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Dr. A. M. Ramsay, much loved by patient or physican and all who had the privilege to meet him, died a few weeks prior to the First World Symposium on M.E., which he was instrumental in encouraging.
Below are two transcripts from Dr.A. Melvin Ramsay's numerous articles and papers on ME



          A Baffling Syndrome With a Tragic Aftermath
By A. Melvin Ramsay M.D., Hon Consultant Physician, Infectious Diseases Dept, Royal Free Hospital. [M.E. Association Journal 1986 UK]

The syndrome which is currently known as Myalgic Encephalomyelitis in Great Britain and Epidemic Neuromyasthenia in the USA ** leaves a chronic aftermath of debility in a large number of cases. The degree of physical incapacity varies greatly, but the dominant clinical feature of profound fatigue is directly related to the length of time the patient persists in physical efforts after its onset: put in another way, those patients who are given a period of enforced rest from the onset have the best prognosis.

Although the onset of the disease may be sudden and without apparent cause, as in those whose first intimation of illness is an alarming attach of acute vertigo, there is practically always a history of recent virus infection associated with upper respiratory tract symptoms though occasionally there is gastro-intestinal upset with nausea and vomiting. Instead of making a normal recovery the patient is dogged by persistent profound fatigue accompanied by a medley of symptoms such as headache, attacks of giddiness, neck pain, muscle weakness, paraesthesia, frequency of micturition or retention, blurred vision and/or diplopia and a general sense of ‘feeling awful’. Many patients report the occurrence of fainting attacks which abate after a small meal or even a biscuit, an in an outbreak in Finchley, London in 1964 three patients were admitted to hospital in an unconscious state presumably as a result of acute hypoglycaemia. There is usually a low-grade pyrexia which quickly subsides. Respiratory symptoms such as a sore throat tend to persist or recur at intervals. Routine physical examination and the ordinary run or laboratory investigations usually prove negative and the patient is then often referred for psychiatric opinion. In my experience this seldom proves helpful and is often harmful; it is a fact that a few psychiatrists have referred the patient back with a note saying, ‘this patient’s problem does not come within my field’. Nevertheless by this time the unfortunate patient has acquired a label of ‘neurosis’ or ‘personality disorder’ and may be regarded by both doctor and relatives as a chronic nuisance. We have records of three patients in whom the disbelief of their doctors and relatives in the validity of their symptoms led to suicide, one of these was a young man or 22 years of age.

The too facile assumptions that such an entity - despite a long series of cases extended over several decades - can be solely attributed to psychological stress is simply untenable. Although the aetiological factor or factors have yet to be established there are good grounds for postulating that persistent virus infection could be responsible. It is fully accepted that viruses such as herpes simplex and varicella-zoster remain in the tissue from the time of the initial invasion and can be isolated from nerve ganglia post-mortem; so these may be added measles virus the persistence of which is responsible for subacute sclerosing panencephalitis that may appear several years after the attack and there is now a considerable body of circumstantial evidence associating the virus with multiple sclerosis. There should surely be no difficulty in considering the possibility that other viruses may also persist in the tissues. In recent years routing antibody tests on patients suffering from myalgic encephalomyelitis have shown raised titres to Coxsackie Group B viruses. It is fully established that these viruses are the aetiological agents of ‘Epidemic Myalgia’ or ‘Bornhom Disease’ and that, together with ECHO viruses, they comprise the commonest known virus invaders of the central nervous system. This must not be taken to imply that Coxsackie viruses are the sole agents of myalgic encephalomyelitis since any generalised virus infection may be followed by a period of post-viral debility. Indeed, the particular invading microbial agent is probably not the most important factor. Recent work that the key to the problem is likely to be found in the abnormal immunological response of the patient to the organism.

A second group of clinical features found in patients suffering from myalgic encephalomyelitis would seem to indicate circulatory disorder. Practically without exception they complain of coldness of the extremities and many are found to have abnormally low temperatures of 94 or 95 degrees F. In a few these are accompanied by bouts of severe sweating even to the extent of waking during the night lying in a pool of water. A ghostly facial pallor is a well known phenomenon and this as often been detected by relatives some 30 minutes before the patient complains of being ill.

The third component of the diagnostic triad of myalgic encephalomyelitis related to cerebral activity. Impairment of memory and inability to concentrate are features in every case. Many report difficulty in saying the right word and are conscious of the fact that they continue to say the wrong one, for example, ‘cold’ when they mean ‘hot’. Others find that they start a sentence but cannot complete it whilst some have difficulty comprehending the written or spoken word. A complaint of acute hyperacusis is not infrequent; this can be quite intolerable but alternates with periods of normal hearing or actual deafness. Vivid dreams generally in colour are reported by persons with no previous experience of such a phenomenon. Emotional lability is often a feature in a person of previous stable personality while sudden bouts of uncontrollable weeping may occur. Impairment of judgement and insight in severe cases completes the ‘encephalitic’ component of the syndrome.

I would like to suggest that in all patients suffering from chronic debility for which a satisfactory explanation is not forthcoming a renewed and much closer appraisal of their symptoms should be made. This applies particularly to the dominant clinical feature of profound fatigue. While it is true that there is considerable variation in degree from one day to the next or from one time of the day to another, nevertheless in those patients whose dynamic or conscientious temperaments urge them to continue effort despite malaise or in those who, on the false assumption of ‘neurosis’ have been exhorted to ‘snap out of it’ and ‘take plenty of exercise’ the condition finally results in a state of constant exhaustion. This has been amply borne out by a series of painstaking and meticulous studies carried out by a consultant in physical medicine, himself an M.E. sufferer for 25 years. These show clearly that the recovery of muscle power after exertion is unduly prolonged. After moderate exercise from which a normal person would recover with nothing more than a good night’s rest an M.E. patient will require at least 3 to 4 days while after more strenuous exercise the period can be prolonged to 2 or 3 weeks or more. Moreover, if during this recovery phase, there is a further expenditure of energy the effect is cumulative and this is responsible for the unrelieved sense of exhaustion and depression which characterises the chronic case. The greatest degree of weakness is likely to be found in those muscles which are most in use, thus in right handed persons the muscles of the left arm and hand are found to be stronger than those on the right. Muscle weakness is almost certainly responsible for delay in accomodation which gives rise to blurred vision and the characteristic feature of all chronic cases, namely, a proneness to drop articles together with clumsiness in performing quite simple manoeuvres; the constant dribbling of saliva which is also a feature is obvious but in others a careful palpitation of all muscles will often reveal unsuspected minute foci of acute tenderness; these are to be found particularly in the trapezii, gastrocnemii and abdominal rectii muscles.

The clinical pattern of myalgic encephalomyelitis has much in common with that of multiple sclerosis but, unlike the latter, the disease is not progressive and the prognosis should therefore be relatively good. However, this is largely dependent on the management of the patient in the early states of the illness. Those who are given complete rest from the onset do well and this was illustrated in the aforementioned three patients admitted to hospital in an unconscious state; all three recovered completely. Those whose circumstances make adequate rest periods impossible are at a distinct disadvantage but no effort should be spared to given them the all-essential basis for successful treatment. Since the limitations which the disease imposes vary considerably from case to case the responsibility for determining these rests upon the patient. Once these are ascertained the patient is advised to fashion a pattern of living that comes well within them. Any excessive physical or mental stress is likely to precipitate a relapse.

It can be said that a long-term research project into the cause of the disease has been launched and there are good grounds for believing that this will demonstrate beyond doubt that the condition is organically determined.

**Eponyms such as ‘Akuryeru Disease’. ‘Iceland Disease’ and ‘Royal Free Disease’ have also been used in the case of particular outbreaks. These have the disadvantage that they obscure the all important fact that the disease has been reported world-wide.



( It is fortunate that a second edition of my monograph affords me the opportunity to demonstrate that the clinical features of Myalgic Encephalomyelitis provide a sharp contrast to all other forms of postviral fatigue syndrome.)

"The Myalgic Encephalomyelitis Syndrome"

A. Melvin Ramsay M.A. M.D.

The clinical identity of the Myalgic Encephalomyelitis syndrome rests on three distinct features, namely:

  1. A :-  A unique form of muscle fatiguability whereby, even after a minor degree of physical effort, 3, 4, 5 days or longer elapse before full muscle power is restored.
  2. B :-  Variability and fluctuation of both symptoms and physical findings in the course of a day. And,
  3. C :-  An alarming tendency to become chronic.

If we take the well known condition of post influenzal debility as an example of a postviral fatigue state we see that in all these particulars it constitutes a complete contrast. The fatigue of post influenzal debility is part of a general debility with no distinguishing characteristic of its own, it shows no variation in intensity in the course of a day and although it may last weeks or even many months it has no tendency to become chronic.

The clinical course of the Myalgic Encephalomyelitis syndrome is consistent with a virus type of infection. It most commonly commences with an upper respiratory tract infection with sore throat, coryza, enlarged posterior cervical glands and a characteristic low-grade fever with temperatures seldom exceeding 101°F. Alternatively there may be a gastro-intestinal upset with diarrhoea and vomiting. In 10% of the 53 cases we reported between 1955 and 1958 the onset took the form of acute vertigo often accompanied by orthostatic tachycardia.

The prodromal phase is characterised by intense persistent headache, paraesthesiae, blurring of vision and sometimes actual diplopia. Intermittent episodes of vertigo may occur at intervals both in the prodromal and later phases of the disease. Loss of muscle power is accompanied by an all-pervading sense of physical and mental wretchedness. Some patients lack the mental initiative to cope with the situation; on the other hand the more extrovert types show a determination not to give in to the disease but their efforts to compel their muscles to work only serves to make the condition worse.

Once the syndrome is fully established the patient presents a multiplicity of symptoms but these can conveniently be discussed under three headings, namely:

  1. 1 :-  Muscle Phenomena

    The unique form of muscle fatiguability described above is virtually a sheet-anchor in the diagnosis of Myalgic Encephalomyelitis and without it a diagnosis should not be made. I am informed of two families who are said to have all the conditions conforming to the clinical picture but lacking the muscle fatiguability. These cases should be very carefully reviewed. It is quite common to find that muscle power is normal during a remission and in such cases tests for muscle power should be repeated after exercise.

    In severe cases of M.E. muscle spasm and twitchings are a prominent feature and these give rise to acute muscle tenderness. In less severe cases muscle tenderness may not be so readily elicited but careful palpation of the trapezii and gastrocnemii (the muscle groups most commonly involved in M.E.) with the tip of the forefinger should enable the examiner to detect minute foci of exquisite tenderness. It is interesting to note that Dr. Garnet Simpson in Sydney, Australia (1986) without any prior knowledge of my writings devised the identical technique and found that detection of these foci 'will make the patient yelp'. In the aftermath of the disease patients frequently complain of a tendency to 'fumble' with relatively simple manoeuvres such as turning a key in the lock or taking a cork out of a bottle.

  2. 2 :-  Circulatory Impairment

    Most cases of M.E. have cold extremities and hypersensitivity to climatic change but the most striking illustration of this conditionis the observation by relatives or friends of an ashen-grey facial pallor some 20 or 30 minutes before the patient complains of feeling ill.

  3. 3 :-  Cerebral Dysfunction

    Impairment of memory, impairment of powers of concentration and emotional lability are the cardinal features. Inability to recall recent events, difficulty in completing a line of thought thus becoming 'tongue-tied' in the middle of a sentence and a strong inclination to use wrong words, saying 'door' when they mean 'table' or 'hot' when they mean to say 'cold' are all common deviations from normal cerebral function. Complete inability to comprehend a paragraph even after a second reading is very noticeable. These may be accompanied by bouts of uncontrollable weeping which proves acutely embarrassing to those of a stoical temperament who regard such an event as demeaning to their philosophy of life. Alterations of sleep rhythm and/or vivid dreams are common and these occur in patients with no previous experience of such phenomena. In a very tragic case in a young University student complete reversal of sleep rhythm led to suicide.

Frequency of micturition and hyperacusis are an almost invariable accompaniment of these cerebral features and together with episodic sweating and orthostatic tachycardia can only be attributed to involvement of the autonomic nervous system. Though less frequently encountered episodic sweating is a very striking event. The wife of one such case is a trained nurse and reports that her husband may wake around 4 a.m. lying in a pool of water and with a temperature of 94 to 95°F. I diagnosed this patient as a case of M.E. fifteen years ago; the sweating episodes still persist.

Variability and fluctuation of both symptoms and physical findings in the course of a day is a constant feature in the clinical picture of M.E.

The Chronicity of Myalgic Encephalomyelitis

The alarming tendency of M.E. sufferers to become chronic is the final distinguishing feature from all other forms of postviral fatigue syndrome. In a group of 150 members of the Association in the North of England 36 have had the disease for 10 years or more. Of 55 members in a small group in Surrey 29 have had the disease for 10 years or more; of these 4 have had the disease for over 20 years, 4 have had it for over 30 years and one for over 40 years. One member in the north country group has also had it for over 40 years. I am fully satisfied that at a conservative estimate 25% of victims of M.E. have had the disease for 10 years or more. Only Myalgic Encephalomyelitis has such a legacy.

The chronic case of M.E. can take two different forms. In the first there is a recurring cycle of remission and relapse. In three doctors who contracted the infection between 1955 and 1958 the endless alternation of remission and relapse, still continues. In my experience a remission can last as long as 3 years. Marinacci and Von Hagen record one of seven years. The second form of chronic M.E. is more tragic in that no remission occurs. The patient lives a very restricted existence, unable to walk more than a short distance and that with considerable difficulty, unable to read for any length of time and in many cases subject to disturbance of sleep rhythm and/or vivid dreams and always the almost invariable frequency of micturition, hyperacusis and dizzy spells. A few of these chronic cases are compelled to sleep upright as a result of permanent weakness of the intercostal and abdominal recti musculature.