M.E. Is Not Fatigue

  1. Use of the word “fatigue” either to name this illness or to describe this illness is erroneous. Patients and patient groups who want to “change the name” must first take responsibility accurately to describe the symptomatology. This is a disease wherein extending beyond a certain threshold of activity leads to severely disabling symptoms and physical dysfunctionality, possibly resulting from low cardiac output (see ourCardiac Insufficiency Hypothesispage), symptoms which can be described in specific, accurate terminology without reference to broad or demeaning terminology such as “fatigue” or “poor stamina.” M.E. is a disease, and patients are sick, with often excruciating symptoms that can be clearly articulated. The defining characteristic of M.E. is that patients relapse with physical exertion and develop disease progression  and severe physical dysfunctionality with continued physical exertion. Hence, the defining characteristic is exercise intolerance, post-exertional muscle weakness, generalized weakness, faintness, and pain; and post-exertional relapsing of symptoms. In some cases symptoms remit with rest, and in other cases they do not. Recent research has shown that viruses, an upregulated RNase L pathway, and mitochondrial dysfunction lead to low cellular energy in the heart, which results in diastolic dysfunction with reduced stroke volume and low cardiac output, and that postural stress and exercise exacerbates cardiac insufficiency in this disease. So if a patient improves with exercise, that patient does not have M.E. and may have some illness other than M.E. (for example, arthritis, depression, osteoporosis, and a number of other medical conditions do improve with exercise).

In addition to the above central characteristic, Ramsay described three main components of M.E.: (1) Muscle weakness and a delayed or impaired recovery of muscle function after exercise. This has been explained by lactic acid build up as well as cardiomyopathy and microcirculatory impairment under our research-updated interpretive hypothesis. (2) Circulatory impairment. This could include both macrocirculatory problems such as low cardiac output and microcirculatory problems such as coagulopathy, abnormal erythrocyte morphology, and other factors affecting the circulatory system such as dysautonomia and low plasma and/or erythrocyte volume, resulting in exercise and orthostatic intolerance. (3) Cerebral involvement: encephalopathy, encephalitis (see our reference to Dr. Bruce Duffy’s QEEG work below), neurological, and neuropsychiatric impairment. While all three must be present for a diagnosis of M.E., some patients’ symptoms may be brain predominant, others muscle predominant, etc. The 2003 Canadian Consensus Panel Case Definition for ME/CFS requires more narrow selection criteria than the 1994 CDC “CFS” case definition to make the diagnosis, including post-exertional malaise and fatigue, sleep disturbance, and pain; neurological, neurocognitive, dysautonomic, neuroendocrine, cardiac, and immune manifestations. It might be useful for researchers to stop using the CDC’s 1994 selection criteria for doing studies and to use the newer, 2003 ME/CFS selection criteria, as well as to subset M.E./CFS according to presentation of illness, degree of illness, and research findings to achieve more consistency in the research data.

While the word “fatigue” was occasionally used both by Ramsay and in the Canadian definition,  “fatigue” is too broad and inaccurate a term. There are more specific ways of describing the symptoms, such as dramatic loss of muscle power after exercise, delayed recovery of muscle function, orthostatic faintness, cardiac output problems, and other more specific terminology than “fatigue.” In 1921, Muscio suggested that “fatigue” should be banned from strict scientific discussion. The defining characteristics of M.E./CFS can be easily outlined without reference to “fatigue.”  What all patients must have, at least according to both of these definitional frameworks, is an abnormal muscle metabolism — a delayed or impaired recovery of muscle function after exercise, which patients experience as paralytic muscle weakness and pain, not “fatigue.” Tissue hypoxia-ischemia with its resulting elevated lactic acid can lead to muscle weakness and pain, and tissue hypoxia-ischemia destroys the respiratory chain and affects the mitochondria, which cannot function without adequate oxygen. According to recent research, mitochondrial dysfunction leads to diastolic dysfunction and low cardiac output – a heart that cannot meet the demands of physical exertion.  Dr. Paul Cheney has shown that mitochondrial dysfunction results in poor filling properties in the heart (because it takes more energy for the heart to relax and fill with blood than it does for it to squeeze and pump blood), resulting in reduced cardiac output and hence severe functional impairment in ME/CFS. Cardiac muscle pathologic changes have been documented in the research by Dr. A. Martin Lerner, and recent research by Dr. Cheney has also documented cardiac muscle pathologies.  A disease this severe should be given a more serious name than “fatigue.”


The symptoms of the disease are exacerbated by physical exertion, mental exertion, mental stress, or orthostatic stress. In severe cases, even slight orthostatic stress triggers relapses. Symptoms may range from mild, to severe, to life-threatening (such as tachyarrythmias or siezures). The level of activity that precipitates these symptoms may vary greatly in afflicted individuals, and the symptoms that relapse may vary. They may include: sore throat, flu, fever, chills, body aches, sweats, low body temperature, lymphadenopathy, muscle weakness, muscle pain, hypoglycemia, weight change, nausea, vomiting, vertigo, chest aches, chest pain, cardiac arrhythmia, resting tachycardia (this has been explained as compensating for low stroke volume to help increase cardiac output), orthostatic tachycardia, orthostatic fainting or faintness, opthalmoplegia, eye pain, stroke-like episodes, difficulty swallowing, paresthesias, peripheral neuropathic pain, polyneuropathy, extreme pallor, sleep disorder, myoclonus, hyperreflexia, temporal lobe and other types of seizures, cognitive, memory and concentration impairment, attention deficit, anxiety, confusion, disorientation, light/sound sensitivity, blurred vision, wavy visual field, and other visual and neurological disturbances. Allergic hypersensitivity is also common in the disease. The above information is taken from four sources: (1) Ramsay’s observations, (2) the Canadian Clinical Case Definition, (3) patient reports, and (4) reports from other publications.

Turning to those publications:

Case Definitions

  1. Most of the current research articles, especially in America, on findings that fit our above-described M.E. framework were published on under the name “chronic fatigue syndrome” (“CFS”). Unfortunately, because of the broadness of the CDC’s 1994 case definition for  “CFS,” known as the “Fukuda criteria,” “CFS” became something of an umbrella term for a number of diverse diseases. Selection bias became a problem, and everything from depression to viral cardiomyopathy was published on under the name “CFS.” Using the ME/CFS case definitions instead of the U.S. government case definition and conducting research on precise subsets could help remedy this problem. (See our Research-Based Subsets page.)

Currently, two incompatible categories of “CFS” exist: (1) The CFS of the 1994 U.S. government case definition, the Fukuda criteria, which fails to select patients using any past or current research. It does not select for muscle weakness, cardiocirculatory, orthostatic, or neuroendocrine immune disease; it does not describe any published lab work; and it focuses on “fatigued persons,” making post-exertional sickness or malaise optional. These criteria were a government invention and are too broad to define any disease. Dorland’s Medical Dictionary states that to “diagnose” is to engage in “the art of distinguishing one disease from another.” The too-broad Fukuda criteria lump heterogeneous conditions and hence fail in defining a disease. It is widely recognized that the CDC case definition selects a heterogeneous patient population, as does the concept of “fatigue,” which was forced on patients and researchers by Holmes et al. (1988 US government case definition) who were new to the field. (2) The other version of “CFS” is the “CFS” of volumes of articles on cardiac disease, circulatory disease, dysautonomia and endocrine disorders, abnormal muscle metabolism, mitochondrial disease, immune disease, viral and bacterial disease, orthostatic problems, cardiac output problems, etc. Yet none of these telling research findings are listed or required for diagnosis in the CDC’s case definition. We will leave it to the reader to judge whether this is government bureaucratic incompetence or a deliberate attempt to cover up important research. But the newer research-updated Canadian Clinical Case Definition more accurately describes the disease, and should be used for diagnosis and modified and adopted by the government for research.

M.E. and CFS are not two different diseases (even if they are two different case definitions). Disease entities are facts and phenomena, while names and case definitions are mere human constructs. Some constructs are more accurate than others. Some select a different population than others. The name “CFS” and the 1994 CDC Fukuda case definition were constructs that were simply inaccurate — they were too broad, selected a heterogeneous population, and failed to be based on important research findings. The solution to these confusions is to stop using the CDC’s case definition. Recent research findings on cardiac output problems in ME/CFS make the U.S. government’s case definition even more obsolete. Canada, New Zealand, and Australia have begun to use the ME/CFS definition, and in the U.S. a pediatric case definition is in the works for ME/CFS.

As regards naming, there is little research on “myelitis” (although we do not discourage such research). There has been some research on “encephalitis” because systemic herpes infections also infect the brain (in addition to infecting the heart, as Lerner has described). QEEG tests done by Harvard neurologist Frank Duffy, M.D., showed a very high amplitude alpha rhythm and epilepsy-like discharges in the temporal lobes of patients with the disease.  The temporal lobes have a predilection for infection by herpesviruses in herpes encephalopathy and encephalitis. <color=”#31659c”>(For newer research on brain and neurological impairment in ME/CFS, see our Research-Based Subsets page.)

Scientific progress cannot be made when researchers focus on a poorly defined symptom like “fatigue.” The term “chronic fatigue syndrome” focuses on a poorly defined symptom that does not accurately characterize the symptomatology experienced by patients, promotes misunderstanding, and contributes to the disparaging manner in which patients are treated by physicians. The name has negatively impacted the quality of medical care patients are able to obtain. Many researchers, patient groups, and authors of government documents in the UK, Australia, New Zealand, Canada, and the U.S. have chosen to use the name ME/CFS as an interim compromise and to link this encephalopathy/cardiomyopathy disease worldwide until a more suitable name that eliminates the terms “chronic” and “fatigue” can be found.

M.E. Is Not “Medically Unexplained”

3. Unlike somatization disorder, M.E./CFS is not “medically unexplained.” M.E./CFS is a disease which, like lupus, has no single marker. While M.E./CFS is a multi-system disease with many organ and bodily systems affected, producing a myriad of symptoms, and while no single etiology has been found for M.E./CFS, many aspects of the pathophysiology of the disease have, indeed, been medically explained in volumes of research articles. Circulatory impairment, which the CDC case definition fails to mention, has been explained in terms of coagulopathy (Berg) and/or abnormal erythrocyte morphology (Simpson), low plasma and/or erythrocyte volume (Streeten), and low cardiac output (Cheney). Brain/neurological impairment has been documented by numerous researchers.  There are well-documented, scientifically sound explanations for why patients are often bedridden and unable to maintain an upright posture.  We ask the reader to visit our Cardiac Insufficiency Hypothesis page, our home page, our References page, and our Research-Based Subsets page to study these scientifically sound medical explanations.

The most compelling research to date that explains the severe physical dysfunctionality in ME/CFS is the research on low cardiac output available on our cardiac page. Writer Laura Hillenbrand, in her 2003 article in the New Yorker,  stated: “I was sure that being moved would kill me.” In 2005 and 2006, research finally showed that in ME/CFS, cardiac output is sometimes too low to meet the demands of movement, and any attempt to exert oneself beyond one’s own capacity for cardiac output – that is when demand exceeds cardiac capacity – would indeed result in death. Studies on dogs have shown that when the demands of the body exceed cardiac output by even 1%, the organism dies. ME/CFS patients reduce demand and reduce their exertion level to stay within the bounds of their low cardiac output to stay alive.


  1. M.E./CFS appears to be a “different insult/same result” disease, and no single viral, bacterial, or environmental etiology is likely to be found, although we are open to any discovery to the contrary. However, as Ramsay states, “the particular invading microbial agent is probably not the most important factor . . . the key to the problem is likely to be found in the abnormal . . . response of the patient to the organism.” Identifying and treating infections early in the disease is important to halt any aberrant immune responses. While the insults may be different, there may be a common pathophysiology.

Inappropriate Treatments

  1. Cognitive Behavioral Therapy (CBT), Graded Exercise Therapy (GET), and antidepressants are not effective treatments for M.E. In fact, these therapies generally make M.E. worse. For an excellent criticism of the CBT/GET studies from the Canadian Clinical Case Definition, see Dr. Cheney’s theory on why SSRI antidepressants make ME/CFS patients worse in some cases, order his 2006 lecture, “The Heart of the Matter.”. (See cardiac page.)

Progressive Cases

  1. M.E. can be progressive (going from bad to worse, increasing in scope or severity), degenerative (change of tissue to a lower or less functioning form, as in heart failure), chronic, relapsing and remitting, acute (having a short or a severe course), or lead to terminal complications ending in death.  Many cases of M.E. are progressive and degenerative (around 30% of cases), and some have led to complications that were terminal (see the National CFIDS Foundation Web site). Drs. Arnold Peckerman and A. Martin Lerner argue that the disease is progressive. Leonard Jason, Ph.D., recently published a morbidity and mortality study showing premature deaths from heart failure and cancer. Deaths in England due to heart failure and some due to severe dehydration have been documented. In M.E., as in lupus, patients do not die specifically of the disease, but of complications, often prematurely in their 30’s and 40’s. Some groups, researchers, and films claim that most deaths are from suicide. The IN MEMORIUM list we refer to does not confirm that piece of propaganda.

In her recent paper (Jan 01), “THE LATE EFFECTS OF ME,” the well-known English ME specialist Dr. Betty Dowsett wrote: “…..FINAL STAGE (1,2) After a variable interval, a multi-system syndrome may develop, involving permanent damage to skeletal or cardiac muscle and to other “end organs” such as the liver, pancreas, endocrine glands and lymphoid tissues, signifying the further development of a lengthy chronic, mainly neurological condition with evidence of metabolic dysfunction in the brain stem. Yet, stabilization, albeit at a low level, can still be achieved by appropriate management and support. The death rate of 10% occurs almost entirely from end-organ damage within this group (mainly from cardiac or pancreatic failure). It has to be said that suicide in younger patients and in earlier stages of the disability is related to the current climate of disbelief, rejection of welfare support and loss of educational and employment prospects.”
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References  (For additional references, see our Research-Based Subsets page and our Cardiac Insuffiency Hypothesis page.)

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