An approach to chronic fatigue syndrome in adults

Abstract:

BACKGROUND: The neurologist is often asked to evaluate patients with a chief complaint of fatigue. Many neurologists do not believe in the pathologically based disease known as chronic fatigue syndrome, yet as a group, neurologists are well suited to guide the diagnostic work up of such patients to pinpoint treatable disorders in the realm of neurology, general medicine, and psychiatry.

REVIEW SUMMARY: Every patient should be carefully evaluated for certain medical, psychiatric, and neurologic disease that can cause fatigue as the most prominent symptom. This is most pressing because new work in virology, immunology, and imaging holds promise but still does not provide any diagnostic test or a mechanism for the production of these symptoms. Only a few treatments meet with even modest success in CFS. The goal of this paper is to provide the clinical neurologist with a framework for the investigation and management of this challenging group of patients.

CONCLUSIONS: Neurologists are typically also trained in psychiatry and general medicine, and this is a strong position to evaluate the patient with fatigue. Because no presently available test can make the diagnosis of CFS, the assessment is vital to seek out more treatable illnesses.

 

Source: Sabin TD. An approach to chronic fatigue syndrome in adults. Neurologist. 2003 Jan;9(1):28-34. http://www.ncbi.nlm.nih.gov/pubmed/12801429

 

The neuroendocrinology of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a common and disabling problem; although most likely of biopsychosocial origin, the nature of the pathophysiological components remains unclear. There has been a wealth of interest in the endocrinology of this condition, which will be reviewed in this article. Most studied has been the hypothalamic-pituitary-adrenal (HPA) axis; although the quality of many studies is poor, the overall balance of evidence points to reduced cortisol output in at least some patients, with some evidence that this is linked to symptom production or persistence.

There is evidence for heightened negative feedback and glucocorticoid receptor function and for impaired ACTH and cortisol responses to a variety of challenges. However, there is no evidence for a specific or uniform dysfunction of the HPA axis. Given the many factors that may impinge on the HPA axis in CFS, such as inactivity, sleep disturbance, psychiatric comorbidity, medication, and ongoing stress, it seems likely that HPA axis disturbance is heterogeneous and of multifactorial etiology in CFS. Studies assessing GH, dehydroepiandrostenedione and its sulfate, melatonin, leptin, and neuroendocrine-monoamine interactions are also reviewed.

There is some evidence from these studies to suggest alterations of dehydroepiandrostenedione sulfate function and abnormal serotonin function in CFS, but whether these changes are of functional importance remains unclear. To obtain a clearer assessment of the etiological and pathophysiological relevance of endocrine changes in CFS, it is suggested that more prospective cohort studies be undertaken in groups at high risk for CFS, that patients with CFS are followed up into recovery, and that multidimensional assessments are undertaken to unravel the influence of the various confounding factors on the observed endocrine changes in CFS.

 

Source: Cleare AJ. The neuroendocrinology of chronic fatigue syndrome. Endocr Rev. 2003 Apr;24(2):236-52. http://www.ncbi.nlm.nih.gov/pubmed/12700181

 

Systematic review of the current literature related to disability and chronic fatigue syndrome

Abstract:

Objective: The objective of this evidence report was to perform a systematic review of the published literature to provide the Social Security Administration (SSA) with the best available evidence and most current medical knowledge regarding disability in persons with Chronic Fatigue Syndrome (CFS).

Search Strategy: English language and adult population published literature from 1988 to November 2001 was searched using MEDLINE, Current Contents, Cochrane Library, and PsychINFO databases and supplemented by a manual review of bibliographies of all accepted papers.

Selection Criteria: Interventional or observational studies of at least two adult patients reporting CFS according to either the CDC 1988, CDC 1994, Oxford 1991, or Australia 1990 criteria were accepted. Studies were required to report disability (evidence of a medically determinable physical or mental impairment) and data regarding employment or work.

Data Collection and Analysis: Data on patients, interventions, and outcomes were extracted from accepted studies. Studies were scored for quality and level of evidence. Data were summarized for study, patient, and treatment level characteristics as well as outcomes of interest. A panel of diverse technical experts and peer reviewers provided review and commentary on the draft report.

Main Results: Of 3,840 citations identified, 53 studies describing 4,558 patients with CFS met all eligibility criteria. Twenty-two of these studies described comparator groups of healthy controls totaling 775 patients. The majority of CFS patients represented in the 37 studies reporting employment status were unemployed. The evidence suggests that some individuals with CFS have cognitive or affective impairments on neuropsychological tests, but results are not consistent. Depression of greater severity is associated with unemployment, but no other impairment appeared to be consistently associated with disability or work outcomes. No specific interventions have been proven to be effective in restoring the ability to work. No specific patient characteristics have been identified as best predictors of positive employment outcomes in CFS patients. The patient’s level of functioning at the time of diagnosis should be compared to functioning prior to the onset of illness especially as it relates to work, school, social and home activities.

The major limitations of this review are related to the weaknesses inherent in the current medical and scientific published literature regarding CFS. Study designs were not sufficiently homogeneous to allow quantitative synthesis of individual study results, and external validity was low. While some studies reported test and scale results, this was highly variable with relatively sparse and inconsistent reporting of both baseline and outcome data. No studies specifically measured the impact of baseline impairment data or treatment interventions on work function or employment outcomes.

Conclusions: While relationships between various impairment measures and work/disability status might be explored in some cases, the best available evidence from the literature did not allow for determination of causality. The limitations inherent in the current literature review are noted and the research community is urged to conduct methodologically rigorous, longitudinal, interventional studies to determine what baseline characteristics are associated with inability to work, and what interventions are effective in restoring the ability to work in the CFS population.

 

Source: Ross SD, Levine C, Ganz N, Frame D, Estok R, Stone L, Ludensky V. Systematic review of the current literature related to disability and chronic fatigue syndrome. Evid Rep Technol Assess (Summ). 2002 Dec;(66):1-3. http://www.ncbi.nlm.nih.gov/books/NBK36735/ (Full article)

 

Chronic fatigue syndrome: a review

Abstract:

OBJECTIVE: Chronic fatigue syndrome is an illness characterized by disabling fatigue of at least 6 months, accompanied by several other symptoms. This review summarizes the current state of knowledge about chronic fatigue syndrome.

METHOD: The case definition, prevalence, clinical presentation, evaluation, and prognosis of chronic fatigue syndrome are discussed. Research on the pathophysiology and treatment of chronic fatigue syndrome is reviewed.

RESULTS: Chronic fatigue syndrome is diagnosed on the basis of symptoms. Patients with chronic fatigue syndrome experience significant functional impairment. Pathophysiological abnormalities exist across many domains, suggesting that chronic fatigue syndrome is a heterogeneous condition of complex and multifactorial etiology. Evidence also is beginning to emerge that chronic fatigue syndrome may be familial. Although chronic fatigue syndrome has significant symptom overlap and comorbidity with psychiatric disorders, several lines of research suggest that the illness may be distinct from psychiatric disorders. Patients’ perceptions, attributions, and coping skills, however, may help perpetuate the illness. Treatment for chronic fatigue syndrome is symptom-based and includes pharmacological and behavioral strategies. Cognitive behavior therapy and graded exercise can be effective in treating the fatigue and associated symptoms and disability.

CONCLUSIONS: Chronic fatigue syndrome is unlikely to be caused or maintained by a single agent. Findings to date suggest that physiological and psychological factors work together to predispose an individual to the illness and to precipitate and perpetuate the illness. The assessment and treatment of chronic fatigue syndrome should be multidimensional and tailored to the needs of the individual patient.

Comment in:

On chronic fatigue syndrome. [Am J Psychiatry. 2004]

On chronic fatigue syndrome. [Am J Psychiatry. 2004]

 

Source: Afari N, Buchwald D. Chronic fatigue syndrome: a review. Am J Psychiatry. 2003 Feb;160(2):221-36. http://www.ncbi.nlm.nih.gov/pubmed/12562565

 

Interventions for the treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis

This article summarises the research evidence presented in a recent issue of Effective Health Care on interventions for the treatment and management of chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME). It provides an overview of the evidence from a systematic review of randomised controlled trials commissioned by the Department of Health. The results of the systematic review were found to be similar to those of another systematic review carried out in the USA at the same time, and the two have been combined and published together in 2001.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1743629/pdf/v011p00284.pdf

 

Source: Bagnall AM, Whiting P, Richardson R, Sowden AJ. Interventions for the treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis. Qual Saf Health Care. 2002 Sep;11(3):284-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1743629/pdf/v011p00284.pdf (Full article)

 

Systematic review of mental health interventions for patients with common somatic symptoms: can research evidence from secondary care be extrapolated to primary care?

Abstract:

OBJECTIVES: To determine the strength of evidence for the effectiveness of mental health interventions for patients with three common somatic conditions (chronic fatigue syndrome, irritable bowel syndrome, and chronic back pain). To assess whether results obtained in secondary care can be extrapolated to primary care and suggest how future trials should be designed to provide more rigorous evidence.

DESIGN: Systematic review.

DATA SOURCES: Five electronic databases, key texts, references in the articles identified, and citations from expert clinicians.

STUDY SELECTION: Randomised controlled trials including participants with one of the three conditions for which no physical cause could be found. Two reviewers screened sources and independently extracted data and assessed quality.

RESULTS: Sixty one studies were identified; 20 were classified as primary care and 41 as secondary care. For some interventions, such as brief psychodynamic interpersonal therapy, little research was identified. However, results of meta-analyses and of randomised controlled trials suggest that cognitive behaviour therapy and behaviour therapy are effective for chronic back pain and chronic fatigue syndrome and that antidepressants are effective for irritable bowel syndrome. Cognitive behaviour therapy and behaviour therapy were effective in both primary and secondary care in patients with back pain, although the evidence is more consistent and the effect size larger for secondary care. Antidepressants seem effective in irritable bowel syndrome in both settings but ineffective in chronic fatigue syndrome.

CONCLUSIONS: Treatment seems to be more effective in patients in secondary care than in primary care. This may be because secondary care patients have more severe disease, they receive a different treatment regimen, or the intervention is more closely supervised. However, conclusions of effectiveness should be considered in the light of the methodological weaknesses of the studies. Large pragmatic trials are needed of interventions delivered in primary care by appropriately trained primary care staff.

Comment in: Review: cognitive behavioural interventions may be effective for chronic fatigue syndrome and chronic back pain. [Evid Based Ment Health. 2003]

 

Source: Raine R, Haines A, Sensky T, Hutchings A, Larkin K, Black N. Systematic review of mental health interventions for patients with common somatic symptoms: can research evidence from secondary care be extrapolated to primary care? BMJ. 2002 Nov 9;325(7372):1082. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC131187/ (Full article)

 

On the history of the concept neurasthenia and its modern variants chronic-fatigue-syndrome, fibromyalgia and multiple chemical sensitivities

Abstract:

This article deals with the history of the terminological and nosological development of the concept neurasthenia introduced in 1869 by George Miller Beard and in particular with its reappearance in western medicine in the 1980 s. Beginning with its predecessors in antiquity and continuing with hypochondria, which became a fashionable disease in the 18 th century, the concept neurasthenia reached a high point and world-wide medical acceptance at the end of the 19 th/beginning of the 20 th century. However, between the 1930 s and 1960 s it declined in popularity and gradually disappeared until finally it only had a rudimentary nosological role in the term “pseudoneurasthenia”. In the countries of the Far East, on the contrary, the concept of neurasthenia has been in continual use since its importation in the first decades of the last century. In the 1980 s, when an interest in the symptoms of chronic fatigue was reawakened in western medicine, the concept neurasthenia reappeared, this time to define the particular form of a neurotic disorder.

Parallel to these developments increasing importance was attached to clinical descriptions of illnesses which on account of their similarity to the symptoms of neurasthenia could be termed modern variants of the concept neurasthenia. These are “Chronic-Fatigue-Syndrome”, “Fibromyalgia” and “Multiple Chemical Sensitivities” which have more or less adopted the organic inheritance of Beard’s former concept of neurasthenia, despite the fact that so far the question of organicity could not be decisively answered in a single case. In order to clarify possible influences on the development of the concept neurasthenia and its variants, the theories and ideas of E. Shorter, medical historian at the University of Toronto, are discussed in the final part of the article, whereby the particular cultural background in each case has a decisive influence on the manifestation of the psychosomatic symptoms.

 

Source: Schäfer ML. On the history of the concept neurasthenia and its modern variants chronic-fatigue-syndrome, fibromyalgia and multiple chemical sensitivities. Fortschr Neurol Psychiatr. 2002 Nov;70(11):570-82. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/12410427

 

Role of fatigue in limiting physical activities in humans with neuromuscular diseases

Abstract:

New methods of examining both central and peripheral fatigue are now available. A broader understanding of the mechanisms of fatigue in healthy human subjects has begun to emerge. The mechanisms of fatigue in patients with various neuromuscular diseases are even more complex than in healthy persons. Examples of both central and peripheral fatigue in various neuromuscular diseases and other disorders are presented, including metabolic myopathy, chronic fatigue syndrome, postpolio syndrome, and amyotrophic lateral sclerosis.

 

Source: Miller RG. Role of fatigue in limiting physical activities in humans with neuromuscular diseases. Am J Phys Med Rehabil. 2002 Nov;81(11 Suppl):S99-107. http://www.ncbi.nlm.nih.gov/pubmed/12409815

 

Recovery from infectious mononucleosis: a case for more than symptomatic therapy? A systematic review

Abstract:

Infectious mononucleosis is usually an acute, transiently incapacitating condition, but for some sufferers it precipitates chronic illness. It is unclear which patients are at risk of a prolonged state of illness following onset of infectious mononucleosis and if there are any useful preventive measures that would facilitate recovery. The aim of this study was to review all cohort studies and intervention trials that provide information on: (a) the longitudinal course of ill health subsequent to the onset of infectious mononucleosis; (b) the relationship between psychosocial and clinical factors and recovery rate; and (c) the effect of interventions on recovery.

A systematic review was conducted, based on a search of the PSYCHINFO, MEDLINE, EMBASE and CINHAL databases up to October 2001, and ISI Science and Social Sciences Citation Indices up to 22 November 2001. Eight papers were identified that gave data on illness following onset of infectious mononucleosis. The best evidence concluded that there is a distinct fatigue syndrome after infectious mononucleosis. Eight papers explored risk factors for prolonged illness following acute infectious mononucleosis.

Results varied on the association of acute illness characteristics and psychological features with prolonged ill health. Poor physical functioning, namely lengthy convalescence and being less fit or active, consistently predicted chronic ill health. Three trials reported on interventions that aimed to shorten the time taken to resolve symptoms after uncomplicated infectious mononucleosis. None of the drug trials found any evidence that drug therapy shortens recovery time. The trial that compared the effect of activity with imposed bed rest, found that those patients allowed out of bed as soon as they felt able reported a quicker recovery. More information is needed on the course of ill health subsequent to the onset of infectious mononucleosis. Certain risk factors associated with delay may be amenable to a simple intervention in primary care.

 

Source: Candy B, Chalder T, Cleare AJ, Wessely S, White PD, Hotopf M. Recovery from infectious mononucleosis: a case for more than symptomatic therapy? A systematic review. Br J Gen Pract. 2002 Oct;52(483):844-51. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1316091/ (Full article)

 

A status report on chronic fatigue syndrome

Abstract:

Medical history has shown that clinical disease entities or syndromes are composed of many subgroups–each with its own cause and pathogenesis. Although we cannot be sure, we expect the same outcome for chronic fatigue syndrome (CFS), a medically unexplained condition characterized by disabling fatigue accompanied by infectious, rheumatological, and neuropsychiatric symptoms. Although the ailment clearly can occur after severe infection, no convincing data exist to support an infectious (or immunologic) process in disease maintenance. Instead, data point to several possible pathophysiological processes: a covert encephalopathy, impaired physiological capability to respond to physical and mental stressors, and psychological factors related to concerns about effort exacerbating symptoms. Each of these is under intense investigation. In addition, some data do exist to indicate that environmental agents also can elicit a state of chronic fatigue. We expect data to accumulate to support the belief that CFS has multiple causes.

 

Source: Natelson BH, Lange G. A status report on chronic fatigue syndrome. Environ Health Perspect. 2002 Aug;110 Suppl 4:673-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241224/ (Full article)