Abstracts

Atypical febrile seizures have been associated with the mesial temporal lobe epilepsy syndrome. However, its impact on brain development remains poorly understood. In adult patients with mesial temporal lobe epilepsy and a history of atypical febrile seizures in early life, MRI volume and signal abnormalities have been reported. Recently, we have demonstrated that a localized cortical microgyrus predisposes immature rats to atypical hyperthermic seizures (HS) and chronic epilepsy. The purpose of this study is to investigate the effect of this atypical HS on brain development. Freeze lesions (focal microgyri) were induced in the right fronto-parietal cortex of rats on postnatal day (P)1. HS were then induced at P10 by exposure to moderately-heated dry air. To evaluate the impact of the HS on the cerebral asymmetry; right and left hemispheric, cortical, subcortical and hippocampal volumes were estimated at P22 and P80 using the Cavalieri method after having sectioned the brains and determined the area of each section using the public domain NIH Image program. The degree of hemispheric asymmetry was estimated by calculating a ratio between the volumes of the right and left structures. Controls were sham-operated and na[iuml]ve rats with and without HS (non-lesioned controls) and rats that only received the lesion (lesioned controls). At both ages, there was no difference in the volumes between the non-lesion controls therefore these results were pooled. At P22, the ratio of hemispheric volumes in lesioned rats with HS (0.960 [plusmn] 0.037) was significantly smaller than that observed in non-lesioned controls (1.007 [plusmn] 0.008, P[lt]0.02). When the hemispheres were divided into cortical and subcortical volumes, asymmetry was only seen in the cortex (0.947 [plusmn] 0.049 vs. 1.018 [plusmn] 0.012, P[lt] 0.01). At P80, similar results were obtained only this time all three ratios, hemispheric, cortical and subcortical, in lesioned rats with HS were significantly smaller than those obtained in non-lesioned controls. When the ratios of hippocampal volumes in lesioned rats with HS were compared at P22 (0.948 [plusmn] 0.070) and P80 (0.902 [plusmn] 0.075) they were both significantly smaller than non-lesioned controls ratios (P22: 1.027 [plusmn] 0.083, P[lt] 0.02 and P80: 0.987 [plusmn] 0.070, P[lt] 0.05). Our results show a progressive hemispheric asymmetry including the hippocampus in lesioned rats with HS. This is in line with studies of volume and signal abnormalities in humans. Ongoing studies will let us determine the underlying pathophysiological mechanisms. (Supported by the Hospital for Sick Children Foundation (LC), the Ste-Justine Hospital Foundation (LC, SAG), a CIHR MD/PhD scholarship (SAG) and a CIHR/Epilepsy Canada post-doctoral scholarship (MHS).)