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      A Comprehensive Update of the Current Understanding of Chronic Fatigue Syndrome

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          Abstract

          This is a comprehensive literature review of chronic fatigue syndrome (CFS). We provide a description of the background, etiology, pathogenesis, diagnosis, and management regarding CFS. CFS is a multifaceted illness that has many symptoms and a wide array of clinical presentations. As of recent, CFS has been merged with myalgic encephalomyelitis (ME). Much of the difficulty in its management has stemmed from a lack of a concrete understanding of its etiology and pathogenesis. There is a potential association between dysfunction of the autoimmune, neuroendocrine, or autonomic nervous systems and the development of CFS. Possible triggering events, such as infections followed by an immune dysregulation resulting have also been proposed. In fact, ME/CFS was first described following Epstein Barr virus (EBV) infections, but it was later determined that it was not always preceded by EBV infection. Patient diagnosed with CFS have shown a noticeably earlier activation of anaerobic metabolism as a source of energy, which is suggestive of impaired oxygen consumption. The differential diagnoses range from tick-borne illnesses to psychiatric disorders to thyroid gland dysfunction. Given the many overlapping symptoms of CFS with other illnesses makes diagnosing it far from an easy task. The Centers for Disease Control and Prevention (CDC) considers it a diagnosing of exclusion, stating that self-reported fatigue for at minimum of six months and four of the following symptoms are necessary for a proper diagnosis: memory problems, sore throat, post-exertion malaise, tender cervical or axillary lymph nodes, myalgia, multi-joint pain, headaches, and troubled sleep. In turn, management of CFS is just as difficult. Treatment ranges from conservative, such as cognitive behavioral therapy (CBT) and antidepressants, to minimally invasive management. Minimally invasive management involving ranscutaneous electrical acupoint stimulation of target points has demonstrated significant improvement in fatigue and associated symptoms in a 2017 randomized controlled study. The understanding of CFS is evolving before us as we continue to learn more about it. As further reliable studies are conducted, providing a better grasp of what the syndrome encompasses, we will be able to improve our diagnosis and management of it.

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          Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

          Background and main text Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies. Conclusions This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.
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            Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease

            Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.
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              A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors

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                Author and article information

                Contributors
                Journal
                Anesth Pain Med
                Anesth Pain Med
                10.5812/aapm
                Kowsar
                Anesthesiology and Pain Medicine
                Kowsar
                2228-7523
                2228-7531
                26 June 2021
                June 2021
                : 11
                : 3
                : e113629
                Affiliations
                [1 ]Mount Sinai Medical Center, Department of Anesthesiology, Miami Beach, FL, USA
                [2 ]Louisiana State University Health Shreveport, Department of Anesthesiology, Shreveport, LA, USA
                [3 ]Southcoast Health, Southcoast Physician Group Pain Medicine, MA, USA
                [4 ]Louisiana State University Health Shreveport School of Medicine, Shreveport, LA, USA
                [5 ]Pain Research Center, Department of Anesthesiology and Pain Medicine, Iran University of Medical Sciences, Tehran, Iran
                [6 ]Department of Anesthesiology, Tehran Medical Science, Islamic Azad University, Tehran, Iran
                [7 ]Paolo Procacci Foundation, Via Tacito 7, Roma, Italy
                [8 ]Valley Anesthesiology and Pain Consultants – Envision Physician Services, Phoenix, AZ, USA
                [9 ]Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, USA
                [10 ]University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA
                Author notes
                [* ]Corresponding Author: Mount Sinai Medical Center, Department of Anesthesiology, Miami Beach, FL, USA. Email: naz9noor@ 123456gmail.com
                [** ]Corresponding Author: Department of Anesthesiology, Tehran Medical Science, Islamic Azad University, Tehran, Iran. Email: mahnaznarimani@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-3652-6085
                https://orcid.org/0000-0001-7961-3931
                https://orcid.org/0000-0003-2464-0187
                https://orcid.org/0000-0003-0814-0772
                https://orcid.org/0000-0002-3822-2923
                https://orcid.org/0000-0002-6124-7037
                Article
                10.5812/aapm.113629
                8438707
                34540633
                5f82e6d7-2e9a-42c0-805c-7c07a47a9e4a
                Copyright © 2021, Author(s)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

                History
                : 07 February 2021
                : 31 May 2021
                : 03 June 2021
                Categories
                Review Article

                chronic fatigue syndrome,myalgic encephalomyelitis,systemic exertion intolerance disease,chronic fatigue immune disorder

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