Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome

Abstract:

The weight of current evidence supports the presence of the following factors related to hypothalamic-pituitary-adrenal (HPA) axis dysfunction in patients with chronic fatigue syndrome (CFS): mild hypocortisolism; attenuated diurnal variation of cortisol; enhanced negative feedback to the HPA axis; and blunted HPA axis responsiveness. Furthermore, HPA axis changes seem clinically relevant, as they are associated with worse symptoms and/or disability and with poorer outcomes to standard treatments for CFS.

Regarding etiology, women with CFS are more likely to have reduced cortisol levels. Studies published in the past 8 years provide further support for a multifactorial model in which several factors interact to moderate HPA axis changes. In particular, low activity levels, depression and early-life stress appear to reduce cortisol levels, whereas the use of psychotropic medication can increase cortisol. Addressing these factors-for example, with cognitive behavioral therapy-can increase cortisol levels and is probably the first-line approach for correcting HPA axis dysfunction at present, as steroid replacement is not recommended.

Given what is now a fairly consistent pattern of findings for the type of HPA axis changes found in CFS, we recommend that future work focuses on improving our understanding of the cause and relevance of these observed changes.

Comment in: Neuroendocrine correlates of childhood trauma in CFS. [Nat Rev Endocrinol. 2012]

 

Source: Papadopoulos AS, Cleare AJ. Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome. Nat Rev Endocrinol. 2011 Sep 27;8(1):22-32. doi: 10.1038/nrendo.2011.153. https://www.ncbi.nlm.nih.gov/pubmed/21946893

 

Chronic fatigue syndrome: understanding a complex illness

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating illness that affects many people. It has been marred by controversy, from initial scepticism in the medical community about the existence of the condition itself to continuing disagreements–mainly between some patient advocacy groups on one side, and researchers and physicians on the other–about the name for the illness, its aetiology, its pathophysiology and the effectiveness of the few currently available treatments. The role of the CNS in the disease is central in many of these discussions. Nature Reviews Neuroscience asked four scientists involved in CFS research about their views on the condition, its causes and the future of research aimed at improving our understanding of this chronic illness.

 

Source: Holgate ST, Komaroff AL, Mangan D, Wessely S. Chronic fatigue syndrome: understanding a complex illness. Nat Rev Neurosci. 2011 Jul 27;12(9):539-44. doi: 10.1038/nrn3087. https://www.ncbi.nlm.nih.gov/pubmed/21792218

 

Chronic fatigue syndrome, the immune system and viral infection

Abstract:

The chronic fatigue syndrome (CFS), as defined by recent criteria, is a heterogeneous disorder with a common set of symptoms that often either follows a viral infection or a period of stress. Despite many years of intense investigation there is little consensus on the presence, nature and degree of immune dysfunction in this condition.

However, slightly increased parameters of inflammation and pro-inflammatory cytokines such as interleukin (IL) 1, IL6 and tumour necrosis factor (TNF) α are likely present. Additionally, impaired natural killer cell function appears evident. Alterations in T cell numbers have been described by some and not others.

While the prevalence of positive serology for the common herpes viruses appears no different from healthy controls, there is some evidence of viral persistence and inadequate containment of viral replication. The ability of certain herpes viruses to impair the development of T cell memory may explain this viral persistence and the continuation of symptoms. New therapies based on this understanding are more likely to produce benefit than current methods.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Bansal AS, Bradley AS, Bishop KN, Kiani-Alikhan S, Ford B. Chronic fatigue syndrome, the immune system and viral infection. Brain Behav Immun. 2012 Jan;26(1):24-31. doi: 10.1016/j.bbi.2011.06.016. Epub 2011 Jul 2. https://www.ncbi.nlm.nih.gov/pubmed/21756995

 

Multi-source synthesis of data to inform health policy

Abstract:

OBJECTIVES: To propose a new method for comparing and integrating original qualitative data with systematic reviews of quantitative and qualitative studies, demonstrated by a study of the psychosocial needs of chronic fatigue syndrome (CFS) sufferers in Québec.

METHODS: A systematic literature review was performed across various databases for English and French language studies, on the psychosocial aspects of CFS. Qualitative, quantitative, and mixed method studies published between January 1994 and July 2008 were included. Unpublished literature and reference lists of included studies were also searched. Themes identified in the literature were used to guide semi-structured interviews with seventeen CFS-sufferers, mostly recruited from a large specialist practice in Montreal. Interviews were transcribed verbatim and validated by a research assistant. Transcripts were coded using the identified themes. New codes were created when new issues arose. All themes were subsequently synthesized into overall categories using a constant comparative method.

RESULTS: The literature search yielded thirty-one papers: twenty-eight primary studies and three systematic reviews. Twelve themes were identified and synthesized into four overall problem categories, such as “Lack of professional recognition.” Interviews confirmed findings from the literature, but also revealed unidentified needs specific to CFS-sufferers in Québec. Policy recommendations were provided to address these needs.

CONCLUSIONS: Multi-Source Synthesis provides a systematic method for synthesizing data from original studies with literature findings, thereby broadening the knowledge base and the local relevance of decisions concerning specific patient populations.

 

Source: Pedersen VH, Dagenais P, Lehoux P. Multi-source synthesis of data to inform health policy. Int J Technol Assess Health Care. 2011 Jul;27(3):238-46. doi: 10.1017/S0266462311000213. Epub 2011 Jul 8. https://www.ncbi.nlm.nih.gov/pubmed/21736858

 

Chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is defined by a profound, debilitating fatigue, lasting for at least 6 months and resulting in a substantial reduction of occupational, personal, social and educational status. CFS is a relatively poorly recognized clinical entity, although everyday experience shows that there are many patients with CFS symptoms.

The incidence and prevalence of CFS remain unknown in most countries; however, the working population is most affected with predominantly female patients in generative period. Although, CFS was first mentioned four centuries ago, mysterious aethiopathogensis of CFS still intrigues scientists as hundreds of studies are still published every year on the subject. About 80 different aetiological CFS factors are mentioned, which can be classified into five basic groups: genetics, immunology, infectious diseases, endocrinology and neuropsychiatry-psychology.

Even today the condition is passed established based on the diagnosis by exclusion of organic and psychiatric disorders, which demands a multidisciplinary approach. As the syndrome is often misdiagnosed and mistreated, self-medication is not uncommon in CFS patients’. In addition, such patients usually suffer for years tolerating severe fatigue. Thus, at the moment there are three priorities regarding CFS; understanding pathogenesis, development of diagnostic tests and creating efficient treatment program.

 

Source: Brkić S, Tomić S, Ruzić M, Marić D. Chronic fatigue syndrome. Srp Arh Celok Lek. 2011 Mar-Apr;139(3-4):256-61. https://www.ncbi.nlm.nih.gov/pubmed/21618868

 

Chronic fatigue syndrome

Abstract:

INTRODUCTION: Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men.

METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS: We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, cognitive behavioural therapy (CBT), corticosteroids, dietary supplements, evening primrose oil, galantamine, graded exercise therapy, homeopathy, immunotherapy, intramuscular magnesium, oral nicotinamide adenine dinucleotide, and prolonged rest.

 

Source: Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. Chronic fatigue syndrome. BMJ Clin Evid. 2011 May 26;2011. pii: 1101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275316/ (Full article)

 

Quality and acceptability of patient-reported outcome measures used in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review

Abstract:

PURPOSE: To review the quality and acceptability of condition-specific, domain-specific and generic multi-item patient-reported outcome measures (PROMs) used in the assessment of adults with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

METHODS: Systematic literature searches were made to identify PROMs. Quality and acceptability was assessed against an appraisal framework, which captured evidence of both the thoroughness and results of evaluations: evidence of measurement (reliability, validity, responsiveness, interpretability, data quality/precision) and practical properties (feasibility, patient acceptability), and the extent of active patient involvement was sought.

RESULTS: A total of 11 CFS/ME-specific, 55 domain-specific and 11 generic measures were reviewed. With the exception of the generic SF-36, all measures had mostly limited evidence of measurement and/or practical properties. Patient involvement was poorly reported and often cursory.

CONCLUSIONS: The quality and acceptability of reviewed PROMs is limited, and recommendations for patient-reported assessment are difficult. Significant methodological and quality issues in PROM development/evaluation were identified by the appraisal framework, which must be addressed in future research. Clear discrepancies exist between what is measured in research and how patients define their experience of CFS/ME. Future PROM development/evaluation must seek to involve patients more collaboratively to measure outcomes of importance using relevant and credible methods of assessment.

 

Source: Haywood KL, Staniszewska S, Chapman S. Quality and acceptability of patient-reported outcome measures used in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review. Qual Life Res. 2012 Feb;21(1):35-52. doi: 10.1007/s11136-011-9921-8. Epub 2011 May 18. https://www.ncbi.nlm.nih.gov/pubmed/21590511

 

Neuroimaging and the case of chronic fatigue syndrome

Abstract:

This article analyzes the use of neuroimaging in research into chronic fatigue syndrome. It reviews some works published in the 1990 s and investigates a specific aspect of these studies, namely the search for a cerebral abnormality, in the form of an altered activation pattern, which could provide a pattern for diagnosis and treatment of the disease. The understanding of chronic fatigue syndrome as a disease reduced to some cerebral findings is analyzed, arguing in favor of a broader vision of this disease that includes psychosocial elements of the patient’s life as opposed to entirely somatic explanations.

 

Source: Ortega F, Zorzanelli R. Neuroimaging and the case of chronic fatigue syndrome. Cien Saude Colet. 2011 Apr;16(4):2123-32. [Article in Portuguese]http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-81232011000400012&lng=en&nrm=iso&tlng=en (Full article)

 

A review and meta-synthesis of qualitative studies on myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

OBJECTIVE: To review and synthesize findings across qualitative studies on Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS).

METHODS: Articles were systematically reviewed and analyzed within a meta-analytic framework. Analyses included a multi-perspective examination of ME/CFS, as well as a comparative analysis of ME/CFS versus other chronic conditions.

RESULTS: Thirty-four qualitative studies on ME/CFS were included. Findings include three substantive thematic areas that focus on: (1) experiences of people with ME/CFS, (2) experiences of physicians, and (3) themes that intersect both of these groups. For patients, illness development influenced identity, reductions in functioning, and coping. Physician-specific themes described lack of awareness about ME/CFS and recommended improvement in educational resources. Intersecting themes expressed issues with diagnosis creating tensions and fueling the stigmatization of ME/CFS.

CONCLUSIONS: Findings indicate multilayered, context-specific experiences and ways in which both people with ME/CFS, as well as those involved in their lives (e.g., family or the medical community), interpret this illness. Future qualitative studies should recognize the various facets of the ME/CFS experience, the network members of people with ME/CFS, and the sociocultural environment through which the illness is understood.

PRACTICE IMPLICATIONS: Health care professionals can gain unique insight from patient experiences, allowing for more accurate diagnoses and treatment recommendations.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

 

Source: Anderson VR, Jason LA, Hlavaty LE, Porter N, Cudia J. A review and meta-synthesis of qualitative studies on myalgic encephalomyelitis/chronic fatigue syndrome. Patient Educ Couns. 2012 Feb;86(2):147-55. doi: 10.1016/j.pec.2011.04.016. Epub 2011 May 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229648/ (Full article)

 

XMRV, prostate cancer and chronic fatigue syndrome

Abstract:

BACKGROUND: A new retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), was identified in 2006 and an association was claimed between it and a genetic polymorphism predisposing to cancer of the prostate. In 2009 the same virus was identified in a cohort of patients with chronic fatigue syndrome (CFS). In 2010 a second related virus was identified in a separate group of CFS patients. A series of studies from disparate geographical areas have failed to substantiate this work. Most recently several papers have suggested that the detection of these viruses was explained by laboratory contamination.

SOURCES OF DATA: All papers including the wording XMRV were abstracted from the NIH library of medicine database and included in the analysis.

AREAS OF AGREEMENT: XMRV is a newly described retrovirus whose nucleic acid has been identified in samples from patients with both prostate cancer and CFS.

AREAS OF CONTROVERSY: Opinions differ as to whether the detected nucleic acid indicates infection with this virus in this disease or whether laboratory contamination of samples accounts for its presence.

GROWING POINTS: An increasing number of papers now refute the association of XMRV with human disease in humans although there is some evidence of serological reactivity to the virus. While it is unlikely that XMRV is a major cause of either prostate cancer or CFS, it can infect human cells and might yet have a role in human disease.

AREAS TIMELY FOR DEVELOPING RESEARCH: Further studies to either prove or disprove the disease association of the virus are ongoing.

 

Source: Kenyon JC, Lever AM. XMRV, prostate cancer and chronic fatigue syndrome. Br Med Bull. 2011;98:61-74. doi: 10.1093/bmb/ldr010. Epub 2011 May 6. https://www.ncbi.nlm.nih.gov/pubmed/21551158