Purpose of study: To describe the histological effects of botulinum toxin on gastrocnemius muscle affected by cerebral palsy.

Method: Samples of gastrocnemius were obtained at the time of surgery. Ethical committee approval had been obtained for the study. Details of timing and doses of botulinum toxin previously administered to the muscle were recorded. A variety of immunohistochemical tests were employed to identify any changes in the muscle. Alterations in the distribution of myosin isoforms were identified with antibodies for fast, slow and neonatal myosin. The presence of persistent denervation was inferred from fibres deficient in neuronal nitric oxide synthase (nNOS). Mitochondrial abnormalities were assessed with an NADH stain and the presence of chronic atrophic fibres (nuclear clumps) noted.

Results: Our first case had received 3 botulinum injections over a period of 5 years, the last one 3 years prior to biopsy. Histology showed pronounced abnormalities with a wide variation in fibre size, areas of myofibrillar disruption and 50% of fibres co-expressing fast and slow myosin. Other samples showed less change but showed more frequent nuclear clumps than controls, indicating chronic atrophy and more hybrid fibres than controls, but always less than 10%. Treated muscles also showed a small, variable number of atrophic fibres without nNOS. Treated samples showed no apparent fibre type grouping, a feature associated with collateral sprouting of peripheral nerves following denervation.

Conclusions: Moderate doses of botulinum toxin appear to produce an alteration in muscle histology apparent several years afterwards. No correlation could be found between the timing of the previous injection or the dose of botulinum toxin injected and the severity of the changes. Botulinum toxin remains a valuable aid in the management of spastic muscle. However consideration should be given to other methods of treatment if an effective non surgical alternative exists.