Perspectives on fatigue from the study of chronic fatigue syndrome and related conditions

Abstract:

Fatigue is a symptom whose causes are protean and whose phenotype includes physical, mood, and behavioral components. Chronic fatigue syndrome (CFS) is an illness that has strong biological underpinnings and no definite etiology. Diagnostic criteria established by the Centers for Disease Control and Prevention have helped classify CFS as an overlap of mood, behavioral, and biological components. These include the presence of fatigue for more than 6 months associated with a diminution of functional activity and somatic symptoms, and pain not attributable to a specific diagnosis or disease. Four of the following criteria need to be present: sore throat, impaired memory or cognition, unrefreshing sleep, postexertional fatigue, tender glands, aching stiff muscles, joint pain, and headaches.

Many researchers have observed that CFS shares features in common with other somatic syndromes, including irritable bowel syndrome, fibromyalgia, and temporomandibular joint dysfunction. Correlations between inflammation and infection, augmented sensory processing, abnormalities of neurotransmitters, nerve growth factors, low levels of serotonin and norepinephrine, abnormalities of homeostasis of the stress system, and autonomic dysfunction may be hallmarks of CFS. The relative contributions of each of these abnormalities to the profound fatigue associated with CFS need to be explored further to better evaluate and treat the syndrome.

Copyright (c) 2010 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

 

Source: Clauw DJ. Perspectives on fatigue from the study of chronic fatigue syndrome and related conditions. PM R. 2010 May;2(5):414-30. doi: 10.1016/j.pmrj.2010.04.010. https://www.ncbi.nlm.nih.gov/pubmed/20656623

 

Neuroendocrine and immune contributors to fatigue

Abstract:

Central fatigue, a persistent and subjective sense of tiredness, generally correlates poorly with traditional markers of disease. It is frequently associated with psychosocial factors, such as depression, sleep disorder, anxiety, and coping style, which suggest that dysregulation of the body’s stress systems may serve as an underlying mechanism in the maintenance of chronic fatigue (CF).

This article addresses the endocrine, neural, and immune factors that contribute to fatigue and describes research regarding the role of these factors in chronic fatigue syndrome as a model for addressing the biology of CF. In general, hypoactivity of the hypothalamic-pituitary-adrenal axis, autonomic nervous system alterations characterized by sympathetic overactivity and low vagal tone, as well as immune abnormalities, may contribute to the expression of CF. Noninvasive methods for evaluating endocrine, neural, and immune function are also discussed.

Simultaneous evaluation of neuroendocrine and immune systems with noninvasive techniques will help elucidate the underlying interactions of these systems, their role in disease susceptibility, and progression of stress-related disorders.

Copyright (c) 2010 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

 

Source: Silverman MN, Heim CM, Nater UM, Marques AH, Sternberg EM. Neuroendocrine and immune contributors to fatigue. PM R. 2010 May;2(5):338-46. doi: 10.1016/j.pmrj.2010.04.008. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933136/ (Full article)

 

What is fatigue? Pathological and nonpathological fatigue

Abstract:

Aid in understanding issues surrounding the construct validity of fatigue including the distinction between pathological versus nonpathological fatigue. Fatigue is a universal symptom reported by individuals in the general population as well as by those suffering from different medical and psychological illnesses, including cancer, multiple sclerosis, chronic fatigue syndrome, depression, and anxiety. Chronic fatigue is a significant problem in many primary care settings, and the debilitating and prolonged nature of fatigue can pose significant economic consequences for society. Researchers have struggled to better assess and understand the etiology and classification of fatigue within different illness groups.

Copyright (c) 2010 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

 

Source: Jason LA, Evans M, Brown M, Porter N. What is fatigue? Pathological and nonpathological fatigue. PM R. 2010 May;2(5):327-31. doi: 10.1016/j.pmrj.2010.03.028. https://www.ncbi.nlm.nih.gov/pubmed/20656613

 

The central role of cognitive processes in the perpetuation of chronic fatigue syndrome

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) is considered to be one of the functional somatic syndromes (FSS). Cognitions and behavior are thought to perpetuate the symptoms of CFS. Behavioral interventions based on the existing models of perpetuating factors are quite successful in reducing fatigue and disabilities. The evidence is reviewed that cognitive processes, particularly those that determine the perception of fatigue and its effect on behavior, play a central role in the maintenance of symptoms.

METHOD: Narrative review.

RESULTS: Findings from treatment studies suggest that cognitive factors mediate the positive effect of behavioral interventions on fatigue. Increased fitness or increased physical activity does not seem to mediate the treatment response. Additional evidence for the role of cognitive processes is found in studies comparing the subjective beliefs patients have of their functioning with their actual performance and in neurobiological research.

CONCLUSION: Three different cognitive processes may play a role in the perpetuation of CFS symptoms. The first is a general cognitive representation in which fatigue is perceived as something negative and aversive and CFS is seen as an illness that is difficult to influence. The second process involved is the focusing on fatigue. The third element is formed by specific dysfunctional beliefs about activity and fatigue.

Copyright 2010 Elsevier Inc. All rights reserved.

 

Source: Knoop H, Prins JB, Moss-Morris R, Bleijenberg G. The central role of cognitive processes in the perpetuation of chronic fatigue syndrome. J Psychosom Res. 2010 May;68(5):489-94. doi: 10.1016/j.jpsychores.2010.01.022. Epub 2010 Mar 16. https://www.ncbi.nlm.nih.gov/pubmed/20403509

 

Chronic fatigue syndrome: Is it one discrete syndrome or many? Implications for the “one vs. many” functional somatic syndromes debate

Abstract:

There is a current debate as to whether “functional somatic syndromes” (FSSs) are more similar to or different from each other. While at the same time, there is evidence of heterogeneity within single syndromes. So, it could be that these syndromes are all part of one big process/illness, are discrete in their own right, or that they are heterogeneous collections of different illnesses lumped together by common symptoms but separated by uncommon pathophysiologies. The example of chronic fatigue syndrome (CFS) is instructive. There is evidence to support all three models of understanding. Three recent large studies have suggested that FSSs are both similar and dissimilar at the same time. The solution to the debate is that we need to both “lump” and “split.” We need to study both the similarities between syndromes and their dissimilarities to better understand what we currently call the FSSs.

Copyright 2010 Elsevier Inc. All rights reserved.

 

Source: White PD. Chronic fatigue syndrome: Is it one discrete syndrome or many? Implications for the “one vs. many” functional somatic syndromes debate. J Psychosom Res. 2010 May;68(5):455-9. doi: 10.1016/j.jpsychores.2010.01.008. Epub 2010 Mar 17. https://www.ncbi.nlm.nih.gov/pubmed/20403504

 

A retrospective review of the sleep characteristics in patients with chronic fatigue syndrome and fibromyalgia

Abstract:

This study characterizes findings on sleep testing and Human Leukocyte Antigen (HLA) markers in a group of patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS). One hundred eighteen patients seen in a general neurology practice over 5 years meeting standard clinical criteria for FM or CFS were analyzed retrospectively. Cases of untreated sleep apnea or restless legs syndrome were excluded prior to inclusion in this study.

Ninety-two patients had multiple sleep latency testing (MSLT). Seventy-three (80%) were abnormal by standard criteria. Of 57 females having positive MSLTs, 22 (39%) had one or more periods of sleep onset rapid eye movement (SOREM), and 5 of 16 (31%) males with positive MSLTs had one or more SOREM. Highly fragmented sleep, as previously described in FM, was seen but not analyzed quantitatively. HLA DQB1*0602 was obtained in 74 patients, and positive in 32 (43%), P < 0.0001 compared with published values in 228 populations.

In our patients, who presented with neuromuscular fatigue or generalized pain, we found a sleep disorder characterized by objective hypersomnia. Some patients had characteristics of narcolepsy. Objective assessment by sleep studies can assist the diagnostic process, aid future research, and provide rationale for treatment.

 

Source: Spitzer AR, Broadman M. A retrospective review of the sleep characteristics in patients with chronic fatigue syndrome and fibromyalgia. Pain Pract. 2010 Jul-Aug;10(4):294-300. doi: 10.1111/j.1533-2500.2009.00352.x. Epub 2010 Mar 2. https://www.ncbi.nlm.nih.gov/pubmed/20230458

 

Alternative medical interventions used in the treatment and management of myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia

Abstract:

BACKGROUND: There have been several systematic reviews attempting to evaluate the efficacy of possible treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM). However, information regarding the efficacy of complementary and alternative medicine (CAM) has not been comprehensively or systematically covered in these reviews, despite its frequent use in the patient community.

PURPOSE: The purpose of this study was to systematically review and evaluate the current literature related to alternative and complementary treatments for ME/CFS and FM. It should be stressed that the treatments evaluated in this review do not reflect the clinical approach used by most practitioners to treat these illnesses, which include a mix of natural and unconventionally used medications and natural hormones tailored to each individual case. However, nearly all clinical research has focused on the utility of single CAM interventions, and thus is the primary focus of this review.

METHODS: Several databases (e.g., PubMed, MEDLINE,((R)) PsychInfo) were systematically searched for randomized and nonrandomized controlled trials of alternative treatments and nonpharmacological supplements. Included studies were checked for references and several experts were contacted for referred articles. Two leading subspecialty journals were also searched by hand. Data were then extracted from included studies and quality assessments were conducted using the Jadad scale.

RESULTS: Upon completion of the literature search and the exclusion of studies not meeting criterion, a total of 70 controlled clinical trials were included in the review. Sixty (60) of the 70 studies found at least one positive effect of the intervention (86%), and 52 studies also found improvement in an illness-specific symptom (74%). The methodological quality of reporting was generally poor.

CONCLUSIONS: Several types of alternative medicine have some potential for future clinical research. However, due to methodological inconsistencies across studies and the small body of evidence, no firm conclusions can be made at this time. Regarding alternative treatments, acupuncture and several types of meditative practice show the most promise for future scientific investigation. Likewise, magnesium, l-carnitine, and S-adenosylmethionine are nonpharmacological supplements with the most potential for further research. Individualized treatment plans that involve several pharmacological agents and natural remedies appear promising as well.

 

Source: Porter NS, Jason LA, Boulton A, Bothne N, Coleman B. Alternative medical interventions used in the treatment and management of myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia. J Altern Complement Med. 2010 Mar;16(3):235-49. doi: 10.1089/acm.2008.0376. https://www.ncbi.nlm.nih.gov/pubmed/20192908

 

Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy?

Abstract:

IMPORTANCE OF THE FIELD: Chronic fatigue syndrome (CFS) is a prevalent but poorly understood condition mainly characterized by debilitating, persistent or recurrent fatigue; increased physical and mental fatigability; cognitive impairment and widespread musculoskeletal pain. Despite intensive treatment research, the role of pharmacotherapy in the illness remains uncertain.

: An updated review is given of pharmacotherapy in CFS, with a focus on non-antidepressant, controlled drug trials performed between 1988 and August 2009.

WHAT THE READER WILL GAIN: Antiviral, immunological and antibiotic therapies, although sometimes associated with symptom amelioration, can be more harmful than beneficial in CFS. Stimulants seem to benefit some CFS patients but their long-term effects is uncertain. Although antidepressants are not curative for the illness, they might be useful for some symptomatic aspects and co-morbid anxiety and depression. There is little or no evidence that CFS patients benefit from other pharmacological agents (e.g., steroids) or from dietary supplements and complementary medicine products. Future research into treatment should take specific subgroups into account and should target immunological aspects of the illness as well as the complex relationships between CFS, stress and depression.

TAKE HOME MESSAGE: Pharmacotherapy can currently not be considered first-line treatment in CFS and should always be used in a context of self-management and rehabilitation.

 

Source: Van Houdenhove B, Pae CU, Luyten P. Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy? Expert Opin Pharmacother. 2010 Feb;11(2):215-23. Doi: 10.1517/14656560903487744. https://www.ncbi.nlm.nih.gov/pubmed/20088743

 

Cognitive functioning in chronic fatigue syndrome: a meta-analysis

Abstract:

BACKGROUND: Cognitive problems are commonly reported in persons with chronic fatigue syndrome (CFS) and are one of the most disabling symptoms of this condition. A number of cognitive deficits have been identified, although the findings are inconsistent and hindered by methodological differences. The current study therefore conducted a meta-analysis of research examining cognitive functioning in persons with CFS in order to identify the pattern and magnitude of any deficits that are associated with this condition.

METHOD: A comprehensive search of the PubMed and PsycINFO databases for studies that examined cognitive functioning in CFS between 1988 and 2008 identified 50 eligible studies. Weighted Cohen’s d effect sizes, 95% confidence intervals and fail-safe Ns were calculated for each cognitive score.

RESULTS: Evidence of cognitive deficits in persons with CFS was found primarily in the domains of attention, memory and reaction time. Deficits were not apparent on tests of fine motor speed, vocabulary, reasoning and global functioning.

CONCLUSIONS: Persons with CFS demonstrate moderate to large impairments in simple and complex information processing speed and in tasks requiring working memory over a sustained period of time.

Comment in: Letter to the Editor: Plausible explanations for neurocognitive deficits in ME/CFS, aggravation of neurocognitive impairment induced by exertion. [Psychol Med. 2010]

 

Source: Cockshell SJ, Mathias JL. Cognitive functioning in chronic fatigue syndrome: a meta-analysis. Psychol Med. 2010 Aug;40(8):1253-67. doi: 10.1017/S0033291709992054. Epub 2010 Jan 5. https://www.ncbi.nlm.nih.gov/pubmed/20047703

 

Treatment of chronic fatigue syndrome: findings, principles and strategies

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating condition characterized by serious medically unexplained mental and physical fatigue. The high prevalence and both direct and indirect health costs of CFS patients represent a huge problem for contemporary health care. Moreover, the prognosis of CFS, even when treated, is often poor. In this paper, we first critically review current evidence based treatments of CFS. Second, we discuss the growing insights into the etiopathogenesis of CFS, and the need to translate and integrate these insights into future treatments. In particular, we formulate a pragmatic and empirically testable treatment approach, tailored to the individual needs of patients, which aims at restoring the mental and physical equilibrium of CFS patients by trying to bring about sustained life style changes.

 

Source: Luyten P, Van Houdenhove B, Pae CU, Kempke S, Van Wambeke P. Treatment of chronic fatigue syndrome: findings, principles and strategies. Psychiatry Investig. 2008 Dec;5(4):209-12. doi: 10.4306/pi.2008.5.4.209. Epub 2008 Dec 31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796012/ (Full article)