Novel variant of cortical dysplasia in two cases of infantile intractable epilepsy

Abstract

Cortical dysplasia (CD) is a frequent cause of intractable epilepsy (IE), especially infantile spasms. CD is defined by neuropathologic features of neuronal disarray, dysmorphism and heterotopia, frequently together with neuronal cytologic abnormalities and “balloon cells”. We report two cases of infantile IE, a 5‐year‐old male and a 17‐year‐old female in whom neuroimaging studies showed findings consistent with CD and histopathologic examination of the corticectomies revealed severe CD with abundant Rosenthal fibers (RF), widely distributed throughout subpial regions and within subcortical white matter. The abundance and location of RF was reminiscent of neuropathologic changes seen in Alexander's disease. Sequencing of the GFAP gene was performed on DNA extracted from resected frozen tissue in one case and although no mutation was found three previously known SNPs were identified. Rare similar cases have been reported (Kupsky & Frosch 1993). The abundant RF seen in association with CD may represent a dysregulation of synthesis/metabolism of alpha B‐crystallin, the main component of the RF, aggregating in association with GFAP, or be secondary to the severity of the CD which produces a dys/upregulation of GFAP to levels sufficient to induce RF and localized leukodystrophy due to astrocytic dysfunction.