Abstracts

Rationale: Status epilepticus (SE) is the most common neurological emergency of childhood and a cause of high morbidity and mortality. The standard of care for the treatment of pediatric SE is an intravenous benzodiazepine followed immediately by a secondary antiepileptic drug. This treatment regimen provides seizure control in only two-thirds of cases and poorer performance in prolonged SE. Here we investigated whether allopregnanolone (5α,3α-P), an alternative positive allosteric positive modulator of GABA(A) receptors, could provide equal or better SE control with fewer side effects. Methods: Young rats (P9) were injected with kainic acid (2 mg/kg, i.p.), which reproducibly induced continuous tonic-clonic seizures. Ten or 40 min after the kainic acid injection, the animals received 5α,3α-P (30 mg/kg, i.p.) or diazepam (DZP; 5 mg/kg, i.p.). Treatment outcome (absence vs. presence of ongoing seizure activity) was recorded at 30 and 70 min after kainic acid administration. Results: When administered early (10 min) both 5α,3α-P and DZP caused freedom from status epilepticus at the 30 and 70 min evaluation time points. When administered at the late time point (40 min) DZP caused seizure freedom in 25% of animals whereas 5α,3α-P eliminated status epilepticus in 100% of animals at the 70 min time point. With vehicle, an average of 67% of animals were status-free at 30 min following kainic acid versus 0% at 70 min Conclusions: Both treatments, DZP and 5α,3α-P, were fully effective in our pediatric SE animal model when administered early in the course of SE. However, 5α,3α-P was significantly more effective than DZP when administered late. This suggests that 5α,3α-P may represent a superior initial treatment for children with SE, especially in cases where seizure activity is prolonged. This work was funded by a research grant from People Against Childhood Epilepsy (P.A.C.E.), New York.