Motor Fatigability, Depressive Symptoms Associated With MS Fatigue Severity

Tilburg, Netherlands. Living room portrait of a mature adult woman suffering from Multiple Sclerosis sitting besides her wheelchair.
Central corticomotor deficits, motor fatigability from whole body exercise, and depressive symptoms may influence fatigue severity in multiple sclerosis.

Central corticomotor deficits, heightened motor fatigability, and depressive symptoms may be predictive of fatigue severity in patients with multiple sclerosis (MS). Additionally, motor fatigability from large muscle mass exercise in patients with low MS disability is largely due to peripheral muscle fatigability, according to study results published in the Journal of Neurophysiology.

Study researchers sought to better understand the etiology of motor fatigability in patients with MS, as well as the role of motor fatigability in relation to other contributing factors to fatigue in this population.

This cross-sectional study enrolled 13 “highly fatigued” patients with MS, 13 non-fatigued patients with MS, and 13 healthy controls. Levels of fatigue were assessed using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) score. An FSS score of at least 4 and MFIS score of at least 34 classified patients as highly fatigued. Low levels of perceived fatigue were classified by no self-reported fatigue and lower FSS and MFIS scores.

Participants completed a step test until volitional exhaustion was reached on a cycle ergometer. The cycle ergometer was designed to switch quickly between cycling and isometric knee extension. The study researchers performed neuromuscular assessments involving femoral nerve electrical stimulation, as well as transcranial magnetic stimulation every 3 minutes during cycling.

At baseline, the motor evoked potential (MEP) 100 and MEP 50 amplitudes were significantly smaller for the highly fatigued group compared with controls (P =.008 and P =.011, respectively). Additionally, highly fatigued patients with MS had significantly longer MEP latencies than non-fatigued patients with MS (P =.041) at 100% maximal voluntary contraction force (MVC).

Compared with controls, highly fatigued patients also had significantly longer MEP latency at all contraction intensities, including 50% (P =.047), 75% (P =.014), and 100% (P =.033). In addition, patients with MS who were considered highly fatigued also had a greater decline in MVC at volitional exhaustion than patients with less fatigue (P =.049).

In a hierarchical regression analysis, variables predictive of fatigue severity on the FSS included prolonged MEP latencies (change in r2 = 0.389), elevated peripheral muscle fatigability (change in r2 = 0.138), and depressive symptoms (change in r2 = 0.213).

Limitations of the study were the small number of participants, the inability to exclude all medications, and the inclusion of only patients with MS who had mild physical disability.

The study researchers concluded that “motor fatigability from dynamic, large-muscle-mass exercise in people with low MS disability is primarily due to peripheral muscle fatigability.” However, they added that the study results warranted additional “research examining the effects of exercise training on motor fatigability in” patients with MS “and its impact on perceived fatigue.”


Coates KD, Aboodarda SJ, Krüger RL, et al. Multiple sclerosis-related fatigue: the role of impaired corticospinal responses and heightened exercise fatigability. J Neurophysiol. 2020;124(4):1131-1143. doi:10.1152/jn.00165.2020