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

Alderson, Kathy MD
Holds, John B. MD
Anderson, Richard L. MD

Department of Neurology (Dr. Alderson), and the Division of Oculoplastic Surgery, Department of Ophthalmology (Drs. Holds and Anderson), University of Utah School of Medicine, and Neurology Division, Veterans Administration Medical Center (Dr. Alderson), Salt Lake City, UT.

Address correspondence and reprint requests to Dr. Kathy Alderson, Department of Neurology, University of Utah Medical Center, 50 North Medical Drive, Salt Lake City, UT 84132.

Supported in part by a grant from the Benign Essential Blepharospasm Foundation and Veteran's Administration Medical Research. Drs. Holds and Anderson received support from Allergan Pharmaceuticals for unrelated animal studies of botulinum toxin.

Presented in part at the 42nd annual meeting of the American Academy of Neurology, Miami Beach, FL, May 1990.

Received December 3, 1990. Accepted for publication in final form May 3, 1991.

Neurology 41(11):p 1800-1805, November 1991.

Article abstract

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.