Myalgic encephalomyelitis

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Myalgic encephalomyelitis (ME) is a chronic, inflammatory, physical 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][2] 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.[1][3]

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

ME has occurred in both epidemic and sporadic forms.

According to the CDC the hallmark symptom of myalglc encephalomyelitis is post-exertional malaise (PEM), which is the worsening of ME/CFS symptoms after minimal physical, mental, or emotional effort.[5][6][7][8][3] Other key symptoms include muscle weakness and easy muscle fatigability, sleep disturbance, plus either orthostatic intolerance or cognitive dysfunction. Orthostic intolerance is autonomic nervous system dysfunction causing the worsening of symptoms when standing or sitting upright, and may include feeling faint, dizziness, feeling weak, blurred vision, postural orthostatic tachycardia (POTS), reduced heart rate variability at night, and both cold and heat intolerance. Other ME/CFS common symptoms include muscle pain, nerve pain, neck and spine stiffness, and sensory symptoms including sensitivity to light, sound, touch, 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.[2] New onset has been observed in children[10] and in adults usually between the ages of 40-60.[11] 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.[12]

There are no approved pharmacological treatments for ME anywhere in the world except in Argentina, which has approved the immunomodulator Ampligen (rintatolimod) for severe ME/CFS as of August 23, 2016.[13]

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. Image source: Wasteland (video) 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 and she appears in the documentary Forgotten Plague.

The World Health Organization's ICD-8 manual 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][14] 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.[15]:29

In the ICD-9, which was published in 1989, the entry for myalglc encephalomyelitis is uses code 323.9:[16]

Main article: History of myalgic encephalomyelitis and chronic fatigue syndrome

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 myalgic encephalomyelitis outbreak was caused by the 2019-2022 Coronavirus pandemic outbreak.

Disease name[edit | edit source]

Main article: Names of myalgic encephalomyelitis and chronic fatigue syndrome
Poster of breakdown of parts of the name myalgic encephalomyelitis

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.[18][17][19] 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).[17][20] The central nervous system (brain and spinal cord) are inflamed.[17]

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.[17][21][22] Merryn Crofts had very severe ME, was bedbound and unable to eat. Merryn weighed under six stone (84 lbs) at her death, and was just 21 years-old. Merryn's death certificate was the second in the UK to attribute a death to ME.[21]

Disease of a thousand names[edit | edit source]

Myalgic Encephalomyelitis has been referred to as the "disease of a thousand names".[23] 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).[23][15] 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.[17]

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.[24]

Myalgic encephalomyelitis (ME) was the original name for chronic fatigue syndrome (CFS); the names are sometimes used interchangeably or with the acronym ME/CFS.[20]

Onset[edit | edit source]

Main article: Onset of ME/CFS

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.[25] In the majority but not all cases, an infection or infectious process is evident.[25] 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.[26][25]

Signs and symptoms[edit | edit source]

Myalgic encephalomyelitis is a neurological disease that affects multiple bodily systems, causing a widespread combination of symptoms.[27] 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.[3][28] Overexertion can exacerbate all symptoms, and post-exertional malaise is often delayed by 24 hours or more.[3] The US National Institutes of Health (NIH) notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.[29]

Post-exertional malaise[edit | edit source]

Main article: Post-exertional malaise

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.[1][3]

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 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

Some studies show that patients who have been ill for longer are more likely to uave severe ME/CFS. ME/CFS oftens becomes more severe when patients try to push through their symptoms and continue to repeatedly exceed their personal physical or cognitive limits, for instance by attempting to keep working, which typically entails anaerobic activity.[30][31]

Clinical findings[edit | edit source]

Main article: List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis
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
Main article: Definitions of myalgic encephalomyelitis and chronic fatigue syndrome

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 and has been retired due to the risk of many different fatiguing illnesses being misdiagnosed as chronic fatigue syndrome.[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.[27] The CCC requires neurological, autonomic, neuroendocrine, immune system, and myalgia symptoms to meet its ME/CFS diagnostic criteria.[7]

Differential diagnosis[edit | edit source]

The signs and symptoms of myalgic encephalomyelitis can be similar to other medical illnesses, including cancer, multiple sclerosis, lupus, Hashimoto's thyroiditis (hypothyroidism), diabetes mellitus, brucellosis, anemia and others.[46][7] Standard medical tests are needed to help distinguish ME from these other illnesses, and additional testing may also be needed.[45][46][47]

Course and prognosis[edit | edit source]

Main article: Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome

The prognosis for myalgic encephalomyelitis and chronic fatigue syndrome (ME and CFS) is considered to be poor with only a small minority (a median estimate of 5%) returning to pre-morbid levels of functioning.[48] The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients[49] and the prognosis in adolescents is considered to be better than in adults.[50][51]

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
Main article: List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis

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 forcibly taken to a mental hospital in 2003. An independent neuropathologist found Sophia's spine contained a massive inflammation. Her death certificate was the first in the UK to attribute a death to CFS.[30]
Main article: Central nervous system

Autonomic nervous system[edit | edit source]

Main article: Autonomic nervous system

Cardiovascular[edit | edit source]

Main article: Cardiovascular system

Gastrointestinal system[edit | edit source]

Main article: Gastrointestinal system

Immune system[edit | edit source]

Main article: Immune system

Musculoskeletal system[edit | edit source]

Main article: Muscle

Peripheral nervous system[edit | edit source]

Main article: Peripheral nervous system

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
Main article: Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome

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.[12] 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."[52]

Risk factors and potential causes[edit | edit source]

Main article: Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome

Genetic risks[edit | edit source]

Myalgic encephalomyelitis and chronic fatigue syndrome have been reported to run in families, although ME and CFS are not considered inherited illnesses, there is evidence of a genetic predisposition.[53][54][55]

Main article: Genetics of chronic fatigue syndrome

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.[56][57] 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.[58][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.[59][60] 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.[61][62]

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]

Main article: Virus

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[63][64][65] suggests a potential viral contribution in at least some individuals. Some researchers have stated that evidence from epidemic myalgic encephalomyelitis strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.[36][66]

Bacteria[edit | edit source]

Main article: Bacteria

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.[67][68] Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.[69]

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.[citation needed]

Transmission via blood[edit | edit source]

Main article: Blood donation

Given the uncertainty regarding the cause, ME and CFS patients are barred from [donating blood or organs in the United Kingdom (even after recovery),[70] most of Canada,[71] Australia,[72][73] New Zealand (while symptoms persist), and and for a time also in the United States.[74][75][76]

In the US, the American Association of Blood Banks advises to either accept or defer ME/CFS donors based on "clinical judgment of the donor's health status".[77] Patient charities discourage ME/CFS patients from donating blood,[78]

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
Main article: Treatments

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.[13] However the effectiveness of Ampligen is under dispute.[79] Other medications have been used off-label for ME with varying effectiveness in some patients.[7][27]

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.[27]

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.[80] The antiviral Valganciclovir failed in a controlled nine month study against ME patients positive for Herpes Simplex 6 and Epstein Barr viral infections.[81]

Epidemiology[edit | edit source]

Main article: Epidemiology of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome

ME has been found world-wide, in at least 75 epidemics documented in published papers from the 1930s to the 1980s.[82] 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.[12] In children the sex ratio is approximately equal.[52]

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)
Main article: Comorbidities of Myalgic Encephalomyelitis

Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions, and increased risks for secondary diseases in patients with ME.[7][3] 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.[39][83]

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.[86]

Notable studies[edit | edit source]

Main article: Notable studies

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.

News and articles[edit | edit source]

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 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
  2. ↑ 2.0 2.1 "Possible Causes | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. January 18, 2019. Retrieved April 13, 2019.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Symptoms | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. May 18, 2018. Retrieved November 21, 2018.
  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. ↑ "Information for Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. December 27, 2021. Retrieved March 28, 2022.
  6. ↑ Friedman, Kenneth J.; Murovska, Modra; Pheby, Derek F.H.; Zalewski, Paweł (March 2021). "Our Evolving Understanding of ME/CFS". Medicina. 57 (3): 200. doi:10.3390/medicina57030200. ISSN 1648-9144. PMID 33652622.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 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
  8. ↑ Speight, Nigel (2013). "Myalgic encephalomyelitis/chronic fatigue syndrome: Review of history, clinical features, and controversies". Saudi J Med Med Sci. 1 (1): 11–13. doi:10.4103/1658-631x.112905.
  9. ↑ Howes, S; Goudsmit, EM (July 7, 2015). "Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report" (PDF). Physical Medicine and Rehabilitation - International. 2 (6): 1052.
  10. ↑ "ME/CFS in Children | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. January 18, 2019. Retrieved April 13, 2019.
  11. ↑ "What is ME/CFS? | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. January 18, 2019. Retrieved April 13, 2019.
  12. ↑ 12.0 12.1 12.2 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.
  13. ↑ 13.0 13.1 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.
  14. ↑ World Health Organization (2016). "G93 Other diseases of the nervous system - ICD-10 Version:2016". World Health Organization. Retrieved April 13, 2019.
  15. ↑ 15.0 15.1 15.2 Institute of Medicine (2015). Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington, DC: The National Academies Press. doi:10.17226/19012.
  16. ↑ 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.
  17. ↑ 17.0 17.1 17.2 17.3 17.4 17.5 17.6 17.7 17.8 Hooper, Malcolm. "The Terminology of ME & CFS".
  18. ↑ "A new clinical entity?" (PDF). Lancet. 1: 789–790. 1956.
  19. ↑ Ramsay, A. Melvin (October 30, 1965). "Hysteria and "Royal Free Disease."". British Medical Journal. 2 (5469): 1062. ISSN 0007-1447. PMC 1847119.
  20. ↑ 20.0 20.1 Smith, David G (1989). Understanding M.E.: The Phenomenon of Myalgic Encephalomyelitis and Acute Onset Post Viral Fatigue Syndrome. p. 20.
  21. ↑ 21.0 21.1 Taylor, Jim (July 27, 2018). "'Vindication' for woman who wanted ME on death certificate". BBC Radio 5 Live.
  22. ↑ 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
    Inclusions
    chronic fatigue syndrome
    myalgic encephalomyelitis
    Exclusions
    Fatigue (MG22)
  23. ↑ 23.0 23.1 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.
  24. ↑ "#MEAction RFI Poll Report (Part 1 of 3) - #MEAction". #MEAction. August 7, 2016. Retrieved September 8, 2018.
  25. ↑ 25.0 25.1 25.2 Evans, Meredyth; Jason, Leonard (2018). "Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis" (PDF). Research on Chronic diseases. 2 (1): 2–3.
  26. ↑ Hyde, Byron (2016), The Nightingale Research Foundation Definition of Myalgic Encephalomyelitis (M.E.), IACFS/ME
  27. ↑ 27.0 27.1 27.2 27.3 27.4 27.5 27.6 27.7 27.8 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.1365q-2796.2011.02428.x. ISSN 0954-6820. PMC 3427890. PMID 21777306.
  28. ↑ International Association for Chronic Fatigue Syndrome / Myalgic Encephalomyelitis; Friedberg, Fred; Bateman, Lucinda; Bested, Alison C; Davenport, Todd; Friedman, Kenneth J; Gurwitt, Alan R; Jason, Leonard A; Lapp, Charles W; Stevens, Staci R; Underhill, Rosemary A; Vallings, Rosamund (2014), Chronic Fatigue Syndrome Myalgic Encephalomyelitis Primer for Clinical Practitioners (PDF), Chicago, USA: International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, The illness can vary from mild to severe, with symptoms that may fluctuate significantly from hour to hour and day to day.
  29. ↑ "ME/CFS - Pathways to Prevention - Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". National Institutes of Health. December 8, 2016. Retrieved March 28, 2022. Effects of the illness can range from moderate to debilitating, and can substantially impact everyday functioning. Routine daily activities such as cooking meals, brushing teeth, and caring for children become difficult. Additionally, sensitivity to environmental factors (e.g., noise, light, chemicals) may force many individuals with ME/CFS into seclusion or withdrawal from society.
  30. ↑ 30.0 30.1 Vink, Mark (September 10, 2015). "The Aerobic Energy Production and the Lactic Acid Excretion are both Impeded in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Journal of Neurology and Neurobiology (ISSN 2379-7150). 1. doi:10.16966/2379-7150.112.
  31. ↑ Vink, Mark; Vink-Niese, Alexandra (September 20, 2019). "Work Rehabilitation and Medical Retirement for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. A Review and Appraisal of Diagnostic Strategies". Diagnostics. 9 (4): 124. doi:10.3390/diagnostics9040124. ISSN 2075-4418. People with ME/CFS often feel under pressure to continue working when they first become ill or when their symptoms worsen. Unfortunately, trying to push through this illness is counterproductive, potentially causing longer sickness absences and slower recovery.
  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. ↑ 36.0 36.1 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. ↑ 39.0 39.1 "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.
  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". ammes.org. 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. ↑ Haney, Elizabeth; Smith, M.E. Beth; McDonagh, Marian; Pappas, Miranda; Daeges, Monica; Wasson, Ngoc; Nelson, Heidi D. (June 16, 2015). "Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop". Annals of Internal Medicine. 162 (12): 834. doi:10.7326/m15-0443. ISSN 0003-4819.
  44. ↑ "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm". nationalacademies.org. 2015.
  45. ↑ 45.0 45.1 "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness: Clinicians' Guide" (PDF). National Academies. 2015.
  46. ↑ 46.0 46.1 46.2 46.3 46.4 "Other Conditions for Evaluation | Information for Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. July 12, 2018. Retrieved March 28, 2022.
  47. ↑ "Evaluation | Information for Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. April 28, 2021. Retrieved April 1, 2022.
  48. ↑ Cairns, R.; Hotopf, M. (January 2005). "A systematic review describing the prognosis of chronic fatigue syndrome". Occupational Medicine (Oxford, England). 55 (1): 20–31. doi:10.1093/occmed/kqi013. ISSN 0962-7480. PMID 15699087.
  49. ↑ Joyce, J.; Hotopf, M.; Wessely, S. (March 1997). "The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review". QJM: monthly journal of the Association of Physicians. 90 (3): 223–233. ISSN 1460-2725. PMID 9093600.
  50. ↑ "Prognosis | Presentation and Clinical Course | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. July 10, 2018. Retrieved October 28, 2018.
  51. ↑ Rowe, Peter C.; Underhill, Rosemary A.; Friedman, Kenneth J.; Gurwitt, Alan; Medow, Marvin S.; Schwartz, Malcolm S.; Speight, Nigel; Stewart, Julian M.; Vallings, Rosamund (2017). "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer". Frontiers in Pediatrics. 5. doi:10.3389/fped.2017.00121. ISSN 2296-2360.
  52. ↑ 52.0 52.1 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.
  53. ↑ 53.0 53.1 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. ↑ Dibble, Joshua J; McGrath, Simon J; Ponting, Chris P (August 3, 2020). "Genetic risk factors of ME/CFS: a critical review". Human Molecular Genetics. 29 (R1): R117–R124. doi:10.1093/hmg/ddaa169. ISSN 0964-6906. PMC 7530519. PMID 32744306.
  55. ↑ Hajdarevic, Riad; Lande, Asgeir; Mehlsen, Jesper; Rydland, Anne; Sosa, Daisy D.; Strand, Elin B.; Mella, Olav; Pociot, Flemming; Fluge, Øystein; Lie, Benedicte A.; Viken, Marte K. (May 1, 2022). "Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential risk loci". Brain, Behavior, and Immunity. 102: 362–369. doi:10.1016/j.bbi.2022.03.010. ISSN 0889-1591.
  56. ↑ Rasa, Santa; Nora-Krukle, Zaiga; Henning, Nina; Eliassen, Eva; Shikova, Evelina; Harrer, Thomas; Scheibenbogen, Carmen; Murovska, Modra; Prusty, Bhupesh K.; European Network on ME/CFS (EUROMENE) (October 1, 2018). "Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)". Journal of Translational Medicine. 16 (1). doi:10.1186/s12967-018-1644-y. ISSN 1479-5876. PMID 30285773.
  57. ↑ 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.
  58. ↑ 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.
  59. ↑ Sotzny, Franziska; Blanco, Julià; Capelli, Enrica; Castro-Marrero, Jesús; Steiner, Sophie; Murovska, Modra; Scheibenbogen, Carmen (2018). "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease". Autoimmunity Reviews. 17 (6): 601-609. doi:10.1016/j.autrev.2018.01.009.
  60. ↑ "Klimas ME CFS Genes Study". facebook.com. November 23, 2015. Retrieved September 8, 2018.
  61. ↑ "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.
  62. ↑ Hardcastle, S.L.; Brenu, E.W.; Staines, D.R.; Marshall-Gradisnik, S. (2014). "Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells" (PDF). Biological Markers and Guided Therapy. 1 (1=): 25. doi:10.12988/bmgt.2014.3122.
  63. ↑ 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.
  64. ↑ "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.
  65. ↑ 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.
  66. ↑ O'Neal, Adam J.; Hanson, Maureen R. (2021). "The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review". Frontiers in Medicine. 8: 688486. doi:10.3389/fmed.2021.688486/abstract. ISSN 2296-858X.
  67. ↑ Tovey, JE (September 5, 2018). "Chlamydia pneumoniae infection a treatable cause of Chronic Fatigue Syndrome". The BMJ.
  68. ↑ "New ME/CFS Study at Stanford: Dr. Montoya to test for scores of Infections - Prohealth". Prohealth. June 4, 2010. Retrieved September 8, 2018.
  69. ↑ Nicolson, Garth L.; Haier, Jörg (2009). "Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioral, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 1". British Journal of Medical Practitioners. 2 (4): 20–28.
  70. ↑ "Knowledgebase". My Donor Record - Health, Eligibility & Travel. Retrieved October 8, 2021.
  71. ↑ Wilson, Kumanan; Atkinson, Katherine; Keelan, Jennifer (April 8, 2014). "The Use of Preliminary Scientific Evidence in Public Health: A Case Study of XMRV". PLOS Medicine. 11 (4): e1001623. doi:10.1371/journal.pmed.1001623. ISSN 1549-1676. PMC 3979645. PMID 24714396.
  72. ↑ "Chronic Fatigue Syndrome". Australian Red Cross. Retrieved November 17, 2023.
  73. ↑ "Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?". Australian Red Cross. Retrieved May 25, 2022.
  74. ↑ Stein, Rob (December 3, 2010). "Red Cross bars chronic fatigue patients from donating blood". Washington Post. Retrieved May 25, 2022.
  75. ↑ Stein, Rob (December 3, 2010). "Chronic fatigue patients barred from blood donation". Washington Post. ISSN 0190-8286. Retrieved September 8, 2018.
  76. ↑ "Detailed eligibility criteria". NZ Blood. Retrieved September 8, 2018.
  77. ↑ American Association of Blood Banks (October 2012). "Xenotropic Murine Leukemia Virus-Related Virus (XMRV) and other Polytropic Murine Leukemia Viruses (pMLV)" (PDF). p. 3. Retrieved May 25, 2022. An updated AABB Association Bulletin #12-05 (November 2012) states that individual collectors of blood and cellular therapy products should accept or defer donors with a history of CFS based on their clinical judgment of the donor's health status.
  78. ↑ "AABB's recommendation on ME/CFS and blood donation". Massachusetts ME/CFS & FM Association. November 25, 2015. Retrieved May 25, 2022.
  79. ↑ George, John (December 2, 2009). "FDA rejects Hemispherx's chronic fatigue drug Ampligen". bizjournals.com. Retrieved August 12, 2018.
  80. ↑ Johnson, Cort (November 26, 2017). "Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails - Simmaron Research". Simmaron Research. Retrieved September 7, 2018.
  81. ↑ 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.
  82. ↑ Bassett, Jodi (September 2010). "M.E.: The medical facts". The Hummingbirds' Foundation for M.E. Retrieved September 8, 2018.
  83. ↑ 83.0 83.1 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.
  84. ↑ 84.0 84.1 84.2 "Comorbid Conditions | Diagnosis | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Centers for Disease Control and Prevention. November 8, 2018. Retrieved February 26, 2019.
  85. ↑ 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.
  86. ↑ 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.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

central nervous system (CNS) - One of the two parts of the human nervous system, the other part being the peripheral nervous system. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system consists of nerves that travel from the central nervous system into the various organs and tissues of the body.

World Health Organization (WHO) - "A specialized agency of the United Nations that is concerned with public health. It was established on 7 April 1948, and is headquartered in Geneva, Switzerland. The WHO is a member of the United Nations Development Group. Its predecessor, the Health Organization, was an agency of the League of Nations." The International Statistical Classification of Diseases and Related Health Problems (ICD) is maintained by WHO.

See World Health Organization.

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

See post-exertional malaise.

See postural orthostatic tachycardia syndrome.

postural orthostatic tachycardia syndrome (POTS) - A form of orthostatic intolerance where the cardinal symptom is excessive tachycardia due to changing position (e.g. from lying down to sitting up).

An immunomodulator is a substance that affects the functioning of the immune system[1]

immunomodulator An immunomodulator is a substance that affects the functioning of the immune system

International Classification of Diseases (ICD) - A system of medical diagnostic codes, created by the World Health Organization (WHO), to classify diseases and other health related conditions for the purpose of international diagnostic consistency. By having common diagnostic codes around the world, health researchers are better able to quantify and track disease burdens. The most current version is called ICD-11. (Learn more: www.who.int)

See International Classification of Diseases.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) - Chronic Fatigue and Immune Dysfunction Syndrome is another term for Chronic Fatigue Syndrome, but one which emphasizes the immunological aspects of the disease. Popular in the 1990s, this term has apparently fallen into disuse.

See Chronic Fatigue and Immune Dysfunction Syndrome.

systemic exertion intolerance disease (SEID) - A term for ME/CFS that aims to avoid the stigma associated with the term "chronic fatigue syndrome", while emphasizing the defining characteristic of post-exertional malaise (PEM). SEID was defined as part of the diagnostic criteria put together by the Institute of Medicine (IOM) report of 10 February 2015.

See systemic exertion intolerance disease.

See National Institutes of Health.

National Institutes of Health (NIH) - A set of biomedical research institutes operated by the U.S. government, under the auspices of the Department of Health and Human Services.

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

somatic symptom disorder A psychiatric term to describe an alleged condition whereby a person's thoughts somehow cause physical symptoms. The actual existence of such a condition is highly controversial, due to a lack of scientific evidence. It is related to other psychiatric terms, such as "psychosomatic", "neurasthenia", and "hysteria". Older terms include "somatization", "somatoform disorder", and "conversion disorder". Such terms refer to a scientifically-unsupported theory that claims that a wide range of physical symptoms can be created by the human mind, a theory which has been criticized as "mind over matter" parapsychology, a pseudoscience.

See somatic symptom disorder.

cognition Thought processes, including attention, reasoning, and memory.

PACE trial A controversial study which claimed that CBT and GET were effective in treating "CFS/ME", despite the fact that its own data did not support this conclusion. Its results and methodology were widely disputed by patients, scientists, and the peer-reviewed scientific literature.

International Consensus Criteria (ICC) - A set of diagnostic criteria, based on the Canadian Consensus Criteria, that argued for the abandonment of the term "chronic fatigue syndrome" and encouraged the sole use of the term "myalgic encephalomyelitis".

See International Consensus Criteria.

See Canadian consensus criteria.

Canadian Consensus Criteria (CCC) - A set of diagnostic criteria used to diagnose ME/CFS, developed by a group of practicing ME/CFS clinicians in 2003. The CCC is often considered to be the most complex criteria, but possibly the most accurate, with the lowest number of patients meeting the criteria. Led to the development of the International Consensus Criteria (ICC) in 2011.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

See Centers for Disease Control and Prevention.

National Academy of Medicine (NAM) - An American non-profit, non-governmental organization which provides expert advice to governmental agencies on issues relating to biomedical science, medicine and health. Formerly known as the Institute of Medicine (IOM).

relating to hormones that influence the nervous system[2]

neuroendocrine relating to hormones that influence the nervous system

central nervous system (CNS) - One of the two parts of the human nervous system, the other part being the peripheral nervous system. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system consists of nerves that travel from the central nervous system into the various organs and tissues of the body.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

brainstem Region of the midbrain in adults, includes midbrain, pons, and medulla oblongata and develops.

somatic symptom disorder A psychiatric term to describe an alleged condition whereby a person's thoughts somehow cause physical symptoms. The actual existence of such a condition is highly controversial, due to a lack of scientific evidence. It is related to other psychiatric terms, such as "psychosomatic", "neurasthenia", and "hysteria". Older terms include "somatization", "somatoform disorder", and "conversion disorder". Such terms refer to a scientifically-unsupported theory that claims that a wide range of physical symptoms can be created by the human mind, a theory which has been criticized as "mind over matter" parapsychology, a pseudoscience.

See somatic symptom disorder.

phase three Last phase of clinical trials before a drug can be approved for public use. Whereas Phase one assesses basic safety, and Phase two assesses basic efficacy, Phase three uses many trial participants to fully assess both safety and efficacy, and overall benefit/risk.

BMJ The BMJ (previously the British Medical Journal) is a weekly peer-reviewed medical journal.

chronic disease a disease or condition that usually lasts for 3 months or longer and may get worse over time. Chronic diseases are long-term (typically incurable and requiring long-term management) but are not necessarily severe.

somatic symptom disorder A psychiatric term to describe an alleged condition whereby a person's thoughts somehow cause physical symptoms. The actual existence of such a condition is highly controversial, due to a lack of scientific evidence. It is related to other psychiatric terms, such as "psychosomatic", "neurasthenia", and "hysteria". Older terms include "somatization", "somatoform disorder", and "conversion disorder". Such terms refer to a scientifically-unsupported theory that claims that a wide range of physical symptoms can be created by the human mind, a theory which has been criticized as "mind over matter" parapsychology, a pseudoscience.

The BMJ (previously the British Medical Journal) is a weekly peer-reviewed medical journal.

BMJ The BMJ (previously the British Medical Journal) is a weekly peer-reviewed medical journal.

genome an organism's complete set of DNA, including all of its genes

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

BMJ The BMJ (previously the British Medical Journal) is a weekly peer-reviewed medical journal.

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