Skeletal muscle mechanics and spasticity management: Human and animal experiments

Being the most common motor disability in childhood, cerebral palsy (CP) describes a movement disorder for which the exact underlying mechanism is unclear, and no cure is available. Yet, local injection of botulinum toxin type-A (BTX-A) is used for spasticity management. In this thesis, the relationship between the mechanics of spastic muscles and the impaired joint motion was investigated in patients, and the long-term effects of BTX-A on muscular mechanics were assessed in animals. Experiments on spastic knee flexors showed that passive muscle forces are much less than active forces (e.g., 26%), and epimuscular myofascial force transmission (EMFT) arising from intermuscular mechanical interactions significantly increases active forces (up to 132%). Combined with musculoskeletal models developed based on gait analysis data, EMFT effects were shown to be compatible with metrics characterizing patients' pathological gait, indicating that intermuscular mechanical interactions may be a source of high flexor forces in flexed joint positions. Experiments in the rat anterior crural compartment showed that long-term after injection, BTX-A yields in addition to decreased active forces, both unintended (a narrower range of force exertion by 23% and increased passive forces by 12%, for the injected muscle) and uncontrolled effects (similar effects on compartmental muscles due to the spread of the toxin). BTX-A also leads to collagen content increase (by several folds) for muscles exposed, which explains elevated passive forces and impacts also active forces. These effects are of high potential clinical importance as they conflict with therapeutic goals. Particularly, controlling the effects of BTX-A on connective tissue adaptation is critical for better spasticity management.