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

 

XMRV: does this virus hold the key to myalgic encephalomyelitis/CFS?

Abstract:

In October 2009 a team of researchers from the Whittemore Peterson Institute, in association with the National Cancer Institute and the Cleveland Clinic in the USA, made a discovery that could potentially open the door to useful treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The researchers, led by Judy Mikovits, discovered a significant correlation between ME/CFS and an infectious retrovirus called xenotropic murine leukaemia virus-related virus (XMRV). XMRV is classified as a gammaretrovirus, belonging to the same broad family as HIV, but more closely related to a group of viruses that cause cancers such as leukaemia. XMRV is the first member of the gammaretrovirus genus of retroviruses to be found in humans; the research to fully understand the connection between ME/CFS and XMRV, as well as what it means to have the virus, is ongoing. The disastrous impact of AIDS on human health has significantly raised the profile of retroviruses as human pathogens, and XMRV has potentially serious health implications not only for patients, but also for those caring for people with ME/CFS.

 

Source: Crowhurst G. XMRV: does this virus hold the key to myalgic encephalomyelitis/CFS? Br J Nurs. 2010 Jul 22-Aug 11;19(14):919-22. https://www.ncbi.nlm.nih.gov/pubmed/20647985

 

TLR3 agonists as immunotherapeutic agents

The interaction of innate and adaptive immune responses is extremely complex and just beginning to be understood in detail. The tendency for biomedical research to establish reproducible models, cell systems and receptor pathways, and then to focus on these systems can sometimes result in opportunity that is not appreciated. The Toll-like receptor (TLR)3 pathway as a therapeutic target falls into this category. There is an immense body of data that has been developed for more than 40 years; all of which is highly relevant to the TLR3 story and yet most of which predates the elucidation of the TLR pathways. A new recognition of TLR3, its unique properties that distinguish it from other TLR pathways, the specificity of relevant and long-available TLR agonists, and new studies of this biology utilizing modern assay methodology suggest that this target may be especially valuable as an adjunct to multiple immunotherapy strategies currently in use or in development.

You can read the rest of this article here: http://www.futuremedicine.com/doi/full/10.2217/imt.10.8 (Full article)

 

Source: Christopher F Nicodemus and Jonathan S Berek. TLR3 agonists as immunotherapeutic agents. Immunotherapy, March 2010 ,Vol. 2, No. 2, Pages 137-140 , DOI 10.2217/imt.10.8 (doi:10.2217/imt.10.8)  http://www.futuremedicine.com/doi/full/10.2217/imt.10.8 (Full article)

Measuring fatigue in clinical and community settings

Abstract:

OBJECTIVE: The Chalder Fatigue Scale (CFQ) is a widely used instrument to assess fatigue in both clinical and nonclinical settings. Psychometric properties of the scale and discriminative abilities were examined.

METHODS: A total of 361 patients with CFS and 1615 individuals in the community were assessed with the CFQ. Principal component analysis (PCA) was used to explore the structure of the scale. Receiver-operating characteristic curve (ROC) was used to investigate the discriminative properties.

RESULTS: Two components, physical and mental fatigue, were identified in the CFS patient group and in the general population samples. Area under the curve for ROC was .91. The fatigue scale effectively discriminates, at high scores, between CFS patients and the general population.

CONCLUSION: Physical and mental fatigue are clearly separable components of fatigue. The CFQ can discriminate reliably between clinical and nonclinical conditions.

Copyright (c) 2010 Elsevier Inc. All rights reserved.

 

Source: Cella M, Chalder T. Measuring fatigue in clinical and community settings. J Psychosom Res. 2010 Jul;69(1):17-22. doi: 10.1016/j.jpsychores.2009.10.007. Epub 2009 Dec 11. https://www.ncbi.nlm.nih.gov/pubmed/20630259

 

Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate

Abstract:

This study investigates the response of the underlying sleep disorder associated with Chronic Fatigue Syndrome (CFS) and fibromyalgia (FM) to treatment. We retrospectively reviewed 118 cases clinically consistent with CFS or FM, treated in a neurology practice. Abnormal findings on sleep studies and associated human leukocyte antigen markers, and a clinical pattern suggestive of narcolepsy, are present in a high proportion of patients. When considered appropriate based on the clinical picture and test results, treatment with sodium oxybate was offered to these patients. Sixty percent of patients treated with oxybate experienced significant relief of pain, while 75% experienced significant relief of fatigue. We postulate that the response to oxybate in CFS and FM suggests a disturbance of sleep similar to narcolepsy. These findings support this novel approach to intervention and further research. The inability to distinguish CFS and FM by testing and response to treatment suggests that they may represent variations of the same disorder or may be closely related disorders.

 

Source: Spitzer AR, Broadman M. Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate. Pain Pract. 2010 Jan-Feb;10(1):54-9. doi: 10.1111/j.1533-2500.2009.00334.x. https://www.ncbi.nlm.nih.gov/pubmed/20629967

 

Measuring substantial reductions in functioning in patients with chronic fatigue syndrome

Abstract:

PURPOSE: All the major current case definitions for chronic fatigue syndrome (CFS) specify substantial reductions in previous levels of occupational, educational, social, or personal activities to meet criteria. Difficulties have been encountered in operationalizing ‘substantial reductions.’ For example, the Medical Outcomes Study Short Form-36 Health Survey (SF-36) has been used to determine whether individuals met the CFS disability criterion. However, previous methods of using the SF-36 have been prone to including people without substantial reductions in key areas of physical functioning when diagnosing CFS. This study sought to empirically identify the most appropriate SF-36 subscales for measuring substantial reductions in patients with CFS.

METHOD: The SF-36 was administered to two samples of patients with CFS: one recruited from tertiary care and the other a community-based sample; as well as a non-fatigued control group. Receiver operating characteristics were used to determine the optimal cutoff scores for identifying patients with CFS.

RESULTS: The SF-36 Role-Emotional subscale had the worst sensitivity and specificity, whereas the Vitality, Role-Physical, and Social Functioning subscales had the best sensitivity and specificity.

CONCLUSION: Based on the evidence from this study, the potential criteria for defining substantial reductions in functioning and diagnosing CFS is provided.

© 2011 Informa UK, Ltd.

 

Source: Jason L, Brown M, Evans M, Anderson V, Lerch A, Brown A, Hunnell J, Porter N. Measuring substantial reductions in functioning in patients with chronic fatigue syndrome. Disabil Rehabil. 2011;33(7):589-98. doi: 10.3109/09638288.2010.503256. Epub 2010 Jul 9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170036/ (Full article)

 

Relationships among rhinitis, fibromyalgia, and chronic fatigue

Abstract:

New information about the pathophysiology of idiopathic nonallergic rhinopathy indicates a high prevalence in chronic fatigue syndrome (CFS). This article shows the relevance of CFS and allied disorders to allergy practice. CFS has significant overlap with systemic hyperalgesia (fibromyalgia), autonomic dysfunction (irritable bowel syndrome and migraine headaches), sensory hypersensitivity (dyspnea; congestion; rhinorrhea; and appreciation of visceral nociception in the esophagus, gastrointestinal tract, bladder, and other organs), and central nervous system maladaptations (central sensitization) recorded by functional magnetic resonance imaging (fMRI).

Neurological dysfunction may account for the overlap of CFS with idiopathic nonallergic rhinopathy. Scientific advances are in fMRI, nociceptive sensor expression, and, potentially, infection with xenotropic murine leukemia-related virus provide additional insights to novel pathophysiological mechanisms of the “functional” complaints of these patients that are mistakenly interpreted as allergic syndromes. As allergists, we must accept the clinical challenges posed by these complex patients and provide proper diagnoses, assurance, and optimum care even though current treatment algorithms are lacking.

 

Source: Baraniuk JN, Zheng Y. Relationships among rhinitis, fibromyalgia, and chronic fatigue. Allergy Asthma Proc. 2010 May-Jun;31(3):169-78. doi: 10.2500/aap.2010.31.3311. https://www.ncbi.nlm.nih.gov/pubmed/20615318

 

Illness trajectories in the chronic fatigue syndrome: a longitudinal study of improvers versus non-improvers

Abstract:

The natural progression of chronic fatigue syndrome (CFS) in adults is not well established. The aims of this longitudinal study were to (a) compare CFS Improvers and Non-Improvers; (b) determine whether an initial diagnosis of fibromyalgia (FM) was associated with CFS nonimprovement; and (c) determine whether this effect could be explained by the presence of nonspecific physical symptoms.

Consecutive referrals to a tertiary clinic that satisfied case criteria for CFS were invited to enroll in a longitudinal study. After an initial on-site physical examination and psychiatric interview, a total of 94 female care-seekers completed biannual telephone surveys, including the Short Form-36 physical functioning (PF) scale, over a period of 2(1/2) years. There were very few differences between Improvers and Non-Improvers at baseline but at final assessment Improvers had less disability, less fatigue, lower levels of pain, fewer symptoms of depressed mood, and fewer nonspecific physical complaints.

Participants with FM at baseline were 3.23 times (p < 0.05) more likely to become Non-Improvers than those without FM. Participants identified initially as Somatizers were 3.33 times (p < 0.05) more likely to become Non-Improvers. Patients with CFS who bear the added burden of FM are at greater risk of a negative outcome than patients with CFS alone. This effect could not be explained by the presence of multiple, nonspecific symptoms.

 

Source: Ciccone DS, Chandler HK, Natelson BH. Illness trajectories in the chronic fatigue syndrome: a longitudinal study of improvers versus non-improvers. J Nerv Ment Dis. 2010 Jul;198(7):486-93. doi: 10.1097/NMD.0b013e3181e4ce0b. https://www.ncbi.nlm.nih.gov/pubmed/20611051