An electrophysiological study of the mechanism of fatigue in multiple sclerosis

Abstract

Fatigue is a common and disabling symptom in multiple sclerosis but is poorly understood. We investigated 'physiological' fatigue in 21 patients with multiple sclerosis who complained of disabling fatigue by measuring the decline in strength during a 45 s maximal contraction of the adductor pollicis muscle. The results were compared with those from a control group of 19 healthy subjects. The strength of control subjects declined by approximately 20% during the contraction; twitch interpolation showed central drive remained almost maximal throughout, and therefore that the fatigue was peripheral in origin. Patients had normal baseline strength, but developed greater fatigue (approximately 45%), which was central in origin. In both cases, the decline in strength followed a roughly linear time course suggesting that the patients, like the normals, were trying to maintain a maximum voluntary effort. Evidence for frequency-dependent conduction block (FDCB) in the patients' central motor pathways was sought by measuring the EMG responses to single and paired transcranial magnetic stimuli. Fatigue had no effect on the latency or size of EMG responses to transcranial magnetic stimulation, suggesting that FDCB was unlikely to have occurred. This was supported by measurements of the maximum speed of voluntary muscle contraction; although the patients showed relatively slow speeds before exercise, the decline in speed after fatigue was no greater than in normal subjects. We conclude that excessive 'physiological' fatigue contributes to the symptom of fatigue in multiple sclerosis and is central in origin. However, since the degree of exercise-induced fatigue did not correlate with the baseline complaint of fatigue, other factors must also be operating to produce the full range of clinical symptoms. We found no conclusive evidence that central fatigue is related to increased dysfunction in the primary central motor pathways and no evidence that FDCB is the pathophysiological mechanism. We postulate that central fatigue in multiple sclerosis is due to impaired drive to the primary motor cortex and several lines of evidence strongly suggest that this is not due to a lack of motivation.

The effect of exercise therapy on fatigue in multiple sclerosis

“…Efferent high-frequency fatigue is thereby prevented, but the maximal muscle strength is also reduced. 43,44 In healthy subjects RT improves central motor activation, 45 in MS patients RT enhances the efferent motor drive, 46 and in MS RT seems to reduce MS fatigue. The perception of worsened fatigue after overtraining may occur as a consequence of afferent inhibition from strained muscles.…”

Thermoregulation in multiple sclerosis

“…Using transcranial magnetic stimulation, a noninvasive technique used to measure conduction properties of the corticospinal tract and excitability of the motor cortex, White et al (84) demonstrated that fatigue induced by raising core temperature by 0.8°C via indirect whole body heating in MS patients produces a corresponding decrease in central motor conduction time and cortical excitability. These results most likely occurred as a result of slowed or blocked conduction in demyelinated lesions in the CNS (28, 31) associated with alterations in central activation (58,70).…”

Are the neurophysiological techniques useful for the diagnosis of diaphragmatic impairment in multiple sclerosis (MS)?

“…We found that FDS score was directly related to EDSS and duration of the disease, as expected, this could mean that greater fatigue developed in weaker subjects and with longer history of disease. FDS was also directly related to TMS findings from AbdV8; previous reports found that the degree of symptomatic fatigue was proportional to that of pyramidal tract involvement , but this was not confirmed by others (Sheean et al, 1997). Conversely, the score of fatigue did not significantly correlate to TMS findings from Dia and any of the respiratory parameters.…”