IMPACT OF PREVENTING PROLONGED FEBRILE SEIZURES IN THE PREDISPOSED BRAIN

Objectives: We have shown that pups with a focal cortical dysplasia develop prolonged hyperthermia-induced seizures (a model of febrile seizures) and temporal lobe epilepsy. The goal of this study was to demonstrate that preventing prolonged seizures in our model of temporal lobe epilepsy would improve long-term outcome, even in the predisposed individuals.

Methods: We studied 4 groups of pups. The first had the dysplastic lesion and hyperthermia (LH=17), the second LH plus diazepam (LHD=10), the third hyperthermia alone (H=10) and the fourth hyperthermia plus diazepam (HD=10). Animals were monitored for the severity and duration of the acute seizure at P10 and their brain removed 2 weeks later to assess the histological damage induced by the seizure.

Results: The LH group had the most severe seizures, lasting up to 34.68±7.4 versus 25.37±4.9 minutes in the H group. Diazepam reduced seizure duration to 7.26±0.88 (LHD) versus 8.43±2.81 (HD). Intra-peritoneal diazepam proved to be effective in every animal. At 2 weeks post hyperthermia, hippocampal asymmetry was seen only in LH rats. Moreover, 30% (5/17) of the LH rats had severe hippocampal atrophy, more than 2SD reduction, a condition not seen in the other groups.

Conclusion: Diazepam therapy can prevent hippocampal damage associated with prolonged hyperthermia-induced seizures in the predisposed brain. Studies are ongoing to assess its impact on the long-term risk of developing temporal lobe epilepsy and hippocampal dysfunction.