title: Are developmental dysplastic lesions epileptogenic?
abstract: Cortical dysplasia of various types, reflecting abnormalities of brain development, have been closely associated with epileptic activities. Yet, there remains considerable discussion about if/how these structural lesions give rise to seizure phenomenology. Animal models have been used to investigate the cause-effect relationships between aberrant cortical structure and epilepsy. In this article, we discuss three such models: (1) the Eker rat model of tuberous sclerosis, in which a gene mutation gives rise to cortical disorganization and cytologically abnormal cellular elements; (2) the p35 knockout mouse, in which the genetic dysfunction gives rise to compromised cortical organization and lamination, but in which the cellular elements appear normal; and (3) the methylazoxymethanol-exposed rat, in which time-specific chemical DNA disruption leads to abnormal patterns of cell formation and migration, resulting in heterotopic neuronal clusters. Integrating data from studies of these animal models with related clinical observations, we propose that the neuropathologic features of these cortical dysplastic lesions are insufficient to determine the seizure-initiating process. Rather, it is their interaction with a more subtly disrupted cortical "surround" that constitutes the circuitry underlying epileptiform activities as well as seizure propensity and ictogenesis.
authors.affiliation: Department of Neurological Surgery, University of California-Davis, One Shields Ave., Davis, CA 95616, U.S.A. paschwartzkroin@ucdavis.edu
authors.forename: Philip A
authors.initials: PA
authors.lastname: Schwartzkroin
authors.forename: H Jürgen
authors.initials: HJ
authors.lastname: Wenzel
mesh_terms: D000818:Animals; D002273:Carcinogens; D004195:Disease Models, Animal; D004827:Epilepsy / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D054220:Malformations of Cortical Development / Q000150:complications* / Q000175:diagnosis / Q000473:pathology*; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives; D051379:Mice; D018345:Mice, Knockout; D010770:Phosphotransferases / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D014402:Tuberous Sclerosis / Q000473:pathology
chemical_list: D002273:Carcinogens; C492236:Cdk5r1 protein, mouse; D008746:Methylazoxymethanol Acetate; D010770:Phosphotransferases; C030667:methylazoxymethanol