Abstracts

Focal cortical dysplasia (FCD) and glioneuronal tumors (GNT) are recognized causes of chronic intractable epilepsy. The cellular mechanism(s) underlying their epileptogenicity remain largely unknown. An increasing number of observations in experimental models of seizures suggest an important and complex role of cytokines, such as the interleukin-1[beta] (IL1[beta]), in the occurrence of seizures and in epileptogenesis. We investigated the brain expression and cellular distribution pattern of IL-1[beta] and the IL-1 receptor type 1 (IL-1R1) in FCD and GNT (ganglioglioma, GG and dysembryoplastic neuroepithelial tumors, DNT) specimens from patients with medically intractable epilepsy. Immunocytochemical expression of IL-1[beta] and IL-1R1 was investigated in specimens of FCD (n= 7; type IIB), GG (n= 9) and DNT (n= 9) obtained during epilepsy surgery. In non-epileptic control brain, IL-1[beta] and IL-1R1 expression was below detection in both glial and neuronal cells. In contrast, IL-1[beta] and its receptor were highly expressed in the neuronal component of the large majority of FCD, GG and DNT specimens. The IL-1[beta] and IL-1R1 immunoreactivity (IR) was found in neurons of different size, including large dysmorphic neurons and balloon cells in FCD cases. Glial cells with astrocytic morphology showed IR for IL-1[beta] and IL-1R1 in FCD and GNT specimens. No notable IR was found in oligodendroglial cells in DNT. Perilesional regions, with histological normal cortex, did not show increased staining compared to normal control cortex. However, IL-1[beta] IR was observed in reactive astrocytes in GNT cases with diffuse perilesional reactive gliosis. In addition, neuronal and glial expression of IL-1[beta] and IL-1R1 were detected outside the lesion in GNT cases in which the tumor was bordered by dysplastic cortex and in the hippocampus in cases with dual pathology. Our findings indicate high expression of IL-1[beta] and its receptor (IL-1R1) in both FCD and GNT specimens. Thus, the IL-1 system might represent a novel target for therapeutic approaches aimed at controlling the intrinsic and high epileptogenicity of these developmental lesions, which represent two major causes of medically intractable pediatric epilepsy. (Supported by the National Epilepsy Fund - [ldquo]Power of the Small[rdquo] and Hersenstichting Nederland (NEF 02-10; E. Aronica)., and by Fondazione Mariani Onlus (R-05-46; A.Vezzani).)