnormalities occur in all 8 (only 2 of 13 in children), seizures are absent, and ESR is normal [3]. Histological findings are also different in adult cases. Small vessel PCNSV in adults is less clearly defined than in children.

Diagnosis of cPACNS should be considered and brain biopsy performed in a child presenting with new-onset seizures, severe headaches, and cognitive decline, associated with elevated ESR, CSF pleocytosis and elevated protein, and MRI evidence of vasculitis.