ME and CFS Medical Abnormalities – Overview

 

Following is a list of overview articles about medical abnormalities in ME and CFS.

Links to the more than 1,000 peer-reviewed journal articles are listed on the M.E. and CFS Medical Abnormalities page of this website.

 

Rusin A, Seymour C, Mothersill C. Chronic fatigue and immune deficiency syndrome (CFIDS), cellular metabolism, and ionizing radiation: a review of contemporary scientific literature and suggested directions for future research. Int J Radiat Biol. 2018 Mar;94(3):212-228. PMID: 29297728

This study investigated biochemical pathways known to be involved in radiation response and in CFIDS to determine if there might be common underlying mechanisms leading to symptoms experienced by those accidentally or deliberately exposed to radiation and those suffering from CFIDS. Evidence for involvement of the alpha-synuclein, cytochrome c oxidase, αB-crystallin, RNase L, and lactate dehydrogenase/STAT1 pathways is strong and suggests a common underlying mechanism involving mitochondrial dysfunction mediated by ROS and disruption of ATP production. The downstream effect of this is compromised energy production.

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Hatziagelaki E, Adamaki M, Tsilioni I, Dimitriadis G, Theoharides TC. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Metabolic Disease or Disturbed Homeostasis? J Pharmacol Exp Ther. 2018 Aug 3. PMID: 30076265

The ME/CFS phenotype has been associated with abnormalities in energy metabolism, mostly with mitochondrial dysfunction, resulting in reduced oxidative metabolism. The authors propose that stimulation of hypothalamic mast cells activates microglia leading to focal inflammation in the brain and disturbed homeostasis.

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Nagy-Szakal D, Barupal DK, Lee B, Che X, Williams BL, Kahn EJR, Ukaigwe JE, Bateman L, Klimas NG, Komaroff AL, Levine S, Montoya JG, Peterson DL, Levin B, Hornig M, Fiehn O, Lipkin WI. Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics. Sci Rep. 2018 Jul 3;8(1):10056. PMID: 29968805

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Lacourt TE, Vichaya EG, Chiu GS, Dantzer R, Heijnen CJ. The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure. Front Behav Neurosci. 2018 Apr 26;12:78. PMID: 29755330

The authors propose a model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation and discuss how chronic low-grade inflammation can lead to reduced cellular-energy availability. They then present evidence for these metabolic pathways in models of persistent fatigue, focusing on chronic fatigue syndrome and cancer-related fatigue.

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de Vega WC, Erdman L, Vernon SD, Goldenberg A, McGowan PO. Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome. Epigenomics. 2018 May;10(5):539-557. PMID: 29692205

DNA methylome profiles in immune cells were integrated with symptomatology from 70 women with ME/CFS using similarity network fusion to identify subtypes. The researchers concluded that ME/CFS subtypes are associated with specific DNA methylation differences and health symptomatology.

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Tomas C, Newton J. Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review. Biochem Soc Trans. 2018 Jun 19;46(3):547-553. PMID: 29666214

This mini-review offers a brief summary of current research into the identification of metabolic abnormalities in CFS/ME which may represent potential biomarkers for the disease. The progress of research into key areas including immune dysregulation, mitochondrial dysfunction, 5′-adenosine monophosphate-activated protein kinase activation, skeletal muscle cell acidosis, and metabolomics are presented here.

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Monro JA, Puri BK. A Molecular Neurobiological Approach to Understanding the Aetiology of Chronic Fatigue Syndrome (Myalgic Encephalomyelitis or Systemic Exertion Intolerance Disease) with Treatment Implications. Mol Neurobiol. 2018 Sep;55(9):7377-7388. PMID: 29411266

Evidence demonstrating a biological aetiology for CFS/ME/SEID is adduced from a study of the history of the disease and a consideration of the role of the following in this disease: nitric oxide and peroxynitrite, oxidative and nitrosative stress, the blood-brain barrier and intestinal permeability, cytokines and infections, metabolism, structural and chemical brain changes, neurophysiological changes and calcium ion mobilisation.

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Komaroff AL, Takahashi R, Yamamura T, Sawamura M. Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review. Brain Nerve. 2018 Jan;70(1):41-54. PMID: 29348374

Recent studies of neuroimaging as well as analysis of blood markers, energy metabolism and mitochondrial function have revealed many objective biological abnormalities in ME/CFS. Specifically, it is suspected that the symptoms of ME/CFS may be triggered by immune activation – either inside or outside the brain – through release of inflammatory cytokines. In this review, we summarize potentially important recent findings on ME/CFS, focusing on objective evidence.

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Kuratsune H. Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Brain Nerve. 2018 Jan;70(1):11-18. PMID: 29348370

We present here the Japanese clinical diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS) that were proposed in 2016 by the Japanese Ministry of Health, Labour and Welfare study group. The clinical diagnosis criteria of ME/CFS were created to be used by healthcare agencies in charge of primary care practice. We also explain the current prognosis in ME/CFS and medical treatments used in major medical institutions in Japan.

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de Vega WC, McGowan PO. The epigenetic landscape of myalgic encephalomyelitis/chronic fatigue syndrome: deciphering complex phenotypes. Epigenomics. 2017 Nov;9(11):1337-1340. PMID: 29043854

Mechanistic research is needed to understand how epigenetic modifications affect functional changes in ME/CFS, and whether or not such adverse epigenetic changes can be reversed or treated. An important step in the right direction is to identify and validate biomarkers for objective diagnosis. Two main approaches are needed: deep phenotyping of the disease and co-morbid conditions, focusing more on patients than case/(healthy) control comparisons, and integration of phenotype and biological data that includes epigenetic profiles.

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Komaroff AL. Inflammation correlates with symptoms in chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2017 Aug 22;114(34):8914-8916. PMID: 28811366

This is an overview article on the state of ME/CFS research, written by a Harvard physician who has been studying the illness for more than 30 years.

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Jain V, Arunkumar A, Kingdon C, Lacerda E, Nacul L. Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS. BMC Neurol. 2017 Jun 20;17(1):117. PMID: 28633629

Cognitive and sleep symptoms are more common in ME/CFS patients than in MS patients and healthy controls, providing further support for existing evidence of central nervous system abnormalities in ME/CFS. Findings suggest that people with ME/CFS who are smokers, or have a low income, are more likely to report severe cognitive and sleep symptoms.

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Mensah FKF, Bansal AS, Ford B, Cambridge G. Chronic fatigue syndrome and the immune system: Where are we now? Neurophysiol Clin. 2017 Apr;47(2):131-138. PMID: 28410877

In this review, the authors discuss the potential of different components of the immune system to be involved in the pathogenesis of ME/CFS.

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Glassford JA. The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndome (ME/CFS). Front Physiol. 2017 Feb 17;8:88. PMID: 28261110r

The symptomatology of ME/CFS appears to emanate from a variety of sources of chronic neurological disturbance and associated distortions, and chronicity, in noxious sensory signaling and neuroimmune activation. This article incorporates a summary review and discussion of biomedical research considered relevant to this essential conception perspective.

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McManimen SL, Devendorf AR, Brown AA, Moore BC, Moore JH, Jason LA. Mortality in Patients with Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. Fatigue. 2016;4(4):195-207. PMID: 28070451

This study sought to determine if patients with ME or CFS are reportedly dying earlier than the overall population from the same cause. The findings suggest patients in this sample are at a significantly increased risk of earlier all-cause and cardiovascular-related mortality, and they had a directionally lower mean age of death for suicide and cancer compared to the overall U.S. population.

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Jason LA, Zinn ML, Zinn MA. Myalgic Encephalomyelitis: Symptoms and Biomarkers. Curr Neuropharmacol. 2015;13(5):701-34. PMID: 26411464

The authors summarize advances in the physiological and neurological approaches to understanding, diagnosing, and treating ME.

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Fischer DB, William AH, Strauss AC, Unger ER, Jason L, Marshall GD Jr, Dimitrakoff JD. Chronic Fatigue Syndrome: The Current Status and Future Potentials of Emerging Biomarkers. Fatigue. 2014 Jun 1;2(2):93-109. PMID: 24932428

The authors review potential CFS biomarkers related to neurological and immunological components of the illness.

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Bansal AS, Bradley AS, Bishop KN, Kiani-Alikhan S, Ford B. Chronic fatigue syndrome, the immune system and viral infection. Brain Behav Immun. 2011 Jul 2. PMID: 21756995

The authors review what is known about the immune system in CFS. 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.

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May M, Emond A, Crawley E. Phenotypes of chronic fatigue syndrome in children and young people. Arch Dis Child. 2010 Apr;95(4):245-9. PMID: 19843509

Exploratory factor analysis was performed on symptoms present at assessment in 333 children and young people with CFS/ME. Three phenotypes were identified using factor analysis: Factor 1, muscoloskeletal, had loadings on muscle and joint pain and hypersensitivity to touch, and was associated with worse fatigue, physical function and pain. Factor 2, migraine, loaded on noise and light hypersensitivity, headaches, nausea, abdominal pain and dizziness and was most strongly associated with physical function and pain. Factor 3, sore throat, had loadings on sore throat and tender lymph nodes and was not associated with fatigue or pain.

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Carlo-Stella N, Cuccia M. Demographic and clinical aspects of an Italian patient population with chronic fatigue syndrome. Reumatismo. 2009 Oct-Dec;61(4):285-9. PMID: 20143004

Besides persistent fatigue, a clinical syndrome of CFS with infectious, neurological and rheumatological characteristics is outlined from the data in Italy.

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Bassi N, Amital D, Amital H, Doria A, Shoenfeld Y. Chronic fatigue syndrome: characteristics and possible causes for its pathogenesis. Isr Med Assoc J. 2008 Jan;10(1):79-82. PMID: 18300582

Several mechanisms have been suggested to play a role in CFS, such as excessive oxidative stress following exertion, immune imbalance characterized by decreased natural killer cell and macrophage activity, immunoglobulin G subclass deficiencies (IgG1, IgG3) and decreased serum concentrations of complement component. Autoantibodies were also suggested as a possible factor in the pathogenesis of CFS. Recent studies indicate that anti-serotonin, anti-microtubule-associated protein 2 and anti-muscarinic cholinergic receptor 1 may play a role in the pathogenesis of CFS. It has been demonstrated that impairment in vasoactive neuropeptide metabolism may explain the symptoms of CFS.

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Hooper M. Myalgic encephalomyelitis: a review with emphasis on key findings in biomedical research. J Clin Pathol. 2007 May;60(5):466-71. PMID: 16935967

A review of research findings in CFS, termed a “chronic multiple-symptom, multiorgan, multisystem illness.”

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Klimas NG, Koneru AO. Chronic fatigue syndrome: inflammation, immune function, and neuroendocrine interactions. Curr Rheumatol Rep. 2007 Dec;9(6):482-7. PMID: 18177602

Studies of CFS patients show a variety of dysfunctions, including mitochondrial dysfunction and immune dysfunction.

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Miike T. Childhood chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):1099-104. PMID: 17561704

For children and adolescents with CFS, four major symptoms are important: sleep disorders, easy fatigability, disturbed learning and memorization and immunological problems.

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Kuratsune H. Overview of chronic fatigue syndrome focusing on prevalence and diagnostic criteria. Nihon Rinsho. 2007 Jun;65(6):983-90. PMID: 17561686

Recent studies reveal that CFS can be understood to be a special condition based on the abnormality of neuroendocrine-immunologic system caused by the psycho-social stress and some genetic components. Under these conditions, a reactivation of various kinds of herpes virus infections and/or chronic infections might occur as a result of immune dysfunction, causing the abnormal production of several cytokines. A distinctive feature of CFS is thought to be the secondary brain dysfunction caused by the abnormal production of several cytokines.

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Janal MN, Ciccone DS, Natelson BH. Sub-typing CFS patients on the basis of ‘minor’ symptoms. Biol Psychol. 2006 Aug;73(2):124-31. PMID: 16473456

The authors did an analysis of a population of CFS patients and came up with musculoskeletal, infectious and neurological subtypes.

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Gurbaxani BM, Jones JF, Goertzel BN, Maloney EM. Linear data mining the Wichita clinical matrix suggests sleep and allostatic load involvement in chronic fatigue syndrome. Pharmacogenomics. 2006 Apr;7(3):455-65. PMID: 16610955

The authors provide basic data about a group of CFS sufferers in Wichita, Kansas.

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Jason LA, Taylor RR, Kennedy CL, Jordan K, Huang CF, Torres-Harding S, Song S, Johnson D. A factor analysis of chronic fatigue symptoms in a community-based sample. Soc Psychiatry Psychiatr Epidemiol. 2002 Apr;37(4):183-9. PMID: 12027245

Individuals with chronic fatigue have symptoms that can be differentiated into theoretically distinct factors, including: Lack of Energy, Physical Exertion, Cognitive Functioning, and Fatigue and Rest.

 

 

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