Effect of botulinum toxin (BoNT-A) injections on intrinsic and reflexive contributions to ankle joint resistance for patients with spasticity

Spasticity is a common syndrome caused by various brain and neural injuries with several negative consequences, e.g. impaired walking ability and functional independence. Botulinum neurotoxin type A (BoNT-A) injections are a frequently used clinical intervention for the reduction of muscle tone and spasticity. The current clinical evaluation of the effect of BoNT-A has mainly been assessed using the Modified Ashworth Scale (MAS). Unfortunately, the MAS can only be used to assess muscle tone, and it has a questionable reliability and low responsiveness to change. Thus, the clinical effect and cost-effectiveness of spasticity treatment using BoNT-A is not well investigated nor understood, while BoNT-A injections are actively used as clinical intervention. To get increased insight into the beneficial and adverse effects of BoNT-A interventions, it is important to quantify the effect of BoNT-A interventions on the different contributions to joint (hyper-)resistance. Thus, potentially improving clinical decision making and cost-effectiveness.
The state-of-the-art to quantify the different contributions to joint resistance to investigate BoNT-A interventions is based on musculoskeletal modelling. These methods model the musculoskeletal system based on previously investigated characteristics of smaller elements of the system and as such use a large number of a-priori assumptions. The lack of a golden standard, makes it difficult to understand whether the published (conflicting) results are due to reality or erroneous models. Therefore, we propose to use a system identification technique to separate spasticity (reflexive ankle joint resistance) from the combination of muscle tone and tissue properties (intrinsic ankle joint resistance). System identification methods model the musculoskeletal system directly from an experimental dataset. This dataset is obtained in a dedicated experiment in which the ankle joint is externally perturbed by a motor and the subsequent biomechanical response, i.e. the resistance to these perturbations, is analyzed. Main benefit of the proposed method is that it only relies on a single biological assumption, namely that the ankle stretch reflex has a 40ms neural delay. The validity to use the system identification methodology as pre-posttest assessment technique to quantify the effect of clinical interventions on joint resistance has been shown in several studies.
The main objective of the study is to evaluate the effect of BoNT-A injections on the intrinsic an reflexive contributions to ankle joint resistance for patients with spasticity. Secondary objectives are to examine the (across-subject) effect of the number of BoNT-A injections on the difference in reflexive ankle joint resistance and the difference in intrinsic ankle joint resistance before and 6 weeks after injection.

We hypothesize that, with respect to baseline, reflexive joint resistance should be decreased 6 weeks after injection, while returning back to baseline values after 12 weeks

T0: Prior to the botox injections
T1: 6 weeks after the botox injections
T2: 12 weeks after the botox injections