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      Myalgic encephalomyelitis: International Consensus Criteria

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          Abstract

          Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles ACP, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisbik S, Mena I, Mikovits JA, Murovska M, Pall ML, Stevens S (Independent, Vancouver, BC, Canada; Independent, Calgary, AB, Canada; Department of Physiology and Medicine, Vrije University of Brussels, Himmunitas Foundation, Brussels, Belgium; Department of Medicine,University of Miami Miller School of Medicine and Miami Veterans Affairs Medical Center, Miami, FL, USA; Department of Medicine, University of Alberta, Edmonton, AB, Canada; Honorary Consultant for NHS at Peterborough/Cambridge, Lowestoft, Suffolk, UK; Gold Coast Public Health Unit, Southport, Queensland; Health Sciences and Medicine, Bond University, Robina, Queensland, Australia; Faculty of Health Sciences, McMaster University and St Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; Independent, Durham, UK; Howick Health and Medical Centre, Howick, New Zealand; Fatigue Consultation Clinic, Salt Lake Regional Medical Center; Internal Medicine, Family Practice, University of Utah, Salt Lake City, UT, USA; ME/CFS Center, Oslo University Hospital HF, Norway; Department of Paediatrics, State University of New York, Buffalo, NY; Independent, Pavia, Italy; Harbor-UCLA Medical Center, University of California, Los Angeles, CA; EV Med Research, Lomita, CA, USA; University of Limerick, Limerick, Ireland; Pain Clinic, Konyang University Hospital, Daejeon, Korea; Donvale Specialist Medical Centre, Donvale, Victoria, Australia; Departments or Anesthesiology, Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah, USA; Health Sciences and Medicine, Bond University, Robina, Queensland, Australia; Department of Medicina Nuclear, Clinica Las Condes, Santiago, Chile; Whittemore Peterson Institute, University of Nevada, Reno, NV, USA; Miwa Naika Clinic, Toyama, Japan; A. Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia; Department of Biochemistry & Basic Medical Sciences, Washington State University, Portland, OR; Department of Sports Sciences, University of the Pacific, Stockton, CA USA). Myalgic encephalomyelitis: International Consensus Criteria (Review). J Intern Med 2011; 270: 327–338.

          The label ‘chronic fatigue syndrome’ (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term ‘myalgic encephalomyelitis’ (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization’s International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.

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          Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome.

          Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines after their exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.
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            A report--chronic fatigue syndrome: guidelines for research.

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              Immunological aspects of chronic fatigue syndrome.

              Chronic fatigue syndrome (CFS) is a specific clinical condition that characterises unexplained disabling fatigue and a combination of non-specific accompanying symptoms for at least 6 months, in the absence of a medical diagnosis that would otherwise explain the clinical presentation. Other common symptoms include headaches, myalgia, arthralgia, and post-exertional malaise; cognitive difficulties, with impaired memory and concentration; unrefreshing sleep; and mood changes. Similar disorders have been described for at least two centuries and have been differently named neurasthenia, post-viral fatigue, myalgic encephalomyelitis and chronic mononucleosis. Recent longitudinal studies suggest that some people affected by chronic fatigue syndrome improve with time but that most remain functionally impaired for several years. The estimated worldwide prevalence of CFS is 0.4-1% and it affects over 800,000 people in the United States and approximately 240,000 patients in the UK. No physical examination signs are specific to CFS and no diagnostic tests identify this syndrome. The pathophysiological mechanism of CFS is unclear. The main hypotheses include altered central nervous system functioning resulting from an abnormal immune response against a common antigen; a neuroendocrine disturbance; cognitive impairment caused by response to infection or other stimuli in sentient people. The current concept is that CFS pathogenesis is a multifactorial condition. Various studies have sought evidence for a disturbance in immunity in people with CFS. An alteration in cytokine profile, a decreased function of natural killer (NK) cells, a presence of autoantibodies and a reduced responses of T cells to mitogens and other specific antigens have been reported. The observed high level of pro-inflammatory cytokines may explain some of the manifestations such as fatigue and flu-like symptoms and influence NK activity. Abnormal activation of the T lymphocyte subsets and a decrease in antibody-dependent cell-mediated cytotoxicity have been described. An increased number of CD8+ cytotoxic T lymphocytes and CD38 and HLA-DR activation markers have been reported, and a decrease in CD11b expression associated with an increased expression of CD28+ T subsets has been observed. This review discusses the immunological aspects of CFS and offers an immunological hypothesis for the disease processes.
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                Author and article information

                Journal
                J Intern Med
                J. Intern. Med
                joim
                Journal of Internal Medicine
                Blackwell Publishing Ltd (Oxford, UK )
                0954-6820
                1365-2796
                October 2011
                22 August 2011
                : 270
                : 4
                : 327-338
                Affiliations
                [1 ]simpleIndependent Vancouver, BC, Canada
                [2 ]simpleIndependent Calgary, AB, Canada
                [3 ]simpleDepartment of Physiology and Medicine, Vrije University of Brussels, Himmunitas Foundation Brussels, Belgium
                [4 ]simpleDepartment of Medicine, University of Miami Miller School of Medicine and Miami Veterans Affairs Medical Center Miami, FL, USA
                [5 ]simpleDepartment of Medicine, University of Alberta Edmonton, AB, Canada
                [6 ]simpleHonorary Consultant for NHS at Peterborough/Cambridge Lowestoft, Suffolk, UK
                [7 ]simpleGold Coast Public Health Unit Southport, Queensland
                [8 ]simpleHealth Sciences and Medicine, Bond University Robina, Queensland, Australia
                [9 ]simpleFaculty of Health Sciences, McMaster University and St. Joseph's Healthcare Hamilton Hamilton, ON, Canada
                [10 ]simpleIndependent Durham, UK
                [11 ]simpleHowick Health and Medical Centre Howick, New Zealand
                [12 ]simpleFatigue Consultation Clinic, Salt Lake Regional Medical Center Salt Lake City, UT, USA
                [13 ]simpleInternal Medicine, Family Practice, University of Utah Salt Lake City, UT, USA
                [14 ]simpleME/CFS Center, Oslo University Hospital HF Norway
                [15 ]simpleDepartment of Paediatrics, State University of New York Buffalo, NY, USA
                [16 ]simpleIndependent Pavia, Italy
                [17 ]simpleHarbor-UCLA Medical Center, University of California Los Angeles, CA
                [18 ]simpleEV Med Research Lomita, CA, USA
                [19 ]simpleUniversity of Limerick Limerick, Ireland
                [20 ]simplePain Clinic, Konyang University Hospital Daejeon, Korea
                [21 ]simpleDonvale Specialist Medical Centre Donvale, Victoria, Australia
                [22 ]simpleDepartments of Anesthesiology, Neurobiology and Anatomy, University of Utah Salt Lake City, UT, USA
                [23 ]simpleDepartment of Medicina Nuclear Clinica Las Condes, Santiago, Chile
                [24 ]simpleWhittemore Peterson Institute, University of Nevada Reno, NV, USA
                [25 ]simpleMiwa Naika Clinic Toyama, Japan
                [26 ]simpleA. Kirchenstein Institute of Microbiology and Virology, Riga Stradins University Riga, Latvia
                [27 ]simpleDepartment of Biochemistry & Basic Medical Sciences, Washington State University Portland, OR
                [28 ]simpleDepartment of Sports Sciences, University of the Pacific Stockton, CA USA
                Author notes
                Dr Bruce Carruthers, 4607 Blenheim St., Vancouver, British Columbia V6L 3A3, Canada. (fax: +1 604 263 9059; e-mail: bcarruth@ 123456telus.net ); and Dr. Gordon Broderick, Division of Pulmonary Medicine, Department of Medicine, University of Alberta, WMC 2E4.41 WC Mackenzie Health Sciences Bldg, 8440 – 112 Street, Edmonton AB T6G 2R7, Canada. (fax: +1 780 407 6384; e-mail: gordon.broderick@ 123456ualberta.ca ).

                Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms

                Article
                10.1111/j.1365-2796.2011.02428.x
                3427890
                21777306
                6e9797d6-fa66-4884-82af-56f479830496
                © 2011 The Association for the Publication of the Journal of Internal Medicine

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                Categories
                Review Article

                Internal medicine
                chronic fatigue syndrome,criteria,myalgic encephalomyelitis,diagnosis,definition
                Internal medicine
                chronic fatigue syndrome, criteria, myalgic encephalomyelitis, diagnosis, definition

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