NEURONAL MIGRATION DISORDERS INCREASE SUSCEPTIBILITY TO HYPERTHERMIA-INDUCED SEIZURES IN DEVELOPING RATS

Purpose: Retrospective studies suggest that adult patients with intrac table epilepsy may have a history of febrile seizures in childhood. Ri sk factors for a febrile seizure may include the rate of increase in t he core temperature (T-core), its peak (T-max), the duration of the te mperature increase, or an underlying brain pathology. Recently, neuron al migration disorders (NMD) have been diagnosed with increasing frequ ency in patients with epilepsy, but the link between NMD, febrile seiz ures, and epilepsy is unclear. We studied rat pups rendered hypertherm ic to ascertain the incidence of seizures, mortality, and extent of hi ppocampal cell loss in each group. Methods: We exposed 14-day-old rat pups with experimentally induced NMD (n = 39) and age-matched controls (n = 30) to hyperthermia (core body temperature >42 degrees C). Resul ts: The incidence of hyperthermia-induced behavioral seizures and mort ality rate were significantly higher in rats with NMD than in controls (p < 0.05), The longer duration of hyperthermia resulted in a higher incidence of behavioral seizures and higher mortality rate (p < 0.05). In rats with NMD, hyperthermia resulted in hippocampal pyramidal cell loss independent of seizure activity; the extent of neuronal damage c orrelated positively with the duration of hyperthermia. In control rat s, occasional neuronal loss and astrocytosis occurred only after prolo nged hyperthermia. Conclusions: In immature rats, NMD lower the thresh old to hyperthermia-induced behavioral seizures and hyperthermia in th e presence of NMD may cause irreversible hippocampal neuronal damage.