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.

Multiple sclerosis-related fatigue: the role of impaired corticospinal responses and heightened exercise fatigability.

It is unclear whether motor fatigability and perceived fatigue share a common pathophysiology in people with multiple sclerosis (PwMS). This cross-sectional investigation explored the relationship between the mechanisms of motor fatigability from cycling and fatigue severity in PwMS. Thirteen highly fatigued (HF) and thirteen nonfatigued (LF) PwMS and thirteen healthy controls (CON) completed a step test until volitional exhaustion on an innovative cycle ergometer. Neuromuscular evaluations involving femoral nerve electrical stimulation and transcranial magnetic stimulation were performed every 3 min throughout cycling. One-way ANOVA at baseline and exhaustion uncovered evidence of consistently smaller motor evoked potential (MEP) amplitudes (P = 0.011) and prolonged MEP latencies (P = 0.041) in HF as well as a greater decline in maximal voluntary contraction force (HF: 63 ± 13%; LF: 75 ± 13%; CON: 73 ± 11% of pre; P = 0.037) and potentiated twitch force (HF: 35 ± 13%; LF: 50 ± 16%; CON: 47 ± 17% of pre; P = 0.049) in HF at volitional exhaustion. Hierarchical regression determined that fatigue severity on the Fatigue Severity Scale was predicted by prolonged MEP latencies (change in r2 = 0.389), elevated peripheral muscle fatigability (change in r2 = 0.183), and depressive symptoms (change in r2 = 0.213). These findings indicate that MS-related fatigue is distinguished by disrupted corticospinal responsiveness, which could suggest progressive pathology, but fatigability from whole body exercise and depressive symptoms also influence perceptions of fatigue in PwMS.NEW & NOTEWORTHY The etiology of fatigability from whole body exercise was examined for the first time to accurately elucidate the relationship between fatigue and fatigability in multiple sclerosis (MS). Compromised corticospinal responsiveness predicted fatigue severity, providing a novel, objective indicator of fatigue in MS. Although the impaired corticomotor transmission did not aggravate muscle activation in this group of people with multiple sclerosis (PwMS) of lower disability, heightened muscle fatigability was seen to contribute to perceptions of fatigue in PwMS.

The short-term recovery of corticomotor responses in elbow flexors.

BACKGROUND: The recovery of neurophysiological parameters at various time intervals following fatiguing exercise has been investigated previously. However, the repetition of neuromuscular assessments during the recovery period may have interfered with the true corticomotor excitability responses. In this experiment, fatiguing contractions were combined with a single post-fatigue assessment at varying time points. Ten participants undertook 5 bouts of 60-s maximal voluntary contractions (MVC) of the elbow flexors, separated by 20 min. Before and after each 60-s fatiguing exercise (FAT), participants performed a series of 6-s contractions at 100, 75 and 50% of their MVC during which transcranial magnetic, transmastoid electrical and brachial plexus electrical stimuli were used to elicit motor evoked potentials (MEP), cervicomedullary motor evoked potentials (CMEP) and compound muscle action potentials (Mmax) in the biceps brachii muscle, respectively. Post-FAT measurements were randomly performed 0, 15, 30, 60, or 120 s after each FAT. RESULTS: MVC force declined to 65.1 ± 13.1% of baseline following FAT and then recovered to 82.7 ± 10.2% after 60 s. The MEP·Mmax-1 ratio recorded at MVC increased to 151.1 ± 45.8% and then returned to baseline within 60 s. The supraspinal excitability (MEP·CMEP-1) measured at MVC increased to 198.2 ± 47.2% and fully recovered after 30 s. The duration of post-MEP silent period recorded at MVC elongated by 23.4 ± 10.6% during FAT (all P < 0.05) but fully recovered after 15 s. CONCLUSIONS: The current study represents the first accurate description of the time course and pattern of recovery for supraspinal and spinal excitability and inhibition following a short maximal fatiguing exercise in upper limb.