Botulinum-induced alteration of nerve-muscle interactions in the human orbicularis oculi following treatment for blepharospasm.

To assess longstanding alterations in human muscle innervation induced by botulinum toxin, we studied motor axons in the orbicularis oculi of nine patients previously injected with botulinum toxin for treatment of benign essential blepharospasm (BEB). Compared with untreated BEB and normal orbicularis oculi, muscle exposed to botulinum toxin developed persistent and cumulative alterations of innervation, including (1) thin, unmyelinated axonal collaterals that contact muscle end plates, (2) an increased number of muscle fibers innervated by individual terminal motor axons, (3) a profusion of unmyelinated axonal sprouts that end blindly, (4) an increased range of end plate sizes, and (5) multiple end plates on individual muscle fibers. The findings suggest that axonal sprouts which develop after botulinum-toxin-induced functional denervation can form new end plates. A single muscle fiber may then be innervated at separate sites by more than one axon.