Walking-induced motor fatigability in Multiple Sclerosis: a pilot study on underlying mechanisms and the feasibility of sequential resistance and walking-specific endurance training

In Multiple Sclerosis (MS) the ability to walk long distances is not only
influenced by disease severity, but is also progressively affected during a
single continuous bout of exercise. This motor fatigability is poorly
understood and not targeted in rehabilitation interventions. Understanding the
underlying mechanisms and exploring new treatments of motor fatigue is highly
relevant, because it may lead to more effective treatments to improve quality
of life and promotion of a healthy life style. In addition, we will assess the
feasibility and preliminary effect of a targeted sequential training program in
which resistance training of the lower leg muscles serves as a preconditioning
phase for high intensity endurance training on a treadmill. It is hypothesized
that by using this sequential step-wise exercise approach, persons with more
severe walking-induced motor fatigability will be prepared and able to exercise
at a higher intensity level.

a) To study the relationship between ankle push off and walking-induced motor
fatigability and the potential confounders of this relationship in persons with
progressive MS and healthy controls.
b) To assess the feasibility of a targeted, sequential resistance plus
walking-specific endurance training regime on walking-induced motor
fatigability in persons with MS.

pre-post intervention pilot-study in patients with MS, plus a healthy-control
assessment (reference group).

Patients with MS will receive a sequential exercise program for 4 months, 3x
per week, in which the first 8 weeks consist of progressive resistance training
(2-3 sets, 8-12 reps, 60-70% 1RM), followed by 8 weeks of progressive walking
endurance training (High Intensity Interval Training, 3-6 cycles, 90%HRmax vs.
comfortable walking speed).

Gait impairments can already be seen in the early stage of MS and cause
difficulties in ambulation for a large number of patients with MS (pwMS).
Ambulation has been shown to be an important factor in the ability to engage in
social participation and health-related quality of life. Moreover, reduced
ambulation may greatly affect the ability to maintain physical fitness and
healthy activity levels, and might even further exaggerate deconditioning,
disease progression and specific symptom experience like fatigue and cognitive
function. The multi-dimensional assessment of walking-induced fatigability and
the underlying mechanisms that may explain some of the gait characteristics may
benefit future treatment of patients with MS. As part of this pilot study, a
targeted sequential exercise training regime is used to assess the feasibility
and preliminary effects on walking-induced motor fatigability in MS. The use of
healthy controls as reference allows for a better understanding of
walking-induced motor fatigability that can be attributed to MS.

Healthy participants will not benefit from participation. They will, however,
contribute to future treatment of walking problems in patients with MS. In both
healthy as well as person with MS, the risks and burden of the experiments may
be related to walking on the GRAIL (dual-belt instrumented treadmill), to
cardiopulmonary exercise testing, central and peripheral muscle fatigue
testing, or in the case of the pwMS, the sequential exercise training. Patients
with MS may benefit from the sequential training program on a function,
activity, and participation level. All measurements and exercise therapy are
non-invasive, and have been shown safe. The risk classification for this study
is *negligible*.