Abstracts

The reported association between atypical febrile seizures and temporal lobe epilepsy (TLE) is controversial and thus far has not been supported by cohort or experimental studies. We have recently demonstrated that focal cortical dysplasia resulted in atypical hyperthermic seizures (HS). The purpose of this study is to determine whether HS in lesioned rats will result in subsequent spontaneous recurrent seizures along with visuo-spatial learning and memory deficits paralleling that seen in patients with TLE. Freeze lesions (focal microgyri) were induced in the right fronto-parietal cortex of rats on postnatal day (P) 1, followed by HS at P10. To evaluate for spontaneous recurrent seizures, male rats [gt] P 60 were video monitored for 5 hours/ day for 10 days. In a subgroup of animals, EEGs were then recorded 20 minutes/day for 5 days from the amygdala ipsilateral to the lesion. Prior to the EEG study visuo-spatial learning and memory were evaluated using the Morris water maze test. Controls were sham-operated and na[iuml]ve rats with and without hyperthermic seizures (non-lesioned controls) and rats that received the lesion alone (lesioned controls). Recurrent behavioural seizures were observed in 4/11 (36%) of lesioned rats with HS and were characterized by freezing in association with head nodding and less frequently jaw-myoclonus. This activity was often preceded or followed by wet dog shakes. Of this group spontaneous electrographic seizures were recorded in 6/7 (86%) of rats and were characterized by runs of epileptic spikes and/or rhythmic slow (1-2HZ) spike or polyspikes and wave activity. EEG seizures were associated with behavioural manifestations similar to that observed on video-monitoring. Behavioural seizures were also seen in (1/7) 14% of the sham-operated rats with HS and electrographic seizure activity were recorded in 4/6 (66%). Behaviour or electrographic seizures were not observed in the other control groups. Regarding the Morris water maze testing there were no differences in the mean search difference score (MSD) between the non-lesioned control groups therefore their results were pooled. The MSD in lesioned rats with HS (Mean [plusmn] SD; 25.6[plusmn] 12.8, n=13) was significantly lower than in non-lesioned controls (34.7[plusmn]10.3, n=20; p[lt]0.05). The MSD in lesioned controls was in between that of lesioned rats with HS and that of non-lesioned controls, but did not statistically differ from the two groups. This study demonstrates a link between the atypical febrile seizure and the development of TLE as well as learning and memory deficits; supporting a complicating role for cortical dysplasia and possibly significant neonatal stress for the development of these conditions, following febrile seizures. (Supported by Saint Justine Research Foundation, Epilepsy Canada / CIHR, Hospital for Sick Children Foundation)