Test Abnormalities in ME/CFS

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http://bit.ly/QojAyd

National Alliance for

Myalgic Encephalomyelitis

Test Abnormalities in ME/CFS

" I take great issue with the current recommendations that

no additional testing should ever be done. I believe there

are indications for more advanced testing. "

-Dr. - (http://bit.ly/Qosn3n)

There have been over 4,000 peer reviewed articles on ME

and CFS, and there are many websites with

comprehensive research article listings. (See our Links

(http://bit.ly/QotAro) page for those websites.) On our

Research Categories pages we list some of the more

notable articles, some as abstracts and some full journal

articles, that firmly support our Goals

(http://bit.ly/QotVue). There are many overlapping body

systems involved in ME and CFS, since the central

nervous system (CNS) is the " master control " of all body

functions, and much of the research points to damage

and dysfunction of the CNS. CNS damage and

dysfunction will affect all body systems--immune,

cardiovascular, endocrine--while dysfunction of these

body systems in turn affect others, including the CNS.

So some of the articles and abstracts contained here

may be listed in more than one category. (For example,

an article concerning orthostatic intolerance may be in

both the circulatory and the neurological sections.)

*****************

Legal and Scientific Considerations of

the Exercise Stress Test

(http://bit.ly/Qoyp3W)

Ciccolla, s, 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.”.

*****************

Tests for Abnormalities in ME/CFS

(http://bit.ly/QojAyd)

a comprehensive overview of test abnormalities as listed

in the Overview of the 2003 Consensus Document.

Top 10 Tests for Myalgic Encephalomyelitis & CFS

Labeled Patients (http://bit.ly/QoAXyQ)

an article that refutes CDC's claims that specialized

testing is of no value to the M.E. & CFS patients.

*****************

Tests for Abnormalities in ME/CFS

(See National ME/FM Action Network of Canada for

sources of some specialized tests (http://bit.ly/QoChSA)

From Myalgic Encephalomyelitis/Chronic Fatigue

Syndrome: A Clinical Case Definition and Guidlines for

Medical Practitioners (http://bit.ly/QoD1qE) ©2005

Carruthers, van de Sande

While there is not one definite test for ME/CFS, many

tests may indicate abnormalities. The standard battery of

tests may be inadequate to reveal abnormalities in

ME/CFS patients. Many of the following tests are not

available in general medical laboratories but may be

available in research facilities or more generally available

in the future:

* Virology, etc: viral antibodies, including sackie B?

bacteria, including HHV6? mycoplasma, etc. (Wisconsin

Viral Research Group (http://bit.ly/QoED3T)

* 37kDa 25A RNase L immunoassay: protein, activity,

PKR cleavage, & elastase activity assays. (Red

Laboratories, Belgium (http://bit.ly/QoF8ef)

* Other immunological markers: NK cell levels and

function per cell for low NK cell cytotoxicity? CD4CD8

ratio? ANA? activated immune complexes – IgG

sub-fractions including IgG1 and IgG3, circulating

immune complexes IL2 & IL4? Th1 –Th2 response to

mitogen stimulation (high levels of Th2 indicate

autoimmunity), flow cytometry for activated/elevated

lymphocytes? antilamin antibodies may indicate

autoimmunity and brain cell damage (lamin B antibodies

are evidence of autoimmunity)? humoral autoimmunity for

polypeptides of the nuclear envelope (NE)? antibodies in

neuronal cells MAP2 (kinase regulators) (Red

Laboratories, Belgium, UNEVX (http://bit.ly/QoFCkl)

* Urinary markers: 24hour urine free cortisol? elevated

amino-hydroxy-N-methyl-pyrrolidine correlate with

quantity of symptoms? IAG – tryptophan metabolite, is

usually positive and indicates a leaky gut, which in turn

is indicative of a leaky blood brain barrier? urinary

creatine & other muscle metabolites.

* 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

* Increased 5HT neurotransmission

* Chronic orthostatic intolerance: Use tilt-table test or

monitor the pulse and blood pressure while standing.

Note: This monitoring must be done with caution and

someone standing beside the patient.

* Cardiac Dysfunction: 24-hour Holter monitoring -

Specifically ask to either view the results yourself or to

report repetitive oscillating T-wave inversion and T-wave

flats. This pattern is typical of many ME/CFS patients

but may not be reported.

* Cardiopulmonary Exercise Testing: AMA Guide for

Evaluation of Permanent Impairment. Lower

cardiovascular and ventilatory values at peak exercise

help determine functional capacity, and peak oxygen

consumption levels determine disability categories.

* Computer Science and Application (CSA™) Actigraph is

a small device that measures frequency and intensity of

activity in one minute intervals for up to 22 days.

Typically, less intense and shorter activity peaks

followed by longer rest periods are identified. It is helpful

to have the patient keep a daily diary of activities during

this period and/or wear a speedometer.

* CNS, ANS: Romberg test? nystagmus test (may

fluctuate from positive & negative throughout the day)?

altered sympathetic modulations? subnormal and/or

fluctuating diurnal body temperature

* Cognitive performance: decreased processing speed,

working memory, information learning, etc.

* SPECT scans may reveal significantly lower

cortical/cerebellar regional cerebral blood flow frequently

in the frontal, parietal, temporal, occipital, brain stem and

throughout the cerebral cortex.

* PET scans may reveal decreased glucose metabolism

in the right mediofrontal cortex, and significant

hypoperfusion and hypometabolism in the brain stem.

* MRI brain scans: Elevated numbers of punctuate

lesions, particularly in the frontal lobes and subcortical

areas, suggest demyelination or edema. Do spinal MRI

for disc herniation and minor stenosis.

* qEEG brain topography: Elevated EEG activity in theta

and beta frequencies and increased intracerebral

electrical sources in left frontal region delta and beta

frequencies in eyes closed condition may be identified.

Reduced sources in right hemisphere (beta) may be

noted during verbal cognitive processing.

* Hypercoagulability: flow cytrometry fibrinogen,

thrombin/anti-thrombin complexes, etc.

* Positive tests for fibromyalgia syndrome and myofascial

pain syndrome should be noted.

* Skin conductivity and skin temperature: The

combination of a lower ability of the skin to conduct

electrical current in response to visual and auditory

stimuli, and a higher skin temperature of fingers indicate

a down-regulation of autonomic sympathetic tone.

* Sleep studies may indicate that there is insufficient time

spent in the deeper stages of sleep, and alpha wave

intrusion into delta waves within non-REM sleep.

* Ocular test: slowed and marked jerkiness of saccades?

difficulty with and slowed changing of visual fixation,

constricted peripheral fields? low and/or incomplete

blinking? small pupils? light hypersensitivity, tear film

abnormalities such as low tear breakup time, inadequate

production of the oil or mucus layer in tears, rose Bengal

corneal staining? visual midline shift.

* Allergies or sensitivities? Lung function testing? Liver

function: CPK and liver function

Printable version (http://bit.ly/QoJ4eY)

*****************

TOP 10 TESTS for MYALGIC

ENCEPHALOMYELITIS & CFS

LABELED PATIENTS

by 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

(http://bit.ly/QoD1qE), they list some of the tests that

can delineate the disease. (You can also view and print

a brief summary of these tests here

(http://bit.ly/QoKupP)

*****************

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 (http://bit.ly/QoMz5d)

TEST #2: Brain neuro SPECT & PET scans and MRI

brain scan (http://bit.ly/QoMSNi)

TEST #3: Mitochondrial Dysfunction (http://bit.ly/QoNaDI)

TEST #4: TH1/TH2 imbalance (http://bit.ly/QoNFhe)

TEST #5: Natural Killer Cell Function (Activity) testing

(http://bit.ly/QoOhDr)

TEST #6: abnormalities of the 2-5A pathway (RNase-L

ratio) (http://bit.ly/QoOyXd)

TEST #7: Virology (http://bit.ly/QoOSoB)

TEST #8: Heart Function (http://bit.ly/QoP1IF)

TEST #9: Neurocognitive testing & sleep studies

(http://bit.ly/QoPgDK)

TEST #10: Endocrine testing (http://bit.ly/QoPyun)

Commentary

Additional References & Poor man's tilt table testing

description (http://bit.ly/QoM0Il)

*****************

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. : " 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 (http://bit.ly/QoQZZy) (Abstract)

J. Mark VanNess PhD, R. Snell PhD, Staci

R. s

”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 (http://bit.ly/Qoyp3W), Ciccolla, s,

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

http://bit.ly/QoVrrg 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 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://bit.ly/QoFCkl

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 (http://bit.ly/QoWJTf)

*****************

TEST #5: Natural Killer Cell Function (Activity) testing

Immune testing availability: UNEVX (http://bit.ly/QoFCkl)

Red Labs Belgium (http://bit.ly/QoYkbN)

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 (http://bit.ly/QoF8ef)

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:

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 sackie B? bacteria,

including HHV6? mycoplasma, Wisconsin Viral Research

Group (http://bit.ly/QoED3T)

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 (http://bit.ly/MKB0t0)

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 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 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

s M. Kogelnik a, Loomis b, Mette

Hoegh-sen c, Rosso a,c,

Hischier b, 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

(http://bit.ly/MKBmjj)

Abnormal Impedance Cardiography Predicts Symptom

Severity in Chronic Fatigue Syndrome

(http://bit.ly/MKBqzH) - (Peckerman procedure: 10

minutes lying down followed by 5 minutes standing up)

Abnormal Heart Pumping After Exercise Linked to

Chronic Fatigue Syndrome (http://bit.ly/MKBsHU)

Peckerman Q & A: http://bit.ly/MKBwHB

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 (http://bit.ly/MKBCyY)

The Cardiac Insufficiency Hypothesis

(http://bit.ly/MKBHT2) 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 (http://bit.ly/MKBUpo) - J of Chronic Fatigue

Syndrome, Vol 14, No. 2, 2007, pp. 61-75 Margaret

Ciccolella EdD, JD, Staci R. s MA, 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 (http://bit.ly/MKC3sU) - Journal

of Chronic Fatigue Syndrome, Vol. 14, No. 2, 2007, pp.

77-85 J. Mark VanNess PhD, R. Snell PhD,

Staci R. s

**Also, in the whole area of neuro-cardiology is the tilt

table testing since Dr. 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 (http://bit.ly/Qp6QHR) (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.

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 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, 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 (http://bit.ly/Qp7Z1V) 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, (

significant fragmented sleep architecture, © 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)

(http://bit.ly/Qp9ZY3) 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; 0. Behan, DSc,

D, FACP, FRCP

" SPECT Imaging of the Brain: Comparison of Findings in

Patients with Chronic Fatigue Syndrome, AIDS Dementia

Complex, and Major Unipolar Depression, " B.

chwartz, L. Komaroff, Basem M. Garada,

Marcy Gleit, H. Doolittle, W. Bates,

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.

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Immune Function References:

Evidence for the Presence of Immune Dysfunction in

Chronic Fatigue Syndrome (http://1.usa.gov/QpbpBM) -

H. Natelson,Mohammad H. Haghighi,and

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, DL,

Henry B, Wormsley SB, Geiger A, Ablashi DV,

Salahuddin SZ, Saxinger C, Biddle R, et al. ls 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 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.

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.

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Description of poor man's tilt table testing procedure

(courtesy of Dr. 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://bit.ly/QpdtK9

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; Rowe, MD; 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)

(http://bit.ly/Qpe8ey)

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