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Botulinum toxin: caveat injector
PERSONAL PRACTICE
Botulinum toxin: caveat injector
meetings urging a degree of caution against the overuse of botulinum. More recently Heinen and Schroder reported the lasting effects of botulinum on the adult calf muscle. Having been sensitized to the possibility of long term negative effects of botulinum toxin I was interested to hear from my physiotherapy colleagues in satellite clinics of patients they had encountered who had received multiple botulinum treatments leaving them with woody muscles that lacked the usual potential for stretching and growth in response to mechanical stimuli. In terms of evidence of a long term structural effect, two papers comparing serial casting for the calf with botulinum toxin and serial casting showed better calf length in the patients receiving placebo and casting at 12 months.
A Roberts
The hope of injectable spasticity control The upper motor neurone syndrome is often accompanied by motor disorders, typically spasticity or dystonia leading to negative effects on posture and function. The advent of botulinum toxin as a therapeutic agent transformed the care of patients affected by abnormal posture and discomfort but, as with all new technology, widespread application of the treatment often gives way to a more measured approach. Early, well publicized, work suggested that in mice the effect on muscle was reversible as new synapses were formed. The heterodoxy of reversibility gave the treatment a benign reputation and allowed it to be viewed as a bridging treatment during childhood enabling postural management to be continued until such time as some definitive treatment became feasible in later childhood. As an active clinician with a large case load of children with mainly spastic cerebral palsy I used botulinum toxin regularly with the calf being my most common target. With time, I came to appreciate the relative futility of injecting structurally short muscle and converged with the emerging consensus that the effects of injection lessened after the first couple of treatments in any one muscle. I used low dilutions of toxin under general anaesthesia, peppering the target muscles with toxin at a conservative dose.
Current practice I continue to use botulinum toxin in children with cerebral palsy for specific indications. Dystonia responds poorly to surgical management and botulinum toxin can prove useful in the management of pain associated with extreme posture especially in the upper limb. Where upper limb tendon transfers are under consideration a reversible procedure can be undertaken using botulinum toxin provided robust assessments are used pre and post injection to enable an evaluation of the effect. Where unrestrained muscle activation is likely to complicate a surgical procedure, a pre-emptive botulinum toxin treatment to the likely offending muscles can be considered. A final category of treatment is where dynamic tone is leading to abnormal posture during gait particularly in infants. A multilevel botulinum toxin treatment aimed at flexor spasticity at the knee and hip coupled with accurately tuned ankle foot orthoses and an intensive package of therapy can often allow the child to enter a more normal gait pattern with beneficial long term effects. In short, botulinum toxin is a powerful therapeutic agent that needs handling with respect and, in my view, should be combined with some other measure acting as an enabler rather than being a recurring 6 monthly treatment. A
Disillusionment I have the good fortune to work with a team of clinicians involved in muscle disorders and took advantage of this to document the features of muscle affected by spasticity in cerebral palsy. The study remit was not concerned with the effects of botulinum toxin on muscle but our muscle pathologist confronted me over one of the biopsy subjects suggesting that the child had a dystrophic problem rather than cerebral palsy. It transpired that this child had received botulinum toxin in the biopsied muscle many months previously but the muscle showed lasting damage. As we reviewed our data in the light of the dystrophic findings we found a relationship between damage and the use of botulinum given many months or even years previously and generally at a very conservative dose. At around this time a colleague, Janice Quinby in Newcastle upon Tyne, reported similar findings in hamstrings injected with botulinum toxin. We publicized our findings at paediatric orthopaedic
FURTHER READING Ackman JD, Russman BS, Thomas SS, et al. Comparing botulinum toxin A with casting for treatment of dynamic equinus in children with cerebral palsy. Dev Med Child Neurol Sep 2005; 47: 620e7. Boyd RN, Hays RM. Current evidence for the use of botulinum toxin type a in the management of children with cerebral palsy: a systematic review. Eur J Neurol Nov 2001; 8(suppl 5): 1e20. Cosgrove AP, Graham HK. Botulinum toxin a prevents the development of contractures in the hereditary spastic mouse. Dev Med Child Neurol May 1994; 36: 379e85. Kay RM, Rethlefsen SA, Fern-Buneo A, Wren TA, Skaggs DL. Botulinum toxin as an adjunct to serial casting treatment in children with cerebral palsy. J Bone Joint Surg Am Nov 2004; 86-A: 2377e84. Schroeder AS, Ertl-Wagner B, Britsch S, et al. Muscle biopsy substantiates long-term MRI alterations one year after a single dose of botulinum toxin injected into the lateral gastrocnemius muscle of healthy volunteers. Mov Disord Jul 2009; 24: 1494e503. Schroeder AS, Koerte I, Berweck S, Ertl-Wagner B, Heinen F. How doctors think and treat with botulinum toxin. Dev Med Child Neurol Sep 2010; 52: 875e6.
A Roberts FRCS DM is the Children’s Orthopaedic Surgeon at the Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, UK. Conflict of interest: none.
PAEDIATRICS AND CHILD HEALTH 23:9
414
Ó 2013 Published by Elsevier Ltd.
Botulinum toxin: caveat injector
meetings urging a degree of caution against the overuse of botulinum. More recently Heinen and Schroder reported the lasting effects of botulinum on the adult calf muscle. Having been sensitized to the possibility of long term negative effects of botulinum toxin I was interested to hear from my physiotherapy colleagues in satellite clinics of patients they had encountered who had received multiple botulinum treatments leaving them with woody muscles that lacked the usual potential for stretching and growth in response to mechanical stimuli. In terms of evidence of a long term structural effect, two papers comparing serial casting for the calf with botulinum toxin and serial casting showed better calf length in the patients receiving placebo and casting at 12 months.
A Roberts
The hope of injectable spasticity control The upper motor neurone syndrome is often accompanied by motor disorders, typically spasticity or dystonia leading to negative effects on posture and function. The advent of botulinum toxin as a therapeutic agent transformed the care of patients affected by abnormal posture and discomfort but, as with all new technology, widespread application of the treatment often gives way to a more measured approach. Early, well publicized, work suggested that in mice the effect on muscle was reversible as new synapses were formed. The heterodoxy of reversibility gave the treatment a benign reputation and allowed it to be viewed as a bridging treatment during childhood enabling postural management to be continued until such time as some definitive treatment became feasible in later childhood. As an active clinician with a large case load of children with mainly spastic cerebral palsy I used botulinum toxin regularly with the calf being my most common target. With time, I came to appreciate the relative futility of injecting structurally short muscle and converged with the emerging consensus that the effects of injection lessened after the first couple of treatments in any one muscle. I used low dilutions of toxin under general anaesthesia, peppering the target muscles with toxin at a conservative dose.
Current practice I continue to use botulinum toxin in children with cerebral palsy for specific indications. Dystonia responds poorly to surgical management and botulinum toxin can prove useful in the management of pain associated with extreme posture especially in the upper limb. Where upper limb tendon transfers are under consideration a reversible procedure can be undertaken using botulinum toxin provided robust assessments are used pre and post injection to enable an evaluation of the effect. Where unrestrained muscle activation is likely to complicate a surgical procedure, a pre-emptive botulinum toxin treatment to the likely offending muscles can be considered. A final category of treatment is where dynamic tone is leading to abnormal posture during gait particularly in infants. A multilevel botulinum toxin treatment aimed at flexor spasticity at the knee and hip coupled with accurately tuned ankle foot orthoses and an intensive package of therapy can often allow the child to enter a more normal gait pattern with beneficial long term effects. In short, botulinum toxin is a powerful therapeutic agent that needs handling with respect and, in my view, should be combined with some other measure acting as an enabler rather than being a recurring 6 monthly treatment. A
Disillusionment I have the good fortune to work with a team of clinicians involved in muscle disorders and took advantage of this to document the features of muscle affected by spasticity in cerebral palsy. The study remit was not concerned with the effects of botulinum toxin on muscle but our muscle pathologist confronted me over one of the biopsy subjects suggesting that the child had a dystrophic problem rather than cerebral palsy. It transpired that this child had received botulinum toxin in the biopsied muscle many months previously but the muscle showed lasting damage. As we reviewed our data in the light of the dystrophic findings we found a relationship between damage and the use of botulinum given many months or even years previously and generally at a very conservative dose. At around this time a colleague, Janice Quinby in Newcastle upon Tyne, reported similar findings in hamstrings injected with botulinum toxin. We publicized our findings at paediatric orthopaedic
FURTHER READING Ackman JD, Russman BS, Thomas SS, et al. Comparing botulinum toxin A with casting for treatment of dynamic equinus in children with cerebral palsy. Dev Med Child Neurol Sep 2005; 47: 620e7. Boyd RN, Hays RM. Current evidence for the use of botulinum toxin type a in the management of children with cerebral palsy: a systematic review. Eur J Neurol Nov 2001; 8(suppl 5): 1e20. Cosgrove AP, Graham HK. Botulinum toxin a prevents the development of contractures in the hereditary spastic mouse. Dev Med Child Neurol May 1994; 36: 379e85. Kay RM, Rethlefsen SA, Fern-Buneo A, Wren TA, Skaggs DL. Botulinum toxin as an adjunct to serial casting treatment in children with cerebral palsy. J Bone Joint Surg Am Nov 2004; 86-A: 2377e84. Schroeder AS, Ertl-Wagner B, Britsch S, et al. Muscle biopsy substantiates long-term MRI alterations one year after a single dose of botulinum toxin injected into the lateral gastrocnemius muscle of healthy volunteers. Mov Disord Jul 2009; 24: 1494e503. Schroeder AS, Koerte I, Berweck S, Ertl-Wagner B, Heinen F. How doctors think and treat with botulinum toxin. Dev Med Child Neurol Sep 2010; 52: 875e6.
A Roberts FRCS DM is the Children’s Orthopaedic Surgeon at the Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, UK. Conflict of interest: none.
PAEDIATRICS AND CHILD HEALTH 23:9
414
Ó 2013 Published by Elsevier Ltd.