Assessment of effects of botulinum toxin on muscle mechanics

Abstract

E ects of widely used Botulinum toxin (BTX) treatment on muscular mechanics are highly important, but their mechanism and time course are not well understood. Present thesis is focused on mechanical mechanism of BTX treatment using nite element method and animal experiments. In an isolated muscle model partial paralyzation is shown to cause (i) the sarcomeres to attain higher lengths throughout the entire muscle (e.g., at short muscle length, the inactivated fascicles of middle half paralyzed muscle and the same parts within BTX-free muscle shortened by 29-27% and 32-29%, respectively), (ii) enhanced potential of active force production of the non-paralyzed muscle parts (up to 14.5% for BTX cases), and (iii) decreased muscle length range of force exertion. It is shown that intramuscular myofascial force transmission is central to these e ects. Additionally, experimental results showed diminished epimuscular MFT and intramuscular collagen increase. Due to information on the loss of interactions between muscles and increased ECM sti ness due to increased collagen, temporal changes within the muscle during treatment is examined. Modeling of time course of the BTX treatment showed that sarcomeres attain even higher lengths with increased ECM sti ness and is reversed at longer muscle lengths. Consequently, force production capacity of activated sarcomeres gets further enhanced in the long-term and a narrower length range of force exertion (20.3%, 27.1% and 3.4%, acute, long-term and post BTX treatment, respectively) is a consistent nding. If such sti ness increase were shown to remain post-treatment, enhanced capacity would become permanent for the entire muscle. It is concluded that mechanical e ects and morphological changes shown can a ect muscular mechanics adversely if not managed accordingly.|Keywords : Botulinum toxin, Myofascial force transmission, Finite element modeling, length-force characteristics, longer sarcomere e ect, time course of BTX.