Assessment of effects of Botulinum Toxin on muscle mechanics

Effects 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 finite 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 effects. Additionally, experimental results showed diminished epimuscular MFT and intramuscular collagen increase. Due to information on the loss of interactions between muscles and increased ECM stiffness 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 stiffness 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 finding. If such stiffness increase were shown to remain post-treatment, enhanced capacity would become permanent for the entire muscle. It is concluded that mechanical effects and morphological changes shown can affect muscular mechanics adversely if not managed accordingly.