Laboratory Research Electroencephalographic Characterization of an Adult Rat Model of Radiation-Induced Cortical Dysplasia Shinji Kondo, Imad Najm, Takeharu Kunieda, Scott Perryman, Karina Yacubova, Hans O. Lu ¨ders Section of Epilepsy, Department of Neurology, The Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A. Summary: Purpose: Cortical dysplasia (CD) is a frequent cause of medically intractable focal epilepsy. The mechanisms of CD-induced epileptogenicity remain unknown. The diffi- culty in obtaining and testing human tissue warrants the iden- tification and characterization of animal model(s) of CD that share most of the clinical, electroencephalographic (EEG), and histopathologic characteristics of human CD. In this study, we report on the in vivo EEG characterization of the radiation- induced model of CD. Methods: Timed-pregnant Sprague–Dawley rats were irradi- ated on E17 using a single dose of 145 cGy or left untreated. Their litters were identified and implanted with bifrontal epi- dural and hippocampal depth electrodes for prolonged continu- ous EEG recordings. After prolonged EEG monitoring, animals were killed and their brains sectioned and stained for histologic studies. Results: In utero–irradiated rats showed frequent spontane- ous interictal epileptiform spikes and spontaneous seizures aris- ing independently from the hippocampal or the frontal neocortical structures. No epileptiform or seizure activities were recorded from age-matched control rats. Histologic stud- ies showed the presence of multiple cortical areas of neuronal clustering and disorganization. Moreover, pyramidal cell dis- persion was seen in the CA1CA3 areas of the hippocampal formations. Conclusions: Our results further characterize the in vivo EEG characteristics of the in utero radiation model of CD using long-term EEG monitoring. This model may be used to study the molecular and cellular changes in epileptogenic CD and to test the efficacy of newer antiepileptic medications. Key Words: Epilepsy—Cortical dysplasia—Radiation—Rat— Seizures—Spikes. Histopathologic confirmation of human cortical dys- plasia (CD) in the setting of medically intractable epi- lepsy was first reported by Taylor et al. (1) in 1971. Since then, several reports described a high correlation be- tween various histologic types of CD and epileptogenic- ity in patients with drug-resistant epilepsy (2,3). The advent of high-resolution magnetic resonance imaging (MRI) techniques has allowed the better noninvasive identification of neocortical lesions that correspond to EEG-defined epileptogenic foci, including small CD le- sions (4–7). Although human CD is a frequent cause of medically intractable focal epilepsy and carries a worse postsurgi- cal seizure outcome than mesial temporal lobe sclerosis (8,9), little is known about the mechanism(s) of epilep- togenicity in these lesions. The difficulty in obtaining and testing human tissue warrants the identification and characterization of animal model(s) of CD that share most of the clinical, electroencephalographic (EEG), and histopathologic characteristics of human CD. To date, several animal models of CD have been described such as the focal cold injury model (10,11), the in utero al- kylating agent model (12–15), and the in utero radiation– induced model (16,17). These models are associated with some histopathologic changes that are similar to those observed in human CD. Previous studies showed an in- creased in vitro epileptogenicity in hippocampal and cor- tical slices of in utero–irradiated rats. Moreover, an increased susceptibility to in vivo anesthesia-induced seizures was reported in the same irradiation model (17). Thus far, spontaneous seizures have been observed only in some genetic models of epilepsy (18,19), but continuous EEG monitoring to study the occurrence of spontaneous in vivo interictal or ictal epileptic activity in the rat irradiation model of CD or other animal models of injury-induced cortical malformation has not been re- ported (20). The present study reports on the in vivo EEG of the in utero radiation–induced CD model using the continuous digital EEG monitoring technique with bilat- Revision accepted June 7, 2001. Address correspondence and reprint requests to Dr. I. M. Najm at Section of Epilepsy, 9500 Euclid Avenue, S51, Cleveland, OH 44195, U.S.A. E-mail: najmi@ccf.org Epilepsia, 42(10):1221–1227, 2001 Blackwell Science, Inc. © International League Against Epilepsy 1221