The results of a double-blind, randomized, placebo-controlled trial of oral diazepam administered only at the time of fever are reported from Tufts University School of Medicine and Boston University School of Public Health, Boston. Among 406 children of mean age 24 months who received diazepam, 0.33 mg/kg/body wt, or placebo orally every 8 hours during febrile illnesses, the reduction in risk of recurrence of febrile seizures in the diazepam-treated group, based on an intention-to-treat analysis, was 44% during a mean follow-up of 1.9 years. An analysis restricted to children who had seizures while actually taking the prescribed medication (45 seizures in 36 children) showed 29 seizure occurrences in the placebo group and only 7 in the diazepam group, an 82% reduction in recurrence risk. Moderate side effects, including ataxia, lethargy, or irritability, were reported in 59 (39%) of 153 children who took at least one dose of diazepam. Mild side effects occurred with the same frequency. 
COMMENT. The authors advocate the prevention of recurrence of all febrile seizures and recommend oral diazepam, taken at the first sign of illness, as the optimal prophylactic medication. The benefit demonstrated in this zealously monitored study may not be duplicated in practice when compliance is often less than satisfactory. In a previous controlled trial, Autret and colleagues in France found the results of intermittent oral diazepam therapy disappointing, a lack of efficacy explained by poor compliance . An approved rectal preparation of diazepam for the home treatment of the acute febrile seizure in high risk patients may offer one alternative to the universal prophylactic intermittent regimen proposed. A survey of pediatric neurologists found only 22% in favor of diazepam (mean dose, 0.46 mg/kg/day at times of fever) in 1990 . A more general acceptance of diazepam by pediatricians and parents may be expected following the Boston report, and the results of this wider experience will determine the practical value and safety of this form of treatment.
A clearer understanding of the mechanism of susceptibility to febrile seizures may lead to more specific therapies. Experiments at Ehime Univ School of Medicine, Japan, demonstrate a hyperthermia-induced increase in cortical extracellular glutamate correlating with a decrease in seizure threshold temperature in rats.