Invited reviewClinical neurophysiology of fatigue
Introduction
Fatigue is a universal and daily phenomenon and is ranked third on the list of most reported problems in the general practitioner’s surgery (Lamberts, 1991). The symptom of fatigue is, however, a difficult, multidimensional concept and hence poses a complex problem for the physician.
As a chronic symptom, fatigue is a well-known manifestation of a number of somatic disorders, among which cancer, multiple sclerosis (MS), Parkinson’s disease (PD) and cerebrovascular disorders. It also occurs as a side-effect of pharmacological agents like β-blockers and it has been described in depression and during stress. In addition, there is a group of severely fatigued patients that do not have a somatically demonstrable disease. If the fatigue has persisted for more than 6 months and patients fulfil a number of additional criteria (see Table 1), the disorder is diagnosed as chronic fatigue syndrome (CFS; Fukuda et al., 1994). It is estimated that in the Netherlands about 30,000–40,000 people suffer from CFS (Health Council of the Netherlands, 2005). It is less well known that chronic fatigue also often occurs in neuromuscular disorders, with considerable impact on the patients. As one such patient remarked: “Personally, I see fatigue as a greater problem than my quantifiable somatic symptoms and impairments. The fatigue makes me miss out on numerous things, whereas I could learn to live with my somatic disabilities. If the problem of my fatigue were to be solved, I would be able to function normally in society despite my somatic problems.”
In the basic sciences, especially physiology, fatigue has been defined as a time-related phenomenon of decline in the maximal force-generation capacity (Gandevia et al., 1995, Hill, 1913, Vøllestad, 1997). Usually, this is expressed by a deterioration in maximal voluntary contraction (MVC). In clinical medicine fatigue had not been investigated thoroughly until recently, possibly because the term was regarded as subjective and ill defined (Lou et al., 2001). Given our enhanced insights into the different aspects of chronic fatigue and our capability to measure these reliably, subjective feelings can now be studied scientifically, which has persuaded both researchers and clinicians to view fatigue as a problem meriting closer study (Bleijenberg, 2003, Krupp, 2003).
As it is such a multifaceted problem, it is crucial to delineate the different levels of fatigue carefully. By definition, a patient who complains of fatigue is experiencing fatigue. In the next sections, the various types of fatigue and the available or recommended assessment tools are described (also see Table 2), followed by a description of fatigue as observed in central and peripheral nervous system (CNS and PNS) disorders.
Section snippets
Experienced fatigue
When patients or physicians are invited to describe fatigue, this will prompt a variety of descriptions, including accounts of sleepiness, weakness, exercise intolerance or exhaustion. Thus, the term fatigue may be confusing, especially when used in the context of neuromuscular disorders in which weakness is usually the main symptom.
Medical literature usually defines fatigue in the sense of’experienced fatigue’ as an overwhelming sense of tiredness, lack of energy and feeling of exhaustion (
Physiological fatigue
In physiology, fatigue is usually defined as the loss of voluntary force-producing capacity during exercise (Bigland-Ritchie et al., 1978). Physiological fatigue is not necessarily accompanied by self-perceived fatigue, nor vice versa. The loss of force-producing capacity can both (and simultaneously) have a peripheral and a central origin (Table 2). This decline in force or force-generating capacity may originate from various levels of the neural axis, from motor cortex, spinal cord to
Fatigue in CNS disorders
Even though many disorders affecting the CNS are associated with feelings of fatigue (see Table 3), comprehensive data are lacking (for a review, see Chaudhuri and Behan, 2004). The disease best known for fatigue is multiple sclerosis (MS). Here, the fatigue can be a prodromal sign of many years and is described as the single most disabling symptom. It has a prevalence of about 70% and tends to seriously impair approximately one-third of all MS patients. Recent reports indicate that fatigue is
Fatigue in PNS disorders
Despite the many different neuromuscular disorders, the number of associated symptoms is limited. Muscle weakness is the most typical. Other common symptoms are pain, muscle loss, involuntary movements (e.g. fasciculations, cramps), myotonia, and contractures (De Visser et al., 1999). Fatigue is not the same as weakness; it is an independent symptom. Most patients experiencing fatigue without weakness usually do not have a known neuromuscular disorder (Layzer, 1993). Conversely, fatigue is not
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