Abstracts

The role of febrile seizures (FS) in epileptogenesis and the contribution of fever to the long-term consequences of prolonged FS and febrile status epilepticus (SE) are poorly understood. Controversy remains regarding any causal relationship between prolonged FS and temporal lobe epilepsy.
This study investigated the contribution of hyperthermia per se to SE-induced epileptogenesis, using the lithium-pilocarpine model of SE in immature rats, and carefully controlling for brain temperature and seizure severity., SE was induced in rats at postnatal day 10 (P10) by administration of lithium (3mEq/kg, i.p.), and 24 hours later by pilocarpine (60 mg/kg, s.c.). Body temperature was maintained during 30 min of SE at 39[plusmn]1⁰C (hyperthermic animals) or at 35[plusmn]1⁰C(normothermic animals). SE was terminated by diazepam (0.5 mg/kg, i.p.). Control animals received lithium and diazepam in presence of hyperthermia or normothermia. The course of SE was recorded by video/EEG for 24 hours. The severity of SE was assessed by measuring the following parameters: duration of SE (time of last seizure), and total seizure time (time spent in seizures subtracting interictal time) using Harmonie Software. Separate groups of animals, subjected to SE at P10 without surgery, were monitored four months later for the occurrence of spontaneous recurrent seizures (SRS) by telemetry/videotape continuously for one month., We were able to control brain and body temperature during and after SE in both study groups: hyperthermic (39[plusmn]1⁰C) and normothermic (35[plusmn]1⁰C).
Terminating SE by diazepam was effective in both groups (10.2[plusmn]1.5 min in hyperthermic animals and 12.3[plusmn]2.2 min in normothermic animals). Total seizure time (54.5[plusmn]15.2 min after SE in hyperthermic animals and 56.7[plusmn]12.1 min after SE in normothermic animals) and duration of SE (87.2[plusmn]23.2 min after SE in hyperthermic animals vs. 95.2[plusmn]28.2 min after SE in normothermic animals) were similar between groups.
Only hyperthermic animals developed convulsive seizures (50%). Both groups of animals that experienced SE at P10 developed electrographic seizures 4 months later (83 vs 55%). However, the frequency and seizure severity were significantly higher in hyperthermic animals (12.5[plusmn]3.5 vs 4.2[plusmn]2.0 SRS/day)., Since the precise role of hyperthermia during SE in long-term consequences such as epileptogenesis and neuronal injury has never been adequately defined, this study tightly controlled seizure duration and seizure severity in order to isolate hyperthermia as the main variable and to study its consequences. In this model, hyperthermia greatly increased the epileptogenicity of SE, leading to subsequent behavioral seizures not seen in the normothermic group, and increased the severity and incidence of spontaneous electrographic seizures., (Supported by Grant NS13515 from NINDS, National Institutes of Health, and by the Research Service of the Veterans Health Administration.)