Increased muscle fiber size and pathology with botulinum toxin treatment of upper extremity muscles in cerebral palsy

Intramuscular injections of botulinum toxin A (BTX) are regularly used to treat skeletal muscle spasticity and relieve pain during rehabilitation therapy. However, while numerous preclinical studies have shown dramatic atrophic changes in muscle, little is known about the long-term effect of toxin on human skeletal muscle. In this study, muscle morphology was analyzed in biopsies taken from spastic upper extremity muscles of 8 cerebral palsy patients treated with BTX 5 months to 4 years prior sampling and was compared to muscles from 7 patients who had not ever received BTX treatment (overall 25 muscle biopsies obtained from 6 different muscles.). The most important (and surprising) finding was that BTX-treated muscles contained significantly larger fibers compared to untreated muscles. A strong correlation between fiber size and age was observed but the growth rate in the BTX group was larger. Pathological signs such as central nuclei, neonatal myosin heavy chain expression, angular fibers and hybrid fibers (expressing both slow and fast myosin heavy chain fibers) were significantly greater in BTX-treated muscles compared to untreated muscles. Capillarization was also increased in BTX-treated muscle compared to untreated muscles and was the best predictor of fiber size. We suggest that, in the context of spasticity, BTX may block negative, atrophy-inducing pressure of the central nervous system on skeletal muscle or may allow an altered use pattern that should be considered a positive adjuvant to current rehabilitation therapies.