Botulinum toxin-induced myopathy in the rat.

We have used histological and histochemical techniques at the light microscopical level, and electron microscopy to examine the myopathological changes in rat muscle up to 30 weeks following botulinum toxin injection. Apart from muscle fibre atrophy and related myofibrillar structural changes, the results show a number of striking abnormalities which developed and disappeared at different stages. During the first 4 weeks after toxin injection, vacuoles of variable size were seen in the sarcoplasm near myonuclei, both at and away from endplates. Following this, between 4 and 10 weeks post-injection, progressive degeneration of junctional folds and separation of some nerve terminals from the simplified postsynaptic membranes were observed. At different time points following recovery from the toxin-induced paralysis (evidenced by the increase in muscle fibre size and return of function) a number of abnormalities were still detectable in muscle fibres. These included the appearance within them of multiple arrays of sarcotubular profiles, focal areas lacking myofibrillar organization and mitochondria, abnormal mitochondrial aggregates showing crystalline inclusions, and extension of the postsynaptic densities along the full depth of junctional folds. Furthermore, targetoid-like areas were detected histochemically following recovery from the toxin-induced paralysis. The early extensive vacuolation of the sarcoplasm and the degeneration of junctional folds suggest a myotoxic effect of botulinum toxin. The late changes are likely to be (at least in part) related to the process of recovery following reinnervation.