"This illness is to fatigue what a nuclear bomb is to a match. It’s an absurd mischaracterization."
-
Laura Hillenbrand, Bestselling author of Seabiscuit

“The term[s] ‘fatigue’ and ‘chronic fatigue’ never existed in this entity until it was put into [the name] in 1988…The whole concept of fatigue has warped our understanding of this illness.”  - Byron Hyde, M.D., The Nightingale Research Foundation, Ottawa, Canada

 
 
   

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Spotlight on:

The M.E. Society of America is an organization that seeks to promote understanding of the disease known as myalgic encephalomyelitis (ME/CFS), a multi-system disease adversely affecting the cellular mitochondria and the heart, brain, neuroendocrine, immune, and circulatory systems. M.E. was first described in the 1950’s following the recognition of many cases around the world, including a number of cases at the Royal Free Hospital in England. Many different viruses, bacteria, or toxins in combination with genetic factors may be involved in the etiology of the disease, which usually begins in childhood or early adulthood with an acute infection. Studying research-based subsets is the key to scientific progress in this area of investigation.  In a number of publications, Dr. A. Melvin Ramsay outlined a definitional framework for M.E. that described abnormal muscle metabolism, circulatory impairment, and cerebral involvement. 

Unfortunately, in 1988, what was historically known both as myalgic encephalomyelitis and as the well-documented epidemic neuromyasthenia was renamed “Chronic Fatigue Syndrome” by employees at the Centers for Disease Control (CDC), who imposed the misleading “fatigue” term onto patients and researchers.  In 1994, more damage was done when the CDC broadened the definition for CFS to include many diverse, unrelated diseases, for which “CFS” became an umbrella term.  Broadening the case definition led to conflicting research data. In 2007, the CDC virtually wrote the disease out if existence by broadening the case definition for "CFS" even more, to include anyone with "fatigue" and to exclude those with documentable neurological, circulatory, cardiac, and other conditions that would identify one with what was previously known as and called myalgic encephalomyelitis. However, there is a current, research-based case definition available on this Web site that was compiled by the Canadian Consensus Panel for ME/CFS in 2003, which includes neuroendocrine, immune, and cardiocirculatory symptoms as well as abnormal muscle metabolism, circulatory impairment, and cerebral/neurological involvement, and also lists neurally mediated hypotension, postural orthostatic tachycardia syndrome, and cardiac arrhythmia. In one study, this Canadian Clinical Case Definition selected patients who had more physical functional impairment, neurological, and cardiocirculatory symptoms and had variables that significantly differentiated them from a psychiatric comparison group. The ICD-10 code for ME/CFS is G93.3.

The M.E. Society of America Web site features research and advocacy issues pertaining to ME and ME/CFS as it is defined by the Canadian Clinical Case Definition and the 1988 Holmes et al. case definition for CFS, and does not represent patients with so-called "CFS" as it is currently defined by the U.S. Centers for Disease Control and Prevention.

Mounting research indicates that orthostatic intolerance, in some cases involving a virally induced dysfunction of the autonomic nervous system, low plasma and/or erythrocyte volume, left-ventricular failure upon postural stress, and diastolic cardiomyopathy with often left atrial cavitation upon upright posture is a prominent feature of ME/CFS. For something so severe, the term "fatigue" is vague and inaccurate. A more accurate use of language would be to use  “muscle weakness and pain” or “delayed muscle recovery after exercise,” orthostatic faintness, and cardiac output problems to characterize the symptomatology. To access new research on these topics and to view a streaming video of a lecture on CFS and diastolic cardiomyopathy, see our Cardiac Insufficiency Hypothesis page.

There is strong evidence that mitochondrial dysfunction plays a role in the pathophysiology of ME/CFS and of other neurological diseases. Research has shown respiratory chain deficits and damage to the mitochondrial DNA, and, when the degree of illness is severe, acquired myopathic changes in some subsets.

Some have argued that muscle and neuroendocrine dysfunction may follow from inadequate oxygen delivery to tissues, either from coagulopathy, blood viscosity, and deposits of fibrin; or blood with high values of red cells with altered margins – or both. Poor organ perfusion due to low cardiac output has also been described. When the capacity of cells to take up and release oxygen is impaired, the body shifts to anaerobic metabolism, wherein incomplete metabolism of glycogen leads to the formation of lactic acid, which further impairs oxygen delivery.  Brain, nerves, heart, skeletal muscles, and endocrine glands have higher requirements for oxygen and nutrient substrates, require more energy, and react to deficiencies with more serious consequences.

The mitochondria and respiratory chain are adversely affected by tissue hypoxia-ischemia; they are also adversely affected by elevated nitric oxide, another common finding in the disease. Some infectious agents also adversely affect the mitochondria.  Mitochondrial metabolism is the principle source of energy intermediates as well as of free radicals. Acquired mitochondrial defects could be responsible for the neuronal degeneration. Mitochondrial respiratory chain dysfunction has been reported in association with primary mitochondrial DNA abnormalities. But defects in oxidative phosphorylation and increased free radical production have also been observed in diseases that are not due to inherited mitochondrial abnormalities including in ME/CFS. In these cases, the mitochondrial failure is likely to be an epiphenomenon. As in other conditions in which the respiratory chain is compromised, ME/CFS is a multi-system disease affecting many organ systems of the body. Accumulated damage to the mitochondrial DNA over many years could lead to similar problems as in inherited mitochondrial diseases. '

ME/CFS has been described recently on Medscape as "low output heart failure secondary to mitochondrial failure." New research is emerging that viruses, an upregulated R-Nase-L pathway, and mitochondrial dysfunction lead to low energy in the heart. Since it takes more ATP energy for the heart to relax and fill than it does for the heart to pump, low energy leads to diastolic dysfunction and hence reduced cardiac output, leading to circulatory impairment, and poor organ perfusion to maintain life-preserving blood pressure. (Again, see our Cardiac Insufficiency Hypothesis page.) Both macrocirculatory and microcirculatory factors have been shown to impair organ perfusion in ME/CFS. The end result of the above-described cascade may be a crisis in the cells of the skeletal muscles, heart, brain, kidney, endocrine, and other systems.

In her recent paper (Jan 01), "The Late Effects of  ME," the well-known English M.E. 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)."

The M.E. Society of America disseminates cutting-edge research on the disease regardless of the name under which it was published.  We do not play the role of a support group. We are a research-information and advocacy group only.  (Information on obtaining updates from the M.E. Society is available here.)

References   (For further references and new research, see also our Research-Based Subsets page and out Cardiac Insufficiency Hypothesis page.)

Written by Maryann Spurgin, Ph.D. 
 
 

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Page last updated: September 2, 2009

    For more information, read:
"Founding Principles and M.E. Society Definitional Framework -- Discussion"