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Unpublished data: ISRCTN Register (www.controlled-trials.com), correspondence with colleagues and drug companies, and requests at international conferences.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.

 

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.

 

摘要

背景

治療嬰兒點頭性痙攣症

嬰兒點頭性痙攣症(infantile spasms)(West syndrome)是一種罕見的癲癇發作型式，即點頭痙攣，其腦波異常放電的形式被稱作hypsarrhythmia。後續追蹤時常會發現精神與運動發育遲緩。大約2/3的患病嬰兒有可被發現的潛在神經系統異常，但是，我們對於嬰兒點頭性痙攣症的病生理基礎知識還知之甚少，目前該疾病的治療還是一個難解的問題。

目標

比較使用單一藥物來治療嬰兒點頭性痙攣症，在痙攣發作的控制、異常腦波之回復、復發率、精神與運動發育、後續其他種類癲癇之發生、副作用、死亡率等方面的治療成果。

搜尋策略

搜尋已發表的資料：Cochrane Epilepsy Group Specialised Register、CENTRAL (The Cochrane Library，2007年第4期)，MEDLINE、EMBASE。及所收錄文章的參考文獻列表。搜尋未發表的資料：ISRCTN Register (www.controlledtrials.com)，癲癇專家和製藥公司的回應，及於國際研討會中徵求意見。

選擇標準

選擇所有對嬰兒點頭性痙攣症病患實施藥物治療的隨機對照試驗

資料收集與分析

三位文獻回顧作者獨立使用一標準表格收集所有相關公開發表資料。資料分析包括評估試驗的品質，與尋找異質性來源。

主要結論

我們發現12個小規模的RCT(收納的受試者人數少於60)以及2個大規模的RCT(收納的人數超過100)。這14個臨床試驗共有了681位病人，接受了9個不同的藥物。整體說來研究方法品質不好，一部分是因為遭遇了倫理困境，例如是否應該向嬰兒注射安慰劑。有2個試驗顯示，安慰劑在緩和痙攣發作方面不如有效藥物的治療。根據最強的證據，指出激素療法比Vigabatrin可更快且有更多病患能得到緩和痙攣發作。針對能達到預防復發的效果來說，這兩種藥物的療效則沒有差別。同一個試驗指出，比起Vigabatrin，激素療法(prednisolone或 tetracosactide)更可以改善那些無法找到嬰兒點頭性痙攣症潛在原因的幼兒的長期發育結果。

作者結論

到目前為止，僅有極少數設計合宜的RCT考慮到嬰兒點頭性痙攣症的治療以及收納受試者可能太少。因總體研究方法較差，所以，我們不清楚該療法是否是治療此類癲癇症的最佳療法。激素療法比Vigabatrin更能夠緩和痙攣發作，但是這種效果也許會，也許不會演變成較好的長期效果。如果使用prednisone或Vigabatrin來治療，則建議使用高劑量。Vigabatrin可能是結節性硬化症之首選治療。能夠將異常的腦波回復至正常可能是治療的重點，但此點並未得到證實。我們還需要有大規模的臨床試驗使用良好的方法來進一步研究。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

針對嬰兒點頭性痙攣症的最佳治療仍需要進一步驗證，其中部分的原因是現有的臨床試驗的研究目的有許多分歧點。不過從這些試驗中，我們還是可以得到有一些有用的結論。嬰兒點頭性痙攣症是一種罕見的癲癇發作型態，常和嚴重的學習障礙有關。目前在治療該疾病方面，各地採取不同的治療方法，也嘗試過了許多方法，但是經常收效甚微。不是所有的療法均取得各個國家的許可。多數療法仍有許多明顯的副作用。我們需要對各種療法在癲癇發作控制和神經發育方面的長期好處，進行更深入的研究。有兩個試驗顯示，安慰劑在緩和痙攣發作方面不如有效藥物的治療。根據最強的證據，指出激素療法比Vigabatrin可更快且有更多病患能得到緩和痙攣發作。針對能達到預防復發的效果來說，這兩種藥物的療效則沒有差別；但有一個試驗指出，比起Vigabatrin，激素療法(prednisolone或 tetracosactide)更可以改善那些無法找到嬰兒點頭性痙攣症潛在原因的幼兒的長期發育結果。因此激素療法在這群嬰兒的治療上，顯得較為吸引人。我們仍需要獲取更多的資訊和進行更多的臨床試驗，來比較現有各種療法的治療成果。