How is neuromuscular fatigability affected by perceived fatigue and disability in people with multiple sclerosis?

Whereas fatigue is recognized to be the main complaint of patients with multiple sclerosis (PwMS), its etiology, and particularly the role of resistance to fatigability and its interplay with disability level, remains unclear. The purposes of this review were to (i) clarify the relationship between fatigue/disability and neuromuscular performance in PwMS and (ii) review the corticospinal and muscular mechanisms of voluntary muscle contraction that are altered by multiple sclerosis, and how they may be influenced by disability level or fatigue. Neuromuscular function at rest and during exercise are more susceptible to impairement, due to deficits in voluntary activation, when the disability is greater. Fatigue level is related to resistance to fatigability but not to neuromuscular function at rest. Neurophysiological parameters related to signal transmission such as central motor conduction time, motor evoked potentials amplitude and latency are affected by disability and fatigue levels but their relative role in the impaired production of torque remain unclear. Nonetheless, cortical reorganization represents the most likely explanation for the heightened fatigability during exercise for highly fatigued and/or disabled PwMS. Further research is needed to decipher how the fatigue and disability could influence fatigability for an ecological task, especially at the corticospinal level.