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TOP 10 TESTS for MYALGIC
ENCEPHALOMYELITIS
& CFS LABELED PATIENTS
by
Steven Du Pre
©2008
[updated 2012]
Though the CDC steadfastly says there are no tests for M.
E./CFS, there are in fact a number of non-routine tests that
delineate Myalgic Encephalomyelitis clearly and can be used
for diagnostic or disability purposes. Evidence-based
diagnostic tests are superior to questionnaires based on
subjective symptoms or shoddy criteria like the Fukuda
definition or Reeves wrongheaded empirical definition. The
tests listed below also, through the work of scientists &
clinicians, firmly contradict the falsehood that CDC claims
there are no tests for this disease.
To
the credit of the
2003 M.E./CFS Consensus Criteria, they list some of the
tests that can delineate the disease. (You can also view and
print a brief summary of these tests
here.)
*************************************************
TOP
10 TESTS for MYALGIC ENCEPHALOMYELITIS & “CFS” LABELED
PATIENTS
Contents
TEST #1: Cardio-Pulmonary Exercise Testing with measurement
of VO2 max, anaerobic threshold, and maximal heart rate and
respiration.
TEST #2: Brain neuro SPECT & PET scans and MRI brain scan
TEST #3: Mitochondrial Dysfunction
TEST #4: TH1/TH2 imbalance
TEST #5: Natural Killer Cell Function (Activity) testing
TEST #6: abnormalities of the 2-5A pathway (RNase-L
ratio)
TEST #7: Virology
TEST #8: Heart Function
TEST #9: Neurocognitive testing & sleep studies
TEST #10: Endocrine testing
Commentary
Additional References & Poor man's tilt table testing
description
------------------------------------------
TEST #1: Cardio-Pulmonary Exercise Testing with measurement
of VO2 max, anaerobic threshold, and maximal heart rate and
respiration.
This test is mentioned in the book Disability and CFS:
Clinical, Legal and Patient Perspectives with this comment by
Dr. Daniel Peterson: "One objective and reproducible technique
for determining and measuring functional disability that
should be used consistently is Cardio-Pulmonary Exercise
Testing with measurement of VO2 max, anaerobic threshold, and
maximal heart rate and respiration. The test is well
established, sedentary and ill norms are published and the
technology is relatively inexpensive and quite available.
Approximately 1700 patients [as in 1997] have been tested over
the past 10 years and the test is now used on the initial
visit to screen patients, to direct rehabilitation, and
adjunctively to determine disability."
Diminished Cardiopulmonary Capacity During Post-Exertional
Malaise
(Abstract) J. Mark VanNess PhD, Christopher R. Snell PhD,
Staci R. Stevens
”Conclusion - In the absence of a second exercise test, the
lack of any significant differences for the first test would
appear to suggest no functional impairment in CFS patients.
However, the results from the second test indicate the
presence of a CFS related post-exertional malaise. It might be
concluded then that a single exercise test is insufficient to
demonstrate functional impairment in CFS patients. A second
test may be necessary to document the atypical recovery
response and protracted malaise unique to CFS.”
Legal and Scientific Considerations of the Exercise Stress
Test
Ciccolla, Stevens, Snell, Van Ness, ©2007 The Haworth Press
"This article examines the legal and scientific basis on which
an exercise stress test can provide medically acceptable
evidence of disability for the CFS patient." This research
group's excellent work proves the post-exertional disability
that ME & CFS patients suffer, much worse on average than
heart failure and COPD patients.”
*************************************************
TEST #2: Brain neuro SPECT & PET scans and MRI brain scan
Evidence From 2007 IACFS/M. E. conference: New methods
in viral studies using refined technology show further
abnormalities in subsets of ME/CFS patients. Increased use of
instruments like MRI, SPECT/SPET, PET and fMRI show some of
the abnormalities in functioning that patients with ME/CFS
experience on a daily basis but these may not have practical
application if a patient cannot have this testing done. A
number of abnormalities with reduced responsiveness on fMRI is
an essential feature of ME/CFS.
Brain imaging shows that, amongst other abnormalities, ME/CFS
patients have reduced blood flow to the brain (especially to
areas that are involved in autonomic nervous system
functioning and in sleep, concentration and pain, including
the pre-frontal cortices, the anterior cingulate and the
cerebellum); altered patterns of brain activation; reduced
grey matter volume; altered serontonergic neurotransmission
and reduced acetyl-carnitine uptake.
A collaboration of researchers from Spain, Belgium and
Australia used SPET scanning to observe patterns of brain
activity; they found that the brain abnormalities correlated
with abnormal immune results.
Patients with ME/CFS require more brain regions to perform
tasks, ie. they have to work harder to achieve the same
results as healthy controls.
One particular area of the brain - the Wernicke area,
essential for understanding and formulating coherent
speech-showed evidence of reduced activity after exercise.
Proton resonance spectroscopy showed greatly increased levels
of brain metabolites (lactate levels were 300% higher than in
controls).
According to Dr Tae Park from South Korea, the unexplained
bright spots on MRI scans of some ME/CFS patients are evidence
of an "arteriolar vasculopathy" or a blood vessel disease. He
believes ME/CFS is a "systemic micro-vascular inflammatory
process" - a process that would affect not only the brain or
the heart or the muscles, but potentially every organ system
in the body. Dr Park found not only capillary inflammation and
perivascular cuffing (the accumulation of immune cells that
surround injured blood vessels), but that all the ME/CFS
patients in his study demonstrated remarkably reduced renal
blood flow. Dr Park noted that diabetics with renal vascular
disease also complain of profound fatigue.
Dr Hiro Kuratsune from Japan gave a summary of what is known
about brain function in ME/CFS. It has been known for over a
decade that frontal and temporal lobe blood flow is reduced in
ME/CFS, and that exercise exacerbates this reduced blood flow
for up to 72 hours. The new evidence is that elevated elastase
and RNase-L levels correlate with reduced blood flow. It is
known that the MRI is abnormal in the majority of people with
ME/CFS due to numerous T2 weighted hypertintense foci, with
evidence of demyelination. Patients with more brain
abnormalities tend to be more physically impaired.
The remarkable similarity in the brain images of patients with
ME/CFS and multiple sclerosis was noted.
Dr Gudrun Lange from New Jersey, USA, stated what can be said
with certainty about the central nervous system findings in
ME/CFS:
1) the major cognitive problem seen is in information
processing
2) studies showing reduced cerebral blood flow are starting to
show consistency
3) there is a problem with serotonergic neurotransmission in
the hippocampus and anterior cingulate regions
4) there are spinal fluid abnormalities
5) fMRI studies are showing altered patterns of brain
activation.
(See references at the end of this article for more
Neuroimaging evidence for ME/CFS diagnosis.)
************************************************
TEST #3: Mitochondrial Dysfunction
The magnetic resonance spectroscopy (MRS) bran scan is
a most informative of the bran scans for ME/CFS. It indicates
mitochondrial dysfunction. Check
www.co-cure.com in the
archives for more info on MRS, and google Dr Cheney's MRS scan
data for his patients.
***MRS scanning has found abnormally high lactic acid spikes
near around the hippocampus in PWME brains which indicates
mitochondrial dysfunction, a central feature being found in
just about all cases through the UKs BioLab testing. An MRI is
good for ruling out gross abnormalities such as tumors and
obvious areas of brain damage while the SPECT can help verify
hypoperfusion in the brain.
From 2007 IACFS/M. E. Conference:
Dr Jonathan Kerr from London stated that his gene expression
studies are finding three main abnormalities in ME/CFS
patients: these involve the immune system, mitochondrial
function and G-protein signaling. There are seven genes
upregulated in ME/CFS - those associated with apoptosis,
pesticides, mitochdonrial function, demyelination and viral
binding sites. Kerr mentioned three genes in particular:
gelsolin, which is involved in apoptosis and amyloidosis; one
that is upregulated by organophosphates, and a mitochondrial
gene involved in the demyelination of nerves.
Also, Mitochondrial abnormalities in the postviral fatigue
syndrome.
Behan WM, More IA, Behan PO Department of Pathology,
University of Glasgow, Scotland. Acta Neuropathol
1991;83(1):61-5
“We
have examined the muscle biopsies of 50 patients who had
postviral fatigue syndrome (PFS) for from 1 to 17 years. We
found mild to severe atrophy of type II fibres in 39 biopsies,
with a mild to moderate excess of lipid. On ultrastructural
examination, 35 of these specimens showed branching and fusion
of mitochondrial cristae. Mitochondrial degeneration was
obvious in 40 of the biopsies with swelling, vacuolation,
myelin figures and secondary lysosomes. These abnormalities
were in obvious contrast to control biopsies, where even mild
changes were rarely detected. The findings described here
provide the first evidence that PFS may be due to a
mitochondrial disorder precipitated by a virus infection.”
**********************************************
TEST #4: TH1/TH2 imbalance
TH1/TH2 Cytokine Production
Immune testing availability:
http://unevx.com/
Th1/Th2 Imbalance – There are two general branches (Th1/Th2)
of the immune system. Some patients appear to have an over
activation of the anti-inflammatory (Th2) branch and an under
activation of the pro-inflammatory (Th1) branch of the immune
system. This could cause increased rates of allergy and
sensitivity on the one hand and difficulty fighting off
pathogens on the other. Further explanation from Dr. Cheney:
Balance the Th1/Th2 Immune System
**********************************************
TEST #5: Natural Killer Cell Function (Activity) testing
Immune testing availability:
UNEVX
Red Labs Belgium
Natural Killer (NK) and T-cell Dysfunction – NK and T-cells
are two other components of the immune response to pathogens.
A set of chronic fatigue syndrome (ME/CFS) patients have been
shown to have reduced NK cell numbers and poor NK and T-cell
functioning. These problems also could interfere with the
ability of the immune system to find infected cells and kill
them. Intriguingly some researchers believe that chronic
immune activation due to an underlying chronic infection has
caused these cells to 'burn out'.
**********************************************
TEST #6: abnormalities of the 2-5A pathway (RNase-L ratio):
37kDa 25A RNase L immunoassay: protein, activity, PKR
cleavage, & elastase activity assays testing at
Redlabs Belgium
Impaired Cellular Immune Response – Two abnormalities in the
responses cells have to infection in the 'interferon pathway'
have been documented. An antiviral enzyme in this pathway
called the RNase L has been shown to be fragmented in many
patients. A subset of chronic fatigue syndrome (ME/CFS)
patients also display increased activity of another enzyme
called protein-kinase R (PKR) that is involved in killing
cells infected with pathogens. These problems suggest the
immune systems of chronic fatigue syndrome (ME/CFS) patients
could have troubles finding pathogens and killing the cells
they've infected. (Note: Immune function Test #s 4-6 are
objective markers of pathophysiology and severity)
From January 2007 International Conference on ME/CFS summary
of immunological abnormalities:
Anthony Komaroff (Professor of Medicine, Harvard) summarized
the immune abnormalities that have been demonstrated in ME/CFS.
These include activated CD8 (T cells); poorly functioning
Natural Killer cells; novel findings -seen only in ME/CFS --
of abnormalities of the 2-5A pathway (RNase-L ratio); cytokine
abnormalities (pro-inflammatory dysregulation); increased TGF,
and 27 times more circulating immune complexes than in
controls.
(More Immune Function references at the end of this article)
**********************************************
TEST #7: Virology
Viral antibodies, including Coxsackie B; bacteria, including
HHV6; mycoplasma, Wisconsin
Viral Research Group
Dr Dharam Ablashi from Santa Barbara, USA, showed that RNase-L
was found to correlate with HHV-6 infection in ME/CFS and that
RNase-L protein is a marker for active infection.
Info on
HHV-6 testing at
The HHV-6 Foundation.
Some patients clearly have a persistence of virus in their
brain.
Enterovirus infections have previously been reported in UK
studies but have not been much explored by US researchers.
Enteroviruses are a genus of RNA viruses that includes
echovirus, coxsackie virus and poliovirus. In a recent US
study by John Chia from California of 108 patients with ME/CFS
who underwent gastric biopsies, 100 revealed chronic
inflammation and 80% were positive for VP1 (enteroviral capsid
protein - first used by Professor James Mowbray et al in the
UK in 1988). Enteroviral RNA was detected in 33% of
patients."Use of valganciclovir in patients with elevated
antibody titers against Human Herpesvirus-6 (HHV-6) and
Epstein Barr Virus (EBV) who were experiencing central nervous
system dysfunction including long-standing fatigue.
Journal of Clinical Virology 37 Suppl. 1 (2006) S33–S38
Andreas M. Kogelnik a, Kristin Loomis b, Mette Hoegh-Petersen
c, Fernando Rosso a,c, Courtney Hischier b, Jose G. Montoya
a,c,*
*Stanford University School of Medicine, Stanford, CA, USA
*HHV-6 Foundation, Santa Barbara, CA, USA
*Palo Alto Medical Foundation Research Institute, Palo
Alto, CA, USA
Symptoms observed in ME/CFS are compatible with a viral
aetiology.
Many infectious agents have been cited as implicated in ME/CFS
including EBV, Lyme, parvovirus, enteroviruses, Q fever, RRV,
mycoplasma and HHV-6.
Over the last ten years there has been increasing evidence
that infection is most likely to be a prime cause of ME/CFS.
**********************************************
TEST #8: Heart Function
(at
least 2 possible tests)
1). Impedance Cardiography (available at many teaching
hospitals):
Chadwick Medical Associates
Abnormal Impedance Cardiography Predicts Symptom Severity in
Chronic Fatigue Syndrome - (Peckerman procedure: 10
minutes lying down followed by 5 minutes standing up)
Abnormal Heart Pumping After Exercise Linked to Chronic
Fatigue Syndrome
Peckerman Q&A:
http://www.cfids.org/archives/2003rr/2003-rr2-article01.asp
2). 24 Hour Holter Monitoring: repetitively
oscillating Twave inversions and/or Twave flats during 24hour
monitoring. Note: this pattern may not be reported or subsumed
under
nonspecific Twave changes. More information at
The Treatment
Center for Chronic Fatigue Syndrome
The
Cardiac Insufficiency Hypothesis is explained at the M.E.
Society of America website.
**Important note:
If the doctor insists on a regular exercise stress test, then
these 2 studies below should be referenced, which show that a
stress test must be followed the next day with another one to
show the extreme disability.
Legal and
Scientific Considerations of the Exercise Stress Test
J of Chronic Fatigue Syndrome, Vol 14, No. 2, 2007, pp. 61-75
Margaret Ciccolella EdD, JD, Staci R. Stevens MA, Christopher
R. Snell PhD, Mark Van Ness PhD
ABSTRACT. This article examines the legal and
scientific bases on which an exercise stress test can provide
medically acceptable evidence of disability for the Chronic
Fatigue Syndrome (CFS) patient. To qualify for disability
benefits, a claimant must establish the existence of a serious
medically determinable impairment (MDI) that causes the
inability to work. The single stress test has been used to
objectively establish whether a claimant can engage in
“substantial gainful employment” and is an important
determinant of the award or denial of benefits. A review of
case law indicates problems associated with a single test
protocol that may be remedied by a “test-retest” protocol. The
results of a preliminary study employing this approach
indicate that the test-retest protocol addresses problems
inherent in a single test and therefore provides an assessment
of CFS related disability consistent with both medical & legal
considerations.
Diminished
Cardiopulmonary Capacity During Post-Exertional Malaise
Journal of Chronic Fatigue Syndrome, Vol. 14, No. 2, 2007, pp.
77-85 J. Mark VanNess PhD, Christopher R. Snell PhD, Staci R.
Stevens
**Also, in the whole area of neuro-cardiology is the tilt
table testing since Dr. Charles Lapp says in his
recommendations for people with this disease, up to 97%
demonstrate vasovagal syncope (neurally mediated hypotension)
on tilt table testing.
Canadian Consensus document (p. 6 in the pamphlet, p. 13
in the PDF file under the title Autonomic Manifestations
describes this orthostatic intolerance. Here's the first
paragraph of a very good explanation from the document which
includes some other very important information regarding
circulation problems in the M.E./CFS:
6.
Autonomic Manifestations
Chronic Orthostatic Intolerance (COI), the inability to
sustain upright activity (standing, sitting or walking), is
very common and may be an important component in ME/CFS. Upon
limited standing, the patient experiences overwhelming
exhaustion, an urgency to lie down, confusion, malaise, and
worsening of other symptoms. Sitting and light walking are
tolerated better than standing still, but no upright activity
is tolerated well. Lying down helps alleviate symptoms.
Tilt-table testing may be helpful in diagnosis but some
patients may have a normal tilt-table test and still have
severe COI. Quiet standing in the office allows for
observation and monitoring the blood pressure and pulse.
NOTE: This just only be done with extreme CAUTION with
someone standing beside the patient at all times in order to
support him/her if s/he begins to feel weak!
(Note: the in-office tilt table testing described in this
paragraph are made more specific by Dr. Mary Schweitzer in a
detailed description below the references at the end of this
post after the references) Additionally, most of us are aware
that Dr Paul Cheney found evidence of diastolic (cardiac)
dysfunction in ME/CFS, with evidence of another cardiac
abnormality (patent foramen ovale, or PFO). This results in
hypoxia (low oxygen levels relative to metabolic needs).
Cheney stated that the cardiac index of ME/CFS patients is so
severe that it falls between the value of patients with
myocardial infarction (heart attack) and those in shock.On
September 9, 2006, Paul Cheney, MD, PhD, presented a seminar
titled "CFS: The Heart of the Matter." This outstanding
seminar contains important, fascinating and unique material
that will eventually be published. There is an overview of
chronic fatigue syndrome, an in-depth look at the
cardiovascular issues in CFS, a new model of the illness, and
a full update on Dr. Cheney's latest study, including the
treatment protocol
available on DVD from the DFW Support Group.
Also, helpful is this testing showing impaired blood flow:
Hypercoagulability - flow cytrometry fibrinogen,
thrombin/anti-thrombin complexes.
**********************************************
TEST #9: Neurocognitive testing & sleep studies
Neurocognitive:
To
ascertain neurological abnormalities in brain neuro SPECT
scan, disability representative may have a licensed
psychologist perform a battery of 6 neurocognitive tests to
test mental performance. Cognitive performance: decreased
processing speed, working memory, information learning, etc.
Sleep Studies:
Testable Major Sleep Dysfunction: This can include all forms
of sleep dysfunctions. All or any of the following may be
present: (a) impaired sleep efficiency, (b) significant
fragmented sleep architecture, (c) movement arousals,
particularly if there is an associated pain syndrome, (d)
absence or significant decrease of type 3 and 4 sleep, (e)
abnormal REM sleep pattern (f) changes in daytime alertness
and (g) sleep reversals.
****************************************************
TEST #10: Endocrine testing
CT
scans may show reduced adrenal gland size; thyroid hormone
levels with attention to bioavailability of T3 & those with
reduced level should be checked for selenium as it regulates
conversion of T4 to T3; reduced HPA function (see this
article):
Diagnosis
and Treatment of Hypothalamic-Pituitary-Adrenal (HPA) Axis
Dysfunction in Patients with Chronic Fatigue Syndrome (CFS)
and Fibromyalgia (FM), J of Chronic Fatigue Syndrome,
Vol. 14, No. 3, 2007, pp. 59-88, by Kent Holtorf MD
****************************************************
These Top 10 Tests also would be appropriate considering Dr.
Ramsey's 1986 definition & criteria:
"A
syndrome initiated by a virus infection (TESTS #4, 5, 6, 7),
commonly in the form of a respiratory or gastrointestinal
illness with significant headache, malaise and dizziness (TEST
#8) sometimes accompanied by lymphadenopathy or rash.
Insidious or more dramatic onsets following neurological (TEST
#2), cardiac (TESTS #1, 8) or endocrine (TEST #10) disability
are also recognised.
"Characteristic
features include:
(1) A multisystem disease, primarily neurological with
variable involvement of liver, cardiac and skeletal muscle,
lymphoid and endocrine organs.
(2) Neurological disturbance - an unpredictable state of
central nervous system exhaustion following mental or
physical exertion which may be delayed and require several
days for recovery; an unique neuro-endocrine profile which
differs from depression in that the
hypothalamic/pituitary/adrenal response to stress is
deficient; dysfunction of the autonomic and sensory nervous
systems; cognitive problems (TEST #9).
(3) Musculo-skeletal dysfunction (TEST #3) in a proportion of
patients (related to sensory disturbance or to the late
metabolic and auto immune effects of infection)
(4) A characteristically chronic relapsing course"
****************************************************
Additional References & Poor man's tilt table testing
description
Neuroimaging References:
Neurological Dysfunction in Chronic Fatigue Syndrome, Journal
of Chronic Fatigue Syndrome (The Haworth Medical Press, an
imprint of The Haworth Press, Inc.) Vol. 6, No. 3/4, 2000, pp.
51-68. Abhijit Chaudhuri, DM, MD, MRCP; Peter 0. Behan, DSc,
MD, FACP, FRCP
"SPECT Imaging of the Brain: Comparison of Findings in
Patients with Chronic Fatigue Syndrome, AIDS Dementia Complex,
and Major Unipolar Depression," Richard B.
Schwartz, Anthony L. Komaroff, Basem M. Garada, Marcy Gleit,
Teresa H. Doolittle, David W. Bates, Russell G. Vasily, B.
Leonard Holman; American Journal of Roentgenology, Vol 162,
943-951, Copyright © 1994 by American Roentgen Ray Society.
Summary: "This study shows that CFS (ME) shares some
similarities on SPECT imaging with AIDS Dementia Complex -
acute changes in radionuclide uptake in the younger population
may be caused by inflammatory processes at the cellular or
micro vascular level .... the findings in CFS (ME) face are
consistent with the hypothesis that CFS (ME) ... results from
a viral infection of neurons, glia or vasculature .....viral
infection can provoke neurological dysfunction by interfering
with intra-cellular mechanisms or membrane transport systems
.... or by cerebral hypoperfusion due to vasculitis".
It
has been known for some time that CFS patients have abnormal
blood flow in their brains; that is, some areas of the brain
are not getting as much blood as they should. Dr. Ismael Mena
has studied M. E./CFS patients' brains using SPECT scans at
the University of California-Los Angeles, where he is a
professor of radiology (Ismael Mena, M.D., "Study of Cerebral
Perfusion by NeuroSPECT in Patients with Chronic Fatigue
Syndrome," The Cambridge Symposium on Myalgic
Encephalomyelitis, 1990; 1: 21-22.)
Gordon R et al. Cortical motor potential alterations in
chronic fatigue syndrome. Int J Molec Med. 1999; 4: 493-99.
Proton magnetic resonance spectroscopy of basal ganglia in
chronic fatigue syndrome. Chaudhuri A, Condon BR, Gow JW,
Brennan D, Hadley DM. Neuroreport. 2003 Feb 10;14(2):225-8.
Costa DC, Brostoff J, Douli V, Eli PJ. Brainstem
hypoperfusion in patients with Myalgic
Encephalomyelitis-Chronic Fatigue Syndrome. Eur J Nucl Med
1992 19:733.
Brainstem perfusion is impaired in chronic fatigue syndrome.
DC Costa, C Tannock and J Brostoff. Quarterly Journal of
Medicine December 1995:88:767-773)
Relationship of brain MRI abnormalities and physical
functional status in chronic fatigue syndrome Cook DB,
Natelson BH. Int J Neurosci 2000:107:(1-2):1-6
Brain positron emission tomography (PET) in chronic fatigue
syndrome: preliminary data Tirelli U et al. Am J Med 1998:105:
(3A):54S-58S
Brain MRI abnormalities exist in a subset of patients with
chronic fatigue syndrome. Lange G, DeLuca J, Maldjian JA, Lee
H, Tiersky LA, Natelson BH. J Neurol Sci. 1999 Dec
1;171(1):3-7.
Chronic fatigue syndrome--aetiological aspects. Dickinson CJ.
Eur J Clin Invest. 1997 Apr;27(4):257-67
Brain MR in chronic fatigue syndrome. Greco A, Tannock C,
Brostoff J, Costa DC. AJNR Am J Neuroradiol. 1997 Aug;18(7):
1265-9.
Relationship of brain MRI abnormalities and physical
functional status in chronic fatigue syndrome. Cook DB, Lange
G, DeLuca J, Natelson BH. Int J Neurosci. 2001
Mar;107(1-2):1-6.
Quantitative assessment of cerebral ventricular volumes in
chronic fatigue syndrome. Lange G, Holodny AI, DeLuca J, Lee
HJ, Yan XH, Steffener J, Natelson BH. Appl Neuropsychol.
2001;8(1):23-30.
---------------------------------------
Immune Function References:
Evidence for the Presence of Immune Dysfunction in Chronic
Fatigue Syndrome. Benjamin H. Natelson,Mohammad H.
Haghighi,and Nicholas M. Ponzio. Departments of
Neurosciences, Pathology, University of Medicine and
Dentistry—New Jersey Medical School, Department of Psychology,
Rutgers University, Newark, New Jersey Clinical and Diagnostic
Laboratory Immunology, July 2002, p. 747-752, Vol. 9, No. 4,
1071-412X/02/$04.00+0 DOI: 10.1128/CDLI.9.4.747-752.2002 2002,
American Society for
Microbiology
Low NK syndrome and its relationship to chronic fatigue
syndrome. Aoki T, Miyakoshi H, Usuda Y, Herberman RB. Clinical
Immunology and Immunopathology 1993; 69(3): 253-65.
A chronic illness characterized by fatigue, neurologic and
immunologic disorders, and active human herpesvirus type 6
infection. Buchwald D, Cheney PR, Peterson DL, Henry B,
Wormsley SB, Geiger A, Ablashi DV, Salahuddin SZ, Saxinger C,
Biddle R, et al. Annals of Internal Medicine 1992; 116(2):
103-13. Immunologic abnormalities associated with chronic
fatigue syndrome. Barker E, Fujimura SF, Fadem MB, Landay AL,
Levy JA. Clinical Infectious Diseases 1994; 18(Supp 1):
S136-41. A comprehensive immunological analysis in chronic
fatigue syndrome. Gupta S, Vayuvegula B. Scandinavian Journal
of Immunology 1991; 33: 319-327. Abstract: A detailed analysis
of cell-mediated and antibody-mediated immunity was performed
in 20 CDC-defined patients with chronic fatigue syndrome (CFS)
and 20 age- and sex-matched healthy controls. CD3+, CD4+,
CD8+, and CD20+lymphocytes were comparable in two groups.
Natural killer cells as defined by CD16, CD56 and CD57
antigens were significantly reduced in CFS. A significant
increase in the proportions of CD4+ ICAM 1+ T cells was
observed in CFS. Monocytes from CFS displayed increased
density (as determined by mean fluorescence channel numbers)
of intercellular adhesion molecule 1 (ICAM-1) and lymphocyte
function associated antigen 1 (LFA-1), but showed decreased
enhancing response to recombinant interferon-gamma in vitro.
The lymphocyte DNA synthesis in response to phytohaemoglobulin
(PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM) was
normal but the response to soluble antigens was significantly
reduced. Serum IgM, IgG, IgA, and IgG subclasses were normal.
In vivo specific antibody response to pneumococcus vaccine was
depressed in CFS. Forty percent of patients showed titres of
anti-human herpes virus 6 (anti-HHV-6) antibody higher than
that in the controls (greater than or equal to 1/80). These
data suggest immunological dysfunction in patients with
chronic fatigue syndrome. The significance of these
observations is discussed. Immunological abnormalities in
patients with chronic fatigue syndrome. Tirelli U, Marotta G,
Improta S, Pinto A.Scandinavian Journal of Immunology 1994;
40(6): 601-8.
Low
NK syndrome and its relationship to chronic fatigue syndrome.
Aoki T, Miyakoshi H, Usuda Y, Herberman RB. Clinical
Immunology and Immunopathology 1993; 69(3): 253-65.
Immunologic abnormalities associated with chronic fatigue
syndrome. Barker E, Fujimura SF, Fadem MB, Landay AL, Levy JA.
Clinical Infectious Diseases 1994; 18(Supp 1): S136-41.
--------------------------
Description of poor man's tilt table testing procedure
(courtesy of Dr. Mary Schweitzer):
You lie still and rest for 15 minutes to 20 minutes. Then
they take your blood pressure and pulse. Then you sit up for
about10 minutes (same thing). Then you stand and lean
slightly against a wall - do NOT flex your muscles or struggle
or talk.
Be calm. (Have somebody there who can catch you if there is
trouble)!
After ten minutes they should do the blood pressure and pulse
again.
Keep leaning. DO NOT FLEX ANY MUSCLES OR TALK.
After another ten minutes, take them again.
If at any time you start to feel sweaty or hot or nauseous or
basically super-M.E., they need to do the bp and pulse right
away and get you lying down. Congratulations.
For Neurally Mediated Hypotension (NMH), you have to have a
20-25 mm drop in systolic blood pressure (the higher number).
If your pulse suddenly rises at least 30 bpm (beats per
minute), then you have Postural Orthostatic Tachycardia
Syndrome (POTS).
Dr. Rowe believes they are both really the same thing - with
either, if you don't get down, you're going to pass out. And
the treatment for both is the same. Rowe published the first
article on the relationship between CFS and autonomic nervous
system dysfunction (NMH/POTS)in JAMA in the fall of 1995.
(Note: See abstract below.)
--------------------------------------
What is neurally mediated hypotension?
Neurally mediated hypotension is also known by the following
names: the fainting reflex, neurocardiogenic syncope,
vasodepressor syncope, the vaso-vagal reflex, and autonomic
dysfunction. Hypotension is the formal medical term for low
blood pressure, and syncope is the term for fainting. Neurally
mediated hypotension occurs when there is an abnormal reflex
interaction between the heart and the brain, both of which
usually are structurally normal.
Dr. Cheney's treatment for NMH:
http://www.immunesupport.com/library/showarticle.cfm/ID/3499/e/1/T/CFIDS_FM/
What is Postural orthostatic tachycardia syndrome?
Postural orthostatic tachycardia syndrome (or POTS) is a
condition of orthostatic
intolerance in which a change from the
supine position to an upright
position causes an abnormally large increase in heart rate,
often, but not always accompanied by a fall in blood pressure.
Patients with POTS also have problems in maintaining
homeostasis when changing position ie moving from one chair to
another or reaching above their heads. The syndrome was
identified as such by Schondorf and Low in
1993. Similar symptoms were collectively described as "idiopathic
hypovolemia" by Fouad in
1986. A comprehensive historical account
is given by Grubb (2002).
Symptoms include an abnormally large increase in heart rate
upon standing, lightheadedness,
extreme fatigue,
nausea, headache,
chest pain,
exercise intolerance and
impaired concentration. Patients may exhibit mild
hypotension while standing, but
most do not experience fainting.
Patients with POTS may frequently be misdiagnosed as having
panic attacks,
chronic fatigue syndrome
or chronic anxiety disorder
(Grubb, 2002). POTS patients are usually significantly
debilitated by their symptoms.
POTS is often difficult to diagnose. A routine physical
examination and standard blood tests usually will not indicate
POTS. A tilt table test is
vital to diagnosing POTS although all symptoms must be
considered before a final diagnosis is made. A test to rule
out pheochromocytoma is
usually performed. Other tests such as multi-site
photoplethysmography a measure of how well the blood vessels
constrict can also be useful. A blood test may be performed to
verify abnormally high levels of
norepinephrine usually present in POTS patients (Raj,
2006).
The
Relationship Between Neurally Mediated Hypotension
and the Chronic Fatigue Syndrome
Issam Bou-Holaigah, MD; Peter Rowe, MD; Jean Kan, MD; Hugh
Calkins, MD
OBJECTIVE:
To compare the clinical symptoms and response evoked by
upright tilt-table testing in healthy individuals and in a
sample of those satisfying strict criteria for chronic fatigue
syndrome.
DESIGN:
Case-comparison study with mean (SD) follow-up of 24 (5)
weeks.
SETTING:
Tertiary care hospital.
PATIENTS AND OTHER PARTICIPANTS:
A sample of 23 patients with chronic fatigue syndrome (five
men and 18 woman; mean age, 34 years), each of whom fulfilled
the strict diagnostic criteria of the Centers for Disease
Control and Prevention, was recruited from regional chronic
fatigue support groups and from the investigators’ clinical
practices. There were 14 healthy controls (four men and 10
women; mean age, 36 years).
INTERVENTIONS:
Each subject completed a symptom questionnaire and underwent a
three-stage upright tilt-table test (stage 1, 45 minutes at
70° tilt; stage 2, 15 minutes at 70° tilt with 1 to 2 g/min of
isoproterenol; and stage 3, 10 minutes at 70° with 3 to 4
g/min of isoproterenol). Patients were offered therapy with
fludrocortisone, ß-adrenergic blocking agents, and
disopyramide, alone or in combination, directed at neurally
mediated hypotension.
MAIN OUTCOME MEASURES:
Response to upright tilt and scores on symptom questionnaires
prior to and during follow-up.
RESULTS:
An abnormal response to upright tilt was observed in 22 of 23
patients with chronic fatigue syndrome vs four of 14 controls
(P<.001). Seventy percent of chronic fatigue syndrome
patients, but no controls, had an abnormal response during
stage 1 (P<.001). Nine patients reported complete or nearly
complete resolution of chronic fatigue syndrome symptoms after
therapy directed at neurally mediated hypotension.
CONCLUSIONS:
We conclude that chronic fatigue syndrome is associated with
neurally mediated hypotension and that its symptoms may be
improved in a subset of patients by therapy directed at this
abnormal cardiovascular reflex. JAMA, September 27, 1995 -
Volume 274, No. 12
Diagnosis: Orthostatic Intolerance (OI)
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