Myalgic encephalomyelitis

Myalgic encephalomyelitis (ME) is a chronic, inflammatory, physically and neurologically disabling immune mediated disease that presents with symptoms involving multiple bodily systems. It is frequently triggered by a viral infection or a flu-like illness. 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. It is classified by the World Health Organization (WHO) as a neurological disease in 1969.

ME has occurred in both epidemic and sporadic forms.

A hallmark symptom of ME is post-exertional malaise (PEM), which is an intolerance to previously achievable cognitive or physical exertion. 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), reduced heart rate variability at night, and both cold and heat intolerance. Other common symptoms include myalgia (muscle pain), neuralgia (neuropathic pain), neck and spine stiffness, and sensory symptoms including sensitivity to light, sound, touch, paraesthesia (skin tingling or numbness) and hyperaesthesia (skin sensitivity and pain, and allodynia). There is a progressive form of ME, but it is rarer than the relapsing-remitting type.

Among adults, ME is more common in women than men. New onset has been observed in children and in adults usually between the ages of 40-60. 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.

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.

Linda Crowhurst is married to Greg Crowhurst; they reside in Belfast, Northern Ireland. Greg is Linda's full-time carer as she is very severely ill with ME. As of June 2018, Linda has been ill for 25 years. This image is a still from the video Wasteland which visually documents Linda's very severe ME. Greg posted a YouTube video in 2006 (reposted in 2007) of Linda speaking of her condition and showing her neurological symptoms which are the first known public visual document of very severe ME. She is now bedbound barely able to move and unable to feed herself

Jennie Spotila is an American ME patient who fell ill on October 6, 1994. Jennie is disabled, mostly housebound, and uses a wheelchair but has been an ME/CFS advocate for many years. She writes the blog Occupy M.E. She served on the Board of Directors of The CFIDS Association of America and testified before the CFSAC

History

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

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 putative outbreak was in Arizona in 1996. 

Disease name

Merryn Crofts was bedbound and unable to eat. Merryn weighed six stone (84 lbs) at her death; her autopsy revealed inflammation of the dorsal root ganglia. It is suspected that in the later years of her illness Merryn also suffered from EDS and MCAD. Her death certificate is the 2nd in the UK to attribute a death to ME

Main article: Names of myalgic encephalomyelitis and chronic fatigue syndrome

• Myalgic adj. - of or relating to myalgia. Is muscle pain.

• Encephalo: Refers to the brain.

• Myel: Relating to the spinal cord.

• Itis: Inflammation.

The name ME was coined by Dr. Melvin Ramsay following the 1955 Royal Free Hospital outbreak 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). The central nervous system (brain and spinal cord) are inflamed.

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.

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

Onset

Main article: Onset of ME/CFS

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. 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.

Signs and symptoms

Symptoms can range from mild to very severe and can include:

Jennifer Brea is an American who was attending Harvard and while on a trip to Kenya she became very ill and never recovered. Brea began experiencing neurological problems. Her neurologist diagnosed her with "conversion disorder" (hysteria). When walking home from his office, she collapsed. Jen now needs to use a wheelchair keeping 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

• ataxia (coordination difficulties)

• cognitive dysfunction
• fatigability
• gastrointestinal symptoms
• headache

• 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. Overexertion can exacerbate all symptoms, and post-exertional malaise often delayed by 24 hours or more. The US National Institutes of Health (NIH) notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.

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

Post-exertional malaise

Main article: Post-exertional malaise

A core symptom, post-exertional malaise (PEM), 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.

Clinical findings

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:

• 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
• postural orthostatic tachychardia (POTS)
• physical and mental exertion, sensory input cause relapse (PEM)

Diagnosis

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.

Other diagnostic criteria

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.) 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, it cannot speak to 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. The CCC requires neurological, autonomic, neuroendocrine, immune system, and myalgia symptoms to meet its ME/CFS diagnostic criteria.

Differential diagnosis

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

Course and prognosis

Main article: Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome

Clinical subtypes

Kerr et al proposed 7 different subsets for 'CFS' as it is defined today:

Whitney Dafoe is an American photographer who has a very severe form of ME. Whitney can no longer speak or handle contact with anyone but his parents. His father is Ron Davis, a world-renowned geneticist who is working to solve his son's disease

• 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.

Pathophysiology

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

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

Main article: Central nervous system

Autonomic nervous system

Main article: Autonomic nervous system

Cardiovascular

Main article: Cardiovascular system

Gastrointestinal system

Main article: Gastrointestinal system

Immune system

Main article: Immune system

Musculoskeletal system

Main article: Muscle

Peripheral nervous system

Main article: Peripheral nervous system

Sex differences

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. 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."

Risk factors and potential causes

Main article: Risk factors and potential causes of myalgic encephalomyelitis and chronic fatigue syndrome

Risk factors

Potential causes

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. 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. 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. 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.

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

Main article: Viruses

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 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

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. Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.

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.

Treatments

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: Potential treatments for myalgic encephalomyelitis and chronic fatigue syndrome

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. However the effectiveness of Ampligen is under dispute. Other off label medications have been used with varying effectiveness in some patients.

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.

Epidemiology

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. 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. In children the sex ratio is approximately equal.

Co-morbidities

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

Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions, and increased risks for secondary diseases in patients with ME. 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.

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

• fibromyalgia
• chronic Lyme disease
• idiopathic intracranial hypertension
• postural orthostatic tachychardia syndrome
• irritable bowel syndrome
• thyroid disease
• Ehlers-Danlos syndrome
• Sjögren's syndrome
• multiple chemical sensitivity

Notable studies

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.

• 2014, Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder

• 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

• Chronic fatigue syndrome
• ME/CFS
• Pediatric myalgic encephalomyelitis and chronic fatigue syndrome
• Severe and very severe ME

• Systemic Exertion Intolerance Disease

Generally accepted criteria for diagnosing ME/CFS and ME

• Canadian Consensus Criteria (CCC) 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) 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) 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

References

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).

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

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.

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.

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".

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.

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).

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.

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.

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.

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.