Myalgic Encephalomyelitis - is it a real disease?

Myalgic Encephalomyelitis - is it a real disease?

Charles Shepherd MB, BS

(Vice President to the M.E. Association)

This article was first published in The Practitioner on 8th January 1989

MYALGIC ENCEPHALOMYELITIS (M.E.) has divided the medical profession for 30 years and has become the subject of considerable media publicity.

As a consequence, many patients who are “tired all the time”, or have “undiagnosed ill health,” want to know if they could have this controversial illness. Many doctors remain perplexed as to whether M.E. has a genuine organic basis.

Current research strongly points to M.E. being the result of a viral illness, with enteroviruses and the reactivation of latent Epstein-Barr virus being the most favoured culprits. The continuing viral presence within the muscle cells causes energy metabolism dysfunction.

Historical perspective

Numerous outbreaks of M.E. have been reported over the past 50 years, particularly from temperate climates and closed communities. However, the disease may also be endemic, as these outbreaks have invariably been associated with individual cases within the local community. Most cases seen today are sporadic.

In Britain, the most famous outbreak involved 292 members of staff at the Royal Free Hospital, London, in 1955, and the hospital was closed from July to October. 

The early symptoms suggested poliomyelitis, but no muscle wasting occurred, the polio virus was never isolated, and electromyographic studies showed no pattern of involvement of the anterior horn cells in the spinal cord.

(The Anterior Horn Cells can be involved with Poliomyelitis-like Syndrome co-occuring diagnosis. Muscle Wasting is also possible)

Some of these cases were written up in The Lancet in 1956, and an accompanying editorial, headed “A new clinical entity,” suggested the condition should be called “Myalgic Encephalomyelitis.”

In 1970, the British Medical Journal published a paper concluding that the Royal Free outbreak had been an example of mass hysteria. 

This was despite the incidence of pyrexia (89%), widespread lymphadenopathy (79%), and palsies of the ocular (43%) and facial (19%) nerves.

The term myalgic encephalomyelitis should not be used as a general term to describe the common, self-limiting period of debility that can follow viral illness. The syndrome is specific, with one cardinal feature - exercise-induced muscle fatigue.

Clinical history

The typical M.E. patient is a previously fit young adult (with females predominating) in the age group of late teens to early forties.

The patients contract an unremarkable viral illness with pyrexia, myalgia, lymphadenopathy, sore throat, and sometimes gastrointestinal or respiratory upset. Then, instead of getting better, they continue to feel “generally unwell” or “flu-like,” want to sleep all the time, and have the highly characteristic neuro-muscular symptoms of M.E.

Muscle symptoms: Exercise-induced muscular fatigability is the most striking symptom and is always present. Although clinical examination reveals little weakness or wasting, minimal physical exertion (e.g., walking for a quarter of a mile) soon produces fatigue, followed by weakness and even exhaustion. There may be accompanying myalgia and fasciculations.

Following the point of fatigue there is a recovery period, when muscle power returns to normal. Patients who exceed their limitations and exert themselves to the point of near exhaustion may find it takes several days before they return to relative normality.

Encephalitic features: These are invariably present and tend to fluctuate according to the level of physical and mental activity. Loss of short-term memory and concentration predominates, and patients complain that their brains don’t seem to function properly. Again, normal function is restored after a period of rest.

As the fatigue increases, patients become clumsy (especially when performing fine tasks), unsteady - “like being drunk all the time” - and even uncoordinated.

Autonomic dysfunction

Disturbances in thermoregulatory control (e.g. feeling weak after a hot bath, insensitivity to temperature extremes, night sweats) are particularly common, and may be the result of hypothalamic involvement. Other features of autonomic dysfunction include palpitations, bladder frequency and cold extremities.

Other symptoms

Symptoms suggestive of abnormal neuromuscular pathology are frequently reported, e.g. sensory disturbances (hypoaesthesia, paraesthesia), tinnitus and defective visual accommodation.

Although these symptoms tend to be chronic, they often vary in severity through the day to day.

Diagnosis

M.E. patients may have considerable difficulty in obtaining the correct diagnosis, and often attend a succession of specialists before the characteristic symptomatology is recognised. The differential diagnosis is summarised in Table 1.

Investigations

The diagnosis of M.E. is made from the patient’s history, and the exclusion of other causes of persistent fatigue. Routine investigations (Table 2) may reveal minor changes, but none is diagnostic.

The pathophysiology of M.E. - a hypothesis

From the current research, evidence is steadily accumulating that M.E. patients fail to make an effective immune response to the “triggering” infection. The virus continues to multiply and then evades the primary lymphatic defence mechanisms, so allowing systemic spread to muscle (and possibly other tissues) to interfere with normal function.

Virology

The possibility of enterovirus involvement was suggested by certain similarities of the illness to polio. First, the patients and certain “risk factors” in common - similar age groups and the fact that physical stress at the time of incubation or initial infection seemed to worsen the prognosis.

Second, the initial clinical picture was similar, and third, an outbreak of M.E. in Iceland in 1948 was followed by polio in 1955, but those patients who had previously succumbed to M.E. seemed to be immune to the cytopathological effects of polio and none was affected.

In the early 1980s analysis of some Scottish outbreaks revealed that large numbers of patients had persistently high levels of neutralising antibodies to Coxsackie B virus. This link with enteroviruses was further implicated by the presence of IgM antibodies in about 10 to 20% of M.E. patients.

However, in areas where Coxsackie infection is common, significant numbers of controls from the normal population also have such antibodies.

Recent research from St Mary’s Hospital, London, has shown that enterovirus can be cultured from the muscles of M.E. patients (where it may be acting as a reservoir of infection), and that about 50% of patients in the study group had the enteroviral VP1 protein in their serum - indicating that an enteroviral infection was present.

The VP1 test

Viral protein one surrounds the genome of each of the 72 enteroviruses. It can be demonstrated using a monoclonal antibody technique. A positive test indicates the presence of enterovirus, but not which one. It is not a test for M.E., which many patients (and some doctors) would wish it to be.

Probably the most exciting ongoing research findings come from Charing Cross Hospital. Using fluorescent probes, it has been possible to demonstrate the presence of enteroviral genome material in the muscle biopsies of about 25% of clinical cases of M.E. In addition, about 10% of these biopsies have Epstein-Barr virus present.

In the United States there is a suggestion that natural killer cell function may be impaired in M.E. patients.

More sophisticated investigations (electromyography, nuclear magnetic resonance, etc.) are research-oriented and require specialist referral.

Activity is decreased, permitting the reactivation of Epstein-Barr virus from the B cells of the immune system.

Muscle pathology

If the virus has entered the muscle cells, how could it cause the fatigue?

An early study of 50 M.E. patients carried out at the Institute of Neurology in Glasgow revealed a variety of abnormalities in the muscle biopsies. These included scattered necrotic fibres, type two fibre predominance, mitochondrial abnormalities, tubular inclusion bodies and deficiencies in some key intracellular enzymes concerned with mitochondrial function and cellular respiration.

Many of these patients also had the phenomenon of increased jitter when examining single fibre electromyograms - suggesting a disturbance of neuromuscular conduction, possibly due to a membrane defect.

However, the most significant findings in muscle pathology have come from nuclear magnetic studies carried out in Oxford by Professor George Radda.

Normal muscle energy production relies on the aerobic breakdown of muscle glycogen, via the Krebs cycle, to produce ATP (Figure 4). In M.E. there appears to be a defect in aerobic metabolism so that, on minimal exertion, a switch to an anaerobic pathway occurs, with the consequent production of excessive lactic acid.

Research at Northwick Park Hospital suggests that the total intracellular RNA levels may be significantly decreased in M.E., indicating a decreased ability to synthesise muscle proteins (Figure 5).

Immunology

A wide variety of immunological changes have been reported from both sides of the Atlantic. Changes involving T4 (helper) and T8 (suppressor) lymphocytes were reported in the Glasgow study, and have also been seen in patients with prolonged debility following infectious mononucleosis.

Some of these patients show decreases in T4 (helper) cells similar to immunodeficiency diseases of the chronic stage, but this may be a reaction to persisting infection. M.E. patients do not succumb to opportunistic infections, so it would be incorrect to describe it as an immunodeficiency disease.

Other patients show minor changes in their immunoglobulin pattern, with raised levels of IgM and lowered IgA being reported.

Perhaps the most interesting suggestion is that these patients may have continually raised levels of interferon (and possibly interleukin 1). If interferon is given as a therapeutic agent, it can induce some of the neuropsychiatric features of M.E. as a side effect. These lymphokines are also known to be capable of causing damage to cell membranes.

Management of M.E.

How then can these patients be managed?

First, they need reassurance that they do not have a life-threatening illness, and that they can recover - although it may take a considerable time.

Second, myths from the widespread media coverage need to be sorted out, and an explanation given that there is an organic basis to the symptomatology - they are not “going mad.”

Patients diagnosed in the very early stages will undoubtedly benefit from a period of strict rest, followed by a gradual convalescence - something that has gone out of fashion in modern medicine.

Patients who remain chronically unwell often have additional psychological, financial, family and employment difficulties.

Secondary depression is quite common and the reasons are probably multifactorial. Although psychotropic drugs should generally be avoided, they may be necessary for true clinical depression (as opposed to being “fed up” with the illness), as well as professional psychiatric help.

It is essential that patients “listen to what their bodies tell them” and do not exceed their physical or mental limitations to the point of exhaustion. Beneficial exercise (e.g., swimming in a warm pool) has to be balanced against the dangers of prolonged immobility.

Certain factors (e.g. excessive physical/mental stress, intercurrent infections, surgery or general anaesthesia, vaccinations and alcohol) seem to exacerbate the condition or cause a relapse, and should be avoided if possible.

At present, no effective drug for treating M.E., although a trial of gammaglobulin is currently being undertaken. There are no effective antiviral drugs available for the RNA enteroviruses, and immuno-stimulant drugs such as Imunovir do not appear to show any benefits.

Immunosuppressive drugs, e.g. steroids, are not indicated in M.E., and in view of the carcinogenic potential of Epstein-Barr virus they may cause harm.

The medical profession can provide little more than practical advice and reassurance, and many patients are spending considerable amounts of money on “alternative” therapies, ranging from anti-candida treatment to colonic irrigation. General practitioners need to be aware of this and try to give some guidance as to which therapies are completely worthless and may merely relieve the patient of more money.

A self-help group, such as the ME Association, can provide support and give sufferers the opportunity of contacting other people, from whom they may obtain practical guidance on coping with a distressing, unpredictable, and disabling condition.

References

1. Youssef GE, Mann GF, Smith DG et al. (1988). Chronic enterovirus infection in patients with postviral fatigue syndrome. Lancet 1:146-150.

2. Archard LC, Behan PO, Bowles NE, Bell EJ, Doyle D. (1988). Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatine kinase. J Roy Soc Med 81:326-329.

3. Strauss SE. (1988). The chronic mononucleosis syndrome. J Infect Dis 157:405-412.

4. Behan PO, Behan WMH, Bell EJ. (1985). The postviral fatigue syndrome: an analysis of the findings in 50 cases. J Infect 10:211-222.

5. Jamal GA, Hansen S. (1985). Electrophysiological studies in postviral fatigue syndrome. J Neurol Neurosurg Psychiatr 48:691-694.

6. Arnold DL, Bore PJ, Radda GK, Styles P, Taylor DJ. (1984). Excessive intracellular acidosis of skeletal muscle on exercise in a postviral fatigue syndrome. Lancet 1:1367-1369.

7. Wakefield D, Lloyd A. (1987). Pathophysiology of Myalgic Encephalomyelitis. Lancet 2:918-919.

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LETS “TALK SHOP”

The “M.E. and YOU” shop which raises funds for research into Myalgic Encephalomyelitis needs your support.

Our little shop is fast becoming a local landmark for being “that little shop” where you can purchase the “whatnot” you had been looking to buy for years.

Our treasured regulars call in just for a chat or to browse through our books and bric-a-brac.

The friendly staff go to any length to find the skirt or jacket that fits just right! We always have time for a chat, and of course, a specially warm welcome awaits any M.E. sufferer.

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Even with all this hard work we desperately need your support. Clean clothes, bric-a-brac, books and small items of furniture are always required. Hand-knitted goods are also welcome.

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M.E. and YOU CHARITY SHOP

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