Abstracts

Focal cortical dysplasia with Taylor type balloon cells (FCDIIb) constitutes a frequent and histopathologically distinct finding in patients with pharmacoresistant focal epilepsies. Recent data indicate a pathogenetic role of TSC1, known to be mutated in Tuberous Sclerosis (TSC), for FCDIIb. TSC1 represents a key factor in the phosphatidylinositol 3-kinase (PI3K) pathway. In order to further elucidate the molecular pathology of FCDIIb, we have analyzed two additional major components of the PI3K-cascade in FCDIIb, i.e. PTEN and Akt which operate upstream of TSC1. Mutational screening of PTEN was performed by single-strand conformation polymorphism analysis (SSCP) in 37 FCDIIb compared to 100 controls. Immunohistochemistry with antibodies against phospho-Akt (Ser473) was carried out in FCDIIb (n=37). We found several silent polymorphisms of PTEN in exon 2 (n=3) and exon 8 (n=1) as well as an amino-acid exchange at position 279 (exon 8) with replacement of phenylalanine by leucine (F279L) in one patient. Using laser assisted microdissected cell samples, this alteration was only found in FCDIIb components but not in adjacent CNS tissue. We demonstrated an increased immunoreactivity for phospho-Akt in balloon cells and dysplastic neurons but not in adjacent normal CNS tissue. These data demonstrate alterations of the PI3K pathway components PTEN and Akt in FCDIIb. This is in line with the hypothetical role of the PI3K cascade in focal cortical dysplasias with Taylor type balloon cells. (Supported by DFG (SFB TR3) and BONFOR)