The term fatigue may be used in different contexts to refer to both a sign and a symptom.
The sign of fatigue, also known as peripheral fatigue, consists of a reduction in muscle strength with repeated muscular contraction. This most characteristically occurs in disorders of neuromuscular junction transmission (e.g., myasthenia gravis), but it may also be observed in disorders of muscle (e.g., myopathy, polymyositis) and neurogenic atrophy (e.g., motor neurone disease). In myasthenia gravis, fatigue may be elicited in the extraocular muscles by prolonged upgaze causing eyelid drooping; in bulbar muscles by prolonged counting or speech causing hypophonia; and in limb muscles by repeated contraction, especially of proximal muscles (e.g., shoulder abduction) leading to weakness in previously strong muscles. Fatigue in myasthenia gravis is understood as a decline in the amount of acetylcholine released from motor nerve terminals with successive neural impulses, along with a reduced number of functional acetylcholine receptors (AChR) at the motor end-plates, due to binding of AChR antibodies and/or complement mediated destruction of the postsynaptic folds.
(A gradual decline in the amplitude and speed of initiation of voluntary movements, hypometria and hypokinesia, as seen in disorders of the basal ganglia, especially Parkinson’s disease, may also be described as fatigue, e.g., "slow" micrographia may be ascribed to "fatigue." Progressive supranuclear palsy is notable for lack of fatigue.) Fatigue as a symptom, or central fatigue, is an enhanced perception of effort and limited endurance in sustained physical and mental activities. This may occur in multiple sclerosis (MS), post-polio syndrome, post-stroke syndromes, and chronic fatigue syndrome (CFS). In MS and CFS, fatigue may be a prominent and disabling complaint even though neurological examination reveals little or no clinical deficit. This type of fatigue is ill-understood: in MS, frequency-dependent conduction block in demyelinated axons has been suggested, as has hypothalamic pathology. Current treatment is symptomatic (amantadine, modafinil, 3,4-diaminopyridine) and rehabilitative (graded exercise).
Fatigue may be evaluated with various instruments, such as the Krupp Fatigue Severity Score.
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