Brain, Vol 120, Issue 2 299-315, Copyright © 1997 by Oxford University Press
GL Sheean, NM Murray, JC Rothwell, DH Miller and AJ Thompson
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.
ARTICLES
An electrophysiological study of the mechanism of fatigue in multiple sclerosis
Department of Clinical Neurophysiology, National Hospital for Neurology and Neurosurgery, London, UK.
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