INTRODUCTION:
Fatigue, defined as the feeling of tiredness and lethargy, is one of the most debilitating symptoms in people with Multiple Sclerosis (PwMS). This phenomenon is reported to worsen with exertion and across the day. Although time- and activity-related effects of fatigue on physical performance (e.g., 6 min walk test) have been largely explored, the underlying neuromuscular responses remain unclear. This study explored the effect of the time of day and prior physical activity on maximal voluntary contraction (MVC) force output, and its associated central and peripheral measures, during clinical walking tests in PwMS. Secondary analyses explored the association between these neuromuscular responses with perceived general health, fatigue, and walking ability – as measured by the 36-item short form survey (SF-36), modified fatigue impact scale (MFIS), and the 12-item Multiple Sclerosis Walking Scale (MSWS-12).
METHODS:
Twenty-four PwMS (18 female) who experience a significant level of fatigue attended three laboratory visits: one in the morning (1 h after waking) and two in the evening (12-14 h after waking). To differentiate between the effect of time of day and prior physical activity on neuromuscular responses, participants performed approximately twice their typical daily activity before one of the evening visits. During each visit, neuromuscular assessments of the knee extensors (KE) and plantar flexors (PF), consisting of a maximal voluntary contraction coupled with peripheral nerve stimuli, were performed before and after a 6-minute walk test, as well as before, during, and after a subsequent 12-minute walking task.
RESULTS:
Mixed-effects ANOVAs revealed significant time-dependent declines in KE MVC (p = 0.006), KE potentiated twitch (Ptw, p < 0.001), PF MVC (p < 0.001), and PF voluntary activation (VA, p = 0.004) with no main effect of visit or visit × time interaction. Linear mixed-effects models further revealed progressive declines in KE MVC and Ptw, and PF MVC across the walking tasks (all p < 0.01). Secondary analyses revealed that a higher MFIS score was associated with greater reductions in KE MVC (r = -0.53, p = 0.005) and KE Ptw (r = -0.62, p < 0.001), whereas KE VA was relatively maintained (r = 0.33, p = 0.005).
CONCLUSION:
These findings indicate that the decline in neuromuscular function during walking tasks in PwMS is independent of time of day and prior physical activity. Higher perceived fatigue severity is associated with greater peripheral fatigue and an attenuated central fatigue response. These results provide novel insights into the neuromuscular responses to clinical walking tests in PwMS and may help clinicians improve rehabilitation program efficacy.