Abstracts

Rationale: Blood gene expression profiles can differentiate neurological diseases including epilepsy (Tang et. al., Arch. Neurol. 62: 210-215, 2005). A previous retrospective analysis of hippocampal pathology in human temporal lobe epilepsy (TLE) revealed patient subcategories associated with different surgical outcomes: mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE) and mass associated TLE (MaTLE) had good surgical outcome, whereas paradoxical TLE (PTLE) had a poor outcome. The objective of this study was to determine if TLE patients could be distinguished from other types of epilepsy, and if MTLE could be distinguished from PTLE on the basis of blood gene expression profiles.Methods: Clinical data was collected, and subjects were categorized using the International League Against Epilepsy classification. Subjects who underwent temporal resections were further characterized as MTLE or PTLE. Whole blood was collected in Tempus RNA tubes, and RNA was isolated using the Tempus protocol. Gene expression profiles were determined by microarray analysis using the Affymetrix human GeneChip U133 Plus 2.0 array. Unsupervised hierarchical cluster analysis and multidimensional scaling was performed to look for class identification. ANOVA analysis was used to determine differentially expressed genes.Results: Twenty-seven epileptic subjects and 8 controls were enrolled. Eleven of the subjects had temporal resections; pathology was MTLE in 9 and PTLE in 2. Eleven subjects had cryptogenic localization-related epilepsy (CLRE) and 5 subjects had idiopathic generalized epilepsy (IGE). The average age of controls was 24.9 yr and subjects with epilepsy – IGE, CLRE, MTLE, and PTLE were 24, 31.1, 43 and 30.5 yr respectively. AED types overlapped between patient groups. Of the subjects on AEDs, 2 were on valproate (VPA) monotherapy, 3 on lamotrigine (LTG) monotherapy, 2 on carbamazepine (CBZ) monotherapy, and 1 on oxcarbazepine (OXC) monotherapy. Postoperative seizure freedom was achieved in 56% of MTLE and 0% of PTLE subjects. Controls clustered separately from all epileptic subjects. Epileptic types did not show independent clustering, but both PTLE subjects were in the same cluster. TLE subjects did not cluster by outcome. Subjects on VPA monotherapy clustered independently of subjects on CBZ monotherapy, LTG monotherapy, or OXC monotherapy.Conclusions: TLE does not have a distinct gene expression profile, but epileptic subjects have a unique profile compared to controls. This difference is not related to seizure freedom or AED therapy. Whereas MTLE subjects are found in several clusters, the PTLE share the same cluster. In agreement with Tang et al. (Acta Neurol. Scand. 109: 159-168, 2004), VPA monotherapy has a unique blood gene expression pattern compared to CBZ monotherapy, and in the present study also LTG and OXC monotherapy. Genes that are differentially expressed between epileptic subjects and controls, and VPA and other monotherapies will be discussed.