This project is designed to study the in situ histological, immunocytochemical and molecular characteristics of dysplastic lesions of the human cortex associated with medically intractable epilepsy. The in situ characteristics will be closely correlated with focal EEG changes on subdural invasive recordings using various EEG recording techniques. The extent of EEG and histological, immunocytochemical and molecular changes will be further correlated with magnetic resonance imaging (MRI) gyral/sulcal abnormalities using 3D volume rendering and FLAIR imaging techniques. This proposal will answer two clinically significant questions: 1) Will in situ histological, immunocytochemical, and molecular changes predict the localization and extent of the EEG focal epileptogenic-lesions in cortical dysplasias (CDS)? 2) Will new MR imaging techniques and ictal DC shift invasive recordings be predictive of cortical dysplasias (CDS) defined by immunocytochemistry (ICC)? 3) Will the MRI/EEG localization better predict success of surgical treatment in patients with CDS? Metabolic changes in intractable epilepsy due to CDS will be related quantitatively to the glutamate receptor subunits at the site of increased epileptogenicity in CD lesions. The study of the roles of glutamate receptors in CDS is critical for the understanding of the mechanisms of epileptogenicity of these lesions. Correlation between in situ immunocytochemical and molecular changes, ictal EEG changes and MRI lesions, with the postoperative surgical outcome will be made. The proposed studies present us with the unique opportunity to apply and quantify new clinical diagnostic modalities for the identification of epileptogenic CDS and to directly correlate clinical data with cellular changes. Medically intractable focal epilepsy due to cortical dysplasias (CDS) is the most frequent type of focal epilepsy after temporal lobe epilepsy (TLE), but it has a worse postsurgical seizure outcome than temporal lobectomy. Most surgeons recognize that unlike the well-established protocols used for the diagnosis and surgical treatment of TLE, with CDS diagnostic accuracies and surgical guidelines have not yet been well established. The proposed research will map the invasive EEG changes using various EEG recording techniques, state of the art imaging techniques and postresection histopathological, immunocytochemical and molecular methods. The results will be compared to clinical data, and validated through a rigorous assessment of postsurgical seizure outcome as an end point. The results will determine the role(s) of various glutamate receptor subunits in the expression of epileptogenicity in CDS, and determine the utility of newer EEG and non-invasive imaging techniques for the presurgical evaluation of patients with CDS and medically intractable epilepsy. This multidisciplinary, quantified approach has not previously been used systematically for the CD epileptic population. Our findings should establish better and more reliable standards for the diagnosis and surgical treatment of epilepsy due to CDS.
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