Project R-14666

A multi-modal tailored and adaptive training program to reduce walking fatigability in persons with progressive MS. (Research)

Prevalent symptoms of progressive MS (pwPMS) are impairments in walking and abnormal fatigue, which can affect daily life activities. Walking dysfunction is caused by a combination of motor impairments, such as muscle weakness, spasticity, and incoordination, as well as attention deficits. Fatigue, on the other hand, is a sense of tiredness reported by pwMS, and fatigability is the magnitude of change in the perception or performance in a given task. We propose a project fitting 'mobility' and 'physical health' in the call of PMSA. Walking fatigability (WF) is observed during prolonged walking and is measured during the 6-minute walking test (6MWT) in clinical research. It can manifest as slowing down and/or worsening of gait quality, and it is prevalent in more than half of pwPMS with a disability higher than EDSS 4.0. Factors related to WF include changes in muscle strength or endurance from lower limbs, deteriorated symptoms, perceived fall risk, and perceived fatigue, which can limit maximal walking speed. Changes in spatiotemporal parameters during the 6MWT have been well-documented, and wearable sensors have been used to measure them during over-ground walking in more disabled pwMS. These changes include decreased gait stability, increased drop foot, and uncoordinated and asymmetric lower limb movements during prolonged walking. Abnormal changes in the joint biomechanics during walking relate to reduced inter-joint and interlimb coordination in MS. The gait changes over time may relate to the hypothesis that pwMS have a limited cortical activation capacity in motor and prefrontal areas to sustain programming of muscle contractions and coordination during prolonged walking, which reflects a decrease in automaticity in the gait control. However, there are good candidate intervention modalities that can improve walking distance in pwMS, such as progressive muscle strength, balance and motor control training, walking training, and combined training. Improvements after task-specific training were associated with improved perceived walking ability and reduced perceived fatigue. The study will rely on updated theoretical informed causal pathways and the patient perspective on motor fatigability. Detailed multifactorial assessment and training procedures and algorithms to tailor the interventions will be set up with patient engagement and experts with clinical experience. The proposed trial will investigate immediate and follow-up effects on walking fatigability and related factors. Identifying and combining multimodalities approaches in research to achieve the best results is especially needed in disabled pwPMS where magnitude of physical training effects were limited in pwPMS. In summary, the study highlights the prevalence and impact of impairments in walking and abnormal fatigue on pwPMS and the need for effective interventions.

01 January 2024 - 28 February 2026