Myalgic encephalomyelitis
Myalgic Encephalomyelitis (ME) is a progressive, chronic, inflammatory, physically and neurologically disabling disease that presents with symptoms involving multiple bodily systems. Frequently triggered by a viral infection, it affects the central nervous system (CNS), autonomic nervous system (ANS), immune system, cardiovascular system, endocrine system, digestive system, and musculoskeletal system.[1][2] It has been classified by the World Health Organization (WHO) as a neurological disease since 1969[3][4] and has occurred in both epidemic and sporadic forms since at least the 1930s.
A hallmark symptom of ME is post-exertional malaise (PEM), which is an intolerance to previously achievable cognitive or physical exertion.[5][6][7][8][9][10] Other key symptoms include muscle weakness and easy fatiguability, sleep disturbance, and cognitive dysfunction. ANS dysfunction is frequent, although specific symptoms vary from patient to patient and may include postural orthostatic tachycardia (POTS), orthostatic hypotension (OI), 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).
Among adults, ME is more common in women than men. New onset has been observed in children and in adults as old as 80 years old. Its course is usually relapsing-remitting with new symptoms occurring either in discrete relapses (or 'crashes') or accruing over time.[11] There is a progressive form of ME but it is rarer than the relapsing-remitting type.[12]
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.[13]
ME is accurately diagnosed with the International Consensus Criteria (ICC) and a diagnosis should be made immediately. Other criterion such as the Canadian Consensus Criteria (CCC) and SEID cannot be used to diagnose immediately nor speak to the array and severity of CNS, neurological, ANS, and immune system symptoms patients experience.
Contents
- 1 History
- 2 Disease Name
- 3 Onset
- 4 Signs and Symptoms
- 5 Clinical Findings
- 6 Diagnosis
- 7 Course and Prognosis
- 8 Clinical Subtypes
- 9 Pathophysiology
- 10 Sex Differences
- 11 Risk Factors and Potential Causes
- 12 Treatments
- 13 Epidemiology
- 14 Co-morbidities
- 15 Notable studies
- 16 See also
- 17 Learn more
- 18 References
History[edit | edit source]
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]
- Myalgic adj. - of or relating to myalgia. Is muscle pain.[14]
- Myel: Relating to the spinal cord.[16]
- Itis: Inflammation.[17]
The name ME[18] was coined by Dr. Melvin Ramsay following the 1955 Royal Free Hospital outbreak[19] and is a portmanteau of several of the key signs and symptoms of the disease: myalgic (muscle pain), encephalo (brain), myel (spinal cord), itis (inflammation).[20] The central nervous system (brain and spinal cord) are inflamed.[21]
Several other names have been used or proposed throughout the history of the disease, including atypical polio, Icelandic disease, benign ME, epidemic neuromyasthenia, CFS, and systemic exertion intolerance disease (SEID). 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 case definitions.
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.[22]
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]
Following after an incubation period of 4 to 7 days, the prodromal phase generally involve a flu-like illness with low-grade fever. In the majority but not all cases, an infection or infectious process is evident.[23] 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.[24][1]
In some patients, the initial presentation involved a severe, incapacitating prolonged illness. In theirs, an apparent remission was followed by relapses brought on by exertion, menstrual period, or cold. In other patients there is no discernible triggering event.
Signs and Symptoms[edit | edit source]
Symptoms can range from mild to very severe and can include:
- low-grade fever, temperature instability
- muscle weakness and fatiguability
- myalgia (muscle pain)
- neck and back or spinal cord stiffness
- neuralgia (nerve pain)
- othostatic intolerance
- post-exertional malaise
- sensitivity to heat or cold
- sensitivity to light, sound and/or touch
- sleep dysfunction
Symptom presentation and severity can vary considerably day to day and even hour to hour.[1] Overexertion can exacerbate all symptoms, and Post Exertional Malaise often delayed by 24 hours or more.[25] [1] The US National Institutes of Health (NIH) notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.[26]
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 [27]
Post-exertional malaise[edit | edit source]
A core symptom, post-exertional malaise, is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.[5][6][7][8][9][10][28]
Clinical Findings[edit | edit source]
Although there is no definitive biomarker, several signs and findings have been frequently observed in clinical settings:- high antibody titers to specific infections (including EBV, HHV-6, and Coxsackie B among others)
- hormone imbalance
- immunological abnormalities
- low natural killer cell function
- low red blood cell magnesium
- natural killer cell (NKC)
- postural orthostatic tachychardia (POTS)
- reaction to physical and mental activity and sensory input (PEM)
Diagnosis[edit | edit source]
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.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 is the broadest and likely least discerning definition. (The US Institute of Medicine report called for its complete retirement.)[29] The US Centers for Disease Control's (CDC) Fukuda criteria, in use since 1994, is also overly broad.
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."[1] Additional testing may be needed to help distinguish ME from these other problems.
Course and Prognosis[edit | edit source]
ME relapses are often a result of over-activity, but can occur without warning with no obvious inciting factors. Exposure to increased sensory information in light, sound, and movement can provoke a sensory storm.
Infections, such as the common cold, influenza and gastroenteritis, also increase the risk for a relapse. Heat and cold can transiently increase symptoms.
Pregnancy can directly affect the susceptibility for relapse. Later pregnancy appears to offer a natural protection against relapses, and there are anecdotal reports of postpartum remission. However, pregnancy does not seem to influence long-term disability.
About 25% of patients become severe or very severely ill with ME.
Clinical Subtypes[edit | edit source]
Kerr et al proposed 7 different subsets for 'CFS' as it is defined today:[30][31]
- Subtype 1 This is one of the more severe subtypes. Effects are cognitive, musculoskeletal, sleep-related and anxiety/depression.
- Subtype 2 This is one of the more severe subtypes. Effects are musculoskeletal, pain and anxiety/depression.
- Subtype 3 This subtype has the mildest symptoms.
- Subtype 4 This subtype is dominated by cognitive issues.
- Subtype 5 Effects are musculoskeletal and gastrointestinal.
- Subtype 6 This subtype is dominated by post-exertional malaise (extreme crash after exercise or exertion.)
- Subtype 7 This is one of the more severe subtypes. Effects are pain, infections, musculoskeletal, sleep-related, neurological, gastrointestinal, neurocognitive and anxiety/depression.[30]
Pathophysiology[edit | edit source]
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]
Autonomic nervous system[edit | edit source]
Peripheral nervous system[edit | edit source]
Musculoskeletal system[edit | edit source]
Immune system[edit | edit source]
According to a strictly immunological explanation of CFS, the inflammatory processes triggered by T cells create leaks in the blood-brain barrier (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins such as Rnase-L. Channelopathy, a reduced ability to move metabolites in and out of cells has been implicated in this process. This may also be applicable to ME.
Chronic infection[edit | edit source]
Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the post-polio syndrome?].
Cardiovascular[edit | edit source]
Hemodynamic abnormalities are widely found, including serum and RBC hypovolemia, neurally mediated hypotension, (NMH) and cerebral hypoperfusion. Vascular and endothelial abnormalities have been published by MERUK. However, none of these studies used research criteria for ME so the results may not be applicable to ME.
Some cardiologic features such as cardiac insufficiency, inverted T-waves and myofiber disarray have been reported in CFS and recently added to by findings of reduced Q-value. This has led clinician and researcher Dr Paul Cheney to posit that CFS is form of partially compensated cardiomyopathy in which orthostatic intolerance and rapid fatiguability are secondary protective mechanisms. Due to the heterogeneity of the population, a single cause is unlikely, but one-third of people with ME have abnormalities when tested with Holter monitors.
Gastrointestinal system[edit | edit source]
Sex Differences[edit | edit source]
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.[32] 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."[33]
Risk Factors and Potential Causes[edit | edit source]
Risk factors[edit | edit source]
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.[34][35][36][37] 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.[38][39] 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.[40] 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.[41][42]
Viruses[edit | edit source]
Other theories describe ME as an immune response to a chronic infection. The association between ME and the Coxsackie B, HHV-6, and HHV-7 viruses[43][44] [45] 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.[46][47] Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.[48]
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.[49][50][51]
Treatments[edit | edit source]
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.[52] Other off label medications have been used with varying effectiveness in some patients.[53][54]
Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself.
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.[55]
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.[56] 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.[57] In children the sex ratio is approximately equal.[58]
Co-morbidities[edit | edit source]
Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions,[59] and increased risks for secondary diseases in patients with ME. 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 idiopathic intracranial hypertension (IH/IIH) are symptoms that can occur in or be co-morbid with numerous conditions, including ME.
The following are some syndromes and diseases that have been associated with or misdiagnosed as ME:
- fibromyalgia
- chronic Lyme disease
- postural orthostatic tachychardia syndrome
- mast cell activation disorder
- small intestinal bacterial overgrowth (SIBO)
- thyroid disease
- Ehlers-Danlos syndrome
- endometriosis
- Sjögren's syndrome
- mold illness
- multiple chemical sensitivity
- environmentally acquired illness
- chronic inflammatory response syndrome
- cancer
- idiopathic intracranial hypertension
- Chiari malformation
- craniocervical instability
- See more diagnoses.
Notable studies[edit | edit source]
- 2016, Metabolic features of chronic fatigue syndrome
- 2016, CDC Multi-site Clinical Assessment of CFS
- 2019, Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy
- List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis
See also[edit | edit source]
- Chronic fatigue syndrome
- ME/CFS
- Pediatric myalgic encephalomyelitis and chronic fatigue syndrome
- Severe and very severe ME
Generally accepted criteria for diagnosing ME/CFS and ME[edit | edit source]
- Canadian Consensus Criteria (CCC)[60] A diagnosis of moderate and severe forms of ME/CFS are accurately made using this criterion. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
- International Consensus Criteria (ICC)[61] This criterion will accurately diagnose myalgic encephalomyelitis (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, Fukuda, and SEID, which all require 6 months in adults.
- Systemic Exertion Intolerance Disease (SEID)[62] ME/CFS (SEID) is accurately diagnosed when the core symptoms are met. The Institute of Medicine report as 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.
Learn more[edit | edit source]
References[edit | edit source]
- ↑ 1.0 1.1 1.2 1.3 1.4 "Myalgic Encephalomyelitis - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved September 7, 2018.
- ↑ Petrison, Lisa (April 4, 2016). "Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations" (PDF). paradigmchange.me. Cite has empty unknown parameter:
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(help) - ↑ "History of chronic fatigue syndrome". Wikipedia. July 22, 2018.
- ↑ "Myalgic Encephalomyelitis - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved September 8, 2018.
- ↑ 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. Cite has empty unknown parameter:
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(help) - ↑ 6.0 6.1 Research Descriptions of M.E. - ME Action UK
- ↑ 7.0 7.1 Ramsey, Melvin (1986). "The Clinical Features of Myalgic Encephalomyelitis". www.cfids-me.org. Retrieved September 7, 2018. Cite has empty unknown parameter:
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(help) - ↑ 8.0 8.1 Dellwo, Adrienne (August 1, 2018). "What is Post-Exertional Malaise? Learn About a Key ME/CFS Symptom". Verywell Health. Retrieved September 7, 2018. Cite has empty unknown parameter:
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(help) - ↑ 9.0 9.1 "Think You Might Have Chronic Fatigue Syndrome? Here are The Symptoms". WebMD. Retrieved September 7, 2018.
- ↑ 10.0 10.1 Spotila, Jennifer (2010). "Post-Exertional Malaise in Chronic Fatigue Syndrome" (PDF). solvecfs.org. The CFIDS Association of America. Cite has empty unknown parameter:
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(help) - ↑ "Postexertion 'Crash,' not Fatigue per se, Marks Syndrome" (Login Needed). medscape.com. Cite has empty unknown parameter:
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(help) - ↑ Howes, S (July 7, 2015). "Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report" (PDF). meassocation.org. Physical Medicine and Rehabilitation - International – via Austin Publishers Group. Cite has empty unknown parameter:
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(help) - ↑ 13.0 13.1 Inc., Hemispherx Biopharma, (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. Cite has empty unknown parameter:
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(help)CS1 maint: extra punctuation (link) - ↑ "myalgic". TheFreeDictionary.com. Retrieved August 12, 2018.
- ↑ "encephalo-". TheFreeDictionary.com. Retrieved August 12, 2018.
- ↑ "myel-". TheFreeDictionary.com. Retrieved August 12, 2018.
- ↑ "Itis". TheFreeDictionary.com. Retrieved August 12, 2018. Cite has empty unknown parameter:
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(help) - ↑ Dellwo, Adrienne (July 23, 2018). "Myalgic Encephalomyelitis: Chronic Fatigue Syndrome's Other Name". Verywell Health. Retrieved August 12, 2018. Cite has empty unknown parameter:
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(help) - ↑ "An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955". British Medical Journal. 2 (5050): 895–904. October 19, 1957. ISSN 0007-1447. PMID 13472002.
- ↑ The Terminology of ME & CFS By Professor Malcolm Hooper
- ↑ 21.0 21.1 Dellwo, Adrienne (November 24, 2018). "Myalgic Encephalomyelitis or Chronic Fatigue Syndrome". Verywell Health. Retrieved November 28, 2018. Cite has empty unknown parameter:
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(help) - ↑ "#MEAction RFI Poll Report (Part 1 of 3) - #MEAction". #MEAction. August 7, 2016. Retrieved September 8, 2018.
- ↑ ME Definition - Nightingale - PDF pg. 6
- ↑ "Nightingale ME Definition En | Chronic Fatigue Syndrome | Infection". Scribd. p. 5. Retrieved September 8, 2018. Cite has empty unknown parameter:
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(help) - ↑ Research, Invest in ME. "Invest in ME Research - Invest in ME Research Home Page". www.investinme.org. Retrieved September 8, 2018.
- ↑ "Pathways to Prevention (P2P) Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)". Office of Disease Prevention. Retrieved September 8, 2018. Cite has empty unknown parameter:
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(help) - ↑ "Unrest - MEpedia". www.me-pedia.org. Retrieved August 12, 2018.
- ↑ "What is Post-Exertional Malaise? Learn About a Key ME/CFS Symptom". Verywell Health. Retrieved September 7, 2018.
- ↑ Swift, Penny. "US NIH Report Calls for UK Definition of ME/CFS to be Scrapped". theargusreport.com. Retrieved September 8, 2018. Cite has empty unknown parameter:
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(help) - ↑ 30.0 30.1 Kerr, JR; Burke, R; Petty, R; Gough, J; Fear, D; Mattey, D L; Axford, J S; Dalgleish, A G; Nutt, D J (May 30, 2008). "Seven genomic subtypes of chronic fatigue phenotypes analysis of gene networks and clinical syndrome/myalgic encephalomyelitis: a detailed" (PDF). me-ireland.com. JCP Online. doi:10.1136/jcp.2007.053553. Cite has empty unknown parameter:
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(help) - ↑ Kerr, J. R.; Burke, B.; Petty, R.; Gough, J.; Fear, D.; Mattey, D. L.; Axford, J. S.; Dalgleish, A. G.; Nutt, D. J. (June 1, 2008). "Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes". Journal of Clinical Pathology. 61 (6): 730–739. doi:10.1136/jcp.2007.053553. ISSN 0021-9746. PMID 18057078.
- ↑ 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.
- ↑ 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.
- ↑ Evans, Meredyth (August 23, 2015). "Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach". via.library.depaul.edu. Cite has empty unknown parameter:
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(help) - ↑ "Vagus nerve infection hypothesis - MEpedia". me-pedia.org. Retrieved September 8, 2018.
- ↑ "Case Presentation - Chronic Fatigue Syndrome". www.clevelandclinicmeded.com. Retrieved September 8, 2018.
- ↑ 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.
- ↑ 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.
- ↑ Schlauch, K A; Khaiboullina, S F; De Meirleir, K L; Rawat, S; Petereit, J; Rizvanov, A A; Blatt, N; Mijatovic, T; Kulick, D (2016). "Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome". Translational Psychiatry. 6 (2): e730–e730. doi:10.1038/tp.2015.208. ISSN 2158-3188.
- ↑ "Klimas ME CFS Genes Study". www.facebook.com. November 23, 2015. Retrieved September 8, 2018. Cite has empty unknown parameter:
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(help) - ↑ "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.
- ↑ 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). m-hikari.com. Cite has empty unknown parameter:
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(help) - ↑ 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.
- ↑ "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. Cite has empty unknown parameter:
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(help) - ↑ 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. 2012: 205085. doi:10.1155/2012/205085. ISSN 1687-8647. PMID 22927850.
- ↑ . John E.Tovey. "Chlamydia pneumoniae infection a treatable cause of Chronic Fatigue Syndrome". The BMJ. September 5, 2018.CS1 maint: others (link)
- ↑ "New ME/CFS Study at Stanford: Dr. Montoya to test for scores of Infections - Prohealth". Prohealth. June 4, 2010. Retrieved September 8, 2018.
- ↑ "Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioral, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 1 | British Journal of Medical Practitioners". www.bjmp.org. 2009. Retrieved September 8, 2018. Cite has empty unknown parameter:
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(help) - ↑ "People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement". www.meassociation.org.uk. August 2010. Retrieved September 8, 2018. Cite has empty unknown parameter:
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(help) - ↑ Stein, Rob (December 3, 2010). "Chronic fatigue patients barred from blood donation". ISSN 0190-8286. Retrieved September 8, 2018.
- ↑ "Detailed eligibility criteria". www.nzblood.co.nz. Retrieved September 8, 2018.
- ↑ George, John (December 2, 2009). "FDA rejects Hemispherx's chronic fatigue drug Ampligen". www.bizjournals.com. Retrieved August 12, 2018. Cite has empty unknown parameter:
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(help) - ↑ "Valganciclovir - MEpedia". www.me-pedia.org. Retrieved August 12, 2018.
- ↑ "Oxymatrine - MEpedia". www.me-pedia.org. Retrieved August 12, 2018.
- ↑ Johnson, Cort (November 26, 2017). "Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails - Simmaron Research". Simmaron Research. Retrieved September 7, 2018. Cite has empty unknown parameter:
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(help) - ↑ Bassett, Jodi (September 2010). "M.E.: The medical facts". The Hummingbirds' Foundation for M.E. Retrieved September 8, 2018. Cite has empty unknown parameter:
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(help) - ↑ 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.
- ↑ 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.
- ↑ "Overlapping Conditions – American ME and CFS Society". ammes.org. Retrieved August 12, 2018.
- ↑ 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, A C 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
- ↑ 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.
- ↑ Clayton, Ellen Wright; Alegría, Margarita; Bateman, Lucinda; Chu, Lily; Cleeland, Charles; Davis, Ronald; Diamond, Betty; Ganiats, Theodore; Keller, Betsy; Klimas, Nancy; Lerner, A Martin; Mulrow, Cynthia; Natelson, Benjamin; Rowe, Peter; Shelanski, Michael (2015). "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness" (PDF). nationacademies.org. Cite has empty unknown parameter:
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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.
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.
cognition Thought processes, including attention, reasoning, and memory.
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).
orthostatic intolerance (OI) - The development of symptoms when standing upright, where symptoms are relieved upon reclining. Patients with orthostatic intolerance have trouble remaining upright for more than a few seconds or a few minutes, depending upon severity. In severe orthostatic intolerance, patients may not be able to sit upright in bed. Orthostatic intolerance is often a sign of dysautonomia. There are different types of orthostatic intolerance, including postural orthostatic tachycardia syndrome (POTS).
flare-up A symptoms flare in ME/CFS is a temporary increase in symptoms, alternatively known as experiencing post-exertional malaise. May be referred to as a "crash" or "collapse".
immunomodulator An immunomodulator is a substance that affects the functioning of the immune system
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".
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.
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.
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.
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.
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.
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.
antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.
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.
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.
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.
flare-up A symptoms flare in ME/CFS is a temporary increase in symptoms, alternatively known as experiencing post-exertional malaise. May be referred to as a "crash" or "collapse".
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.
cognitive behavioral therapy (CBT) - A type of psychotherapy geared toward modifying alleged unhealthy thinking, behaviors or illness beliefs. One of the treatment arms used in the controversial PACE trial.
T cell A type of white blood cell which is mostly produced or matured in the thymus gland (hence T-cell) and is involved in the adaptive immune response on a cellular level. Also known as a T lymphocyte. (Learn more: www.youtube.com)
metabolite A chemical compound produced by, or involved in, metabolism. The term is often used to refer to the degradation products of drugs in the body.
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)
antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.
antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.
graded exercise therapy (GET) - A gradual increase in exercise or activity, according to a pre-defined plan. Focuses on overcoming the patient's alleged unhelpful illness beliefs that exertion can exacerbate symptoms, rather than on reversing physical deconditioning. Considered controversial, and possibly harmful, in the treatment or management of ME. One of the treatment arms of the controversial PACE trial.
serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)
cerebral 1. of or relating to the brain or the intellect 2. of, relating to, affecting, or being the cerebrum.
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.
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.
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.
BMJ 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.
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.