Epidemic myalgic encephalomyelitis

There have been at least 75 documented outbreaks of myalgic encephalomyelitis and chronic fatigue syndrome since the 1930s. The true number of clusters and outbreaks is likely much higher. Many of these outbreaks occurred in institutions like hospitals and schools, and frequently coincided with outbreaks of poliomyelitis.

The first recorded outbreak of epidemic was in 1934 in Los Angeles and the most recent putative outbreak was in Arizona in 1996.

Prior to the 1980s, while no infectious was ever isolated, the outbreaks were widely thought to be caused by an virus related to poliovirus, i.e., by another, yet-to-be-unidentified enterovirus. After the Incline Village outbreak in 1984, herpesviruses and in particular, Epstein-Barr virus was posited as the cause.

History
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.

Onset
The incubation period was generally estimated at 4 to 8 days. The illness generally began with a prodromal period of flu-like symptoms, symptoms of an upper respiratory tract infection, low-grade fever, sore throat or gastrointestinal distress , followed by a symptom complex involving muscle weakness, muscle fatiguability and central nervous system involvement in a significant proportion of cases.

Symptoms
Reported symptoms could vary considerably from outbreak to outbreak. Common symptoms included:


 * muscle fatiguability
 * muscle weakness / paresis (10-80% of cases), commonly occurring in the legs
 * ataxia
 * myalgia and neuralgia
 * severe headache
 * stiffness of the neck and spine
 * tender lymph nodes, spleen and/or liver
 * cognitive symptoms including impaired memory and concentration
 * sleep disturbances
 * sensory symptoms including sensitivity to light and sound, paraesthesiae , hyperaesthesiae
 * autonomic symptoms such as tachychardia, coldness of the extremities, sweating
 * post-exertional malaise, worsening of symptoms with exertion  ("fatigue on walking short distances and on the least exertion was prominent" )

Findings
Findings varied considerably based on the technology of the time and what tests physicians attending to these outbreaks chose or were able to run:


 * Low-grade fever
 * Abnormal electromyogram showing generalized, mild, lower motor neuron changes indicative of a radiculopathy
 * Muscle weakness measured via quantitative muscular-testing
 * Normal or minimal cerebrospinal fluid findings
 * Normal or mildly increased erythrocyte sedimentation rate
 * Mild increase in white blood cell count
 * Autonomic nervous system dysfunction, hypothalamic dysfunction
 * Orthostatic tachycardia
 * Ulnar neuritis, neuropathy or lesion
 * Microscopic infiltration of nerve roots with lymphocytes and mononuclear cells; patchy damage to the myelin sheaths and axon swellings (in monkeys infected with unidentified virus from the Adelaide outbreak)
 * Raised urinary creatine excretion
 * abnormally high lactic dehydrogenase and glutamic oxaloacetic transaminase

In the majority of early epidemics, no viral or bacterial infectious agent was successfully cultured. In a small number of epidemics Coxsackie B or Bethesda-Ballerup paracolon organism were found, although the latter was found. In others, infection of animal models with samples from patients results in identifiable nervous system damage on autopsy and in one case, myocarditis, in spite of being unable to identify the agent.

Epidemiology
Many of these outbreaks occurred at institutions for example, hospitals , schools, army bases or convents. The pattern of spread suggested a highly infectious agent that spread person to person, rather than through contaminated food or drink or exposure to a single toxic agent.

Outbreaks tended to begin in the summer months, with most initial cases reported from April to September in the Northern hemisphere, October to March in the Southern hemisphere.

In outbreaks involving both medical personnel and the general community, medical personnel had a higher attack rate and/or greater central nervous system involvement. A similar pattern was seen in hospital outbreaks, where those in roles that involved more frequent or intimate contact with patients or those working in an infectious disease ward were more affected than other hospital staff. A large proportion of recorded outbreaks have taken place in hospital settings.

In many outbreaks including Los Angeles, Akureyri, Rockville, MD, Royal Free Hospital, and Punta Gorda, Florida, women were affected at higher rates. In other outbreaks, including the 1949-1953 Adelaide outbreak and an outbreak in northern England in 1955, a 1:1 gender ratio was reported. In hospital epidemics, young female nurses were disproportionately affected, but this may have been due to risk factors like higher repeated exposure to the same infection during an epidemic and in some outbreaks, gender-segregated living quarters. However, the higher ratio of women were also reported in outbreaks in the general population. In Akureyri, while the incidence among adults was higher for females, there was no significant difference in incidence between sexes among those under twenty. This comports with patterns of age and sex distribution in sporadic cases.

In most outbreaks, those most affected tended to be adults in their twenties,   although cases of young children and adults as old as 80 have been recorded in outbreaks. In Akureyri, the highest attack rate was among ages 15-19.

Melvin Ramsay observed an absence of cases among sedentary people, and postulated that this might explain why hospital staff frequently became affected, while patients in hospital rarely did.

Pathophysiology
Due to paucity of objective findings, very little was known about the pathophysiology of the disease. Several investigators postulated damage to the hypothalamus owing to the symptoms of orthostatic tachycardia, abnormal glucose regulation, circulatory impairment, and problems with temperature regulation.

Prognosis
Although many patients improved over time, in follow-up studies, a large percentage were still ill months to years later. Many case studies note long periods of convalescence with relapses following exertion   or before or during menstrual periods.

* Follow-up was with those patients considered disabled. Others may have been more mildly affected.

Relationship to polio
Prior to the poliovirus vaccine, several outbreaks of what later came to be called myalgic encephalomyelitis coincided with confirmed outbreaks of poliomyelitis including the 1934 Los Angeles outbreak, the 1948 Akureyri, Iceland outbreak, and 1949 outbreak in Adelaide, Australia. Many outbreaks were initially misinterpreted as clusters of poliomyelitis or abortive poliomyelitis, hence one of ME's earliest names, atypical polio. It is not known whether there is a direct relationship between polio outbreaks and ME or if outbreaks of ME were more likely to be reported when public health authorities were already mobilized for an earlier crisis.

No serological evidence of polio was ever found in these outbreaks and the ultimate pattern of the outbreaks differed in significant ways, chief among them the higher attack rate, the tendency to affect adults rather than children, and the higher morbidity than poliomyelitis but no mortality. Findings in several outbreaks seemed to suggest that symptoms were caused by an enterovirus distinct from but related to polio: findings of mild, diffuse peripheral nervous system damage in monkeys infected with the virus; a stronger response to polio vaccination in children who had been in epidemic areas; and seasonal patterns of infection resembling polio, i.e., the rise in cases during summer months.

There is indirect evidence of cross-immunity between poliovirus and the unidentified virus or viruses in epidemic myalgic encephalomyelitis outbreaks. After the Akureyri outbreak, children in areas that had been affected responded to poliomyelitis vaccination with higher antibody titres, as if these children had already been exposed to an agent immunologically similar to the poliovirus. During the outbreak in Adelaide, cases of classic poliomyelitis dropped by 43%.

Controversy
In 1970, a paper by Colin P. McEvedy and AW Beard claimed that the 1955 Royal Free Hospital outbreak was actually mass hysteria.

Outbreaks of the 1980s and 1990s
The case reports of the 1980s and 1990s differed substantially from those of earlier decades. Whereas reports from the 1930s-1960s focused heavily on neurological and muscle symptoms and findings, and compared and contrasted the disease to poliomyelitis, reports of the 1980s focused far more heavily on fatigue and the possible relationship to herpesviruses.

Learn more

 * "In the Bughouse," The New Yorker by Berton Roueché.
 * Osler's Web by Hillary Johnson