Ramsay sets out the defining features of ME:
1. a unique form of muscle fatiguability whereby, even after a minor degree of physical effort,three, four or five days, or longer, elapse before full muscle power is restored;
2. variability and fluctuation of both symptoms and physical findings in the course of a day; and
3. an alarming tendency to become chronic.
A Melvin Ramsay was Honorary Consultant Physician in Infectious Diseases at the Royal Free Hospital in 1955 at the time of the epidemic in that hospital and spent the rest of his life studying this illness, seeing patients and acting as advocate, right up to his death at the age of 89, while he was preparing to present a paper at a conference on the subject.
He has collated accounts of other outbreaks, 18 of the 52 which he states had been recorded up to the 1986, the date of publication of his book, ‘Post Viral Fatigue Syndrome’, the saga of Royal Free Disease’. (This book was published in a second edition titled ‘Myalgic Encephalomyelitis and Postviral Fatigue States’ by the ME Association, and is still available from the MEA.)
In the preface to this edition, Ramsay states ‘I have never approved of the term ‘postviral fatigue syndrome’ (PVFS) and accepted it with great reluctance when Gower Medical Publishing insisted it should be used as a title for my monograph.’ He goes on to explain that although it obviates the use of two different names for the same illness – ‘epidemic neuromyasthenia’ in the US and ‘myalgic encephalomyelitis’ in Britain, ‘it provided too wide a coverage for the many postviral fatigue states that can quite legitimately be included under such a title.’
The problem of naming, having publishers and editors refuse to use the names researchers give to this illness, and insistence on over-inclusive categories is a major feature of the history of this illness and the controversies surrounding it.
The accounts which Ramsay summarises were generally written by doctors who had been actively involved in the care, attempts at diagnosis, and clinical observation of the patients about whom they were reporting, and had been published in peer-reviewed medical journals. The names used for the illness varied, but there was evident overlap in the constellation of symptoms reported.
Contrary to the impression created by writers who sought to explain the illness in terms of ‘mass hysteria’ many of the symptoms (sore throats, swollen lymph glands, indications of circulatory problems – a pronounced facial pallor appearing before worsening of symptoms, low temperature in extremities – problems in vision ascribable to muscle weakness, ongoing low fever, or markedly subnormal temperature) are impossible to simulate, or to ascribe to anxiety.
Although there were outbreaks, often in hospitals and often among nursing staff, there were also outbreaks in all male settings, among schoolchildren in which the gender ratio was 1:1, and isolated cases spread across wide geographical areas.
The distribution within hospitals, in which many nurses, some doctors and other staff, and virtually no inpatients were affected could equally be explained by the fact that ME occurs among active, energetic individuals who have a physically demanding life-style. Nurses are the hospital staff with the most physically demanding roles, doctors and other hospital staff less so, and the patients are mostly lying in bed.
Yet you might imagine that individuals already sufficiently ill to be in hospital might be the most vulnerable to panic about the possibility of a further severe illness, and therefore most likely to succumb to ‘mass hysteria’.
The symptom on which most reports agreed was ‘extreme exhaustion, especially after exercise’, and where patients who had ME were studied after a significant length of time, many were still very ill, continuously or intermittently.
In the chapter about the endemic form of the disease, Ramsay points out the existence of a number of outbreaks which ‘consisted of groups of sporadic cases with no history of contact with infectious cases’ and he believes that a number of sporadic cases in North London provided ‘the nidus of infection’ which lead to the Royal Free epidemic.
In this chapter, he groups symptoms into
1. muscle phenomena,
2. circulatory impairment and
3. cerebral dysfunction.
He again refers to chronicity, and asserts: ‘Absolute rest in the early stage of the disease can prove a strong determining factor in the outcome. and
‘Relapses resulting from excessive physical or mental stress, or both, or after a further virus infection, are an accepted feature of the disease.’
In the final chapter, on ‘Research projects’, Ramsay discusses work by Dr Peter Behan, a distinguished neurologist and immunologist. In one paper, Behan points out that ‘acute disseminated encephalomyelitis and myalgic encephalomyelitis or epidemic neuromyasthenia may share a common pathway’.
‘Behan’s initial research showed that patients with epidemic myalgic encephalomyelitis had immunological abnormalities consisting of
(1). atypical peripheral lymphocytes;
(2) mild eosinophilia and anticomplementary activity;
(3) increased IgM;
(4) decreased or deficient IgA;
(5) reduced complement factor C4 concentrations;
(6) serum anti-complementary activity; and
(7) a suggestion of increased titres to Coxsackie virus (in some patients specific IgM to Coxsackie virus type A9.
A further research program was undertaken, involving study of several outbreaks, and immunological study of patients who had a similar constellation of symptoms. ‘Behan &
Behan (1977) pointed out that ‘activation of the complement system and the presence of circulating immune complexes’ had been described by them where there was muscle damage thought to be due to a vasculopathy secondary to immune-complex deposition.
They therefore suggested that in ME the pathogenesis may be that of a persistent virus with the formation of immune complexes and widespread deposition of antigen-antibody aggregates in the blood vessels, the central nervous system, muscle.’
A further study of 50 patients showed further immune system abnormalities.
Additionally ‘no muscle weakness was found in any of the patients until they were exercised by squeezing the rubber ball of an ergonometer for one minute, or by going up forty steps; the weakness lasted for up to three hours.
Muscle biopsies were abnormal in all twenty patients examined; these showed widely scattered necrotic muscle fibres in fifteen but there was no inflammatory infiltrate associated with the necrosis.
Histochemical stains showed moderately increased size and numbers of type II fibres, which are concerned with inaugurating muscle movement and, by nature, fatigue rapidly, in all biopsy samples.
Using electron microscopy, mitochondria were seen to be conspicuously increased at the periphery of the fibres and occasional tubular inclusions were present.
‘The authors consider that the results of their investigation suggest ‘that the syndrome is due to the interaction of viral infection and immunological processes which produce damage to infra cellular enzymes and result in abnormal muscle metabolism especially on exercise’.
Further discussion of research concerned with muscle damage associated with muscle damage leads to the conclusion that the mode of action of viruses on the muscle cell is extremely complex….Basic questions such as how viruses infect cells, why they are likely to persist, how they evade immune surveillance and maintain a persistent state, and what underlies the ability of viruses to injure cells and produce disease await answers.’
‘Simon and Goldstone also discussed both how persistent infections become established, and the new concept that some viruses can cause disease not by destroying the cells they infect but by altering the specialised function of the infected cell.
‘They consider that such disorders involve primarily the immune, nervous and endocrine systems. All these systems, particularly the first two, are vitally involved in the pathogenesis of ME.’
These observations, made more than 40 years ago, seem to foreshadow many of the ‘new’ discoveries which are being reported by today’s biomedical researchers.
What has caused the tragic hiatus, during which the psychiatric view of this illness, along with its damaging dismissal of rest as best practice and its replacement by Cognitive Behaviour Therapy and Graded Exercise Therapy has dominated both public perception and medical practice?
It seems that in the wake of the terrible polio epidemics which were features of my own childhood and adolescence (my cousin was paralysed from the waist down when we were both 16), ME patients in the 1934 Los Angeles outbreak were denigrated because their illness turned out not to be polio. The ‘new concept’ referred to above may well have been arrived at during the earlier phases of research into HIV, a virus which emerged in the 1980s, and was mysterious, incurable, and invariably fatal via an accumulation of rather horrible illnesses which a normally functioning immune system could deal with. Sandwiched historically between such dramatic viral illnesses, a group of people whose complaints are numerous, mostly subjective, variable, and purportedly not fatal, are very tempting to dismiss as simply competing for unjustifiable medical attention.
If we believed them, when they tell us how much they are suffering, how helpless they are, we would of course take the matter very seriously. But surely, if they only pulled their socks up and got on with it, like the rest of us have to, they would find good health much preferable to their miserable performance. This is the attitude which too many of us encounter, in our families, in the general public, and when we seek medical help.
That was Then. What about Now? Medical research into ME continues. The psychiatric view is widely accepted and increasingly influential. Nevertheless doctors who see many of these patients, who become patients themselves, or who have close family members who are ill often are, or become persuaded of the physiological nature of ME. Today there are virologists, immunologists, geneticists, epidemiologists, infectIous disease specialists, neurologists, specialists in muscle function, and even some psychiatrists who are continuing to study ME, seeking to understand the pathophysiology involved.
Ramsay’s view seems to have been prescient. It would, I believe, be fair to say that a rough consensus is that ME/CFS is an illness characterised by the criteria which Ramsay set out: it is made worse by exercise, and it seems to be a persisting autoimmune response following a viral infection. The symptoms fluctuate, and it is very long-lasting.