19th century Several descriptions of illness resembling ME/CFS have been reported for at least 200 years. In the 19th century, neurologist
George Miller Beard popularised the concept of
neurasthenia, with symptoms including fatigue, anxiety, headache,
impotence,
neuralgia and depression. This concept remained popular well into the 20th century, eventually coming to be seen as a behavioural rather than physical condition, with a diagnosis that excluded postviral syndromes. Neurasthenia has largely been abandoned as a
medical diagnosis. The
ICD-10 system of the
World Health Organization categorized neurasthenia under (F48 Other neurotic disorders) which specifically excluded chronic fatigue syndrome. The current version of ICD, ICD-11, does not include neurasthenia and "deprecates" its use.
Outbreaks in the 20th century A
United States Public Health Service (USPHS) official,
Alexander Gilliam, described an illness that resembled
poliomyelitis, after interviewing patients and reviewing records of one of several clusters which had occurred in
Los Angeles, during 1934. The
Los Angeles County Hospital outbreak included all or most of its nurses and doctors. 800 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. A 1955 outbreak at the
Royal Free Hospital Group was later called "Royal Free disease" or "benign myalgic encephalomyelitis". The term "benign myalgic encephalomyelitis" was selected to represent the lack of mortality, the severe muscle pain, symptoms suggesting damage to the nervous system, and to the assumed inflammation involved in the illness. 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, both in
monkeys and in 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 etiology.
Psychological framing (1960s and 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. 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
Royal Society of Medicine (RSM) concluded that "epidemic myalgic encephalomyelitis" was a distinct disease entity with a clear organic basis. Despite the criticism, the paper by McEvedy and Beard had a large impact and the view of ME as a psychosomatic disease became prevalent for almost 50 years.
Case definitions (1986 onwards) In 1986,
Melvin Ramsay published the first diagnostic criteria for ME, in which the condition was characterized by: 1) muscle fatiguability in which, even after minimal physical effort, three or more days elapse before full muscle power is restored; 2) extraordinary variability or fluctuation of symptoms, even in the course of one day; and 3) chronicity. By 1988, the continued work of Ramsay had demonstrated that, although the disease rarely resulted in mortality, it was often severely disabling. Because of this, Ramsay proposed that the prefix "benign" be dropped. 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 (EBV) was in use in the U.S., but the magazine used the colloquial 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 a 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) recognize CFS as a serious illness, and launched a campaign in June 2006 to raise public and medical awareness about it.
XMRV controversy 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 (2, 4), 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. ==International classifications==