Botulinum toxin type A in the treatment of lower limb spasticity in cerebral palsy
Editorial Group: Cochrane Movement Disorders Group
Published Online: 24 JAN 2000
Assessed as up-to-date: 17 OCT 1999
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Ade-Hall R, Moore P. Botulinum toxin type A in the treatment of lower limb spasticity in cerebral palsy. Cochrane Database of Systematic Reviews 2000, Issue 1. Art. No.: CD001408. DOI: 10.1002/14651858.CD001408.
- Publication Status: Edited (no change to conclusions)
- Published Online: 24 JAN 2000
Children with cerebral palsy often have spasticity of the legs, a condition in which the legs are stiff because of involuntary muscle overactivity caused by the brain or spinal cord disorder. Spasticity causes poor coordination, spasms, abnormal posture and pain, and contributes greatly to the developmental deformities and disability of cerebral palsy. Conventional treatment with physiotherapy, splinting, oral medications and sometimes plaster casting and surgery may prove inadequate. Open label studies and some RCTs suggest that botulinum toxin injections into the spastic muscles can alleviate the spasticity and help some of these problems. Botulinum toxin blocks the release of acetylcholine from the neuromuscular junction and weakens the muscle. This and other effects may account for the apparent benefit in spasticity, but also highlight the importance of clarifying safety, especially in this group of growing children.
To determine whether botulinum toxin (BtA) is an effective and safe treatment for lower limb spasticity in children with cerebral palsy. Functional outcomes are of particular interest.
Studies for inclusion in the review were identified using the Movement Disorders Review Group trials register, the Cochrane Controlled Trials Register, MEDLINE, pharmaceutical company databases, communication with other researchers in the field and reference lists of papers found using above search strategies.
Studies were considered eligible for inclusion in the review if they evaluated the efficacy of BtA for the treatment of leg spasticity in children with cerebral palsy. They must have been randomised and include a concurrent control group receiving another intervention.
Data collection and analysis
A paper pro forma was used to collect data from the included studies using double extraction by two independent reviewers. Each trial was assessed for internal validity by each of the two reviewers.
Meta-analysis was not possible because results were presented in an incompatible form. A Peto odds ratio was calculated where this was appropriate, otherwise a descriptive summary of the results of the individual studies was compiled.
Three eligible studies were found each with small numbers of subjects. They were short term, used single injection sessions with follow-up of between 4 and 26 weeks.
One study (Koman), of twelve ambulant children, compared BtA with injection of a placebo and found non-significant improvements in gait in the BtA group compared to the placebo group.
Two studies (Corry 1998, Flett 1999) compared BtA with the use of casts. Each included 20 ambulant children and found improvements in gait, range of ankle movement and muscle tone in both the BtA and cast groups . However there were no significant differences between the groups in either trial. One of these trials (Flett 1999) also assessed motor function using the gross motor function measure (GMFM) (Russell 1989) and found significant improvements in each group compared to baseline but no significant differences between the groups. The other trial (Corry 1998) performed 3D gait analysis on those children able to co-operate. Maximal plantar flexion and maximal dorsiflexion during walking were both found to be significantly greater in the BtA group compared to the cast group. In all other dimensions there were no significant differences between the groups.
This systematic review has not revealed strong controlled evidence to support or refute the use of BtA for the treatment of leg spasticity in cerebral palsy.
Ongoing randomised controlled trials are likely to provide useful data on the short term effects of BtA for leg spasticity.
Future research should also assess the longer term use of BtA. Ideally studies should be pragmatic in their approach to dose and distribution of toxin to reflect practise. Outcome measures assessing function and disability would give the most useful information.
Plain language summary
Botulinum toxin type A injections for the treatment of lower limb spasm in cerebral palsy
Cerebral palsy (CP) is a non-progressive lifelong condition resulting from damage to the newborn brain. Most infants have spasms (spasticity) affecting at least one leg that prevents normal movement. It can cause muscle contractures and deformities and the affected muscles do not grow as rapidly as neighbouring bone and soft tissue. Treatment includes physiotherapy, oral anti-spasticity drugs, casts, splints and orthopaedic surgery. Injection of botulinum toxin (BtA) into muscle causes local muscle weakness and so may help counter spasticity. This review found that published, controlled evidence was weak as they identified three controlled trials involving only a small number of children (2 to 11 years). Children receiving a single course of injections of BtA (Botox®, 3 to 8 µg/kg or Dysport®, 15 µg /kg) into the calf muscle tended to have an improved pattern of walking (gait) compared with inactive injections (placebo). Both BtA injections and lightweight walking plaster casts below the knee (for four to six weeks) produced similar significant improvements in gait. Some calf pain was reported among the 26 children injected with BtA and parents reported inconvenience with wearing casts and weakness of legs following removal.
Botulinum toxin type A用於治療腦性癱瘓的下肢痙攣
患有腦性癱瘓的孩童通常都會有腿部痙攣的現象，這是由於腦部或脊髓的失調而導致非自主的肌肉過度活化，造成腿部僵直的現象。痙攣會導致動作不協調、抽蓄、動作異常以及疼痛，且和腦性癱瘓的畸形及和神經功能的失去很有關連。傳統的物理治療，夾板療法，口服藥物治療或有時候可能會打上石膏以及手術是不足夠的。一些開放性研究和隨機對照試驗都顯示在痙攣的肌肉上注射botulinum toxin可以緩解痙攣並且對類似症狀有幫助。Botulinum toxin會阻斷acetylcholine從神經肌肉接合處釋放，並弱化肌肉。這方面及其它的效果對治療痙攣是一個很顯著的好處，但同時也強調了解其安全性的重要，特別是使用在發育期孩童族群時。
我們利用Movement Disorders Review Group trials register、the Cochrane Controlled Trials Register、MEDLINE、藥廠資料庫、和這個領域的其它研究者溝通了解以及上述找到的研究中的參考資料，搜尋本篇評論欲收錄的研究。
我們用預先制定的格式，由兩位評論者分別從收錄的研究中收集數據。每個試驗都分別由兩位作者評估其內部有效性。由於結果表示的方式不一，因此無法做整合分析。在合適的地方會計算Peto odds ratio，或者會根據各別研究做出描述性的總結。
一共找到3個可用的研究，試驗人數都很少。它們都是短期試驗，使用單一注射，並在4到26週間做追蹤。其中一個試驗﹝Koman﹞，包含12位可走動的兒童，比較注射BtA和安慰劑，結果比起安慰劑，BtA的組別在步伐上沒有發現顯著的進步。有2個試驗﹝Corry、Flett﹞比較注射BtA和使用石膏。2個試驗都包含20位可行走的兒童，且發現兩組在步行、腳踝動作範圍以及肌肉張力都有進步。然而2個試驗的組間都沒有發現顯著的差異。這其中的一個試驗﹝Flett﹞同時也利用the gross motor function measure ﹝GMFM﹞﹝Russel，1989﹞評估了運動機能，發現兩組都有顯著的進步，但組間也沒有顯著的差異。另一個試驗﹝Corry﹞有對能夠配合的兒童做3D步伐分析。在BtA的組別，行走時的最大蹠屈和最大背屈都明顯的比使用石膏的組別大。而以其它的角度來看，兩組沒有顯著的差異。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。
Botulinum toxin type A用於治療腦性癱瘓的下肢痙攣 腦性癱瘓﹝CP﹞是一個不會惡化的終身情況，由新生兒腦的損壞造成。許多嬰兒會有至少一條腿有抽蓄﹝痙孿﹞的情況，影響正常行動。這會導致肌肉萎縮和畸形，且受到影響的肌肉不會和鄰近的骨骼或軟組織有一樣快的生長速度。治療方式包括物理治療、口服抗痙攣藥物、使用固定敷料、夾板固定以及骨科手術。在肌肉注射botulinum toxin﹝BtA﹞能弱化局部肌肉，因此有助於對抗痙攣。這篇評論目前發現已發表的對照證據很薄弱，因為找到的3個對照試驗包含的孩童﹝2到11歲﹞數目都很少。接受BtA﹝BotoxR， 3 to 8 μg/kg或DysportR，15 μg /kg﹞單一注射在小腿肌肉的孩童，在走路的步調﹝步伐﹞上，比注射非活性藥物﹝安慰劑﹞的孩童進步。注射BtA和在膝蓋下安置輕量步行石膏﹝使用4到6週﹞對步伐有相似顯著的改善。有26位注射BtA的孩童回報有小腿疼痛的情況，而家長則反映使用石膏的不便性以及在移除石膏後，腿會有疲軟的現象。