Paper presented by Dr Byron Marshall Hyde M.D. – Nightingale Research Foundation
Paper presented by Dr Byron Marshall Hyde M.D. – Nightingale Research Foundation
New South Wales, February 1998
Abstract: At the 1998 M.E./CFS conference in Australia, both Myalgic Encephalomyelitis and Chronic Fatigue Syndrome were used to describe a chronic illness. This paper is a discussion on the similarities and differences in these two terms that may lead to scientific difficulties. The author suggests that the definitional criteria and epidemic history of Myalgic Encephalomyelitis (M.E.) and the inclusion criteria are significantly different from the CDC definitions and history. The three typical phases of M.E. are discussed. A brief review of some of the known deaths in phase 2 of M.E. are also mentioned.
Myalgic Encephalomyelitis (M.E.) This is a term used to describe an epidemic and sporadic disease process that is associated with a chronic debilitating illness of children and adults. Variants of this term M.E. were first used following a series of repeating epidemics starting in May 1955 in the Royal Free Hospital in London England. New outbreaks of this illness continued until 1958 in various London area hospitals. M.E. and these epidemics are well described by A. Melvin Ramsay in his book Myalgic Encephalomyelitis and Post-Viral Fatigue States.
The characteristic M.E. illness is a disease process that can, in its complete form, be separated into three distinct phases.
Phase #1 This prodromal phase is associated with a usually short onset or triggering illness. This onset illness usually takes the form of either, or any combination, of the following, (a) an upper respiratory illness, (b) a gastrointestinal upset, (c) vertigo and (d) a moderate to severe meningitic type headache. These are only the most common onset illnesses or symptoms of which there are several. The onset illness is associated with either a low grade or subnormal temperature, headaches, sometimes persisting and accentuated by movement with intermittent attacks of vertigo or dizziness. In the Royal Free Hospital epidemics, several hundred staff members of the various hospitals were involved and almost no patients. Many of the hospital staff who fell ill had a previous illness, immediately recent immunization or marked work exhaustion that preceded the illness. Evidence of a previous immune insult is found regularly in both epidemic and sporadic cases.
Phase #2: Principal Illness: The acute phase of the principal illness then appeared in these patients. They complained of limb, back and neck pain, paraesthesiae and blurring vision. Muscle cramps, spasms and twitching and deep muscle tenderness were common but the dominant feature was muscle and brain fatigability and irritability even after a minimal degree of physical or intellectual exertion. Evidence of autonomic nervous system involvement was present in many cases. Another major component was cerebral involvement, which usually took the form of impairment of memory, concentration and emotional response. Seizure-like phenomena are not unusual. Many of these Royal Free patients had abnormal EEGs during the phase #2 period. The illness was considered consistent with an encephalomyelitis. The patients often complain of (a) abnormal cardiac rhythm, or (b) unusual cardiac movement. However, when examined by routine ECG, pathological features are rarely observed. In some cases the cardiac symptoms actually represent pectoral or other muscle spasm. In others, orthostatic cardiac irregularities that are not necessarily observed in supine ECG examination may be the cause. Diaphragmatic or counter-peristaltic abnormalities may also cause these sometimes pseudo-cardiac symptoms. During this phase the patient often appears quite ill. This phase can persist for weeks, months, or, in severe cases, one or two years. In a rare small percentage of individuals, phase #2 can persist for years or even permanently. This is unusual. In general, the severity of the complaints, particularly the abnormal muscle movements, seizure phenomena and severe headaches tend to taper off. Autonomic dysfunction, when it is of significant importance, rarely improves. As noted, infrequently phase #2 can become chronic. Very infrequent deaths have been known to occur in this phase and usually are represented by two different pathophysiologies. . Dr. John Richardson of Newcastle upon Tyne, U.K. has noted deaths in professional athletes who return to active professional sports, "to work off the flu". Cause of death has been attributed to orthostatic cardiac irregularity. It is also during this phase that CNS deaths occurred in the Cumberland Epidemic, in the Akureyri epidemic, and in one of the Mediterranean epidemics.
Phase #3: The chronic phase of the principal illness then followed phase #2. In 1988, it was this often-amorphous phase #3 that the CDC labeled Chronic Fatigue Syndrome (CFS). Where M.E. and CFS overlap, they undoubtedly represent the same illness, however, due to the considerable definitional and conceptional differences, CFS and M.E. should not be considered to be the same illness.
In phase #3, the M.E. patient is always prone to unusual and persisting muscle and CNS fatigability after relatively normal physical or intellectual exertion. The patients are not chronically fatigued. When unstressed physically, intellectually or emotionally, the M.E. patient appears totally normal and often has no difficulty doing very short-term tasks. The problem is above all, one of endurance and once exhausted, the increasingly lengthy time to recover to a reasonable degree of activity. The M.E. patient can suffer any or all of the following cognitive and emotional dysfunction: marked irritability, anxiety, panic, depression but most of all memory dysfunction exacerbated by any physical, sensory, environmental, emotional, social or economic stressors. Both from the patient and physicians point of view there were major difficulties in that there was a considerable lack of obvious or substantial physical signs to correlate either the severity of the symptoms or the often marked prostration of the individuals concerned. Depending upon the degree of initial illness, location or character of injury or vulnerability of the individual, this Phase #3 may persist in the fortunate cases for a period of months or up to a year, sometimes in a constant illness or as a recurrent illness triggered by any physical or intellectual activity. The unfortunate individuals, of which there are a great percentage, never recover. It is very hard for many physicians to understand, why an individual, with few or no external stigmata of disease, and no obvious psychiatric illness can be so totally disabled. The M.E. condition could be compared to land full of new Porches or Masserattis with faulty batteries in a country with no battery testing machinery and no spare batteries. They look good, they should go, but they don't. In this phase, despite their severe disability to any stressors, the patient often appears relatively normal to the inexperienced physician. It is in this phase that most accidental and suicidal deaths occur.
Dr. A. Melvin Ramsay followed many of those who fell chronically ill during this 1955-1958 epidemic period for up to 34 years, until he died in 1989. This type of epidemic continuity proved to be quite characteristic of the M.E. epidemics that occurred in Akureyri in 1947-1949, in the Royal Free epidemics and in the North American epidemic period that extended from 1984 to 1988 (In 1983 in New Zealand where this pan-epidemic may have originated. All of these epidemics occurred in the late summer and autumn, decreasing in winter, with a new small peak of new female cases at Christmas in the Northern Hemisphere. The numbers of new cases would then rapidly fall off as the winter months progressed, only to reappear in the late summer again.
Monthly pattern of onset of new M.E. /CFS illness
This M.E. type of epidemic that was first observed and documented in detail in the summer of 1934, Los Angeles County General Hospital Epidemic by Dr. Alexander (Sandy) Gilliam, is not uncommon. Over 60 similar but often less known epidemics have been documented by Dr. J. Gordon Parish.
These epidemics have been associated with certain particular characteristics. Onset can be at any season but most frequently occurs in summer or autumn. There appears to be a high prevalence of epidemics or clusters in schools, hospitals and institutions involving hospital staff. Teachers, residential students or students engaged in team sports or orchestras traveling in groups appear more affected. The illness is less common in patients hospitalized for other causes and non-residential students. In patients seen at Nightingale, staff and teachers at institutional schools, particularly for the physically or mentally disabled appear to be greatly at risk. The usual incubation period of the triggering illness is 4-6 days. The second and third phases of the illness are usually always different in nature from the onset illness and usually become apparent within 1-4 weeks after the onset of the presumed infectious triggering illness. Much interest has been associated with herpes virus in the United States of America, particularly EBV, (incubation period approximately 40 days) and HHV6 (HHV6 is simply the common and innocuous roseola virus of children with an incubation period 10-12 days). Because of their quite different incubation periods, it is highly unlikely that either of these two viruses are significant contributors, if at all, to M.E. illness. (Over the years, the repeated and reputed association of these two herpes viruses with M.E./CFS is perhaps mythological). The herpes virus association is more likely (1) correlation phenomena caused by the glut of herpes virologists in North America. However, perhaps a more important reason is (2) allowing a small group of herpes virologists or their friends at NIH to have control over the funding of M.E./CFS research in the United States of America. British and previous Australian researchers have been historically more interested in the enterovirus association. Enterovirus infections have an incubation period identical to incubation periods noted in most of the M.E. epidemics, that is, of 4-6 days.
Probably the best descriptive definition of M.E. is found in Ramsay's book mentioned earlieri or in the Doctoral Thesis of Dr. Andrew Wallace,vii a Scottish physician who immigrated to Adelaide, Australia. Wallace's thesis discusses an epidemic in Cumberland in Northern England. It is unfortunate that more M.E. physicians have not read it. This thesis is important since it not only represents one of the best descriptions of the epidemic M.E. disease but also documents deaths associated with this illness. The deaths although few in number are important since not only do they give us a useful pathological insight, they also underline the potential and usually unrecognized severity of M.E. Documented deaths have occurred in several M.E. epidemics, but are best documented in the Cumberland epidemic and were well known in the Akureyri epidemic. All of these deaths involved CNS injury. The Akureyri epidemic involved at least 7 prepubertal children in Friedrikshavn who developed M.E. followed by Parkinson-like illness and died. x Documented deaths in sporadic cases of M.E. are known, but it is my experience that treating physicians often become vitriolic when the deaths are attributed to M.E by the families of the deceased. M.E. and CFS may be the only illnesses in history from which some physicians believe the patient is invulnerable to death.
This M.E. definition is important in that unlike the CDC definitions of Chronic Fatigue Syndrome, the Wallace and Ramsay definitions of M.E. observes the importance the initial acute variable infectious type illness associated with subnormal temperatures. They then note the important secondary and resulting chronic illness characterized by CNS and the autonomic nervous system features and intellectual and muscle dysfunctions and their chronic persistence. Enlarged cervical lymph nodes and pharyngitis are almost never observed in the chronic phases of M.E. and yet by definition, they form part of the characteristic findings in CFS. M.E. is also distinguished from CFS in that multiple organ involvement, seizure activity, death, and autonomic nervous system dysfunction occur in M.E. and by definition, these simply do not occur in CFS. Perhaps the most important difference is that chronic fatigue, by definition occurs in 100% of CFS patients. In M.E. chronic fatigue is not an essential factor, but rapid CNS and muscular fatigability with a pathologically slow recovery or loss of stamina is an essential finding. In M.E., the illness, the disease process, its investigation and pathology starts on the day the patient ceases to be well. In CFS, the Atlanta based CDC has decreed that the disease process starts only on the first day of the sixth month.
Having stated this, after having examined more than 2,000 chronic CFS patients, I have almost never found, (1) enlarged cervical glands, (2) obvious pharyngitis, or (3) elevated temperature. Why is this? It is my belief that the initial CDC definition, was created by a group of well meaning researchers and physicians who, with two or three exceptions, had for all purposes never routinely seen or examined CFS patients. Further, it is my opinion, that this group of well meaning individuals, were initially so complicit in believing that EBV was the cause of CFS, that they simply incorporated diagnostic features of infectious mononucleosis (glandular fever) into the CDC, CFS definition. It is a telling fact, that with the exception of two, perhaps three, of the original sixteen authors of the CDC definition, the majority have never again published on CFS or ever routinely seen and examined any CFS patients. It is also important to note that three of the physicians, who had the longest experience with M.E./CFS patients, withdrew from the initial CDC definitional committee.
Conclusions: Definitions are not diseases, they are often simply the best descriptions that physicians and researchers can offer, with their always imperfect knowledge, to describe a disease. Good definitions are good because they correspond closely to the disease state being described. It is thus important that those that attempt to define any disease or illness to have long term clinical experience with patients with this illness. There is simply no place for the bureaucrat in defining illness. All definition of epidemic or infectious illness must be based upon persistent clinical examination of the afflicted patient, an understanding and exploration of the environmental factors producing that illness, and pathophysiological examination of tissue from those patients. For similar reasons, I believe that the inclusion of psychiatrists in the defining of an epidemic and obviously disease of infectious origin, simply muddies the water for any serious understanding of that disease. The UK definition of CFS was developed by a panel of physicians who were primarily psychiatrists, with few if any clinicians who had ever looked at an epidemic of CFS. A serious attempt must be made to look at epidemic disease as and where that disease starts. This has not been done by those who have defined CFS in the USA nor in the United Kingdom and this factor alone is probably the single greatest reason why we know so little about CFS today that we did not know in 1984.