Treatment of infantile spasms
Abstract
Background
Infantile spasms (West's Syndrome) is a syndrome which includes a peculiar type of epileptic seizure, the spasms, and an electroencephalogram (EEG) abnormality often called hypsarrhythmia. Psychomotor retardation is frequently found at follow up. Approximately two thirds of affected infants will have a detectable underlying neurological abnormality, but still little is known about the pathophysiological basis for infantile spasms and treatment remains problematic.
Objectives
To compare the effects of single pharmaceutical therapies used to treat infantile spasms in terms of control of the spasms, resolution of the EEG, relapse rates, psychomotor development, subsequent epilepsy, side effects, and mortality.
Search methods
Published data: Cochrane Epilepsy Group Specialised Register, CENTRAL (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, and the reference lists of all retrieved articles.
Unpublished data: ISRCTN Register (www.controlled‐trials.com), correspondence with colleagues and drug companies, and requests at international conferences.
Selection criteria
All randomised controlled trials of the administration of drug therapy to patients with infantile spasms.
Data collection and analysis
Data collection from all relevant publications was independently undertaken by three review authors using a standard proforma. Analysis included assessment of study quality and looking for sources of heterogeneity.
Main results
We found 12 small RCTs (less than 60 patients enrolled) and two larger RCT (more than 100 patients enrolled). These 14 studies looked at a total of 681 patients treated with a total of nine different pharmaceutical agents. Overall methodology of the studies was poor, partly because of ethical dilemmas such as giving placebo injections to children. Two studies showed that placebo was not as good as active treatment in resolving the spasms. The strongest evidence suggested that hormonal treatment leads to resolution of spasms faster and in more infants than does vigabatrin. Responses without subsequent relapse may be no different. The same study suggests that hormonal treatments (prednisolone or tetracosactide) might improve the long‐term developmental outcome compared with vigabatrin in infants not found to have an underlying cause for their infantile spasms.
Authors' conclusions
To date, there have been few well‐designed RCTs that considered the treatment of infantile spasms, and the numbers of patients enrolled have been small. Overall methodology has been poor, hence it is not clear which treatment is optimal in the treatment of this epilepsy syndrome. Hormonal treatment resolves spasms in more infants than vigabatrin but this may or may not translate into a better long‐term outcome. If prednisone or vigabatrin are used then high dosage is recommended. Vigabatrin may be the treatment of choice in tuberous sclerosis. Resolution of the EEG features may be important but this has not been proven. Further research using large studies with robust methodology is still required.
PICOs
Plain language summary
Treatment of infantile spasms
The optimum treatment for infantile spasms has yet to be proven with confidence, in part because of the different objectives of existing studies. However, some useful conclusions can be drawn from current evidence.
Infantile spasms is a rare seizure disorder commonly associated with severe learning difficulties. Many different treatments are currently used world wide in the treatment of this disorder and many more have been tried in the past, often with little success. Not all treatments are licenced for use in all countries. Most treatments have significant side effects. The long‐term benefits of different therapies on seizure control and on neurodevelopment need more research. Two studies have shown that placebo is not as good as active treatment in resolving the spasms. The strongest evidence we found suggests that hormonal treatment leads to resolution of spasms faster and in more infants than does vigabatrin. Responses without subsequent relapse may be no different but one study suggested that hormonal treatments (such as prednisolone or tetracosactide) might improve the long‐term neurodevelopmental outcome in infants and young children with no underlying cause for their infantile spasms. This makes hormonal treatments more attractive at least for this group of infants. More information and further research is needed to compare the therapies that are currently available.
