1998 GCMAS Best Paper AwardDouble-blind study of botulinum A toxin injections into the gastrocnemius muscle in patients with cerebral palsy
Introduction
Botulinum A toxin injected into a muscle, causes temporary paralysis of the muscle, lasting about 3–6 months [1], [2], [3], [4], [5], [6], [7], [8]. The site of action is at the nerve terminals. Botulinum A toxin blocks the release of acetylcholine by the synaptic vesicles [9]. Recovery occurs by terminal sprouting of the nerves [10].
Previous reports have included randomized, double-blind studies of the use of botulinum A toxin in patients with spasmodic torticollis [8], [11], upper extremity spasticity in stroke [12], upper extremity spasticity in cerebral palsy [13], adductor spasticity in multiple sclerosis [14], and dynamic equinus in cerebral palsy [5]. In each study, botulinum A toxin was demonstrated to be more effective than placebo. Three-dimensional movement measurements were not included in any of these studies and children were subjects in only two investigations.
In the first of the two studies involving children, Koman et al. [4] reported the results in 27 patients, with cerebral palsy, between the ages of 3 and 16 years, who were given botulinum A toxin injections for dynamic deformities. Of the total group, 16 children were ambulatory and had dynamic deformities at the ankle uncontrolled by bracing and physical therapy. All patients in this ambulatory group except one demonstrated decreased tone without systemic weakness. In some cases, components of fixed contractures, that had not been evident in the pre-study examination, were unmasked. The post-injection physician rating scores were significantly improved over the pre-injection evaluation.
Koman et al. [5] described a double-blind study of 12 ambulatory cerebral palsy patients. They were evaluated before and after receiving the drug or placebo utilizing observational gait analysis and a physician rating scale. They reported that five of six subjects receiving the drug improved, and that two of six receiving the placebo improved.
The specific aim of this study was to objectively quantify, using 3-D gait analysis, any changes in functional performance following injection of botulinum A toxin into the gastrocnemius muscles of children with cerebral palsy who demonstrated a dynamic equinus gait pattern.
Section snippets
Study design
This study was a prospective, randomized, double-blind clinical trial of botulinum A toxin (BOTOX®) compared to a placebo which was saline vehicle. The subjects were selected by criteria described in Section 2.2, informed of the research project, and given an opportunity to participate. Our study was a subset of a large multi-site trial. However, the results that we report are based on objective gait analysis measurements obtained in the Motion Analysis Laboratory. The multi-center trial did
Subject demographics
Twenty subjects were enrolled in this double-blind study. Nineteen completed the 8 week protocol, one subject was unable to complete the second gait study in the time frame allotted due to an unrelated illness. The data for this study were collected over a 19 month period between November 1991 and July 1993.
The mean age at the time of the baseline gait study was 6.1 years. The age range was 2.4–12.5 years (Fig. 2.). There were four female and 16 male subjects. Ten subjects had the hemiplegic
Discussion
This is the first double-blind study of botulinum A toxin which used objective outcome data based on gait analysis. The paucity of double-blind, randomized, clinical trials of botulinum A toxin injections in children with cerebral palsy is undoubtedly due to the understandable reluctance of parents to agree to possible placebo injections. We were able to overcome this reluctance by offering voluntary continuation in an open-label study, after completion of the double-blind study. We have
Conclusion
Although there are many questions still to be answered this study has demonstrated that injection of botulinum A toxin offers a safe and efficacious, non surgical treatment, that can be administered on an outpatient basis to control dynamic (non-contractural) equinus deformities in patients with cerebral palsy. Thus, botulinum A toxin is a welcome addition in the overall management of patients with cerebral palsy.
Acknowledgements
The authors wish to thank the Motion Analysis Laboratory staff for their help with the data collection and reduction, and Sherill Marciano and Jill Jordano for the preparation and technical assistance with the manuscript. Funds were received to support this research from Allergan, Inc., Irvine, CA.
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