Dramatic changes in muscle contractile and structural properties after 2 botulinum toxin injections

Introduction: Botulinum toxin is frequently administered serially to maintain therapeutic muscle paralysis, but the effect of repeated doses on muscle function are largely unknown. This study characterized the muscle response to 2 onabotulinum toxin (BoNT) injections separated by 3 months. Methods: Animal subjects received a single toxin injection (n=8), 2 BoNT injections separated by 3 months (n=14), or 1 BoNT and 1 saline injection separated by 3 months (n=8). Results: The functional effect of 2 serial injections was exponentially greater than the effect of a single injection. While both groups treated with a single BoNT injection had decreased torque in the injected leg by approximately 50% relative to contralateral legs, the double BoNT injected group had decreased torque by over 95% relative to the preinjection level. Both single and double BoNT injections produced clear signs of fiber-type grouping. Conclusions: These experiments demonstrate a disproportionately greater effect of repeated BoNT injections.