Investigating skeletal muscle adaptations due to btx-a injections using agent-based modelling

Local application of Botulinum Toxin Type-A (BTX-A) has been the gold standard for spasticity management in children with Cerebral Palsy. The treatment aims to reduce the passive resistance of force at the joint and increase the joint range of motion. However, recent studies have reported results contradictory to treatment aims including increased passive force, increased muscle stiffness and decreased length range of force exertion which have been attributed to the increased collagen content in the muscle Extracellular Matrix (ECM) confirmed by histological findings. Moreover, a recent finite element analysis study has reported that BTX-A injections were found to increase the injected muscle fibers' strain. Hence, to understand these muscle adaptations and the effects of strain on muscle structure and function, the Agent-Based Modelling (ABM) method was used. The advantages of this method over other methods is that it allows studying muscle adaptations at the cellular level with the complex interactions modelled. This study was modelled in three cases comparing the BTX-A model, BTX-A-Free model and a middle half paralyzed (MHP) model similar to that used in the recent finite element model. Two of the cases compared the BTX-A-Free fascicle against the BTX-A and the MHP fascicles and the third case compared the BTX-A-Free case to a modified MHP case which included the reported BTX-A induced atrophy and the decaying effects of BTX-A 7-10 days after injection. The collagen increase in the cases was approximately 33%, 33%, and 20.3% respectively. This study revealed that although the BTX-A induced strain increase was found to increase collagen content of the ECM, other important factors such as the BTX-A induced atrophy may also play a significant role in collagen increase in the muscle ECM.