Myalgic Encephalomyelitis Summary


Myalgic Encephalomyelitis (ME) is an acquired complex disorder characterized by a variety of symptoms and physical findings potentially affecting multiple systems of the body. Many cases are preceded by a viral infection, usually a flu-like or upper respiratory illness, although ME can also be preceded by a non-viral illness or other trauma such as chemical exposure. Onset is usually rapid (acute) but gradual onsets are also reported. Affected individuals do not recover from the infection and instead experience a wide variety of symptoms including an inability to produce sufficient energy to meet daily demands. Marked fatigue and weakness, sickness, cognitive dysfunction and symptom flare-up follows physical and cognitive exertion. Additional symptoms that may occur include headaches, pain, muscle weakness, neck pain, vision abnormalities (such as blurred vision), a sensation of tingling, burning or numbness of the extremities (paresthesia), bladder and bowel dysfunction, and sleep dysfunction. Cardiovascular abnormalities have also been reported. Myalgic encephalomyelitis is a chronic and disabling disorder. Severe cases often leave affected individuals bedridden or housebound. Myalgic encephalomyelitis may occur as an outbreak that affects a large group of people (epidemically) or may only affect an individual (non-epidemically).



There is significant controversy and debate in the medical literature about the relationship between Myalgic Encephalomyelitis. The first outbreak of Myalgic Encephalomyelitis was in 1934 and the term Myalgic Encephalomyelitis first appeared in the medical literature in 1956. Myalgic Encephalomyelitis is recognized as a distinct disorder and has been classified as a specific neurological disorder by the World Health Organization (WHO) since 1969.  Myalgic Encephalomyelitis should retain a strict definition as a distinct neurological disease that includes measurable abnormal changes in the brain and central nervous system. Individuals who meet the strict criteria of the ICC 2011 would be diagnosed with Myalgic Encephalomyelitis.



3 of the more common case definitions include the following                                               


Fukuda et al. (1994) case criteria for CFS:         

The Fukuda case definition was adopted by the Centers for Disease Control and Prevention (CDC), and stresses fatigue as a primary symptom. It also requires the presence of at least four of eight symptoms including:  memory and concentration impairment, sore throat, tender lymph nodes, muscle pain, joint pain, headaches, un-refreshing sleep, and post-exertional malaise). Research has indicated that individuals with a primary psychiatric illness (e.g. primary Major Depressive Disorder) may be misdiagnosed under the Fukuda criteria due to many overlapping symptoms including fatigue and sleep difficulties.                                                                               


Canadian Consensus Criteria for ME and CFS (Carruthers et al., 2003):                                                 

The Canadian Consensus Criteria defines ME/CFS as an acquired, organic, pathophysiological multi-systemic illness that occurs in both sporadic and epidemic forms and requires core symptoms including post-exertional malaise (PEM) and neurocognitive dysfunction, in contrast to the polythetic approach of the Fukuda case definition.             


​Myalgic Encephalomyelitis International Consensus Criteria (ME-ICC 2011).                                                                    The Myalgic Encephalomyelitis – International Consensus Criteria (ME-ICC) advocates for removing fatigue as a characteristic symptom and defines the disorder as an acquired neurological disease with complex global dysfunctions. The ME-ICC also defines specific symptom requirements: post-exertional neuroimmune exhaustion, neurological impairments, immune, gastrointestinal, and genitourinary impairments, and energy metabolism impairments.  



Dr Melvin Ramsay Defintion for Myalgic Encephalomyelitis

"The failure to agree on firm diagnostic criteria has distorted the data base for epidemiological and other research, thus denying recognition of the unique epidemiological pattern of myalgic encephalomyelitis."
-Dr. A. Melvin Ramsay-

In 1956, M.E. pioneer Dr. A. Melvin Ramsay formally coined Sir Donald Acheson's selected name for the disease myalgic encephalomyelitis in a paper describing the 1955 epidemic among staff at Royal Free Hospital in London.   Dr. Ramsay investigated M.E. for more than 30 years, and his sound descriptions of the disease and its accurate name have stood the test of time and have earned him a place of honor in M.E. history.                                                                                       Dr. Byron Hyde notes that Dr. Ramsay was "much loved by patient or physician and all who had the privilege to meet him...."

In Redefinitions of ME/CFS – A 20th Century Phenomenon, Dr. E.G. Dowsett summarizes historic ME and CFS definitions and emphatically states, "To Summarise: I would urge all our colleagues to look again at the literature prior

to 1988 before redefining this illness. Meantime, the Ramsay description of Myalgic Encephalomyelitis in 1986 with slight modifications to form a short definition still remains a useful guide to those new to this work:



The Clinical Features of Myalgic Encephalomyelitis  - Melvin Ramsay, M.D., 1986


The onset of the disease is similar to those described in the various recorded outbreaks. Thus it may be sudden and without apparent cause, as in cases where the first intimation of illness is an alarming attack of acute vertigo, but usually there is a history of infection of the upper respiratory tract or, occasionally, the gastrointestinal tract with nausea and/or vomiting.


Instead of an uneventful recovery the patient is dogged by a persistent and profound fatigue accompanied by a medley of symptoms:

  • Headache

  • Giddiness

  • Widespread muscle pain, cramps or twitching

  • Muscle tenderness and weakness

  • Paraesthesiae (numbnessor tingling in the extremeties)

  • Frequency of micturition (urination)

  • Blurred vision and/or diplopia (double vision)

  • Hyperacusis (sensitivity to noise sometimes alternating with deafness or normal hearing)

  • Tinnitus (constant sound in the ears)

  • General sense of feeling awful


Some patients report the occurrence of fainting attacks relieved by a small meal or just eating a biscuit; these attacks were the result of hypoglycaemia …  All cases run a low-grade pyrexia (fever), seldom exceeding 100°F (c. 38°C) and usually subsiding within a week.

Myalgic Encephalomyelitis 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 [paralytic muscle] fatigue is directly related to the length of time the patient persists in physical effort after its onset; put in another way, those patients who are given a period of enforced rest from the onset have the best prognosis.

Disease in Chronic State
Once the syndrome is fully established the patient presents a multiplicity of symptoms which can most conveniently be described in three groups.

Muscle Phenomena

  •  Fatiguability: Muscle fatigability, whereby, even after a minor degree of physical effort, three, four or five days, or longer, elapse before full muscle power is restored and constitutes the sheet anchor of diagnosis. Without it I would be unwilling to diagnose a patient as suffering from ME, but it is most important to stress the fact that cases of ME or mild or even moderate severity may have normal muscle power in a remission. In such cases, tests for muscle power should be repeated after exercise.

  • Pain: In severe cases of ME, muscle spasms and twitching are a prominent feature and give rise to swollen bands of tissue which are acutely tender. 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) with the tip of the forefinger should enable the examiner to detect minute foci or exquisite tenderness.

  • Clumsiness: In the aftermath of the disease patients frequently fumble with relatively simple maneuvers such as turning a key in a lock or taking the cork of a bottle. 


Circulatory Impairment. Most cases of ME complain of cold extremities, hypersensitivity to climatic change, Ashen grey facial pallor, 20 -30 minutes before the patient complains of feeling ill. 


Cerebral dysfunction

  • The cardinal features:

  • Impairment of memory

  • Impairment of powers of concentration and

  • Emotional lability

  • [Other] common deviations from normal cerebral function:

  • Failure to recall recent or past events,

  • Difficulty in completing a line of thought . . .

  • 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 “cold” . . .

  • Complete inability to comprehend a paragraph even after re-reading it

  • Bouts of uncontrollable weeping . . .

  • Alterations of sleep rhythm or vivid dreams, or both . . 


Accompanying features that can only be attributed to involvement of the Autonomic nervous system:

  • Frequency of Micturition (urination)

  • Hyperacusis (hypersensitivity to noise)

  • Epsisodic Sweating

  • Orthostatic Tachycardia


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




A Baffling Syndrome With a Tragic Aftermath.

                            By A. Melvin Ramsay M.D., Hon Consultant Physician, Infectious Diseases Dept,                                  Royal Free Hospital. [Published 1986]

Myalgic Encephalomyelitis 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 paralytic muscle fatigue is directly related to the length of time the patient persists in physical effort 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 attack 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, parasthesiae, 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, and 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 [fever] which quickly subsides. Respiratory symptoms such as sore throat tend to persist or recur at intervals. Routine physical examination and the ordinary run of laboratory investigations usually prove negative and the patient is then often referred for psychiatric opinion. In my experience this seldom proves helpful 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 the 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 led to suicide; one of these was a young man of 22 years of age.


The too facile assumption that such an entity - despite a long series of cases extending over several decades - can be 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 tissues from the time of the initial invasion and can be isolated from nerve ganglia post-mortem; to 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 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 routine antibody tests on patients suffering from myalgic encephalomyelitis have shown raised titres to Cocksackie B Group viruses. It is fully established that these viruses are the aetiological agents of 'Epidemic Myalgia' or 'Bornholm's 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 Cocksackie viruses are the sole agents of myalgic encephalo- myelitis since any generalized 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 suggests 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 in 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 phenomenom and this has often been detected by relatives some 30 minutes before the patient complains of being ill.


The third component of the diagnostic triad of myalgic encephalo- myelitis relates 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, while some others 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 phenomenom. 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 profound malaise or in those who, on the false assumption of 'neurosis', have been exhorted to 'snap out of it' and 'take plenty of excercise' 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 ME sufferer for 25 years. These show clearly that recovery of muscle power after exertion is unduly prolonged.


After moderate excercise, from which a normal person would recover with nothing more than a good night's rest, an ME patient will require at least 2 to 3 days while after more strenuous excercise 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 characterizes the chronic case.


The greatest degree of muscle weakness is likely to be found in those muscles which are most in use; thus in right- handed persons the muscles of the left hand and arm are found to be stronger than those on the right. Muscle weakness is almost certainly responsible for the delay in accommodation which gives rise to blurred vision and for the characteristic feature of all chronic cases, namely a proneness to drop articles altogether with clumsiness in performing quite simple manoeuvres; the constant dribbling of saliva which is also a feature of chronic cases is due to weakness of the masseter muscles. In some cases, the myalgic element 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 picture 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 stages of the illness. Those who are given complete rest from the onset do well and this was illustrated by 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 give 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.




The Nightingale Research Foundation

Canadian Charity dedicated to Myalgic Encephalomyelitis, uses a strict definition that states Myalgic Encephalomyelitis is an acute onset biphasic epidemic or endemic infectious disease process, where there is always a measureable and persistent diffuse vascular injury of the central nervous system in both the acute and chronic phases. For more information on specific case definitions, see the Resources and References sections of this report.


Byron Hyde's short videos provide an insightful concise perspective .



Dr Hyde had the opportunity to examine two physicians who had become ill during the 1934 polio epidemic outbreak.  At the Los Angeles (LA) County Hospital.  According to Dr Hyde’s slide, 198 healthcare workers, who were immunized With sera from recovering patients, fell ill with ME, but not Polio.

            He believes in this case that the combination of an immunization and viral infection triggered their  M.E.            The two doctors sued the Hospital and the city of LA and received about 2 million dollars each.

Dr Hyde’s hypothesis is that this was a wake up call for Insurance Companies to dismiss the illness and from then onward Anything resembling ME was mocked.  There were times when and even now, where ME patients were put into Psychiatric Hospitals and labeled as crazy  (plus given drugs that made them sick).  So, when CFS came along, it seemed to follow the same pattern.  Same illness, different name, same outcome.  


Unfortunately there is no consensus on nomenclature or classification for these disorders, and different countries, organizations, and researchers continue to use different names to describe these conditions. Until a global consensus is reached on how to name and classify these disorders, confusion will persist, and research will remain inconclusive. 


Causes                                                                                                                                                                                 The exact cause of Myalgic Encephalomyelitis (ME) is not fully understood, although there are several theories. Most investigators agree that the disease is most likely the result of an abnormal immune system and brain function in response to an infection or virus. Although the brain and immune system are most likely impaired or abnormal (dysregulated) in this disease, the exact underlying problems are unknown. A variety of additional factors that have been theorized as playing a role in the development of ME include genetic and environmental factors. Some studies have shown that ME occurs in greater frequency among relatives to the third degree (genetic predisposition). In contrast, some believe that environmental factors play a greater role than genetic ones. However, definitive evidence linking specific environmental factors to the development of Myalgic Encephalomyelitis is lacking.


Some researchers believe that an enterovirus infection could be an underlying cause of the disease. Enteroviruses are small, contagious viruses consisting of ribonucleic acid and proteins. They are the second most common viral agents in humans, behind only rhinoviruses (the viruses that cause the common cold). Enteroviruses can affect anyone of any age. Individual susceptibility to enteroviruses varies. The reason why some individuals develop ME after infection with an enterovirus is unknown.


Other viruses that have been speculated to be associated with ME include cytomegalovirus (CMV/HHV-5), Epstein Barr virus (EBV/HH-4), parvovirus B19, herpes simplex virus (HHV-1 or HHV-2), human herpes virus (HHV 6 or 7), and certain bacterial infections. It is not known whether these viruses caused ME or whether they developed due to an impaired immune system in affected individuals. It was once thought that the ability of the blood-brain barrier — the specialized capillaries that prevent blood contaminants from entering the brain–to block viral entry into the CNS was adequate; however, more recent evidence indicates entry through other routes, such as along the auditory nerve. Additionally, no one virus has been identified that explains all cases of ME. Some studies suggest that in individuals with ME the viruses can trigger cascading events in the central nervous system through chronic activation of the immune system which, in turn, can result in widespread (diffuse) neurological dysfunction, changes at the cellular level, and nerve cell injury and death.


Even when not actively replicating, an infection can lead to profound dysregulation of the immune response, causing neuroinflammation which destabilizes overall brain function, and producing symptoms with widely fluctuating severity levels.  Viruses also do not continually replicate, but do so at times of immune vulnerability, such as at times of physical or psychological stress. Unfortunately, viruses go latent, then they reactivate, and repeat this pattern.  Once in your cells, any elevation of cortisol levels can cause the reactivation.


Affected Populations                                                                                                                               

Because of The controversy regarding the definition and classification of Myalgic Encephalomyelitis (ME) and related disorders, determining their true frequency in the general population is difficult. The exact prevalence and incidence of ME is unknown, but one estimate places the prevalence at approximately 1 million affected individuals in the US general population. Approximately, three times as many women appear to be affected than men. Individuals of any race or ethnicity can be affected. Onset is most frequent between the ages of 30-50.


Disorders  thought to be related

A wide variety of disorders or conditions can have symptoms similar to those seen in Myalgic Encephalomyelitis (ME) including Multiple Sclerosis, Systemic Lupus Erythematous, Lyme Disease, Narcolepsy, Mononucleosis, Multiple Chemical Sensitivities, Gulf War Syndrome, and Chronic Epstein Barr infection. Comparisons may be useful for a differential diagnosis.   It is important to note that ME can not be self diagnosed.   



A diagnosis of Myalgic Encephalomyelitis (ME) is controversial and difficult. Because there are different case definitions for the disease, a specific set of symptoms for diagnosing ME does not exist.   Scientific Research are pursuing consistent and universally accepted biomarkers for ME.  Biomarkers are characteristics or substances that can be measured and evaluated in order to obtain a diagnosis or help obtain a diagnosis. A diagnosis of ME is ultimately based upon identification of characteristic symptoms (depending on the specific case definition used), a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests to exclude other possible diagnoses. Process of elimination, referred to as diagnosis by exclusion, is used by physicians whenever scientific knowledge is scarce, objective methods are absent, and attempt is made to rule out all other known conditions that could potentially explain patient symptoms.


Myalgic Encephalomyelitis is not Chronic Fatigue Syndrome  

The term CFS was first used in the medical literature during the 1980s in the United States. The criteria focused more on fatigue than the encephalitic (inflammation of the brain) features of the disorder. This was unfortunate, since there is more than sufficient robust evidence which illustrates the underlying biological process involving the central nervous system, immune system, energy metabolism and stress system. Consequently, the emphasis on fatigue unfortunately led to defining the disorder being seen as a psychiatric illness. Because little was known about the cause or physiology of CFS, a wide range of patients were diagnosed with CFS even though they may have had a variety of conditions and experienced different symptoms. CFS eventually evolved into a larger disease designation that overlapped with Myalgic Encephalomyelitis. Consequently, some researchers, patients, government organizations, and other organizations began to use the terms interchangeably or with the combined acronym ME/CFS, creating a broad disease category.

Further, some researchers, physicians, and patient advocacy groups have pushed to abandon the illness label of CFS as they argue it is inaccurate and trivializes affected individuals. They want to reclassify these individuals as having Myalgic Encephalomyelitis. Other researchers, physicians, and many ME patient advocacy groups have argued against this change, noting that Myalgic Encephalomyelitis should retain a strict definition as a distinct neurological disease that includes measurable abnormal changes in the brain and central nervous system. Individuals who meet the stricter criteria would be diagnosed with Myalgic Encephalomyelitis.


The term CFS should be reserved for individuals who fail to meet the more stringent criteria for Myalgic Encephalomyelitis and in whom no other underlying disorder or condition can be identified. Many patients who have been diagnosed with CFS would meet the more stringent criteria for Myalgic Encephalomyelitis. Individuals who fail to meet the criteria should be retested for an underlying condition as many individuals initially diagnosed with CFS are eventually diagnosed with an underlying condition such as cancer, multiple sclerosis, lupus, brucellosis, or another condition.


​Standard Therapies & Treatment

There is no cure for ME. Treatment is aimed at relieving symptoms and preventing a worsening of symptoms. Decisions concerning the use of particular therapeutic interventions should be made by physicians and other members of the healthcare team in careful consultation with the patient and/or parents based upon the specifics of his or her case, a thorough discussion of the potential benefits and risks including possible side effects and long-term effects, patient preference, and other appropriate factors. A specific treatment plan will be highly individualized.

Avoiding overexertion is extremely important in maintaining health in affected individuals. Depending on the individual, a variety of therapeutic options exist for alleviating ME symptoms which may include making changes to one’s diet, physical therapy, adjusting the pacing of activity levels, lowering overall exertion by getting a service dog, adjusting sleep parameters (regularizing sleep habits, changing pillows/blankets/mattress, room darkening, temperature, etc.), avoidance of substances (e.g. mold, chemicals) or situations prone to worsen one’s symptoms, and adjusting one’s lifestyle in ways that minimize the impact of physiological and psychological stress in general.


Some researchers have studied a treatment approach called “Pacing” as a potential therapy for some individuals with ME. This treatment option does not involve medications (non-pharmacologic) and strives to help affected individuals self-monitor and self-regulate their energy expenditures. By learning to pace their activity levels, affected individuals can stay within their “energy envelope.” Affected individuals are taught to balance expended energy with available energy to reduce the frequency and severity of some symptoms. Pacing can help affected individuals manage symptoms and, in some cases, can improve some quality of life.


Certain medications have been used to treat individuals with ME. However, many affected individuals are highly sensitive to medication. Additionally, because the underlying nature of ME is not fully understood, any specific medications or treatments should be considered cautiously. Initially, any medications should be given at low doses. No medications for ME are universally effective.


Affected individuals should be treated for any pathogens, toxins, or heavy metals as persistent exposure can worsen symptoms. Referral to an infectious disease specialist is recommended. Any antibiotics or antiviral drugs should be used cautiously.

The International Consensus Criteria  ICC 2011

The label ‘chronic fatigue syndrome’ (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term ‘myalgic encephalomyelitis’ (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization’s International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent

The ICPrimer for Physicians


It's essential to define clearly Myalgic Encephalomyelitis, returning the definition

to its clinical and historic roots and complementing this information with the

certitude of modern scientific testing. That is what the sets out to do."   

ME Expert Dr Byron Hyde



Precise Diagnostic Criteria for Myalgic Encephalomyelitis (M.E.).  his definition of distinct and exclusive of the various ChronicFatigue Syndrome definitions. It is based upon over 30 years of patient investigation and M.E. literature. This definition proposes M.E. and CFS should be considered as separate entities.  Proposal: Myalgic Encephalomyelitis (M.E.), distinct from CFS is the result of an acute and chronic Enteroviral (E.V.) post-encephalitic injury, a close genomic cousin to the three recognized polioviruses. M.E. is diagnosed by (a) the clinical history and at least (b) two reproducible scientific tests, which are: (i) proof of enteroviral infection & (ii) appropriate diagnostic brain SPECT mapping with Segami Oasis Neurogram software. Also these two tests are sufficient to make a diagnosis and to reduce diagnostic costs. Unlike the CDC definition, which requires a six-month wait before a physician can diagnose CFS disease. As in any true disease, both of these tests become positive within the first week of M.E. illness. The (a) localization, (b) degree & (c) variability of SPECT brain injuries accord with the patient’s clinical symptoms and disability.

Sonia Neubauer Grunberg, Clinica Las Condes, Santiago, Chile,.....John Chia, EV Med Research LLC, California, USA,.....Lorenzo Memeo, & Gabriella Timpanaro, Med. Inst. Oncology, Italy, .....Byron Hyde, Nightingale Research Foundation, Ottawa, Canada


The following are the simple and accurate diagnostic criteria for disabling M.E. and can be utilized in arriving at both a clinical diagnosis and for all scientific research papers.

  • The patient conforms to the clinical history of M.E. as described.


  • Proof of E.V. infection at onset or from gastric or GIT biopsy in chronic patients.


  • HMPAO brain SPECT (Single-Photon Emission Computed Tomography) demonstrating significant hypo-perfusion (up to 4 standard deviations below the normal mean) in at least the left temporal lobe and cingulate gyri employing Segami Oasis Neurogram software in all M.E. patients.


  • Increased M.E. disability is associated with an increased and irregular brain hypoperfusion of both cerebral hemispheres, midbrain and basal ganglia injuries. Motor difficulty is associated with hypoperfusion of motor cortex as seen in the following typical brain map of a chronic M.E. patient.  Dysautonomia associated M.E. is associated with insular lobe hypoperfusion (Operculum).

Multiple tests can confirm M.E. disability (eg. Keller, B cardiopulmonary exercise test). These 2 tests confirm M.E. illness itself. Depending upon degree of E.V. brain area injury, dysautonomia, & ongoing muscle weakness can occur.

The Clinical History
M.E. is a biphasic illness: The acute & chronic symptoms are identical to the onset symptoms in poliomyelitis patients as described by Wickman* in 1905, only lacking paralysis. As in polio & most enteroviral (E.V.) infections,
M.E. tends to onset in late summer and autumn. As in Polio, the incubation period is usually from 3-7 days in humans, possibly depending on viral lode.
M.E. is seen in both sexes and at any age, including children, but tends to be most frequently a post-pubertal, illness with circa 80% occurring in females, suggesting an autoimmune role (well carriers may create the appearance of a longer incubation period).

First Phase, The Acute Illness:

The first phase symptoms can be minor or missed, resembling an upper respiratory illness, (b) a significant flu-like illness with headaches, malaise and/or gastric upset, or (c) the first evidence of disease can be the severe second stage symptoms. Elevated temperature might occur but normal or slightly subnormal temperatures are usual. Patients may complain of feeling feverish or having chills and sweats. M.E. is rarely taken seriously at onset & mistaken as influenza, EBV or a short term illness. It is essential for the investigating physician to order E.V. tests to make this diagnosis.

Second Phase: Chronic Illness:

The severe second phase is diagnostic of the illness and in cluster and epidemic situations tends to begin anywhere from day 1 to day 10 following the initial onset phase. Physical signs tend to be limited. The symptoms of the second phase are divided into two parts:

2nd Phase Part One:

Unexplainable severe crippling exhaustion: The patient experiences overwhelming physical lassitude, and may appear semi-conscious and not wanting to move, often due to pain.


Pain may be described as either mild or severe, persisting, transitory or fleeting. There tends to be persisting malaise & migratory pain and infrequently polyarthritis. Pain may include severe headaches and retro-orbital eye pain, visible muscle spasms, chest and abdominal pain. Headaches can be severe as seen in encephalopathy. Many pain syndromes and their intensity tend to decrease over time. Narcotic use can cause persistence and addiction. Their use is cautioned. Narcotic withdrawal can cause increased pain.


(pins & needles) in extremities often occurs, causing physicians to consider multiple sclerosis, but CNS-MRI rarely demonstrate any significant shows abnormalities. Lumbar puncture in first two weeks may show (a) oligoclonal banding suggesting neuronal injury, (b) increased pressure and sometimes (c) leuco-cytosis.


The patient often feels so ill they believe they are dying. A sense of impending doom may prevail. If the patient is sufficiently conscious, anxiety can be a common early complaint. Compassion and physician understanding help. Anti-anxiolytics, anti-depressives and increased activity are often worse than the condition.

Lack of Physical Signs:

Unless (a) EV tests are ordered at onset or (b) EV GIT mucosa tests are examined in chronic patients or (c) appropriate brain SPECT mapping is requested, the most startling finding is the almost total lack of significant physical signs or positive routine tests commensurate with the patient’s severe symptomatic complaints & disability. Temperature increase, cervical glands, neurological signs are absent or infrequent. Inappropriate, routine lab tests tend to be negative.  Due to largely negative physical findings the physician may consider the patient’s illness hysterical or anxiety based. MRI, X-Ray, CT scans and routine blood tests are poor diagnostic tools for a scientific diagnosis of M.E. but are important to exclude other major diseases.

2nd Phase Part Two:

The severely disabling and chronic aspects of M.E.tend to be recognized once the early acute complaints become subdued or the new norm. This phase tends to manifest itself over the next two or more weeks and occurs when the patient attempts to mobilize themself or return to normal pre-illness activity, school or work. Any return to even a reduced physical or intellectual activity can be seriously problematic. The acute disability may persist for months. Major activity at this time has infrequently resulted in deaths. The patient becomes aware of major disabling, persisting and disquieting intellectual and physical changes which can include:  Neurological Associated Symptoms:


These may become permanent but are more significant in early illness.  Many CNS difficulties may occur: short term memory impairments or dysfunctions, mathematical or dyscalculia difficulties, difficulty remembering written material just read, anomia, facial agnosia, word dysfunction. Ataxia, near syncope or syncope, confusion & disorientation are common; (Bastien, S*).

Auditory, inner ear changes can occur frequently. Presbyacusia, auditory pain, balance difficulties and the inability to appreciate music due to acquired tone deafness may occur;

Particularly during the first weeks or months, visual abnormalities & distortions can occur regularly, including tunnel vision, spatial perception & distance judgment difficulties, visual agnosia, loss of night vision, colour perception, retro-optical pain, mild to severe light intolerance is frequent. Rarely, these can become permanent.

Persisting (a) Reynaud’s-like sensory changes in the extremities, peripheral coldness (b) menopausal-like sweats can occur in both men and women, (c) the inability to maintain a normal body temperature are all frequent findings. These neurological complaints can falsely suggest Vit B12 deficiency or M.S.

Inability to return to a normal physical state after minor physical activity is diagnostic. Post-activity disability can continue for days. Forced activity in our experience has resulted in death & in permanent house bound invalids. The young patient (16-60 years) describe themselves as becoming overnight, an ill 80-90- year person;

Major sleep dysfunctions, sleep reversals, hypersomnia and failure of restorative sleep become the norm. At onset, sleep can be associated with terrifying dreams;

Bladder dysfunction and interstitial cystitis commonly seen in polio and simulating bladder infection, also polyuria, interstitial cystitis and nocturia are frequent in women;

Tachycardia, hypotension, dysautonomia, POTS or hypertension can occur on minor activity & are often mistakenly dismissed by physicians as a result of inactivity:

For an additional list of M.E. signs & symptoms see:

For multiple and sometimes treatable causes of fibromyalgia and CFS, see: Missed Diagnoses:

Muscular Dysfunction:

After even minor activity, unusual persisting muscle weakness, malaise, inability to easily climb stairs without stopping occurs. A normal walking distance can cause patient days of muscle weakness and pain. Muscle spasms may occur early in illness.

Significant intercostal muscle pain, pleurodynia and spasm are common in the first years of illness and are often mistaken by the patient as cardiac symptoms.

Psychological Symptoms:

Psychological despair and reactive depression set in, particularly if the patient does not have support or disability pension access. The symptoms can be so severe, the fear the doctors are missing some terminal illness is a common patient sentiment. This becomes more evident when the patient’s physicians, due to unfamiliarity, are unable to find anything to explain the patient’s now chronic illness and the patient’s inability to return to the normal activity expected following what may have been mistakenly as a typical short-term viral infection or influenza.

A sense of abandonment often occurs when friends and family members begin to drift away, and physicians begin to talk of a psychological diagnoses, depression and suggest antipsychotic medications, which if taken, often make the patient worse and if abruptly stopped by the patient due to side effects or lack of funds, has provoked many suicides.

Gastroenterological, GIT Symptoms and Dysfunctions:

Pain, uncomfortable change of bowel habitus often occurs both at onset and in chronicity. Autoimmune bowel illnesses have been seen.  Beware: M.E. patients may have unrelated GIT illnesses not associated with M.E. such as bowel malignancy and ulcers. The physician must be aware of more traditional illnesses.

Conclusion: Any neuropsychology or neurology resident, if given these, acute onset,

post-viral neurological findings on an examination would be expected to place M.E. encephalopathy in the differential diagnosis.

Enteroviral (EV) Testing:

General Preamble: The proof of EV infection has previously always been difficult since there are over 100 different enteroviruses and often, E.V. tests are unavailable locally. E.V. infection can be identified by many ways
today, including:

  • Rising titres to specific enteroviruses at onset

  • Mobray and Yousef Monoclonal antibody test

  • ELISA antibody test for enterovirus, Bell,

  • Various stool tests for enterovirus

  • PCR testing

John Chia’s test has several advantages. Since a large number of M.E. patients complain of gastric difficulties they frequently have had an endoscopy examination where mucosal biopsies are taken and kept unstained for years in paraffin blocks. These are readily obtained unstained on microscopic slides and in Canada at no cost to the patient. The presence of un-typed enterovirus can be identified from these gastric mucosa sections.

Functional Brain Mapping with HMPAO SPECT & Segami Oasis Neurogram software

This requires the M.E. patient brain map called a Tc99m-HMPAO brain perfusion SPECT obtained with Neurogam software by Dr. Sonia Neubauer, Clinica Las Condes, Santiago, Chile on a classical M.E. patient of Dr. Hyde.

This OASIS software was developed by Dr. Ismael Mena & Segami Corp., USA in comparison with age related, healthy, drug, alcohol, tobacco, caffeine free controls.

For views of scans with in-depth explanations please refer to:  definitionofme_nrf_print.pdf

Discussion of Physiological Changes in this Brain Perfusion SPECT

Anterior Temporal Lobe Injury: hypoperfusion involving the left anterior temporal pole (Brodmann 38). It is these temporal (& cingulate) lobe injuries that both define & explain many M.E. disabilities.  


The anterior temporal area is the major brain area responsible for retrieving & processing all intellectual & memory data, including:

  • information gathering from memory storage banks in the cerebrum

  • all visual & auditory information & memory transmission, learning & processing, from the brain & certain external receptors, pass through this essential information center of the brain

  • speech comprehension, naming of items, word retrieval, voice identification

  • humour, irony, music appreciation is mediated through this and the posterior temporal region

Left Temporal Lobe

When the left temporal lobe is injured there is a disruption of learning, data transfer

and cognition. In all of our M.E. patients, the temporal lobe is always injured. Data retreived in Brodmann 38 is processed through the posterior cingulate gyrus.

Over-riding these defects is possible but severely energy costly. It is our belief that

at great energy expenditure the patient can, for short periods, override these

physiological deficits, but this energy expenditure can cause temporary or

long term regional brain activity to significantly decrease.

Insular Cortex Injury: In this patient’s brain map, there is hypoperfusion of the operculum, (the anterior sylvian fissure area of the temporal, frontal and parietal lobe junction). (The operculum overlies the insular cortex.) The insular lobe is a major area responsible for homeostasis and other autonomic, sympathetic and parasympathetic nervous system functions including heart and vascular regulation. This may be the CNS area largely responsible for much of the vascular and autonomic dysfunction of M.E. patients. In our experience, POTS and cardiovascular irregularity are typical findings in some significantly injured M.E. patients. They consistently have severe hypoperfusion in the operculum area.

The Cingulate Lobe of the Limbic System: There is significant hypoperfusion of the left posterior cingulate gyrus (Brodmann 23, 31), as well as the left anterior cingulate lobe (Brodmann area 33, 24) of the limbic system in this and all M.E. patients. However, in this patient there is also hypoperfusion in both left and right cingulate (limbic system).

The posterior cingulate is an area involving learning, memory retrieval, recall, learning complex motor skills, visual processing, emotions, consciousness, sleep and alertness functions. The posterior cingulate, in our experience, is directly related to the anterior temporal lobe (Brodmann 38) discussed above. It is believed to be an important area in regulating important cognitive data and retrieving autobiographical information.

The anterior cingulate (Brodmann 33, 24) shares many of the same intellectual and memory tasks as the posterior cingulate but also pain endurance, visuospatial attention, multi-tasking, auditory attention. There is generally injury in both cingulate areas.

Although significant hypoperfusion is always present in the left temporal and cingulate lobes of the limbic system in M.E. patients as noted by Goldstein* in 1990, in this severely disabled M.E. patient there is bilateral cingulate hypoperfusion. In addition there is hypoperfusion of the left motor cortex.

Other Laboratory Findings Found in M.E.:

The following laboratory findings give understanding to the noted first and second phase illness but are not always found. This may depend upon time after illness onset tests were sampled from the M.E. patient. They are not essential in making the laboratory diagnosis of M.E. but support a disability diagnosis.

  • Lumbar puncture: Positive oligoclonal banding & increased pressure & leukocytosis in first weeks. (Poser) (Suggesting CNS neuronal injury). This requires a lumbar puncture and is rarely done since the physicians tend to mistake the initially weeks of illness as a transitory influenza-like illness. (A small guage needle must be used due to potential increased spinal fluid pressure.)

  • SPECT: Basal ganglia hypoperfusion injuries. These findings can be seen in early & ongoing persisting chronic illness. (Mena; Hyde). Two of our M.E. patients have gone on to develop Parkinson’s disease which may be co-incidental, but this also occurred three years later in children, who then died as a result of the Akureyri M.E. epidemic in Iceland. 

  • Neuropsychological Abnormalities: There are measurable neuropsychological abnormalities on neuropsychological studies (Bastien*).

  • Circulating Blood Volume: There is a significant decrease in circulating blood volume in most patients. (seen in SPECT blood testing.)

  • ecrease in number and activity of Natural Killer Cells in early weeks of illness.

  • Cardio-Vascular Exercise Dysfunction in comparing resting and post activity exercise findings.

  • Sleep Function Studies in early years tend to be significantly abnormal with decreased or absent type 3

Major Contributors to This Presentation
L. Memeo & G. Timpanaro supplied 20 gastric mucosa specimens, 10 patients with gastric malignancy, and 10 from healthy obese patients.


No evidence of EV were found in normal gastric mucosa by J. Chia, who also documented chronic enteroviral infection of the gastric mucosa of all 20 of Hyde’s M.E. patients.


Acute EV identification in these M.E. patients was also made by (i) the Gov. of Ontario, Health Services and by (ii) DN Galbraith and Carron Nain, previously of Ruchill Hospital, Glasgow. Sonia Neubauer Grunberg and Ismael Mena: supplied the resting and post activity brain SPECT maps and a normal database comparison using Neurogam 


Oasis (Segami Corp.) software demonstrating gross perfusion abnormalities of 2, 3 and 4 standard deviations below normal in the affected lobes.


B. Hyde supplied: (a) History based upon 20 M.E. patients, (16 females and 4 males): (b) in-depth exhaustive family and personal histories, and laboratory, chemical, brain MRI and SPECT & vascular assessments, to rule out non-related illnesses. The neuropsychological brain map interpretations, & significance of the hypoperfusion brain injuries were correlated with neuropsychological studies & technological assistance by Drs. Bastien, S; Sweeney, J; Mariani, M; Persinger, M & Keller, B.  For References please see:


General Treatment Advice
In any disease or illness, all effective treatments depend upon an indisputable, reproducible scientific diagnoses. This booklet provides these criteria. This definition allows research scientists and pharmaceutical companies to research effective treatment modalities.  The various broad symptom-based CFS definitions are all non-specific and common to many chronic illnesses. There have been over 50 treatments suggested for CFS since it appeared as a working case diagnosis in 1988. The sheer number is a clear indication that there is no effective treatment for any of the various CFS diseases. Some of the many CFS diseases are treatable if the diagnostic cause is found. CFS is not a disease. It is many different and sometimes treatable diseases.

Clues to Diagnosis:

  • Proof of an enteroviral infection.

  • In the north-temperate latitudes, M.E. & enteroviral infections tend to begin in late summer and early autumn. (3) 80% of patients are women. (4) Students, teachers and health care workers are among the most common groups injured.

  • Immediate post immunization illness (within one week) can be a trigger. Immunizations decrease immune response for 1-3 week, particularly if they are already infected or leaving on a trip to a third world country.

Epstein Barr Virus:

Unlike M.E., EBV infectious mono (glandular fever in the UK) is associated with: (i) A blood picture resembling malignancy. (ii) Throat has a putrid thick white coating.  (iii) Enormous cervical glands. (iv) Often a branny chest rash. Youths usually recover in 3 to 24 months. Those in their thirties can die or have major brain injury. Late pregnancy + EBV can cause death. It is impossible to mistake EBV mono.

M.E. is a Polio Analog:

Ivar Wickman described M.E. in his 1905 epidemiological study of the Stockholm polio epidemic as superior polio as opposed to spinal and bulbar polio. Paralysis and death occur in bulbar and spinal polio due to catastrophic blood vessel injuries supplying the anterior horn cells, which in turn cause permanent nerve injury to muscles. There is no muscle connection in brain neurons, only weakness occurs. If the vascular supply to the neurons is injured as in classical paralytic polio, this might be treatable.

Initial Disease Severity:  

  • Depending upon the degree of upper CNS injury the patient’s illness varies.

  • Those with minor CNS injury tend to recover better. Those with major CNS injury as indicated in the brain SPECTs tend to recover only partially or not at all.

  • Total bed rest is essential during the first two or three months.

  • Then from 3-6 months, a very a slow return to modest activity, if possible. It may take years to recover reasonable functionality. Even mild injuries never fully recover all CNS facilities. Major injuries may never recover pre-illness abilities.

  • The younger the patient the better the chance of recovery. 

  • M.E. is additive in patients with collagen diseases, asthma, genetic associations (Ehlers Danlos Syndrome) or other chronic illnesses.

  • Avoidance of physical and emotional stress is essential during the first year.

Specific Anti-Enterovirus Anti-Viral Medications: Because motor neurons are not destroyed and paralysis has not occurred, the development of enterovirus specific antivirals in the future may provide a reasonable treatment modality. As in the initial statement, several anti-EV medications are being tested in animal models.

Protect the Patient:  Immediate short term disability pensions if available must be provided.  Stress makes M.E. illness physiologically worse and retards any recovery, if any recovery is to occur. A general, non-specific enterovirus immunization would prevent M.E.


Via: Jerrold Spinhirne

This is a list of ME symptoms found in 420 well-characterized ME subjects in the 1990 study "Myalgic encephalomyelitis a persistent enteroviral infection?" Postgrad Med J (1990) 66, 526-530. by E.G. Dowsett, A.M. Ramsay, R.A. McCartney and E.J. Bell.

This important ME study was conveniently not referenced in the IOM report, presumably because it contradicted the IOM panel's instructions from HHS to consider only ill-defined "ME/CFS." Dowsett and Ramsay's study was referenced in the ME-ICC. 

I reformatted the article's symptom list once for my easier reading. It's a fairly devastating group of symptoms.

TABLE II Symptoms and signs in 420 patients with ME

COMMONLY FOUND (>50%) No. % 

Muscle fatigue 420 100 

Emotional lability t 411 98 

Myalgia tt 336 80 

Cognitive disturbance ttt 323, 77 

Headache 310 74 

Giddiness, disequelibrium 302 72 

Autonomic dysfunction tttt 289 69 

Auditory disturbances* 289 69 

Reversal of sleep rhythm 268 64 

Visual disturbances** 260 62 

Parasthaesia, hypo & hyperasthaesia 256 61 

Intercostal myalgia/weakness 247 59 

Fasciculation, spasm, myoclonus 239 57 

Clumsiness*** 235 56 


Gastrointestinal symptoms**** 205 49

Disturbance of micturition § 160 38

Recurrent lymphadenopathy §§ 152 36

Arthralgia 118 28

Orthostatic tachycardia 88 21

Recurrent abacterial conjunctivitis 68 16

Orchitis/prostatism in young males 15/113 13

Seronegative polyarthritis 42 10

Vasculitic skin lesions 42 10

Myo/pericarditis 34 8

Positive Romberg sign 25 6

Thyroiditis in female patients 15/307 5

Mesenteric adenitis §§§ 5 1 

Paresis and muscle wasting 3 1

Notes:  lncludes:

Frustration, elation, depression;

Characteristically affects limbs, shoulder girdle, spinal muscles;  memory, concentration, anomia, dyslexia;  especially circulation and thermoregulation; *hyperacusis, deafness, tinnitus; **mainly loss of accomodation, photophobia, nystagmus; usually due to impaired spatial discrimination; ****nausea/disturbance of intestinal motility;  frequency incontinence, retention; enlargement, recurrent after prodrome; surgical intervention for abdominal pain.

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