ABSTRACT
Individuals with neuromuscular disorders often report that their daily activities are limited by fatigue. In many cases, these people are describing
the need to exert more than the usual amount of effort to accomplish a task. However, in this chapter, we define fatigue as an exercise-induced reduction in the force-generating capacity of the neuromuscular system (Bigland-Ritchie and Woods, 1984; Enoka and Stuart, 1992; Gandevia, 2001). Thus, the mechanical (and electrical) output of the muscles and their activation are measured rather than relying on subjective report. The underlying cause(s) of fatigue (or the force deficit) can reflect failure at one or more levels in the central nervous system (CNS; central fatigue), peripheral nervous system (peripheral fatigue) or both (see the section, Sites of fatigue). In this chapter we first describe how the integrity of each potential site of fatigue can be measured in humans, outlining issues that need consideration when the neuromuscular system is impaired. This is followed by a review of human studies that have evaluated fatigue in individuals who have one of four different disorders: multiple sclerosis, a disease that results in demyelination of central nervous system axons (Figure 9.1;
Compston and Coles, 2002); post-poliomyelitis syndrome, a disorder that involves additional muscle weakness, fatigue and pain many years after the poliomyelitis virus-induced death of spinal and supraspinal neurons (Trojan and Cashman, 2005); myasthenia gravis, an immunological condition that is characterised by rapid turnover of acetylcholine receptors in the postsynaptic membrane of the neuromuscular junction, resulting in decreased receptor availability (Keesey, 2004); and spinal cord injury, which usually results in paralysis (elimination of voluntary control) and paresis (weakness) of muscles innervated from spinal segments below the lesion (Thomas and Zijdewind, 2006). Exercise treatments currently used to reduce fatigue in each disorder are then examined to assess whether they are effective rehabilitation strategies. During exercise of an intact neuromuscular system, fatigue-related changes occur simultaneously at various levels of the force-generating system. The primary site of fatigue is task-dependent (Bigland-Ritchie et al., 1995; Enoka and Duchateau, 2008), but in many situations most of the force decline arises from failure of muscle processes (Allen et al., 2008a, 2008b). We have chosen multiple sclerosis, post-poliomyelitis syndrome, myasthenia gravis and spinal cord injury to illustrate how the primary site of fatigue differs across disorders. Central fatigue is prevalent in multiple sclerosis. The chronic muscle weakness that can accompany death of motoneurons is an issue in poliomyelitis. Failure of neuromuscular transmission is problematic in myasthenia gravis. Increases in the intrinsic fatigability of paralysed muscle fibres largely limit force-generating capacity after spinal cord injury.
