Myalgic encephalomyelitis/he

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history

Myalgic Encephalomyelitis (ME) is a chronic, inflammatory, physically and neurological and immune-mediated disease that presents with symptoms involving multiple bodily systems. It is frequently triggered by a viral infection or a flu-like illness.[1] ME presents with symptoms in the central nervous system (CNS), autonomic nervous system (ANS), immune system, cardiovascular system, endocrine system, digestive system, and musculoskeletal system.[2][3]

Myalgic encephalomyelitis was first classified as a neurological disease by the World Health Organization (WHO) in 1969, with the publication of the ICD-8 manual.[4]

ME has occurred in both epidemic and sporadic forms.

The hallmark symptom of myalglc encephalomyelitis is post-exertional malaise (PEM), which is the result of intolerance to previously achievable cognitive or physical exertion.[5][6][7][8] Other key symptoms include muscle weakness and easy muscle fatigability, sleep disturbance, and cognitive dysfunction. ANS dysfunction is frequent, although specific symptoms vary from patient to patient and may include postural orthostatic tachycardia (POTS), reduced heart rate variability at night, and both cold and heat intolerance. Other common symptoms include myalgia (muscle pain), neuralgia (neuropathic pain), neck and spine stiffness, and sensory symptoms including sensitivity to light, sound, touch, paraesthesia (skin tingling or numbness) and hyperaesthesia (skin sensitivity and pain, and allodynia). There is a progressive form of ME, but it is rarer than the relapsing-remitting type.[9]

Among adults, ME is more common in women than men.[10] New onset has been observed in children[11] and in adults usually between the ages of 40-60.[12] Bakken et. al notes two age peaks for CFS/ME; age group 10 to 19 years and a second peak in the age group 30 to 39 years.[13]

There are no approved pharmacological treatments for ME anywhere in the world except in Argentina, which has approved the immunomodulator Ampligen for severe ME/CFS as of August 23, 2016.[14]

Linda Crowhurst is married to Greg Crowhurst; they reside in Belfast, Northern Ireland. Greg is Linda's full-time carer as she is very severely ill with ME. As of June 2018, Linda has been ill for 25 years. This image is a still from the video Wasteland which visually documents Linda's very severe ME. Greg posted a YouTube video in 2006 (reposted in 2007) of Linda speaking of her condition and showing her neurological symptoms which are the first known public visual document of very severe ME. She is now bedbound barely able to move and unable to feed herself
Jennie Spotila is an American ME patient who fell ill on October 6, 1994. Jennie is disabled, mostly housebound, and uses a wheelchair but has been an ME/CFS advocate for many years. She writes the blog Occupy M.E. She served on the Board of Directors of The CFIDS Association of America and testified before the CFSAC

History[edit | edit source]

Myalgic encephalomyelitis was first classified as a neurological disease by the World Health Organization in 1969, with the publication of the ICD-8 manual.[4]

Hillary Johnson is an American journalist and while ill herself, wrote the book Osler's Web which is the historical account of the early years of a "new" illness that had an outbreak at Incline Village which she shared the same symptoms. The illness came to be known as chronic fatigue syndrome (CFS). Johnson spent nine years investigating the outbreak and the CDC's refusal to acknowledge a devastating disease (deeming sufferers of Incline Village as having "mass hysteria") that can be spread through casual contact. She appears in the documentary Forgotten Plague and currently writes at

The ICD-8 did not include any alternative names for myalgic encephalomyelitis although postinfectious encephalomyelitis and all other encephalomyelitis diseases were classified under the same code; fatigue-related alternative names were not added in any later revisions.[4][15] The alternative name chronic fatigue syndrome (CFS) was not in use at this time; it was proposed in 1987 by the Centers for Disease Control, which adopted new diagnostic criteria the following year.[16]:29

In the ICD-9, which was published in 1989, the entry for myalglc encephalomyelitis is uses code 323.9:[17]

ME has occurred in both epidemic and sporadic form since at least the 1930s, although it has likely been occurring much longer but was not formally named. The first recorded outbreak of epidemic myalgic encephalomyelitis was in 1934 in Los Angeles and was thought to be an outbreak of atypical polio. After the outbreak in Akureyri, Iceland in 1946, the disease came to be called 'Akureyri Disease' or Icelandic disease through much of the 1940s and 1950s. It was named ME after London's Royal Free Hospital outbreak in 1955. Other names included benign myalgic encephalomyelitis and epidemic neuromyasthenia.

After the Incline Village outbreak in Nevada in 1984, the disease came to be called and redefined as chronic fatigue syndrome (CFS). The most recent putative outbreak was in Arizona in 1996

Disease name[edit | edit source]

The name myalgic encephalomyelitis was first used in 1956 in an article in the Lancet medical journal to describ findings from the 1955 Royal Free Hospital outbreak in London, UK.[19][18][20] The term myalgic encephalomyelitis is a portmanteau of several of the key signs and symptoms of the disease: myalgic (muscle pain), encephalo (brain), myel (spinal cord), itis (inflammation).[18][21] The central nervous system (brain and spinal cord) are inflamed.

Benign myalgic encephalomyelitis[edit | edit source]

Benign myalgic encephalomyelitis was the term used by the World Health Organization from 1969,[4] with the prefix "benign" used to denote that M.E. was not fatal, the prefix benign was later dropped since M.E. can cause death, for example the deaths of Merryn Crofts and Sophia Mirza.[18][22][23] Merryn Crofts had very severe ME, was bedbound and unable to eat. She weighed six stone (84 lbs) at her death; her autopsy revealed inflammation of the dorsal root ganglia.[citation needed] Merryn's death certificate was the second in the UK to attribute a death to ME.[22]

Disease of a thousand names[edit | edit source]

Myalgic Encephalomyelitis has been referred to as the "disease of a thousand names".[24] Other names used or proposed in the history of the myalgic encephalomyelitis include atypical polio, Icelandic disease, benign ME, epidemic neuromyasthenia, chronic fatigue syndrome, Chronic Fatigue Immune Dysfunction Syndrome (CFIDS), and systemic exertion intolerance disease (SEID).[24][16] This has lead to much confusion as a variety of names have been used at different times to describe discrete outbreaks as well as a larger and potentially more heterogenous population of sporadic cases, defined by a wide variety of diagnostic criteria. Some names have emphasized particular symptoms or pathology, including chronic fatigue syndrome and myalgic encephalomyelitis.[18]

A survey by The MEAction Network in 2016 found that the majority of patients prefer the name ME to other names including chronic fatigue syndrome.[25]

Myalgic encephalomyelitis (ME) was the original name for chronic fatigue syndrome (CFS); the names are used interchangeably or with the acronym ME/CFS.[21]

Onset[edit | edit source]

According to Dr Byron Hyde, after an incubation period of 4 to 7 days, the prodromal phase generally involve a flu-like illness with low-grade fever.[26] In the majority but not all cases, an infection or infectious process is evident.[26] Two to seven days later, a chronic phase commences, characterized by a measurable diffuse change in the function of the CNS. It is this second phase, persistent phase that most characterizes ME.[27][2][26]

Signs and symptoms[edit | edit source]

Myalgic encephalomyelitis is a neurological disease that affects multiple bodily systems, causing a widespread combination of symptoms.[28] Symptoms can range from mild to very severe and can include:

Myalgic encephalomyelitis is an acquired neurological disease with complex global dysfunctions. Pathological dysregulation of the nervous, immune and endocrine systems, with impaired cellular energy metabolism and ion transport are prominent features. - International Consensus Criteria

Symptom presentation and severity can vary considerably day to day and even hour to hour.[2] Overexertion can exacerbate all symptoms, and post-exertional malaise often delayed by 24 hours or more.[29][2] The US National Institutes of Health (NIH) notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.[30]

Post-exertional malaise[edit | edit source]

A core symptom, post-exertional malaise (PEM), is intolerance to previously trivial mental or physical effort such as attending a child's school event, running an errand or grocery shopping, taking a shower or brushing teeth; this causes a worsening of symptoms, and deterioration of health from persistent or repeated exertion.[5][31][8]

Jennifer Brea is an American who was studying at Harvard; while on a trip to Kenya she became very ill with what would eventually be diagnosed as ME/CFS. Brea began experiencing neurological problems. Her neurologist diagnosed her with "conversion disorder" (hysteria). When walking home from his office, she collapsed. Jen then needed to use a wheelchair to keep her legs up due to POTS as her blood pools into her legs. View her TED Talk What happens when you have a disease doctors can't diagnose

The severity of a patient's symptoms often depends on the time period since the disease was contacted and rate of progression of each patient. The rate of progression can be accelerated by physical or cognitive activity beyond a patient's limits over long periods, which typically entails anaerobic activity.[citation needed]

Clinical findings[edit | edit source]

Alem Matthees is an Australian ME patient that filed an FOI request for data from the PACE trial. At a great cost to his health, Alem appealed the denial of the data and won. This data proved the results published in The Lancet were untrue. Alem's health suffered significantly in part from the efforts required for the FOI request and tribunal

Although there is no definitive biomarker, several signs and findings have been frequently observed in clinical settings:

Diagnosis[edit | edit source]

Tom Kindlon became ill at 16 and never recovered. He is an ME/CFS advocate with published works in Research Gate and PubMed. Kindlon lives in Ireland and is Assistant Chairperson of the Irish ME/CFS Association. Tom and others analyzed the data for the PACE trial proving out that its published results were untrue. He uses a wheelchair and his full-time carer is his mother, Vera

There are several proposed criteria for diagnosing ME including the International Consensus Criteria (ICC) and the Canadian Consensus Criteria (CCC). The original criteria developed by Melvin Ramsay, the Ramsay definition, is not used for diagnosing ME today.

Generally accepted criteria for diagnosing ME/CFS and ME[edit | edit source]

ME/CFS (SEID) is accurately diagnosed when the core symptoms are met. The Institute of Medicine report is a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

Other diagnostic criteria[edit | edit source]

Several, overly broad criteria have been proposed and are in use. These criteria likely capture some patients with the disease characterized in the medical literature on epidemic ME, exclude others, and also include patients with a wide range of other undiagnosed conditions including cancer, depression, and a range of autoimmune diseases. The United Kingdom's Oxford criteria for chronic fatigue syndrome is the broadest and likely least discerning definition. (The US Institute of Medicine report called for its complete retirement.)[43] The US Centers for Disease Control's (CDC) Fukuda criteria, in use since 1994, is also overly broad. The Institute of Medicine report developed the criteria of Systemic Exertion Intolerance Disease (SEID) and although it can diagnose ME patients with the minimum core symptoms,[44][45] it does not describe the array of symptoms those suffering with ME experience. Symptoms such as neurological, immune/gastrointestinal/genitourinary impairment, and energy metabolism/ion transport impairment; these symptoms are necessary for a diagnosis under the ICC.[28] The CCC requires neurological, autonomic, neuroendocrine, immune system, and myalgia symptoms to meet its ME/CFS diagnostic criteria.[6]

Differential diagnosis[edit | edit source]

The signs and symptoms of ME can be similar to other medical problems, "such as cancer, multiple sclerosis, lupus, brucellosis, or another condition."[2][6] Additional testing may be needed to help distinguish ME from these other problems.[45]

Course and prognosis[edit | edit source]

Pathophysiology[edit | edit source]

Vanessa Li lived in Hong Kong, the UK, and the US. She became ill with a flu-like illness while skiing in Italy and never recovered. Vanessa founded a crowdfund for the Microbe Discovery Project. She was in excruciating pain, suffered from breathing issues, and occasional paralysis for 15 years. She took her own life in 2015

ME is a multi-system disease. Numerous biological abnormalities have been found in multiple bodily system, however no common, central cause or mechanism has yet been elucidated.

Central nervous system[edit | edit source]

Sophia Mirza was a very severely ill ME patient who lived in the UK. Sophia's death came not long after a forced entry into her mother's home and being sectioned and taken to a mental hospital in 2003. An independent Neuropathologist found Sophia's spine contained a massive infection. Her death certificate was the first in the UK to attribute a death to CFS

Autonomic nervous system[edit | edit source]

Cardiovascular[edit | edit source]

Gastrointestinal system[edit | edit source]

Immune system[edit | edit source]

Musculoskeletal system[edit | edit source]

Peripheral nervous system[edit | edit source]

Sex differences[edit | edit source]

Florence Nightingale was a British citizen and pioneer of modern nursing. Nightingale was stationed in Crimea when she developed "Crimean fever" (a bacterial infection now known as brucellosis) and never recovered. She remained mostly bedbound the rest of her life. Although ME and CFS were not defined in her lifetime, many current physicians and medical historians believe she developed ME/CFS as a result of a chronic brucellosis infection

A Norwegian CFS/ME study shows that the disease affects all ages, with two peak ages of 10-19 years and 30-39 years; it is more common in women than in men.[46] Research by the Open Medicine Foundation cited in its paper, Metabolic features of chronic fatigue syndrome which studied severe CFS, found that the disease is different in men and women but this is not related to testosterone or estrogen. Michael VanElzakker notes there are male and female differences in neuropathic pain. A study of UK and Dutch cohorts found "younger children had a more equal gender balance compared to adolescents and adults."[47]

גורמי סיכון וסיבות אפשריות[edit | edit source]

סיכונים גנטיים[edit | edit source]

דווח כי מיאלגי'ק אינספלומיאליטיס/תסמונת התשישות הכרונית הופיעו בקרב משפחות. למרות שמיאלג'יק אינספלומיאליטיס ותסמונות התשישות הכרונית אינן נחשבות למחלות תורשתיות, יש עדויות לנטייה גנטית.[48]

Potential causes[edit | edit source]

Although risk factors for myalgic encephalomyelitis have been identified, no single definitive virus has been found in all cases, which has led to the claim that ME is a common end path of a variety of infectious insults.[49][50][51] It is still possible ME involves some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations.[52][53] Several theories suggest that ME is an inappropriate immune response to an infection, a theory bolstered by the observation that there is sometimes a family history of autoimmune disease.[54] There is also a shift from the Th1 type of helper T cells, which fight infection, to the Th2 type, which are more active in allergy and more likely to attack the body.[55][56]

Naomi Whittingham lives in the UK with a severe case of ME. Naomi became ill at age 12 with a routine virus and never recovered. She advocates for ME by doing interviews, writing the blog A Life Hidden, and supporting her brother Tom Whittingham's marathon fund raising for ME Research UK

Viruses[edit | edit source]

Other theories describe ME as an immune response to a chronic infection. The association between ME and the Coxsackie B, Human herpesvirus 6, and HHV-7 viruses[57][58][59] suggests a potential viral contribution in at least some individuals. Evidence from epidemic myalgic encephalomyelitis strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.

Bacteria[edit | edit source]

Others believe ME may sometimes result from a chronic infection with spirochetal bacteria, such as lyme disease. Another bacterium that has been implicated in ME is chlamydia pneumoniae.[60][61] Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.[62]

The vagus nerve infection hypothesis (VNIH) accounts for why so many different infectious onsets could be responsible. The vagus nerve runs from the brain stem and throughout the body and has an impact on many body systems.

Given the uncertainty regarding the cause, ME and CFS patients are barred from donating blood or organs in the United Kingdom, United States and New Zealand while symptoms persist.[63][64][65]

Treatments[edit | edit source]

Karina Hansen became ill as an adult teenager and is severely ill with ME. She was forcibly institutionalized for 3 1/2 years as the Denmark healthcare system designates ME as psychosomatic. Karina is now home with her family where she received cards from well-wishers from around the world. Karina's Danish High Court case and return home were featured in the documentary film Unrest

There is no cure for ME and no country has approved any pharmacological treatment for the disease except, Argentina which has approved Ampligen for the treatment of severe ME/CFS.[14] However the effectiveness of Ampligen is under dispute.[66] Other medications have been used off-label for ME with varying effectiveness in some patients.[6][28]

Treatments for sleep problems, headaches, pain or other symptoms are utilized by some doctors for some patients although these are treating symptoms and not ME itself.[28]

Success of treating symptoms of ME is not well researched or documented.

An immune system modulator drug called Rituximab has failed in a phase III clinical trial.[67] The antiviral Valganciclovir failed in a controlled nine month study against ME patients positive for Herpes Simplex 6 and Epstein Barr viral infections.[68]

Epidemiology[edit | edit source]

ME has been found world-wide, in at least 75 epidemics documented in published papers from the 1930s to the 1980s.[69] Epidemics often occur in enclosed communities such as schools and hospitals.

As observed in many autoimmune disorders, ME is more common in females than males; the mean sex ratio is approximately 2-3 females for every male.[70] In children the sex ratio is approximately equal.[71]

Co-morbidities[edit | edit source]

Char, author at Chronically Hopeful, must use sunglasses due to light sensitivity (photophobia) and noise canceling ear protection due to sound sensitivity (hyperacusis)

Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions, and increased risks for secondary diseases in patients with ME.[6][8] However, as no large-scale epidemiological studies, genetic studies, or family studies have been done, there is little that can be said definitively about the rate or underlying biological reasons for these potentially related conditions. Overlapping diagnostic criteria and the lack of a biomarker in many of these conditions add to the confusion and diagnostic uncertainty. Moreover, certain conditions such as postural orthostatic tachycardia syndrome (POTS) and neurally mediated hypotension (NMH) and idiopathic intracranial hypertension (IIH/IH) and fibromyalgia (FM/FMS) can occur in or be co-morbid with numerous conditions, including ME.[72][73]

The following are some syndromes and diseases that have been associated with or misdiagnosed as ME:

A Swedish study of 234 ME/CFS patients meeting the Canadian Consensus Criteria found that 13.2% had tonsillar herniations severe enough to be considered a Chiari Malformation. 49% had hypermobility and 20% met criteria for hEDS (Ehlers-Danlos syndrome with hypermobility), while 96% had fibromyalgia trigger point pain, with 67% meeting the diagnostic criteria for fibromyalgia.[77]

Notable studies[edit | edit source]

Due to lack of funding by governments around the world there has been little biological research into ME/CFS. There are studies which do reveal neurological involvement, metabolic features, and other abnormalities.

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. Boffey, Philip M. (July 28, 1987). "Fatigue 'Virus' Has Experts More Baffled And Skeptical Than Ever". The New York Times. ISSN 0362-4331. Retrieved February 17, 2019.
  2. 2.0 2.1 2.2 2.3 2.4 "Myalgic Encephalomyelitis - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved September 7, 2018.
  3. Petrison, Lisa (April 4, 2016). "Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations" (PDF).
  4. 4.0 4.1 4.2 4.3 World Health Organization (1969). Manual of the International Statistical Classification of Diseases, Injuries, and Causes of Death Based on the Recommendations of the Eighth Revision Conference (PDF). 2 (8th ed.). Geneva: WHO. p. 173. Encephalomyelitis (chronic),
    (myalgic, benign) 323
  5. 5.0 5.1 "Pathways to Prevention (P2P) Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)". Office of Disease Prevention. Retrieved September 7, 2018.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 Carruthers, Bruce M.; Jain, Anil Kumar; De Meirleir, Kenny L.; Peterson, Daniel L.; Klimas, Nancy G.; Lerner, A. Martin; Bested, Alison C.; Flor-Henry, Pierre; Joshi, Pradip; Powles, AC Peter; Sherkey, Jeffrey A.; van de Sande, Marjorie I. (2003), "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols" (PDF), Journal of Chronic Fatigue Syndrome, 11 (2): 7–115, doi:10.1300/J092v11n01_02
  7. Ramsay, Melvin (1986). "The Clinical Features of Myalgic Encephalomyelitis". Retrieved September 7, 2018.
  8. 8.0 8.1 8.2 8.3 "Symptoms | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. May 18, 2018. Retrieved November 21, 2018.
  9. Howes, S (July 7, 2015). "Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report" (PDF). Physical Medicine and Rehabilitation - International – via Austin Publishers Group.
  10. "Possible Causes | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. January 18, 2019. Retrieved April 13, 2019.
  11. "ME/CFS in Children | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. January 18, 2019. Retrieved April 13, 2019.
  12. "What is ME/CFS? | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. January 18, 2019. Retrieved April 13, 2019.
  13. Bakken, Inger Johanne; Tveito, Kari; Gunnes, Nina; Ghaderi, Sara; Stoltenberg, Camilla; Trogstad, Lill; Håberg, Siri Eldevik; Magnus, Per (October 1, 2014). "Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012". BMC Medicine. 12 (1): 167. doi:10.1186/s12916-014-0167-5. ISSN 1741-7015. PMC 4189623. PMID 25274261.
  14. 14.0 14.1 Hemispherx Biopharma, Inc (August 23, 2016). "Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic". GlobeNewswire News Room. Retrieved August 12, 2018.
  15. World Health Organization (2016). "G93 Other diseases of the nervous system - ICD-10 Version:2016". World Health Organization. Retrieved April 13, 2019.
  16. 16.0 16.1 16.2 Institute of Medicine (2015). Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington, DC: The National Academies Press. doi:10.17226/19012.
  17. World Health Organization & International Conference for the Ninth Revision of the International Classification of Diseases (1978). Manual of the international statistical classification of diseases, injuries, and causes of death : based on the recommendations of the ninth revision conference, 1975, and adopted by the Twenty-ninth World Health Assembly, 1975 revision: alphabetic index (PDF). 2 (9th ed.). Geneva: World Health Organization. p. 182. ISBN 9241540044.
  18. 18.0 18.1 18.2 18.3 18.4 18.5 18.6 18.7 Hooper, Malcolm. "The Terminology of ME & CFS".
  19. "A new clinical entity?" (PDF). Lancet. 1: 789–790. 1956.
  20. Ramsay, A. Melvin (October 30, 1965). "Hysteria and "Royal Free Disease."". British Medical Journal. 2 (5469): 1062. ISSN 0007-1447. PMC 1847119.
  21. 21.0 21.1 Smith, David G (1989). Understanding M.E.: The Phenomenon of Myalgic Encephalomyelitis and Acute Onset Post Viral Fatigue Syndrome. p. 20.
  22. 22.0 22.1 Taylor, Jim (July 27, 2018). "'Vindication' for woman who wanted ME on death certificate". BBC Radio 5 Live.
  23. World Health Organization. "8E49 Postviral fatigue syndrome | ICD-11 - Mortality and Morbidity Statistics". World Health Organization. Retrieved March 19, 2022. 8E49 Postviral fatigue syndrome
    Other disorders of the nervous system
    chronic fatigue syndrome
    myalgic encephalomyelitis
    Fatigue (MG22)
  24. 24.0 24.1 Bell, David S. (1991). Chronic Fatigue/Immune Dysfunction Syndrome. CFIDS: The disease of a thousand names. Lyndonville, NY: Pollard Publications. Archived from the original on February 16, 2010.
  25. "#MEAction RFI Poll Report (Part 1 of 3) - #MEAction". #MEAction. August 7, 2016. Retrieved September 8, 2018.
  26. 26.0 26.1 26.2 Evans, Meredyth; Jason, Leonard (2018). "Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis" (PDF). Research on Chronic diseases. 2 (1): 2–3.
  27. "Nightingale ME Definition En | Chronic Fatigue Syndrome | Infection". Scribd. p. 5. Retrieved September 8, 2018.
  28. 28.0 28.1 28.2 28.3 28.4 28.5 28.6 28.7 28.8 Carruthers, Bruce M.; van de Sande, Marjorie I.; De Meirleir, Kenny L.; Klimas, Nancy G.; Broderick, Gordon; Mitchell, Terry; Staines, Donald; Powles, A.C. Peter; Speight, Nigel; Vallings, Rosamund; Bateman, Lucinda; Baumgarten-Austrheim, Barbara; Bell, David; Carlo-Stella, Nicoletta; Chia, John; Darragh, Austin; Jo, Daehyun; Lewis, Donald; Light, Alan; Marshall-Gradisnik, Sonya; Mena, Ismael; Mikovits, Judy; Miwa, Kunihisa; Murovska, Modra; Pall, Martin; Stevens, Staci (August 22, 2011). "Myalgic encephalomyelitis: International Consensus Criteria". Journal of Internal Medicine. 270 (4): 327–338. doi:10.1111/j.1365-2796.2011.02428.x. ISSN 0954-6820. PMC 3427890. PMID 21777306.
  29. Research. "Invest in ME Research - Invest in ME Research Home Page". Invest in ME Research. Retrieved September 8, 2018.
  30. "Pathways to Prevention (P2P) Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)". Office of Disease Prevention. Retrieved September 8, 2018.
  31. 31.0 31.1 31.2 31.3 31.4 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; Bell, DS; Carlo-Stella, N; Chia, J; Darragh, A; Gerken, A; Jo, D; Lewis, DP; Light, AR; Light, KC; Marshall-Gradisnik, S; McLaren-Howard, J; Mena, I; Miwa, K; Murovska, M; Stevens, SR (2012), Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners (PDF), ISBN 978-0-9739335-3-6
  32. Schmaling, K.B.; Jones, J.F. (January 1996). "MMPI profiles of patients with chronic fatigue syndrome". Journal of Psychosomatic Research. 40 (1): 67–74. ISSN 0022-3999. PMID 8730646.
  33. Cuende JI, Civeira P, Diez N, Prieto J (1997). "[High prevalence without reactivation of herpes virus 6 in subjects with chronic fatigue syndrome]". An Med Interna. 14 (9): 441–4. PMID 9453750.
  34. Komaroff, AL (2006). "Is human herpesvirus-6 a trigger for chronic fatigue syndrome?". J Clin Virol. 37 (Suppl 1): S39-46. doi:10.1016/S1386-6532(06)70010-5. PMID 17276367.
  35. Landay, AL (September 1991). "Chronic fatigue syndrome: clinical condition associated with immune activation". Lancet.
  36. Chia, John (November 2005). "The role of enterovirus in chronic fatigue syndrome". Journal of Clinical Pathology.
  37. Ruiz-Núñez, Begoña; Tarasse, Rabab; Vogelaar, Emar F.; Janneke Dijck-Brouwer, D.A.; Muskiet, Frits A. J. (2018), "Higher Prevalence of "Low T3 Syndrome" in Patients With Chronic Fatigue Syndrome: A Case–Control Study", Frontiers in Endocrinology, 9: 97, doi:10.3389/fendo.2018.00097, PMID 29615976
  38. 38.0 38.1 Brenu, Ekua Weba; Huth, Teilah K.; Hardcastle, Sharni L.; Fuller, Kirsty; Kaur, Manprit; Johnston, Samantha; Ramos, Sandra B.; Staines, Don R.; Marshall-Gradisnik, Sonya M. (April 2014). "Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis". International Immunology. 26 (4): 233–242. doi:10.1093/intimm/dxt068. ISSN 1460-2377. PMID 24343819.
  39. "Etiology and Pathophysiology | Presentation and Clinical Course | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. July 10, 2018. Retrieved October 19, 2018.
  40. Cox, I.M.; Campbell, M.J.; Dowson, D. (March 30, 1991). "Red blood cell magnesium and chronic fatigue syndrome". Lancet (London, England). 337 (8744): 757–760. ISSN 0140-6736. PMID 1672392.
  41. "Overlapping Conditions – American ME and CFS Society". Retrieved August 12, 2018.
  42. Arroll, Megan A.; Attree, Elizabeth A.; O'Leary, John M.; Dancey, Christine P. (April 3, 2014). "The delayed fatigue effect in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)". Fatigue: Biomedicine, Health & Behavior. 2 (2): 57–63. doi:10.1080/21641846.2014.892755. ISSN 2164-1846.
  43. Swift, Penny. "US NIH Report Calls for UK Definition of ME/CFS to be Scrapped". Retrieved September 8, 2018.
  44. "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm". 2015.
  45. 45.0 45.1 "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness: Clinicians' Guide" (PDF). National Academies. 2015.
  46. Bakken, Inger Johanne; Tveito, Kari; Gunnes, Nina; Ghaderi, Sara; Stoltenberg, Camilla; Trogstad, Lill; H åberg, Siri Eldevik; Magnus, Per (October 1, 2014). "Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012". BMC Medicine. 12 (1). doi:10.1186/s12916-014-0167-5. ISSN 1741-7015. PMID 25274261.
  47. Collin, Simon M.; Nuevo, Roberto; van de Putte, Elise M.; Nijhof, Sanne L.; Crawley, Esther (October 28, 2015). "Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts". BMJ open. 5 (10): e008830. doi:10.1136/bmjopen-2015-008830. ISSN 2044-6055. PMID 26510728.
  48. Cite error: Invalid <ref> tag; no text was provided for refs named Schlaub, 2016
  49. Evans, Meredyth (August 23, 2015). "Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach".
  50. "Case Presentation - Chronic Fatigue Syndrome". Retrieved September 8, 2018.
  51. Magnus, Per; Gunnes, Nina; Tveito, Kari; Bakken, Inger Johanne; Ghaderi, Sara; Stoltenberg, Camilla; Hornig, Mady; Lipkin, W. Ian; Trogstad, Lill (November 17, 2015). "Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine". Vaccine. 33 (46): 6173–6177. doi:10.1016/j.vaccine.2015.10.018. ISSN 1873-2518. PMID 26475444.
  52. Underhill, R.A. (2015). "Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease". Medical Hypotheses. 85 (6): 765–773. doi:10.1016/j.mehy.2015.10.011. ISSN 1532-2777. PMID 26604026.
  53. Schlauch, Karen A.; Khaiboullina, Svetlana F.; De Meirleir, Kenny L.; Rawat, Shanti; Petereit, J; Rizvanov, Albert A; Blatt, Nataliya; Mijatovic, Tatjana; Kulick, D; Palotás, András; Lombardi, Vincent C. (2016), "Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome", Translational Psychiatry, 6 (2): e730, doi:10.1038/tp.2015.208
  54. "Klimas ME CFS Genes Study". November 23, 2015. Retrieved September 8, 2018.
  55. "Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis". Cytokine. 72 (1): 1–8. March 1, 2015. doi:10.1016/j.cyto.2014.11.019. ISSN 1043-4666.
  56. Hardcastle, S.L.; Brenu, E.W.; Staines, D.R.; Marshall-Gradisni, S. (2014). "Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells" (PDF).
  57. Bell, E.J.; McCartney, R.A.; Riding, M.H. (1988). "Coxsackie B viruses and myalgic encephalomyelitis". Journal of the Royal Society of Medicine. 81 (6): 329–331. doi:10.1177/014107688808100609. ISSN 0141-0768. PMID 2841461.
  58. "Ramsay Research Team 5 – The Potential Role of HHV-6 in ME/CFS - Solve ME/CFS Initiative". Solve ME/CFS Initiative. VOLKMEDIA. December 16, 2016. Retrieved September 8, 2018.
  59. Chapenko, Svetlana; Krumina, Angelika; Logina, Inara; Rasa, Santa; Chistjakovs, Maksims; Sultanova, Alina; Viksna, Ludmila; Murovska, Modra (2012). "Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome". Advances in Virology: 205085. doi:10.1155/2012/205085. ISSN 1687-8647. PMID 22927850.
  60. Tovey JE (September 5, 2018). "Chlamydia pneumoniae infection a treatable cause of Chronic Fatigue Syndrome". The BMJ.
  61. "New ME/CFS Study at Stanford: Dr. Montoya to test for scores of Infections - Prohealth". Prohealth. June 4, 2010. Retrieved September 8, 2018.
  62. "Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioral, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 1 | British Journal of Medical Practitioners". 2009. Retrieved September 8, 2018.
  63. "People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement". The ME Association. August 2010. Retrieved September 8, 2018.
  64. Stein, Rob (December 3, 2010). "Chronic fatigue patients barred from blood donation". ISSN 0190-8286. Retrieved September 8, 2018.
  65. "Detailed eligibility criteria". Retrieved September 8, 2018.
  66. George, John (December 2, 2009). "FDA rejects Hemispherx's chronic fatigue drug Ampligen". Retrieved August 12, 2018.
  67. Johnson, Cort (November 26, 2017). "Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails - Simmaron Research". Simmaron Research. Retrieved September 7, 2018.
  68. Montoya, Jose G.; Kogelnik, Andreas M.; Bhangoo, Munveer; Lunn, Mitchell R.; Flamand, Louis; Merrihew, Lindsey E.; Watt, Tessa; Kubo, Jessica T.; Paik, Jane (December 2013). "Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome". Journal of Medical Virology. 85 (12): 2101–2109. doi:10.1002/jmv.23713. ISSN 1096-9071. PMID 23959519.
  69. Bassett, Jodi (September 2010). "M.E.: The medical facts". The Hummingbirds' Foundation for M.E. Retrieved September 8, 2018.
  70. Bakken, Inger Johanne; Tveito, Kari; Gunnes, Nina; Ghaderi, Sara; Stoltenberg, Camilla; Trogstad, Lill; H åberg, Siri Eldevik; Magnus, Per (October 1, 2014). "Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012". BMC Medicine. 12 (1). doi:10.1186/s12916-014-0167-5. ISSN 1741-7015. PMID 25274261.
  71. Collin, Simon M.; Nuevo, Roberto; van de Putte, Elise M.; Nijhof, Sanne L.; Crawley, Esther (October 28, 2015). "Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts". BMJ open. 5 (10): e008830. doi:10.1136/bmjopen-2015-008830. ISSN 2044-6055. PMID 26510728.
  72. "Etiology and Pathophysiology | Presentation and Clinical Course | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. November 8, 2018. Retrieved February 17, 2019.
  73. 73.0 73.1 Dankaerts, Wim; Bruyninckx, Frans; Stalmans, Ingeborg; Vansant, Greet; Rasschaert, Ricky; Hulens, Mieke (December 10, 2018). "The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology". Journal of Pain Research. Retrieved February 17, 2019.
  74. 74.0 74.1 74.2 "Comorbid Conditions | Diagnosis | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. November 8, 2018. Retrieved February 26, 2019.
  75. Hoad, A.; Spickett, G.; Elliott, J.; Newton, J. (2008). "Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome". QJM: monthly journal of the Association of Physicians. 101 (12): 961–965. doi:10.1093/qjmed/hcn123. ISSN 1460-2393. PMID 18805903.
  76. 76.0 76.1 76.2 "Other Conditions for Evaluation | Diagnosis | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. November 8, 2018. Retrieved February 26, 2019.
  77. Bragée, Björn; Michos, Anastasios; Drum, Brandon; Fahlgren, Mikael; Szulkin, Robert; Bertilson, Bo C. (2020). "Signs of Intracranial Hypertension, Hypermobility, and Craniocervical Obstructions in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Frontiers in Neurology. 11. doi:10.3389/fneur.2020.00828. ISSN 1664-2295.