History of myalgic encephalomyelitis and chronic fatigue syndrome

Myalgic encephalomyelitis has occurred in both epidemic and sporadic form since at least the 1930s, although is probably much older. The name myalgic encephalomyelitis in an editorial in the Lancet, in 1956, when describing the 1955 Royal Free Hospital outbreak in London, UK. 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 myalgic encephalomyelitis 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. The most recent was putative outbreak was in Arizona in 1996.

19th century
Several descriptions of illness resembling those of chronic fatigue syndrome have been reported for at least two hundred years. In the 19th century, neurologist George Miller Beard popularized the concept of neurasthenia, with symptoms including fatigue, anxiety, headache, impotence, neuralgia and depression. The concept of neurasthenia remained popular well into the middle of the 20th century, eventually coming to be seen as a behavioral or psychiatric fatigue condition rather than physical disease, with the diagnosis excluding cases of Postviral Fatigue Syndrome. Neurasthenia has since largely been abandoned as a medical diagnosis. In the 1990s, the ICD-10 manual of the World Health Organization categorized neurasthenia under F48 Other neurotic disorders, which specifically excluded chronic fatigue syndrome, and Postviral Fatigue Syndrome / Myalgic Encephalomyelitis / Chronic Fatigue Syndrome classed under "Diseases of the Nervous System".

Epidemic myalgic encephalomyelitis (1930s-1960s)
In 1938, Alexander Gilliam described an illness that resembled poliomyelitis, interviewing patients and reviewing records of one of several clusters which had occurred in Los Angeles, United States in 1934. The Los Angeles County Hospital outbreak included all or most of its nurses and doctors. Gilliam called the outbreak "atypical poliomyelitis" and described the symptoms as: rapid muscle weakness, vasomotor instability, clonic twitches and cramps, ataxia, severe pain (usually aggravated by exercise), neck and back stiffness, menstrual disturbance and dominant sensory involvement.

Novices and convent candidates at a Wisconsin convent were diagnosed with "encephalitis" in 1936. Two towns in Switzerland had outbreaks of "abortive poliomyelitis" in 1937, and 73 Swiss soldiers were given the same diagnosis in 1939. Outbreaks in Iceland were called "Akureyri disease" or "simulating poliomyelitis" and were later called "Iceland disease." Eight hundred people in Adelaide, Australia became ill during 1949-1951 with a disease "resembling poliomyelitis." Two smaller clusters in the United States during 1950 were diagnosed as "Epidemic neuromyasthenia" and "resembling Iceland disease simulating acute anterior poliomyelitis." Additional outbreaks of poliomyelitis-like "mystery diseases" occurred from the 1950s through the 1980s, in Denmark, the United States, South Africa, and Australia, among others.

Several outbreaks of a polio-resembling illness occurred in Britain in the 1950s. A 1955 outbreak at the Royal Free Hospital Group was later called Royal Free disease or benign myalgic encephalomyelitis. After the Royal Free Hospital outbreak, a disorder with similar symptoms was found among the general population and the epidemic form came to be considered the exception. Pathology findings, from both monkeys intentionally infected with biological fluids from patients and from rare human casualties, led to the conclusion that the disorder was caused by inflammation of the brain and the spinal cord, particularly the afferent nerve roots, perhaps with neuroimmune disease etiology.

Mass hysteria (1960s-1970s)
In the 1960s and 1970s, chronic fatigue symptoms were often attributed to chronic brucellosis, but typically people were seen as having psychiatric disorders, in particular depression. Epidemic cases of benign myalgic encephalomyelitis were called mass hysteria by psychiatrists McEvedy and Beard in 1970, provoking criticism in letters to the editor of the British Medical Journal by outbreak researchers, attending physicians, and physicians who fell ill. The psychiatrists were faulted for not adequately investigating the patients they described, and their conclusions have been refuted. In 1978 a symposium held at the UK's Royal Society of Medicine concluded that epidemic myalgic encephalomyelitis was a distinct disease entity with a clear organic basis.

Neurological classification
Myalgic encephalomyelitis was first classified as a neurological disease when the World Health Organization published the of ICD-8 classification manual in 1969. Myalgic encephalomyelitis was given ICD-8 code 323, and grouped with the other forms of encephalomyelitis under the Diseases of the Nervous System section.

In the later Ninth revision (1977), the ICD-9, the entry for myalglc encephalomyelitis is uses code 323.9 and remains a disease of the nervous system, along with the other forms of encephalomyelitis. There is no mention of a chronic fatigue syndrome (the term was had not been proposed at the time) and there was no mention of an illness named "chronic fatigue".

Chronic fatigue syndrome (1980s and 1990s)
The illness gained national attention in the United States when the popular magazine Hippocrates ran a cover story of an epidemic at Lake Tahoe, Nevada, in the mid-1980s. The designation Chronic Epstein-Barr Virus was in use in the U.S., but the magazine used the term "Raggedy Ann Syndrome" to note the fatigue and loss of muscle power patients felt.

Researchers investigating the Lake Tahoe cluster did not find evidence that EBV was involved, and they proposed the name chronic fatigue syndrome, describing fatigue as the main symptom of the illness. They published the first working case definition for CFS in 1988. Research increased considerably, and more so after the criteria were relaxed in 1994.

In 1990, researchers presented evidence they found DNA sequences very similar to the human HTLV-II retrovirus in some CFS patients, at a conference in Kyoto, Japan. Their study was later published in the Proceedings of the National Academy of Sciences. A reporter on Prime Time Live stated the announcement made headlines all over the world. The CDC first ignored their findings then later conducted a study and published a paper that refuted the hypothesis.

In the United Kingdom, the Chief Medical Officer Kenneth Calman requested a report from the medical Royal Colleges in 1996. This led to the publication of a joint report in which the term "chronic fatigue syndrome" was found to be most representative. This was followed in 2002 by a further report by the new CMO, Liam Donaldson.

The U.S. Centers for Disease Control & Prevention (CDC) recognized CFS as a serious illness, and launched a campaign in June 2006 to raise public and medical awareness about it.

XMRV study (2009)
A 2009 study published in the journal Science reported an association between a retrovirus xenotropic murine leukemia virus-related virus (XMRV) and CFS. The editors of Science subsequently attached an "Editorial Expression of Concern" to the report to the effect that the validity of the study "is now seriously in question," and in September 2011, the authors published a "Partial Retraction" of their 2009 findings; this was followed by a full retraction by the magazine's Editor in Chief, after the authors failed to agree on a full retraction statement. Also in September 2011, the Blood XMRV Scientific Research Working Group published a report, which concluded "that currently available XMRV/P-MLV assays, including the assays employed by the three participating laboratories that previously reported positive results on samples from CFS patients and controls, cannot reproducibly detect direct virus markers (RNA, DNA, or culture) or specific antibodies in blood samples from subjects previously characterized as XMRV/P-MLV positive (all but one with a diagnosis of CFS) or healthy blood donors." In December 2011, the Proceedings of the National Academy of Sciences published a similar retraction for an August 2010 paper. Some members of the patient community, who had viewed the XMRV findings as a source of hope for a possible cure, initially reacted negatively when the papers were called into question. One UK researcher reported verbal abuse after publishing an early paper indicating that the XMRV studies were flawed.

Institute of Medicine report (2015)
February 15, 2015, The National Academy of Medicine (known as the Institute of Medicine or IOM until June 2015) published a report on ME/CFS, Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness proposing a new name – systemic exertion intolerance disease – and a new diagnostic criteria. It has since influenced government policy and healthcare for the disease in the United States and around the world.

The proposed name proved to be highly unpopular and was not been widely adopted by government agencies or researchers. The CDC adopted the term ME/CFS in place of Chronic Fatigue Syndrome and adopted the IOM's proposed criteria, with post-exertional malaise as a required symptom.

Criticisms of the IOM report include that the diagnostic criteria captured an overlapping but different subset of patients than stricter criteria like the International Consensus Criteria or the Canadian Consensus Criteria. Despite some positive impacts, the IOM report recommendations have remained controversial among many patients and advocacy groups.

Post-exertional malaise as the hallmark symptom and treatments withdrawn
A shift in diagnostic criteria and symptom focus began around 2015-2016, with greatly reduced emphasis on fatigue and with post-exertional malaise (PEM) required as a compulsory symptom and frequently referred to as the "hallmark symptom" of ME/CFS. The disease is increasingly referred to as ME/CFS or Myalgic Encephalomyelitis/Chronic Fatigue Syndrome rather than Chronic fatigue syndrome, including by the CDC from 2017. This change in emphasis has largely resulted from the release of the full PACE trial outcome data in 2016, and the subsequent re-analysis of the Cochrane review of exercise therapy for ME/CFS, which showed that treatment outcome results and impairment differed when post-exertional malaise was a required symptom. Graded exercise therapy and cognitive behavioral therapy were found to be either harmful or ineffective for the vast majority of patients with post-exertional malaise, and the recommendations for the and withdrawn by the CDC in 2017, and mostly abandoned by the UK's National Health Service from late 2021. The biopsychosocial model was largely abandoned, with ME/CFS regarded as a serious physical disease, and a greater focus on the biomedical model for diagnosis and treatment, and future research.