The central theme of this Clinical Center Grant proposal is the clinical phenomenon of Epilepsy. It is a large, complex proposal designed to indicate the interdigitations of 29 individual proposals generated by a large and broad group of multidisciplinary clinical scientists. Thus, the proposed studies include evaluations of several specific forms of pharmacological therapy in adults and children including the evaluation and clinical trial of new anticonvulsant drugs. A series of detailed pharmacokinetic studies are proposed as well as examination of several biological consequences of drugs including changes during pregnancy. Studies in clinical neurophysiology include an attempt to develop EEG predictors of seizure frequency, computer analysis of various elements of the electrophysiological discharge, behavioral activation of EEG to improve diagnostic resolution as well as EEG studies of language localization which can have important consequences in theraputic surgical judgements. Radiologic techniques to improve diagnostic capabilities include the use of the CT scan to resolve ambiguities regarding localization and hopefully to assist in the diagnosis of incisural sclerosis. Frequency of seizures raises a variety of interesting statistical questions and computer modeling of seizure frequency will be examined as well as other statistical studies in epilepsy. These extend into several field studies of epidemiological phenomena as well as the roles of specific enviornmental factors such as stress and depression as determinates of seizure frequency. Such neuropsychological investigations extend into the area of rehabilitation where controlled studies will be undertaken of optimal techniques for evaluating capabilities for job placement and the cost effectiveness of specified rehabilitation measures as well as consumer involvement. Finally, studies to determine the effectiveness of various educational techniques involving both the public as well as the medical profession are proposed including educational efforts in nursing homes and an epilepsy information line which will hopefully uncover those problems of highest priority to patients with epilepsy. Thus, there is a broad spectrum of projects ranging from biological studies to those in the psychosocial area.
| Finnell, R H; Kerr, B M; van Waes, M et al. (1994) Protection from phenytoin-induced congenital malformations by coadministration of the antiepileptic drug stiripentol in a mouse model. Epilepsia 35:141-8 |
| Kroetz, D L; Kerr, B M; McFarland, L V et al. (1993) Measurement of in vivo microsomal epoxide hydrolase activity in white subjects. Clin Pharmacol Ther 53:306-15 |
| Finnell, R H; van Waes, M; Musselman, A et al. (1993) Differences in the patterns of phenytoin-induced malformations following stiripentol coadministration in three inbred mouse strains. Reprod Toxicol 7:439-48 |
| Anderson, G D; Acheampong, A A; Wilensky, A J et al. (1992) Effect of valproate dose on formation of hepatotoxic metabolites. Epilepsia 33:736-42 |
