Elsevier

Epilepsy Research

Volume 26, Issue 2, January 1997, Pages 389-395
Epilepsy Research

Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis1

https://doi.org/10.1016/S0920-1211(96)01006-6Get rights and content

Abstract

Vigabatrin has been shown to be efficient in infants with infantile spasms and tuberous sclerosis, in open studies. In order to compare vigabatrin to oral steroids, a prospective randomized multicenter study was implemented using both drugs as monotherapy in newly diagnosed patients with infantile spasms and tuberous sclerosis. Eleven infants received vigabatrin (150 mg/kg per day) and 11 hydrocortisone (15 mg/kg per day) for 1 month. Spasm free patients continued vigabatrin or progressively stopped hydrocortisone in 1 month, non-responders were crossed to the other drug for a new 2 month-period. All vigabatrin patients (11/11) were spasm-free versus 5/11 hydrocortisone infants (P<0.01). Seven patients were crossed to vigabatrin (six for inefficacy, one for adverse events) and became also totally controlled. Mean time to disappearance of infantile spasms was 3.5 days on vigabatrin versus 13 days on hydrocortisone (P<0.01). Five patients exhibited side effects on vigabatrin but nine on hydrocortisone (P=0.006). Vigabatrin should therefore be considered as the first choice treatment for infantile spasms due to tuberous sclerosis.

Introduction

Infantile spasms, combining epileptic spasms and diffuse paroxysmal EEG abnormalities, is one of the epilepsy syndromes of childhood the most refractory to conventional antiepileptic drugs. Reference drugs are steroids and benzodiazepines which both have frequent and severe adverse effects [8]. Tuberous sclerosis is a major cause of infantile spasms and about half the patients with tuberous sclerosis develop infantile spasms [15]. Infantile spasms due to tuberous sclerosis are particularly refractory to reference drugs and subsequently carry a high risk of severe delay in mental development 13, 14. There is therefore a great need to develop new drugs likely to demonstrate efficacy and safety in such a deleterious condition.

Vigabatrin, a gabaergic compound which selectively inhibits GABA-transaminase, appeared to be a promising treatment in this indication, as open studies have suggested that with vigabatrin, up to 70% of children with refractory infantile spasms will respond with a greater than 50% reduction in seizure frequency, and 40% may become seizure free 2, 3, 4, 5, 18. The efficacy of vigabatrin varies with the etiology, the most impressive results being when the underlying cause is tuberous sclerosis, with up to 80% response rates whether it is used in refractory cases [5]or as the initial treatment 2, 3, 4, 18. Just as important, this is usually seen within a few days and tolerability appears excellent even at doses as high as 150 mg/kg per day. These results were so encouraging that some authors suggested that vigabatrin could be considered as the first line treatment for infantile spasms [3]. Partially because of the ethical restraints on controlled trials in such young children, no comparative studies of vigabatrin in infantile spasms have yet been published.

This randomized trial was performed in order to compare efficacy and safety of vigabatrin and steroids in patients with newly diagnosed infantile spasms due to tuberous sclerosis.

Section snippets

Patient selection

Patients were selected from several French centers on the following criteria: tuberous sclerosis according to Gomez criteria [10], epileptic spasms recorded on EEG or seen by an experienced physician, diffuse interictal paroxysmal activity, age ranging from 1 month to 2 years. Patients who had been previously treated with ACTH, oral corticosteroids or vigabatrin were excluded, and those who had been treated with other antiepileptic medications had to have these withdrawn for a minimum of 1 week

Patient population

Twenty-two evaluable patients entered the study. Table 1 outlines their clinical characteristics. Eleven were randomized to vigabatrin (vigabatrin group) and 11 to hydrocortisone (hydrocortisone group). Clinical baseline characteristics were similar in both groups.

Efficacy on spasms (Table 2)

After 1 month, all the 11 patients randomized to vigabatrin were free of spasms as compared to 5/11 randomized to hydrocortisone (P<0.01). The six non-responders to hydrocortisone together with one infant who exhibited severe side

Discussion

This study clearly demonstrates the better efficacy and tolerability of vigabatrin versus steroids in the treatment of infantile spasms due to tuberous sclerosis. It provides the first prospective randomised data with vigabatrin in infantile epilepsy. Controlled prospective comparative studies of all types of treatment in childhood epilepsy are rare, ethical constraints are usually argued. We show here that significant data can be obtained from small samples of patients in ethically acceptable

References (18)

  • Aicardi, J., Weinman, S., Chevrie, J.J. and Thieffry, S., Les spasmes en flexion du nourrisson. Etude de l'excretion...
  • Aicardi, J. and the Coordinating Peer Review Group, the European IS Vigabatrin Group, European experience with use of...
  • Appleton, R.E. and Monteil-Viecca, F., Vigabatrin in infantile spasms. Why add-on? Lancet, 341 (1992)...
  • Buti, D., Lini, M., Bardini, R., Marvulli, I., Tromboni, P. and Nencioli, L., Early treatment of infantile spasms with...
  • Chiron, C., Dulac, O., Beaumont, D., Palacios, L., Pajot, N. and Mumford, J., Therapeutic trial of vigabatrin in...
  • Dreifuss, F., Farwell, J., Holmes, G. and Joseph, C., Infantile spasms, comparative trial of nitrazepam and...
  • Dulac, O. and Plouin, P., Infantile spasms and West syndrome. In: E. Wyllie (Ed.), The Treatment of Epilepsy:...
  • Dulac, O. and Schlumberger, E., Treatment of West syndrome. In: E. Wyllie (Ed), The Treatment of Epilepsy: Principles...
  • Dulac, O., Chiron, C., Robain, O., Plouin, P., Jambaque, I. and Pinard, J.M., Infantile spasms: a pathophysiological...
There are more references available in the full text version of this article.

Cited by (292)

  • Catherine Chiron

    2021, Child Neurology: Its Origins, Founders, Growth and Evolution
View all citing articles on Scopus
1

This article has also been investigated by C. Allaire, P. Aubourg, M. Besson-Leaud, C. Cieuta, P. Damon, P. Danel, M. Derambure, I. Desguerre, M. Fohlen, J. Motte, P. Parisot, C. Pascal and A. de Saint-Martin.

View full text