"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
Canadian
Clinical
Case Definition
Cardiac
Insufficiency
Hypothesis
Spotlight on:
Research-based subsets
What is ME/CFS? Case definitions that define the disease
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. 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.
|
For our policies on permission to reprint our materials, see our Disclaimer.
© Copyright 2003-2008 M.E. Society of America
Page last updated: August 16, 2008
"Founding Principles and M.E. Society Definitional Framework -- Discussion"
