Vigabatrin in Childhood Epilepsy

Abstract

Sixty-six children with various types of severe drug-resistant epilepsy were entered into a long-term, dose-rising study of vigabatrin after a 4-week run-in placebo period. All the children were receiving one to three other antiepileptic drugs, the doses of which were not changed during the 6-month dose titration phase. Following the introduction of vigabatrin, 11 patients became seizure free, and 28 responded with a greater than 50% reduction in seizure frequency. The following types of epilepsy responded favorably in order of decreasing efficacy: cryptogenic and symptomatic partial epilepsy, other symptomatic generalized epilepsy, and Lennox-Gastaut syndrome. However, three of nine patients with myoclonic epilepsy showed an increase in seizure frequency. Optimal responses were found with vigabatrin doses of 40 to 80 mg/kg/ day, although no significant adverse effects were noted with doses of higher than 100 mg/kg/day. Thirty-eight responders continued on vigabatrin, 19 of whom have been treated for more than 1 year, with generally good efficacy. As a result of discontinuing concomitant antiepileptics, six patients are on monotherapy with vigabatrin, four of whom are seizure free. Vigabatrin tolerability was good, with 39 of 66 children reporting no adverse effects. Hyperkinesia was reported in 17 patients (26%), and two had to drop out of the study. All these patients had a history of hyperkinesia or mental retardation. In patients in whom vigabatrin dose was reduced because of hyperkinesia, a dose increase could later be instituted without recurrence of symptoms. There was no change in neurologic examination and no drug-related abnormalities in clinical laboratory data. It is concluded that this study shows that vigabatrin is safe and effective in the treatment of refractory epilepsy of various types in children. The recommended starting dose is 40 mg/kg/day, which can be increased up to 80 mg/kg/day, depending on clinical response. (J Child Neurol 1991;6(Suppl):2S30-2S37).

Vigabatrin in Partial Seizures in Children

“…But among the symptomatic patients, response is clearly better in tuberous sclerosis than in other causes. If these patients are excluded, efficacy decreases to 65% in symptomatic partial epilepsies, a rate comparable to that reported by Luna et al 15 and Dulac et al 12 Such a favorable response in tuberous sclerosis has already been reported for infantile spasms. 11,27 Secondary generalization from the major tubers was suggested to cause the spasms.…”

“…Efficacy of vigabatrin has been shown to be maintained at 1 to 3 years follow-up in adults,2>9>28>29 and in children, [12][13][14] with one study in adults going up to 6 years.3° However, cases of loss of efficacy have been reported, particularly in infantile spasms for which a rate of 50% is reached in very young children.11 In the present study there is also a relatively high rate of loss of efficacy (40%). This particularly involves some of the best responders-infants with cortical malformations.…”

“…Increase in seizure frequency on vigabatrin has been reported in adults, 1>3>9 and in children, 12,14,15,19 in about 10% of the cases.…”

Treatment options for epileptic myoclonus and epilepsy syndromes associated with myoclonus

“…In a randomized, double-blind, placebocontrolled trial, this drug led to a 42% reduction of drop attacks and overall seizure frequency reduction of 32% [56]. Gabaergic drugs such as gabapentin and vigabatrin frequently worsen the myoclonic seizures in this syndrome [57,58].…”

Vigabatrin

“…VGB can exacerbate myoclonic seizures, and is ineffective for absences. [10][11][12][13][14] VGB has proved to be particularly important in the treatment of West syndrome. In a prospective, randomized, placebo-controlled trial, a reduction in infantile spasms was demonstrated in 78% of infants given VGB and 26% given a placebo.…”