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Meta-Analysis
. 2013 Jun 5;2013(6):CD001770.
doi: 10.1002/14651858.CD001770.pub3.

Treatment of infantile spasms

Eleanor C Hancock  1 , John P Osborne, Stuart W Edwards
Affiliations
Meta-Analysis

Treatment of infantile spasms

Eleanor C Hancock et al. Cochrane Database Syst Rev. .

Abstract

Background: Infantile spasms (West's Syndrome) is a syndrome that includes a peculiar type of epileptic seizure-the spasms-and an electroencephalographic (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: To identify published data, we searched the Cochrane Epilepsy Group Specialised Register (October 2012), CENTRAL (The Cochrane Library 2012, Issue 9), MEDLINE (1946 to September Week 4, 2012), EMBASE (1980 to March 2003), and the reference lists of all retrieved articles.To identify unpublished data, we searched the ISRCTN Register (www.controlled-trials.com), corresponded with colleagues and drug companies, and made requests at international conferences.

Selection criteria: All randomised controlled trials (RCTs) 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 (before 2010) or by two review authors using a standard proforma. Analysis included assessment of study quality and a search for sources of heterogeneity.

Main results: We found 16 small RCTs (fewer than 100 patients enrolled) and 2 larger RCTs (more than 100 patients enrolled). These 18 studies looked at a total of 916 patients treated with a total of 12 different pharmaceutical agents. Overall methodology of the studies was poor, in part 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 (prednisolone or tetracosactide depot) 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 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, few well-designed RCTs have considered the treatment of infantile spasms, and the numbers of patients enrolled have been small. In the majority, 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 better long-term outcomes. If prednisolone or vigabatrin is used, 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 required.

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Conflict of interest statement

Dr Hancock, Professor Osborne, and Dr Edwards are members of the Trial Steering Committee for two multi‐centre, randomised, controlled trials in infantile spasms (United Kingdom Infantile Spasms Study (UKISS) and the International Collaborative Infantile Spasms Study).

Professor Milner was the chairman of the Data Monitoring and Ethics Committee for UKISS.

Professor Osborne is also a co‐author for the Consensus Statement of the West Delphi Group.

Figures

1.1
1.1. Analysis
Comparison 1 Vigabatrin versus placebo, Outcome 1 Cessation of spasms.
1.2
1.2. Analysis
Comparison 1 Vigabatrin versus placebo, Outcome 2 Resolution of hypsarrhythmia.
1.3
1.3. Analysis
Comparison 1 Vigabatrin versus placebo, Outcome 3 Relapse rates ‐ number of patients who remain spasm free.
2.1
2.1. Analysis
Comparison 2 Vigabatrin versus hydrocortisone, Outcome 1 Cessation of spasms.
2.2
2.2. Analysis
Comparison 2 Vigabatrin versus hydrocortisone, Outcome 2 Time taken to cessation of spasms.
3.1
3.1. Analysis
Comparison 3 ACTH versus low‐dose prednisone, Outcome 1 Cessation of spasms.
3.2
3.2. Analysis
Comparison 3 ACTH versus low‐dose prednisone, Outcome 2 Time taken to cessation of spasms.
3.3
3.3. Analysis
Comparison 3 ACTH versus low‐dose prednisone, Outcome 3 Relapse rates ‐ number of patients who remain spasm free.
3.4
3.4. Analysis
Comparison 3 ACTH versus low‐dose prednisone, Outcome 4 Resolution of hypsarrhythmia.
4.1
4.1. Analysis
Comparison 4 High‐dose ACTH versus low‐dose ACTH, Outcome 1 Cessation of spasms.
4.2
4.2. Analysis
Comparison 4 High‐dose ACTH versus low‐dose ACTH, Outcome 2 Relapse rates ‐ number of patients who remain spasm free.
4.3
4.3. Analysis
Comparison 4 High‐dose ACTH versus low‐dose ACTH, Outcome 3 Resolution of hypsarrhythmia.
5.1
5.1. Analysis
Comparison 5 Nitrazepam versus ACTH, Outcome 1 Reduction in spasms.
6.1
6.1. Analysis
Comparison 6 Methysergide versus methylparatyrosine, Outcome 1 Cessation of spasms.
6.2
6.2. Analysis
Comparison 6 Methysergide versus methylparatyrosine, Outcome 2 Reduction in spasms.
6.3
6.3. Analysis
Comparison 6 Methysergide versus methylparatyrosine, Outcome 3 Relapse rates ‐ number of patients who remain spasm free.
7.1
7.1. Analysis
Comparison 7 Low‐dose vigabatrin versus high‐dose vigabatrin, Outcome 1 Cessation of spasms.
7.2
7.2. Analysis
Comparison 7 Low‐dose vigabatrin versus high‐dose vigabatrin, Outcome 2 Resolution of EEG.
7.3
7.3. Analysis
Comparison 7 Low‐dose vigabatrin versus high‐dose vigabatrin, Outcome 3 Relapse rates.
8.1
8.1. Analysis
Comparison 8 Sulthiame versus placebo, Outcome 1 Cessation of spasms.
8.2
8.2. Analysis
Comparison 8 Sulthiame versus placebo, Outcome 2 Resolution of EEG.
9.1
9.1. Analysis
Comparison 9 Vigabatrin versus hormonal treatment, Outcome 1 Cessation of spasms.
9.2
9.2. Analysis
Comparison 9 Vigabatrin versus hormonal treatment, Outcome 2 Resolution of EEG.
9.3
9.3. Analysis
Comparison 9 Vigabatrin versus hormonal treatment, Outcome 3 Seizures at follow‐up.
10.1
10.1. Analysis
Comparison 10 ACTH versus high‐dose prednisolone, Outcome 1 Cessation of infantile spasms.
10.2
10.2. Analysis
Comparison 10 ACTH versus high‐dose prednisolone, Outcome 2 Resolution of EEG.
11.1
11.1. Analysis
Comparison 11 ACTH with magnesium sulphate versus ACTH alone, Outcome 1 Cessation of spasms.
11.2
11.2. Analysis
Comparison 11 ACTH with magnesium sulphate versus ACTH alone, Outcome 2 Resolution of EEG.
12.1
12.1. Analysis
Comparison 12 Vigabatrin +Flunarizine vs Vigabatrin + Placebo, Outcome 1 Cessation of spasms.
See this image and copyright information in PMC

Update of

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    1. Wallace SJ. Management issues in severe childhood epilepsies. Seizure 1995;4:215‐20. - PubMed
Weinmann 1967 {published data only}
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Willig 1980 {published data only}
    1. Willig RP, Lagenstein I. Therapeutic trial with a fragment of ACTH (ACTH 4‐10) in early childhood epilepsy [Therapieversuch mit einem ACTH‐Fragment (ACTH 4‐10) bei Fruhkindlichen Anfallen]. Monatsschrift Kinderheilkunde 1980;128(2):100‐3. - PubMed
Wohlrab 1998 {published data only}
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Yamamoto 1998 {published data only}
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Yamauchi 2004 {published data only}
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Zafeiriou 1996 {published data only}
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References to ongoing studies

ICISS {unpublished data only}
    1. International Collaboration Infantile Spasms Study. Ongoing study May 2007.
ISRCTN 36757519 {unpublished data only}
    1. Ongoing study Starting date of trial not provided. Contact author for more information.
ISRCTN Surgery/AEDs {published data only}
    1. Ongoing study Starting date of trial not provided. Contact author for more information.

Additional references

Aicardi 1994
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References to other published versions of this review

Hancock 2008
    1. Hancock EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD001770.pub2] - DOI - PubMed

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