Fatigue versus activity-dependent fatigability in patients with central or peripheral motor impairments

In the rehabilitation literature, fatigue is a common symptom of patients with any neurological impairment when defined as a subjective lack of physical and mental energy that interferes with usual activities. Some complaints may, however, arise from fatigability , an objective decline in strength as routine use of muscle groups proceeds. By this refined definition of fatigue, exercise or sustained use reduces the ability of muscles to produce force or power, regardless of whether the task can be sustained. Fatigability may be masked clinically because (1) the degree of weakening is not profound, (2) activity-induced weakness rapidly lessens with cessation of exertion, and (3) clinicians rarely test for changes in strength after repetitive movements to objectively entertain the diagnosis. The repetitive movements that induce fatigability during daily activities are an iterative physiological process that depends on changing states induced by activation of spared central and peripheral neurons and axons and compromised muscle. Fatigability may be especially difficult to localize in patients undergoing neurorehabilitation, in part because no finite boundary exists between the central and peripheral components of motor reserve and endurance. At the bedside, however, manual muscle testing before and after repetitive movements could at least put some focus on the presence of fatigability in any patient with motor impairments and related disabilities. Reliable measures of fatigability beyond a careful clinical examination, such as physiological changes monitored by cerebral functional neuroimaging techniques and more standardized central and peripheral electrical and magnetic stimulation paradigms, may help determine the mechanisms of activity-dependent weakening and lead to specific therapies. Testable interventions to increase motor reserve include muscle strengthening and endurance exercises, varying the biomechanical requirements of repetitive muscle contractions, and training-induced neural plasticity or pharmacologic manipulations to enhance synaptic efficacy.