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Journal ArticleDOI

Clinical neurophysiology of fatigue.

TL;DR: The reliability of the psychological and clinical neurophysiological assessment techniques available today allows a multidisciplinary approach to fatigue in neurological patients, which may contribute to the elucidation of the pathophysiological mechanisms of chronic fatigue, with the ultimate goal to develop tailored treatments for fatigue in Neurological patients.
About: This article is published in Clinical Neurophysiology.The article was published on 2008-01-01. It has received 207 citations till now. The article focuses on the topics: Chronic fatigue & Chronic fatigue syndrome.
Citations
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Journal ArticleDOI
TL;DR: In this paper, the authors review issues of epidemiology and clinical manifestations, focusing on the scientific status of chronic fatigue syndrome (CFS) and suggest multidisciplinary prospective studies of CFS in the general population.

921 citations

Journal ArticleDOI
TL;DR: A case is made for a unified definition of fatigue to facilitate its management in health and disease and the proposed framework provides a foundation to address the many gaps in knowledge of how laboratory measures of fatigue and fatigability affect real-world performance.
Abstract: Despite flourishing interest in the topic of fatigue-as indicated by the many presentations on fatigue at the 2015 Annual Meeting of the American College of Sports Medicine-surprisingly little is known about its effect on human performance. There are two main reasons for this dilemma: 1) the inability of current terminology to accommodate the scope of the conditions ascribed to fatigue, and 2) a paucity of validated experimental models. In contrast to current practice, a case is made for a unified definition of fatigue to facilitate its management in health and disease. On the basis of the classic two-domain concept of Mosso, fatigue is defined as a disabling symptom in which physical and cognitive function is limited by interactions between performance fatigability and perceived fatigability. As a symptom, fatigue can only be measured by self-report, quantified as either a trait characteristic or a state variable. One consequence of such a definition is that the word fatigue should not be preceded by an adjective (e.g., central, mental, muscle, peripheral, and supraspinal) to suggest the locus of the changes responsible for an observed level of fatigue. Rather, mechanistic studies should be performed with validated experimental models to identify the changes responsible for the reported fatigue. As indicated by three examples (walking endurance in old adults, time trials by endurance athletes, and fatigue in persons with multiple sclerosis) discussed in the review, however, it has proven challenging to develop valid experimental models of fatigue. The proposed framework provides a foundation to address the many gaps in knowledge of how laboratory measures of fatigue and fatigability affect real-world performance.

513 citations

Journal ArticleDOI
27 Nov 2008-Nature
TL;DR: It is shown that sarcolemma-localized signalling by neuronal nitric oxide synthase (nNOS) in skeletal muscle is required to maintain activity after mild exercise and that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise-induced signalling.
Abstract: Many neuromuscular conditions are characterized by an exaggerated exercise-induced fatigue response that is disproportionate to activity level. This fatigue is not necessarily correlated with greater central or peripheral fatigue in patients, and some patients experience severe fatigue without any demonstrable somatic disease. Except in myopathies that are due to specific metabolic defects, the mechanism underlying this type of fatigue remains unknown. With no treatment available, this form of inactivity is a major determinant of disability. Here we show, using mouse models, that this exaggerated fatigue response is distinct from a loss in specific force production by muscle, and that sarcolemma-localized signalling by neuronal nitric oxide synthase (nNOS) in skeletal muscle is required to maintain activity after mild exercise. We show that nNOS-null mice do not have muscle pathology and have no loss of muscle-specific force after exercise but do display this exaggerated fatigue response to mild exercise. In mouse models of nNOS mislocalization from the sarcolemma, prolonged inactivity was only relieved by pharmacologically enhancing the cGMP signal that results from muscle nNOS activation during the nitric oxide signalling response to mild exercise. Our findings suggest that the mechanism underlying the exaggerated fatigue response to mild exercise is a lack of contraction-induced signalling from sarcolemma-localized nNOS, which decreases cGMP-mediated vasomodulation in the vessels that supply active muscle after mild exercise. Sarcolemmal nNOS staining was decreased in patient biopsies from a large number of distinct myopathies, suggesting a common mechanism of fatigue. Our results suggest that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise-induced signalling.

273 citations

Journal ArticleDOI
TL;DR: The potential contribution of several prevalent medical conditions - allergic rhinitis, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis/osteoarthritis - and chronic fatigue syndrome and clinical sleep disorders - insomnia, obstructive sleep apnea, narcolepsy, periodic limb movement of sleep, and restless legs syndrome - to the risk for drowsy-driving road crashes is reviewed.

207 citations

Journal ArticleDOI
TL;DR: The Six-Minute Walk Test (6MWT) can be safely performed in ambulatory patients with spinal muscular atrophy, correlates with established outcome measures, and is sensitive to fatigue-related changes.
Abstract: Background: In spinal muscular atrophy (SMA), weakness, decreased endurance, and fatigue limit mobility. Scales have been developed to measure function across the wide spectrum of disease severity. However, these scales typically are observer dependent, and scores are based on sums across Likert-scaled items. The Six-Minute Walk Test (6MWT) is an objective, easily administered, and standardized evaluation of functional exercise capacity that has been proven reliable in other neurologic disorders and in children. Methods: To study the performance of the 6MWT in SMA, 18 ambulatory participants were evaluated in a cross-sectional study. Clinical measures were 6MWT, 10-m walk/run, Hammersmith Functional Motor Scale–Expanded (HFMSE), forced vital capacity, and handheld dynamometry. Associations between the 6MWT total distance and other outcomes were analyzed using Spearman correlation coefficients. A paired t test was used to compare the mean distance walked in the first and sixth minutes. Results: The 6MWT was associated with the HFMSE score (r 0.83, p 0.0001), 10-m walk/run (r 0.87, p 0.0001), and knee flexor strength (r 0.62, p 0.01). Gait velocity decreased during successive minutes in nearly all participants. The average first minute distance (57.5 m) was significantly more than the sixth minute distance (48 m) (p 0.0003). Conclusion: The Six-Minute Walk Test (6MWT) can be safely performed in ambulatory patients with spinal muscular atrophy (SMA), correlates with established outcome measures, and is sensitive to fatigue-related changes. The 6MWT is a promising candidate outcome measure for clinical trials in ambulatory subjects with SMA. Neurology ® 2010;74:833–838

160 citations

References
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Journal ArticleDOI
TL;DR: A conceptual framework and a set of research guidelines for use in studies of the chronic fatigue syndrome are developed that cover the clinical and laboratory evaluation of persons with unexplained fatigue; the identification of underlying conditions that may explain the presence of chronic fatigue; revised criteria for defining cases of the Chronic fatigue syndrome; and a strategy for dividing the chronic Fatigue syndrome and other unexplained cases of Chronic fatigue into subgroups.
Abstract: The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.

4,621 citations

Journal ArticleDOI
TL;DR: Evidence for "central" fatigue and the neural mechanisms underlying it are reviewed, together with its terminology and the methods used to reveal it.
Abstract: Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. It may arise not only because of peripheral changes at the level of the muscle, but also because the central nervous system fails to drive the motoneurons adequately. Evidence for “central” fatigue and the neural mechanisms underlying it are reviewed, together with its terminology and the methods used to reveal it. Much data suggest that voluntary activation of human motoneurons and muscle fibers is suboptimal and thus maximal voluntary force is commonly less than true maximal force. Hence, maximal voluntary strength can often be below true maximal muscle force. The technique of twitch interpolation has helped to reveal the changes in drive to motoneurons during fatigue. Voluntary activation usually diminishes during maximal voluntary isometric tasks, that is central fatigue develops, and motor unit firing rates decline. Transcranial magnetic stimulation over the motor cortex during fatiguing exercise has revealed focal cha...

3,200 citations

Journal ArticleDOI
TL;DR: It appears likely that this condition is associated with and likely caused by muscle injury, such that the SR releases less Ca2+ at low frequencies of activation, and LFF could result from a reduced membrane excitability,such that the sarcolemma action potential frequency is considerably less than the stimulation frequency.
Abstract: Fatigue, defined as the failure to maintain the required or expected power output, is a complex problem, since multiple factors are clearly involved, with the relative importance of each dependent on the fiber type composition of the contracting muscles(s), and the intensity, type, and duration of the contractile activity. The primary sites of fatigue appear to be within the muscle cell itself and for the most part do not involve the central nervous system or the neuromuscular junction. The major hypotheses of fatigue center on disturbances in the surface membrane, E-C coupling, or metabolic events. The cell sites most frequently linked to the etiology of skeletal muscle fatigue are shown in Figure 1. Skeletal muscles are composed of at least four distinct fiber types (3 fast twitch and 1 slow twitch), with the slow type I and fast type IIa fibers containing the highest mitochondrial content and fatigue resistance. Despite fiber type differences in the degree of fatigability, the contractile properties undergo characteristic changes with the development of fatigue that can be observed in whole muscles, single motor units, and single fibers. The Po declines, and the contraction and relaxation times are prolonged. Additionally, there is a decrease in the peak rate of tension development and decline and a reduced Vo. Changes in Vo are more resistant to fatigue than Po and are not observed until Po has declined by at least 10% of its initial prefatigued value. However, the reduced peak power by which fatigue is defined results from both a reduction in Vo and Po. In the absence of muscle fiber damage, the prolonged relaxation time associated with fatigue causes the force-frequency curve to shift to the left, such that peak tensions are obtained at lower frequencies of stimulation. In a mechanism not clearly understood, the central nervous system senses this condition and reduces the alpha-motor nerve activation frequency as fatigue develops. In some cases, selective LFF develops that displaces the force-frequency curve to the right. Although not proven, it appears likely that this condition is associated with and likely caused by muscle injury, such that the SR releases less Ca2+ at low frequencies of activation. Alternatively, LFF could result from a reduced membrane excitability, such that the sarcolemma action potential frequency is considerably less than the stimulation frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

1,531 citations

Journal ArticleDOI
TL;DR: The absence of laboratory tests and clear criteria to identify homogeneous (sub)groups in patients presenting with unexplained fatigue, and to assess clinical status and disability in these patients, calls for further assessment methods.

1,140 citations


"Clinical neurophysiology of fatigue..." refers methods in this paper

  • ...Fatigue can best be quantified by means of self-report questionnaires like the Checklist Individual Strength (CIS) which includes an eight-item fatigue subscale and a fatigue-severity subscale (Beurskens et al., 2000; Dittner et al., 2004; Vercoulen et al., 1994)....

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Journal ArticleDOI
TL;DR: A state of pre-existing relative hypocortisolaemia might sensitise the hypothalamic-pituitary-adrenal axis to development of persistent central fatigue after stress.

1,046 citations