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 build a model
of 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. 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.

This is an one-site study with a pre-posttest design. The study consists of 3
sessions: 1 session pre-intervention and 2 sessions (6 and 12 weeks)
post-intervention.

The study does not create direct benefits for the subjects, as the protocol
just adds observational experiments on top of regular clinical care. The burden
is minimal and the risks negligible, as the protocol consists of 10 minutes of
preparation and 25 minutes of non-invasive tests. Moreover, 2 out of 3 visits
will be combined with regular clinical appointments to further minimize the
burden. In total, subjects will participate in 3 sessions over a 12 week
period. Similar test with the ankle dynamometer used have already been
executed/approved multiple times by the METC.