White matter angiopathy is common in pediatric patients with intractable focal epilepsies

Purpose: The blood-brain barrier (BBB) and functional organization of blood vessels is severely affected in many epilepsy disorders. This was repetitively shown with respect to the cause, effect and treatment of seizures. In the present study, we investigated pathomorphological abnormalities of blood vessels in a cohort of young patients with chronic intractable seizures submitted to an epilepsy surgery program. Methods: Histopathological examination was performed in surgical specimens obtained from 87 children with intractable epilepsies. Immunohistochemistry was employed to further characterize the basal membrane as well as specific cellular and tissue reactions. Pathological findings were correlated with clinical data including antiepileptic drug prescription. Results: We identified an intriguing pattern of white matter angiopathy in 64.4% of our patient cohort. Major alterations included splitting of the basal membrane into endothelial and parenchymal leaves, which was restricted to arterioles and capillaries of the white matter and resulted in an extensively enlarged perivascular space. These cavities contained numerous blood cells and showed a spongiform appearance at the ultrastructural level. Angiopathic changes occurred independent from specific epilepsy-associated lesions, i.e., dysplasia, neoplasia, or hippocampal sclerosis, and showed no correlation with antiepileptic drug treatment or seizure semiologies. Discussion: A high frequency of spongiform white matter angiopathy was identified in young patients with chronic epilepsies. The severity of basal membrane pathology and adjacent tissue reaction is compatible with compromised BBB function. Further clinicopathological investigations will be mandatory to clarify its relation to the cause or consequence of seizures in children with intractable seizures.