ReviewRecommendations for the use of botulinum toxin type A in the management of cerebral palsy
Introduction
The use of botulinum toxin type A (BTX-A) for treating spasticity and in particular, the motor problems of children with cerebral palsy, has attracted much attention, both in clinical publications and the popular press. Until very recently, all such use has been unapproved for this indication, since BTX-A (BOTOX®, Allergan and Dysport®, Ipsen) has only been approved for the treatment of blepharospasm, hemifascial spasm, and in some countries, strabismus and cervical dystonia. This, combined with the unusual pharmacokinetic properties and potential toxicity of BTX-A, not to mention the considerable clinical challenge presented by a disorder as complex as cerebral palsy, has resulted in uncertainty about appropriate administration and dosage. Whether widespread use of BTX-A for treating spasticity is justified by the available clinical evidence [1] has been questioned. The recent licensing of BOTOX® for the treatment of equinus deformity in children in several European countries and Australia, together with pending applications for approval elsewhere, further increases the need for a discussion about the value, limitations and appropriate use of BTX-A. This paper follows detailed discussions by all of the authors at a roundtable meeting and represents an attempt, by a group of experienced users of BTX-A, to review developments and produce a clear, detailed and logical set of guidelines for the responsible use of BTX-A in the treatment of children with cerebral palsy. Many of the authors have between 4 and 6 years’ experience of treating spasticity in children by injecting BTX-A, and their combined experience represents more than 1000 children treated for this indication. In many cases this is in addition to an even greater prior experience of using BTX-A for treating dystonia in adults.
Section snippets
Biochemistry
BTX-A is a protein exotoxin derived from Clostridium botulinum. It binds, with high affinity and specificity, to the presynaptic membranes of cholinergic motor neurones, and is then internalised [2]. Once inside the cell, one of its two subunits specifically cleaves components of the cell’s exocytotic machinery (a protein known as synaptosome-associated protein of 25 kDa) so that the discharge of acetylcholine-containing vesicles, and hence neurotransmission at the neuromuscular junction, is
Patient selection and timing of treatment
BTX-A provides a useful way of controlling excessive muscular contraction in the specific muscles injected. It follows that it is most effective in patients with dynamic muscle shortening which is localised to a few muscles. The more this picture is complicated by long-standing contractures and deformity, then the less applicable it is likely to be. Results are also likely to be best in patients who have adequate selective motor control. At what point the spasticity is regarded as ‘generalised’
Physiotherapy
An active physiotherapy programme remains central to treatment, with targeted motor training aiming to achieve carry-over improvements which persist beyond the effects of the injections. Paediatric physiotherapists have an important role in selecting and teaching specific motor tasks for children to practice under the guidance of their caregivers. The physiotherapist encourages practice in an appropriate environment to achieve retention and carry-over of motor skills, as well as maintenance of
Lower limb
What follows are brief guidelines only. A full understanding of the biomechanics of movement at the hip, knee and ankle during gait is crucial to the correct and appropriate use of BTX-A injection.
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Consider the whole child; evaluate all three levels of the lower limb (i.e. trunk/pelvis in relation to the hip, knee, ankle/foot).
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Focus on one or two levels and select the most appropriate target muscles for injection. In more severe cases consider the medial hamstrings and adductors, in less severe
Conclusions
The contributors to this paper represent a wide range of clinical experience and backgrounds, and yet it was remarkable how quickly a consensus on the core issues discussed (patient selection, dosage, injection procedures) was reached. As a result, we feel that we can put forward these recommendations with some confidence. Clearly, on matters of more complexity, such as the use and timing of adjunctive treatments, and the treatment of difficult cases with more generalised spasticity, there is
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