HISTOLOGIC ASSESSMENT OF DOSE-RELATED DIFFUSION AND MUSCLE-FIBER RESPONSE AFTER THERAPEUTIC BOTULINUM-A TOXIN INJECTIONS

Fiber diameter variability, acetylcholinesterase staining properties, and average fiber diameter were determined 5 weeks after varying doses of botulinum A toxin were administered into albino rabbit longissimus dorsi muscle. The average fiber diameter within the muscle appeared t o be a function of the dose of botulinum toxin injected. Fiber diamete r variability correlated with the dose of botulinum toxin administered . Both fiber diameter variability and acetylcholinesterase spread char acteristics showed a distinct diffusion gradient over a defined field within a muscle. At lower doses (1 IU), collapse of the diffusion grad ient occurred over a 15-30-mm segment of muscle. At higher doses (5-10 IU), diffusion of botulinum A toxin effect occurred throughout the en tire muscle with no apparent end point. This study demonstrated that b otulinum A toxin produces a gradient of denervation in a given muscle and that both the magnitude of denervation and the extent of the gradi ent are dose dependent. Furthermore, both muscle fiber diameter variab ility and acetylcholinesterase staining were useful as measures of che modenervation.