The Effect of Ethyl Loflazepate on Refractory Childhood Epilepsy

Abstract

Purpose: A clinical and electroencephalographic study was performed to evaluate the effect of ethyl loflazepate (LOF) on patients with childhood refractory epilepsy. Methods: We investigated the effect of LOF add‐on therapy (0.1–4.0 mg/day, 0.003–0.374 mg/kg/day) on clinical seizures and EEGs as well as side effects in 39 patients, ranging in age from 3 months to 23 years, with 33 of the 39 being under IS years of age. The study population consisted of I3 patients with symptomatic localization‐related epilepsy: frontal lobe epilepsy in 4, temporal lobe epilepsy in I, other types i n 8; 22 with symptomatic generalized epilepsy: Ohtahara syndrome in 1, West syndrome in 6, Lennox‐Gastaut syndrome in 9, other types in 6; and 4 with undetermined epilepsy: severe myoclonic epilepsy in infancy in 1, epilepsy with continuous spike‐wave during slow wave sleep in, and other types in I. The patients underwent the LOF treatment for >3 months (maximum, 2 years and 1 month). Results: (I) LOF had marked effect (complete suppression or >75% reduction of seizures) in 8 cases and moderate effect (50%‐74% reduction of seizures) in 5 cases. Transient benefit for <1 month was observed in I I cases. The remaining 15 cases showed no effect. (2) Marked or moderate effects were found in 18 (72.8%) of 22 cases with symptomatic generalized epilepsy (long‐lasting effects in 8 and only a transient initial effect i n lo), in 3 (23. I%) of 13 cases with symptomatic localization‐related epilepsy, and in 2 (50%) of 4 cases with undetermined epilepsy. (3) Types of seizure in effective (marked or moderate) cases consisted of spasms in 8, tonic seizures in 2, and complex partial seizures in 3 cases. (4) EEG findings in 13 effective cases showed that a decrease in epileptic discharge was seen i n 5 cases with no change in the remaining 8. (5) The correlation between maximum dosage and blood concentration level was investigated in each patient, and the results confirmed a significant correlation (R= 0.691). However, no significant correlation was observed between maximum dose per body weight (kg) and effectiveness. (6) Side‐effects such as sleepiness, hypersalivation, hypotonia, hyperexcitability, and restlessness were observed i n 20 (5 1.3%) patients. In I patient, the drug administration was discontinued due to drug‐induced microseizures during sleep. Conclusion: LOF is an effective drug for symptomatic generalized epilepsy in children who show spasms, although a significant number of cases showed tolerance and only a transient initial effect.