Abstracts

Rationale: Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIB, according to Palmini classification, share histopathologic similarities, specifically the presence of dysmorphic-cytomegalic neurons and balloon cells, which are believed to be the epilepogenic cells and cause pharmacoresistant epilepsy. As our previous studies have demonstrated that overexpression of adenosine kinase (ADK) decreases extracellular adenosine and consequently leads to seizures and overexpression of ADK as a pathological hallmark of temporal lobe epilepsy, we hypothesized that the epileptogenic mechanisms underlying TSC and FCD type IIB is related to changes in ADK expression and that those changes might be associated with the development of epilepsy in these patients. Methods: Surgically resected human epileptic cortical specimens from TSC (n=13) and FCD (n=10) type IIB, we use immunohistochemistry approach to examine the expression of ADK and GFAP; double-label immunohistochemistry for coexpression of ADK and GFAP, and compared with normal control cortical tissue. Western blotting was used to quantify changes of ADK expression in TSC and FCD type IIB versus controls. Results: We demonstrate that lesions in TSC and FCD type IIB contain a broad spectrum of abnormal cell types such as dysmorphic neurons, giant cells, balloon cells and reactive astrocytes. Dysmorphic neurons, giant cells, balloon cells and reactive astrocytes express high levels of ADK, especially in balloon cells. In contrast, Nonplastic neurons in TSC and FCD type IIB express very low ADK levels The increased ADK expression within the dysplastic cortex of TSC and FCD type IIB was confirmed by Western blotting. Conclusions: The dysregulation of ADK in balloon cells and dysplastic neurons within cortical lesions of TSC and FCD type IIB suggested the possible role of this enzyme in the intrinsic and increased epileptogenesis of malformations of cortical development associated epilepsy. ADK may represent a potential antiepileptogenic target in the treatment of epilepsy in TSC and FCD type IIB.