Gait and Cortical Activity Profile of People With Multiple Sclerosis Presenting With Walking Fatigability

Methodology Recruitment strategy. Participants will be recruited from the Flemish MS rehabilitation centers Melsbroek (NMSC) and Overpelt (Noorderhart RMSC), as well as the REVAL research center inUHasselt. Information flyers will be distributed in the centers and via information placed on the website and social media of REVAL and the Flemish MS society. We will search age and sex-matching subjects for the healthy controls, considering a 5-year range per subject.

After giving informed consent, demographics of age and gender, as well as MS-related information such as EDSS, type of MS, and years since diagnosis, will be collected and provided by the centers or via self-report. The participants will be instructed to keep their normal routine and avoid extraneous physical activity at least 24 hours before the data collection session.

Experiment outline. The study proposes two research questions and will be performed in three days. The first day is the clinical assessment/screening of the participants (common for Part A and B). Part A is an observational study (2nd day), and Part B is an observational and feasibility study (3rd day).

Clinical assessment/screening The participants will be contacted to verify their interest and eligibility (inclusion and exclusion criteria) to participate in the study. In the case of inclusion in the study, different questionnaires will be sent to the participants to fill in: Falls Efficacy Scale International (FES-I) for fear of falling, Multiple Sclerosis Walking Scales (MSWS-12) and 10 questions encompassing gait items for walking perceived ability [11], Pittsburgh Fatigability Scale (PFS) for perceived fatigability, Modified Fatigue Impact Scale (MFIS) for perceived fatigue, the Brief Pain Inventory (BPI, short form) for the assessment of perceived pain, Multiple Sclerosis Spasticity Scale 88 (MSWS-88, section 5 and 6) to verify the impact of spasticity in the walking and movement ability and Brief Self-Control Scale (BSCS) for self-control evaluation. Specifically for the pwMS, the Patients Disease Determined Steps (PDDS) will be asked in order to know the self-perceived level of disability. Participants will also be asked and oriented to measure their head's circumference for the functional near-infrared spectroscopy (fNIRS) measurement. In case the patient is contacted in the MS centers (MS Rehabilitation Center- Pelt and National MS Center Melsbroek), the therapist will provide the questionnaires, measure the head size of the participants, and obtain the level of disability (measured by the expanded disability status scale- EDSS). The skin color, type, and color of the hair will be noted to assist in the fNIRS analysis.

Part A- Assessment The study includes 70 pwMS and 30 healthy controls. The study consists of a single visit (1 hour and 30 minutes duration, including equipment preparation and rest periods). Participants will be asked to wear shorts or legging pants for better fixation of the sensors. Anthropometric characteristics such as age, weight, height, and sex will be asked and measured. Moreover, for pwMS, the time from the diagnosis, MS phenotype, and medications that could influence fatigue or walking performance will also be recorded. The symbol digit modalities test (SDMT) will evaluate the cognitive processing speed. Afterward, the modified Ashworth scale (MAS) will be used to check the muscle spasticity of the knee flexors/extensors and ankle flexors/extensors. The motricity index will be performed for muscle strength measurement, followed by the performance of the timed 25-foot walking test (T25FWT). For cortical activity measurement of the prefrontal cortex, supplementary motor area, premotor cortex, and primary motor cortex, a fNIRS will be positioned in the participants head. Wearable sensors will be positioned in a pre-defined body position to measure gait characteristics. Both gait characteristics and cortical brain activation will be measured concomitantly during short walking (10 trials of 15 seconds with 25-30 seconds standing still resting periods between trials, in a block design) before and after and during a prolonged walking (6-minute walking test (6MWT)) protocols. Before the beginning of the 6MWT, two questions will be asked to the participants: "Do you slow down when walking for a while?" and "Do you feel a worsening of your smoothness when walking for a while?" where they will have to rate between 1 ("not at all") and 5 ("Extremely"). A questionnaire about their perceived gait quality changes, comparing the end with the beginning of the 6MWT, will be asked through the Perception of Gait Quality Change (PGQC).