Testing in Myalgic Encephalomyelitis (ME)

 

Testing is part of the Diagnosis and Management of 
Myalgic Encephalomyelitis (ME)

Important - Myalgic Encephalomyelitis (ME) is a testable disease 

Most Important - Please LISTEN TO THE PATIENT & DO NO HARM

Introduction

Myalgic Encephalomyelitis (ME) is a distinct, recognisable disease entity that is not difficult to diagnose and can in fact be diagnosed relatively early and managed well providing that the doctor has knowledge of and some experience with ME, and knows what and how to test.

There has been a great deal of misunderstanding about ME, the degree of physical restriction may not be instantly apparent to the observer; the patient may look okay, despite being unable to walk to the toilet, being unable to sit up for more than a few seconds at a time, unable to watch TV or read a book, and unable go out in a wheelchair. It is vital to listen to the person with suspected and confirmed ME in order to support them fully with their complex care needs. 

There can be harmful consequences for people with ME when they are not listened to and encouraged to push on through their symptoms

Misconceptions about Testing 

Some articles on ME in mainstream media, and some of the medical texts on the illness state that there are no tests which can be utilized to help confirm an ME diagnosis. Wrong.

Mainstream articles tend to state that despite extensive testing no objective or quantifiable abnormalities have ever been found in any patients with ME. Wrong.

Truths about Testing

"As with a wide variety of illnesses – lupus, multiple sclerosis, and ovarian cancer for example – there is as yet no single test which can diagnose M.E. in all patients. Therefore, like these other illnesses, M.E. must be diagnosed by taking a detailed medical history, noting the type and severity of symptomatology and other characteristics of the illness and the type of onset of the symptoms. (An acute or sudden onset of symptoms is always seen in M.E. and this onset type rules out a wide variety of other illnesses associated with gradual onset). A series of tests may also then be necessary to rule out or confirm a suspected M.E. diagnosis.
 
Objective scientific tests are available which can aid in the diagnosis of M.E. and easily prove the severe abnormalities across many different bodily systems seen in M.E. Unfortunately many (in fact most) patients are not given access to these tests. Problems also exist with doctors not being familiar with the abnormalities on testing seen in M.E. and so misinterpreting the results of some tests. 

The problem is not that these tests don’t exist, but that doctors – and many patients – are unaware of this information on testing, that it is not generally accepted due to the nefarious influence of political and financial vested interest groups, and that there are overwhelming financial and political incentives for researchers to IGNORE this evidence in favour of the bogus ‘CFS’ (or ‘subgroups of ‘ME/CFS’) construct. For more information on the lack of access to appropriate testing for M.E. patients see Testing for M.E." ~ The Hummingbirds Foundataion for ME

Objective evidence of organic abnormalities in people with Myalgic Encephalomyelitis (ME) has existed since the 1950’s. 

Below is a sample of biological research findings in people with ME, put together by Paul Watton.

https://app.box.com/s/9s4coexxtys5bnz33i6gvqqygu67ex5o

 

This article provides a summary of 200+ research papers addressing the different aspects of the pathophysiology of ME.

Tests will only all be normal in ME patients, as with most illnesses, if the wrong tests are conducted, or if those tested do not have ME. 

The standard battery of tests e.g. typical full blood profile as done by the GP, is inadequate in revealing the abnormalities seen in ME. These standard tests may be normal in up to 90% of ME patients.

Not only are there a series of tests which readily allow an ME diagnosis to be confirmed, but more than 1,000 medical studies have shown a variety of measurable and in some cases extremely severe abnormalities in many different bodily systems of ME patients. Abnormalities can also be visible on physical exam. 

There are a number of non-routine tests that identify ME clearly and which can be used for diagnostic and disability purposes.  

Evidence-based diagnostic tests are superior to questionnaires based on subjective symptoms. 

The problem with testing in ME is that there is currently no single diagnostic tool to diagnose ME, however an accurate diagnosis can be made by a doctor using accepted diagnostic criteria such as the International Consensus Primer (ICP), which is based on the International Consensus Criteria (ME-ICC).

The tests listed below, through the work of scientists & clinicians, firmly confirm that there are tests for this disease. 

Testing 

(i) Testing as per the International Consensus Primer (ICP)

(ii)Tests available in Ireland via public and private avenues, some of which includes laboratory tests suggested in the ICP

(i) Testing as per the International Consensus Primer (ICP)

It is important that the doctor does a clinical interview (including medical history) and a physical examination of the patient who suspects ME before any tests occur.

• Clinical Interview Recommendations 

The Clinical Interview develops through observations and dialogue that follows the flow of the illness and its impact as felt by the individual patient. The most important feature to be noted is the post exertional response, i.e., Post-exertional neuroimmune exhaustion (PENE) as referred to on pgs 2-4 of the International Consensus Primer, which refers to the crash, lack of stamina, exacerbation of all symptoms often delayed 24-72 hours and lasting days, weeks or longer. Push/crash cycle can lead to serious decline in function. Patients exhibit unique combinations of symptoms.

 

Please see the International Consensus Primer for more on clinical examination.

Clinical Interview and Clinical Application Principles Recommendations in the ICP for Medical Practitioners : page 9, 10 ICP

 

International Consensus primer page 10

• Physical Examination Recommendations 

There are a variety of abnormalities visible on a physical exam in ME patients. These abnormalities are not usual in healthy people. 

 

Please see the International Consensus Primer for more on physical examination.

 

Physical Examinations Recommendations in the ICP for Medical Practitioners:  Top of Page 11 ICP

 

International Consensus Primer top of page 11

• Laboratory Testing Recommendations

It is important that the doctor does laboratory tests to identify abnormalities that detect dysfunction and which can support some symptom management. The ME International Consensus Primer for Medical Practitioners (ICP) lists tests for this purpose, see ICP Recommended Tests for Medical Practitioners: Page 11 and 12  ICP

International Consensus Primer page 11

International Consensus Primer page 12

 

• Patient Doctor Check List Based on ME- ICC from GAME - ICC, thanks to Wendy Boutillier here

• More about the Tests Recommended in the ICP

More details about the ICP recommended tests for ME below, tests which when combined can be used to confirm an ME diagnosis which include:

 

• SPECT and xenon SPECT scans of the brain.
• MRI scans of the brain.
• PET scans of the brain.
• EEG/QEEG brain maps.
• Neurological examination. 
• The Romberg test.
• Immune system tests.
• Insulin levels and glucose tolerance tests.
• Erythrocyte Sedimentation Rate (ESR) tests.
• Circulating blood volume tests.
• 24 hour Holter monitor testing.
• Tilt table examination and standing/sitting/reclining blood pressure tests.
• Exercise testing (CPET) and chemical stress tests.
• Physical exam

Note 1. 

 

These tests are important in the diagnosis of ME although the unfortunate reality is that many people who suspect they have ME do not have access to the appropriate tests or to doctors who could do the tests, or who are able to make a diagnosis.  We will include the following information on testing in ME for anyone fortunate to have an ME-knowledgeable doctor who would refer you to such testing if available and accessible. 

 

Note 2.

 

Those with more severe ME, i.e., people with severe, very severe or profound ME, are either very unlikely to be able to take part in such testing or at best will find some of the tests difficult. 

SPECT Scans

SPECT scans have demonstrated decreased cortical/cerebellar regional cerebral blood flow most frequently in the frontal, parietal, temporal, occipital and brain stem areas of the brain, and throughout the cerebral cortex in ME. This decrease in cerebral blood flow has also found to be worsened further still 24 - 72 hours post-exertion. These abnormalities have also been shown to correlate with clinical status (Carruthers et al. 2003). 

In 2007, Dr Byron Hyde’s Nightingale Definition of ME explained that brain scans can be used in diagnosing ME and to some degree can also be used to predict the future severity of the disease. Dr Hyde writes that:

'The second and chronic phase that clearly defines ME is characterized by various measurable and clinical dysfunctions of the cortical and/or sub-cortical brain structures. If the patient’s illness is not measurable using a dedicated brain SPECT scan such as a Picker 3000 or equivalent, then the patient does not have ME. For legal purposes these changes may be confirmed by PET brain scans with appropriate software and/or QEEG. These changes can be roughly characterized as to severity and probable chronicity using the following two scales: A: Extent of injury and B: degree of injury of CNS vascular function.'

MRI Scans of the Brain

MRI scans have shown the presence of small white matter lesions predominantly in the frontal lobes and subcortical areas. Punctate, subcortical areas of high signal intensity consistent with edema or demyelination were identified by MRI in at least 78% of ME patients (similar to those seen in MS).  

 

Research has shown that at least 80% of ME patients will have abnormal MRI scans (Hyde, 2003) (Carruthers et al. 2003). ME patients with abnormalities on MRI have been reported as being more severely impaired than those without such abnormalities. 

In a comparison of intracranial abnormalities in ME patients by MRI and SPECT, the SPECT scan abnormalities appeared to correlate with clinical status while the MRI changes were irreversible (Carruthers et al. 2003).

 

Researchers have found that the bright spots on MRI scans of ME patients are evidence of an ‘arteriolar vasculopathy’ and that ME is a ‘systemic micro-vascular inflammatory process.’ That is a process that affects not only the brain or the heart or the muscles, but potentially every organ system in the body.  

 

 

Note! MRI scans are not recommended for patients who relapse when exposed to loud noise.  An MRI scan can cause severe and extended relapse in such patients. 

 

Dr Byron Hyde also explains that a normal MRI does not conclusively prove that a person has no CNS dysfunction as the MRI demonstrates only abnormal anatomy and so a normal MRI should never be used to prove that a person does not have CNS dysfunction or is not ill.

 

 

PET scans of the brain

PET scans have shown decreased metabolism of glucose in the right mediofrontal cortex. PET scans have also shown generalised hypoperfusion of the brain with a particular pattern of decreased neuronal metabolism and hypoperfusion in the brain stem.

 

Neuropsychological testing 

 

Of the CNS dysfunctions that make up ME, cognitive dysfunction is easily one of the most disabling characteristics of the illness. The cognitive dysfunction in ME can be extremely severe due to decreased cognitive performance overall, decreased processing speed, problems with working memory and information retention and learning etc. Neuropsychological testing can be used to identify cognitive dysfunction and/or to confirm an ME diagnosis. It should focus on the abnormalities known to differentiate ME from other causes of organic brain dysfunctions. (Carruthers et al. 2003) 

EEG Brain Maps and QEEG Brain Maps 

 

95% of ME patients have been found to have abnormal cognitive-evoked EEG brain maps (Hooper, 2001). Dr Byron Hyde argues that QEEG brain maps are even more accurate:

'An EEG only records activity on the outer millimeter of the brain. A QEEG is simply an EEG attached to a computer that contains appropriate software. A QEEG will immediately demonstrate tumors and brain activity or lack of it related to specific stimuli that are simply not possible to detect on a non-computer-driven EEG. Using QEEG technology operated by an expert physician, we have been able to demonstrate not only lack of normal activity in ME patients but migration of the normal activity centers from injured areas to different parts of the brain'. (Hyde, 2003)

'QEEG brain topography has found evidence in ME of 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 also be noted during verbal cognitive processing'. (Carruthers et al. 2003)

 

Neurological Examination and Romberg Test

A Romberg test is a useful test of damage to the vestibular systems and of brain stem function. At least 95% of M.E. sufferers have been shown to have a positive Romberg test. 

Most ME patients have abnormal neurological examination (Hooper et al. 2001).

The test involves standing with eyes open and then with eyes closed with feet together or one behind the other. A positive Romberg is when the position is maintained with eyes open but not when they are closed. It is a useful test of brain stem function. Professor Malcolm Hooper explains that, ‘Dr Paul Cheney found that more than 90% of patients have an abnormal Romberg versus 0% of controls.’ (Hooper et al. 2001)

 

Neurological Structural & Functional abnormalities pgs 4 & 5 International Consensus Primer

       Neurological Testing Information Sheet from ME International here

Tests of the Immune System 

 

The immune system abnormalities in ME patients indicate a viral infection. Specific findings include (but are not limited to):

• Increased numbers of activated cytotoxic T cells (most patients have evidence of T-cell activation)

• Reduced T-Cell count*

• Low Natural Killer Cell numbers*/percentage and function (cytotoxicity)

• Elevated immune complexes

• Atypical lymphocyte count

• Significantly reduced CD8 suppressor cell population and increased activation marker (CD38, HLA-DR) on CD8 cells

• Abnormal CD4/CD8 ratio

• ANA

• Elevations of circulating cytokines (including IL-6) particularly after exertion (there is an inappropriate and negative immune response to exertion)

• Immunoglobulin deficiencies (most often IgG 1 and IgG 3)

• Th1/Th2 Imbalance* (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 would explain increased rates of allergies and sensitivities, and conversely, difficulty fighting off pathogens).

• Th1 –Th2 response to mitogen stimulation (high levels of Th2 indicate autoimmunity)

• Antilamin antibodies (indicate autoimmunity and brain cell damage. Lamin B antibodies are evidence of autoimmunity)

• Apoptosis is often raised (this is programmed cell death: known to be raised in infection)

• Monocytosis (raised monocytes are suggestive of infection) (McLaughlin, 2004) (Carruthers et al. 2003) (Hooper et al. 2001) (Cheney 2006)

*NK Cell and T-Cell Dysfunction

Natural Killer (NK) Cell and T-cell Dysfunction – NK and T-cells are two components of the immune response to pathogens. A set of ME 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'.

One of the most commonly observed abnormalities in ME patients, and also one of the most striking abnormalities, is that of low numbers and function of natural killer cells. Natural killer cells are clearly impacted in ME. One researcher found that NK cell cytotoxicity in ME patients was ‘as low as we have ever seen it in any disease.’ 

 

The actual NK cell function was found to be very, very low - 9% cytotoxicity. The mean for the controls was 25%. It was found that ME patients ‘represent the lowest cytotoxicity of all populations we've studied’ (Klimas, 1990). Poor T cell functioning is also seen in ME. Researchers believe that chronic immune activation due to an underlying chronic infection has caused these T and NK cells to ‘burn out’ due to overuse. (Cheney 2006) 

*TH1/TH2 Imbalance

TH1/TH2 Cytokine Production Immune testing: 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 here.

RNase L 

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 ME patients. 

A subset of ME 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 ME patients could have trouble finding pathogens and killing the cells they've infected.  A more specific immune system abnormality has been discovered in ME of increased activity and dysfunction of the 2-5A RNase L antiviral pathway in lymphocytes. 

 

The dysregulation of the RNase L pathway strongly supports the hypothesis that viral infection plays a role in the pathogenesis of the illness. Between 80.0 percent and 94.7 percent of ME patients have evidence of an up-regulated 2-5A antiviral pathway. The degree of elevation of 37 kDa RNase L has also been shown to correlate with symptom severity. 

Immune Impairments pages 5 and 6 International Consensus Primer

Immune Testing page 11  International Consensus Primer

Immunology Information Sheet from ME International here 

Erythrocyte Sedimentation Rate (ESR)

This is a common blood test used to detect and monitor inflammation based on the rate at which red blood cells settle in a test tube. An unusually low sedimentation rate of > 5mm/hr is common in ME and can occur in 40% or more of patients. ESR rates as low as 0 have been documented in ME patients, and levels of 1 and 2 are very common (Hooper et al. 2001) (Johnston, 1996, p. 215). 

 

Such low sedimentation rates indicate that ME patients may have difficulty forming red cell membranes  because of a distorted red cell pathology. Dr Byron Hyde reported in 1989 that, “To my knowledge, there are only five diseases that have a pathological low sedimentation level: Myalgic Encephalomyelitis, sickle-cell anemia, hereditary sperocytosis, hyper-gammaglobulinemia [and] hyper-fibrogenemia’ (Johnston, 1996, p. 215).

 

Note to patients re the misinterpretation of this test by doctors: unfortunately, as problems with high sedimentation rates are very common and more well known, doctors may mistakenly be of the opinion that with this test - as with blood pressure tests - ‘lower is better.’ This is a real problem when the low sedimentation rate and the low blood pressure seen in ME are signs of serious abnormal pathology, debilitating symptoms and a potentially fatal disease.

 

 

Although a very low sedimentation rate by itself should not be interpreted as diagnostic of ME, this is a simple and inexpensive test that can be a very strong indicator of ME, if a patient’s symptoms and additional tests also point to the diagnosis. However, patients must be aware that the results of this test may unfortunately be misinterpreted by some doctors.

Immunology Information Sheet from ME International here 

Cardiology Impairments & Testing Specific for ME 

ME is linked to insufficient heart function. ME affects many systems including impaired immunity, neurological abnormalities, broken oxygen exchange, impaired energy production, muscle fatigueabilty, dysfunctional ANS, and more. Low oxygen uptake suspected cause of exertion intolerance.

• A 24-hour Holter monitor (a type of heart monitor) may show repetitively oscillating T-wave inversions and/or a flat T-wave may be found.

• 2 day CPET shows inability to recover. Test may exacerbate symptoms causing possible reduction in function. 

• EP testing: At least 48 hr HR w/symptoms recorded (syncope, chest pain, palpitations, muscle aches), tilt table test (extended time needed to catch abnormalities), standard 12-lead resting electrocardiogram, rest/stress myocardial perfusion study, multigated (radionuclide) rest/stress ventriculographic exam. 

• Monitor BP and heart rate (laying sitting, and standing) 

• Lab testing: BNP Blood Test, CRP levels and assessment of arterial wave reflection may be useful for determining cardiovascular risk. 

• Impedance cardiography – severe patients had significantly lower stroke volume and cardiac output than the controls

Tracking Charts for heart rate, blood pressure and other readings from ME International here

24 Hour-Holter Monitor

A 24-hour Holter monitor (a type of heart monitor) may show repetitively oscillating T-wave inversions and/or a flat T-wave may be found. A standard 12 lead ECG is usually normal however (Hooper et al. 2001). Holter monitors may also show heart rates as high as (or higher than) 150 beats per minute as an immediate or delayed response to the patient maintaining an upright posture, or at rest (Carruthers et al. 2003). Heart rates as low as 40 beats per minute may also be observed during sleep (Hyde, 2003). 

Dr Byron Hyde explains: 'I routinely use a Holter monitor on all patients. The cardiologist often reports these as normal. Do not trust this report. What the cardiologist or computer is basing the report on is the number of ischemic events [which is not relevant to the heart problems caused by ME]. 

 

However, read the lowest heart rate at night, and note that it sometimes falls to the low 40s. Though this may be normal in an athlete, it is not in a sedentary ME patient. For a patient who is not active all day long and has an average heart rate that flirts with 100 beats per minute or more, you know that this is not normal. These abnormal tests, however, are often reported as normal.’ (Hyde, 2003)

Dr Byron Hyde recommends that patients or doctors must always specifically request to be informed of these specific patterns as they may not be reported (or may be subsumed under non-specific T-wave changes) by the interpreter (Hyde, 2003).

Dr Byron Hyde also adds that cardiac irregularity on minor positional changes or after minor physical activity, including inability of the heart to increase or decrease in speed and pump volume in response to increase or decrease in physical activity is often seen in ME and that, ‘In many M.E. patients there is an unusual daytime tachycardia, particularly since these patients are often very sedentary. 

 In doing a 24-hour Holter monitor this may be missed since the 24 hour average is usually given. One should always ask for wake time and sleep time heart rates’ (2007).

 

Cardiopulmonary Exercise Testing (CPET)

The CPET is a cardiopulmonary exercise test that is sometimes used to document impairments in people with Myalgic Encephalomyelitis (ME).

It can also be called a “metabolic/expired air test” or a “V02 max test” or a “metabolic exercise test” or “cardiopulmonary exercise testing.” 

Cardio-Pulmonary Exercise Testing is an objective and reproducible technique for determining and measuring functional disability with measurement of VO2 max, anaerobic threshold, and maximal heart rate and respiration.  

Cardiopulmonary Exercise testing is used for the diagnosis and functional assessment of various cardiac and metabolic disorders and can also be used in the diagnostic evaluation of people with ME. 

Heart rate and blood pressure responses during the exercise test may reveal abnormalities specific to ME including: 

• lower cardiovascular and ventilatory values at peak exercise (patients only being able to attain half the expected maximal workload and oxygen uptake compared to sedentary controls), 

• elevated resting heart rates and 

• an inability to reach maximum age-predicted heart rates (suggesting cardiac or peripheral insufficiency and/or reduced blood volume) (Carruthers et al. 2003).

Important notes!

! If the doctor feels the patient is able and insists on a regular exercise stress test, then a second stress test should be followed the next day to show the extreme disability. The results of a study employing this approach indicate that the test-retest protocol provides an assessment of ME related disability consistent with both medical & legal considerations.

!! It is important to note that more severely affected ME patients will be either too ill to complete such tests altogether, or may be able to complete these tests only at the cost of a potentially severe and unnecessary relapse, which usually peaks 24 - 48 hours post-exercise and will then persist for days, weeks or even months afterward depending on the patient’s illness level.

More information on CPET 

 - Information put together by Lily Silver, US ME patient, explaining why someone might do a CPET, what the CPET measures, the different types of CPET tests available, difficulties for ME patients doing a CPET, safety issues and more here.

 - Sample CPET Report from Workwell Foundation here.

Alternative to CPET - Chemical Testing  

 

As exercise tests are not appropriate for many ME patients, and as Dr Byron states that: 

 

'Several of our patients have reacted severely to the chemical test with excruciating pain. This is not true angina, and although the pain sometimes ceases as soon as the chemical is stopped and the antidote given, sometimes it persists for weeks after the procedure with no sign of coronary artery disease. I do not understand this phenomenon, but it is obviously vascular. The cardiologists state that this pain does not occur with the same frequency in non-ME patients' (2003).

 

Abnormal Responses to Exercise pages 2, 3, 4, 7 International Consensus Primer

Tilt Table Examination  (& Vascular Dysfunctions)

Dr Byron Hyde explains that testable vascular and cardiac dysfunction is the most obvious set of dysfunctions when looked for and is probably the cause behind a significant number of ME complaints, and that all moderate to severe ME patients have one or more and at times multiple of the following vascular dysfunctions: 

• Severe postural orthostatic tachycardia syndrome (POTS)
• Cardiac irregularity on minor positional changes or after minor physical activity
• Raynaud’s phenomenon (vasoconstriction of small arteries or arterioles of extremities, with change in colour of the skin, pallor and cyanosis),
• Circulating blood volume decrease
• Bowel dysfunction caused by vascular dysfunction (vascular dysfunction may be the most significant causal basis of the multiple bowel dysfunctions occurring in ME),
• Persantine effect in ME patients
• ME associated clotting defects (ME represents both a vasculitis and a central and peripheral change in vascular physiology)
• Anti-smooth muscle antibodies (this is an antibody to the muscle tissue in the arterial bed. It is elevated in about 5% of ME patients)
• Cardiac dysfunction (there are a large number of cardiac dysfunctions that can regularly appear in an ME patient).

Note! the primary vascular change in ME is seen in abnormal SPECT brain scans. It should also be noted that a significant number of ME patients may show evidence of all, or almost all, of these vascular abnormalities.

 

Orthostatic Intolerance is very common in ME patients and may manifest as one of, or a combination of the following:
 

• Neurally mediated hypotension (NMH): Involves disturbances in the autonomic regulation of blood pressure and pulse. There is a precipitous drop that would be greater than 20-25 mm of mercury of systolic blood pressure upon standing, or standing motionless, with significant accompanying symptoms. The patient feels an urgency to lie down.

• Postural orthostatic tachycardia syndrome (POTS): Excessive rapidity in the action of the heart (either an increase of over 30 beats per minute or greater than 120 beats per minute during 10 minutes of standing); and a fall in blood pressure occurring upon standing. Syncope can but usually does not occur.

• Chronic Orthostatic Intolerance (COI): The inability to sustain upright activity (standing, sitting or walking), is very common and important component of ME. Upon limited standing, the patient experiences an urgency to lie down, confusion, malaise, various cardiac/vascular symptoms 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. 

• Delayed postural hypotension: As above except the drop in blood pressure occurs many minutes (usually ten or more) after the patient stands rather than upon standing (Carruthers et al. 2003) (Bassett 2009).

More than 97% of patients demonstrate vasovagal syncope (Neurally Mediated Hypotension) on tilt table testing. 

 

Note! If a tilt table test is not available, or a patient is not able to to the test, especially those with more severe ME, doctors can monitor pulse and blood pressure while the patient is standing, and again while lying down. This may need to be repeated several times, and is known as the ‘poor man’s tilt table test, or more modernly as the NASA Lean Test. 

Alternative to Tilt Table Testing - the NASA Lean Test

Note! Most people with ME especially those with more severe ME would not be able to do Tilt Table Testing. An alternative test for those who can get out of bed without difficulties, and who are able to sit up for 10 minutes and then also stand for at least 10 minutes is the NASA Lean Test (same as 'poor man's tilt table test).

Step By Step Procedure in the NASA Lean Test 

 

Ask the patient to lie down and rest quietly for 15 - 20 minutes. 

Then take the first blood pressure and pulse readings and make a note of them.  

 

Ask the patient to sit up for 10 minutes, or as long as they can manage without severe problems, and then take another set of readings and make a note.  

 

Then direct the patient to stand up for 10 minutes, leaning against a wall, but without fidgeting or moving or talking which can affect the result. Then take another set of readings and make a note.  

 

After another 10 minutes of standing and leaning, take the readings again and make a note. 

 

Keep leaning. Do not flex any muscles or talk.   

 

After another ten minutes, take the readings again.

Important Notes for the doctor and patient with regards to the NASA Lean Test!  

 

If at any time the patient starts to feel sweaty or hot or nauseous, the doctor/practitioner needs to take the patient's bp and pulse readings right away and get the patient lying down as soon as possible.   

 

Many patients will not be able to tolerate this much time upright and will need to stop the test partway through. If this happens, take another reading (if possible) and then the patients lies down again.  

 

Failure to stop the tests when the patient becomes severely ill can lead to a loss of consciousness, or severe relapse lasting days, weeks or even months in the very severely affected. Someone should always be standing near the patient to catch them if they fall and serious requests to stop the test must be acted on in a timely manner.

 

Assessing the readings taken: 

 

For Neurally Mediated Hypotension* (NMH), the patient has to have a 20-25 mm drop in systolic blood pressure (the higher number).

If the patient's pulse suddenly rises at least 30 bpm (beats per minute), then it is likely they have Postural Orthostatic Tachycardia Syndrome* (POTS).

Dr. Rowe believes that they are both really the same  thing - with either, if the patient doesn't lie down, they're going to pass out.  And the treatment for both is the same. 

*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.

*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. 

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. POTS patients are usually significantly debilitated by their symptoms.

 

More Information on the NASA Lean Test  

 

'A Simple Way to Assess Orthostatic Intolerance', an information document by Lucinda Bateman, includes images and pdf copies of instructions for medical providers and patients about how to do the NASA Lean Test, see here.

 

Grip Test

 

Research has shown that grip strength is associated with a number of health indicators, including mobility. While grip strength isn't necessarily used when you're walking, it's associated with mobility. People with physical limitations are more likely to have decreased grip strength. A grip test is used as an objective measure of disease status and severity in ME, and correlates it with fatigue and pain severity and with physical and mental functioning. 

 

'Hand grip strength (HGS) is a reliable measurement of localized muscle strength and reflects the force derived from the combined contraction of extrinsic hand muscles. Originally developed for hand surgery to determine capacity after trauma or surgery, hand grip strength correlates well with other muscle function tests such as knee extension strength. 

 

Moreover, reduced HGS has been associated with morbidity and mortality, with low values associated with falls, disability, impaired health-related quality of life and prolonged length of stay in hospital. It has also shown to be strongly correlated with post-operative complications and has been reported as a predictor of loss of functional status and short-term survival in hospitalized patients.' (from Hand Grip Strength as a Clinical Biomarker for ME/CFS and Disease Severity - PMC (nih.gov))

 

‌How to Measure Grip Strength: 

 

Grip strength is measured using an instrument called a dynamometer. Measure your grip strength with a dynamometer using the following steps:‌

 

• Hold your arm with your elbow bent at a 90-degree angle. 

• Squeeze the dynamometer as hard as possible.

• Apply grip force in a smooth motion. Avoid jerking.

• Repeat twice more for a total of three times.

• Your grip strength is the average of the three readings.

 

Overall, patients with ME have significant lower hand grip strength (HGS) values than healthy controls (HC). MS is the most common immune-mediated inflammatory demyelinating disease of the central nervous system. One of the most prominent features of MS is motor weakness. Therefore, it is expected people with MS to display lower HGS. However, ME patients also have significantly lower HGS values compared to HC, even after controlling for age, sex, and BMI, with even mild cases showing lower HGS. 

 

People with ME are not malnourished and have preserved muscle tonus, suggesting that other than local factors related to the integrity of upper limb must be involved. It has been suggested that these might relate to ongoing inflammation or disruption of signaling mechanisms between central nervous system and periphery, and it may also represent an overall measurement of “physical health and functioning.”

 

More here

Cardio Blood Tests

Lab testing: BNP Blood Test, CRP levels and assessment of arterial wave reflection may be useful for determining cardiovascular risk. 

Cardiovascular and Autonomic Impairments page 6, 8  International Consensus Primer

 

North Carolina/Ohio ME & FM Support Group's cardiologist's handout has specific information regarding cardiac issues seen in ME. A chart for tracking info can be found on pages 3 and 4 Cardiologists Handout.

 

ME International's Pulse Oximeter handout has information about using an oximeter and more advice on understanding heart issues in ME.

Blood Testing in People with Myalgic Encephalomyelitis (ME) 

Note: Standard blood tests rarely show up any significant abnormalities in people with ME. But when doctors search beyond standard tests, patterns can begin to emerge. They may not be quite the same for each patient, and rarely will all of the tests show abnormalities. Test results may also vary over time. It is always important to report new symptoms in ME or worsening of current symptoms so that your doctor can decide whether new tests are necessary.

 

 

ICP Blood Tests Recommended for Medical Practitioners  which can aid your doctor in differential diagnosis, and to follow up on treatment efficacy, ICP page 11.

International Consensus Primer page 11

(ii)Tests available in Ireland via public and private avenues, which includes laboratory tests suggested in the International Consensus Primer

Blood Tests for People with Myalgic Encephalomyelitis (ME)

A GP can request a lot of blood tests and an HSE lab is set up to process all of them. This can include 'private' requested blood tests like Lyme Serology and Reverse T3, depending on a willing GP.

You can have your bloods taken for testing at your own GP practice, sometimes there is a cost for having bloods taken at your GPs practice whether you have a medical card or not. Some GPs do not charge medical card holders for blood tests.

Swiftqueue

A possible alternative to having bloods done at your GP is to have them done at a hospital's out patient phlebotomy clinic. Not all hospitals have this facility but you can check and book through Swiftqueue online. Swiftqueue is a hassle free guide to finding a clinic/GP near you. You can find an appointment that suits you and see real time availability, do an easy instant booking, then your appointment is instantly confirmed. There is the option to reschedule or cancel if something changes. You'll need to bring a copy of your GP referral with you.

Blood Tests to be done

The following tests in (A) assumes that the usual full blood count, renal and liver will be done, and includes some of the specific tests recommended beyond the normal panels:

(A) ask the doctor for iron (ferritin& haemoglobin), vitamin D3, B12 (many patients see benefit in higher range), B6, folate, calcium, CoQ10, RBC magnesium, zinc, copper, caeruloplasmin, C-Reactive Protein (CRP), ESR & epstein Barr, Thyroid (TSH, T3,T4, reverse T3, autoimmune), Blood sugar (glucose for a snapshot & HBa1c for a historical look at your blood sugar control), Immunoglobulins including a full screen for coeliac disease to include IgA (total and endomysial, tissue transglutaminase IgA, HLA tissue type), 24 hour urine free cortisol, Amino acid profile, Viral testing, NK cell function, DHEA

Notes:

If you have gastrointestinal symptoms or a tendancy to get a rosacea type rash/acne across your cheeks ask for a referral to a gastroenterologist for investigations into SIBO (small bowel bacterial overgrowth - the simplest test for this is hydrogen breath testing although this can return false positives, some people only produce methane so ensure both hydrogen and methane testing are provided.)

It is almost impossible to get a GP to do reverse T3 (& not necessary as a first port if call) and you will have a fight on your hands to get T3 done due to instructions to GP's regarding its testing via the HSE. You may have to get it done privately.

It may be difficult to get anywhere in Ireland that does all of the tests above in one place.

 

Important Notes:

●            Reverse T3 - an HSE lab will not run a Reverse T3 test, apparently, if your other thyroid tests are in range so this would have to be done privately to get around that issue.

●            Insurance - If you go to a private hospital for blood tests and have insurance, do check to make sure the hospital is covered under your insurance plan. Your insurance may cover one particular hospital and not another. 

●            Consultant Private Blood Test Requests - it seems that a consultant request can only be brought to a private hospital in that consultant’s jurisdiction, so a patient cannot take the consultants request to a community hospital where they live to get blood tests done. Consultant-requested blood tests via the GP can be brought to most community hospitals.  

Information re Private Blood Tests in various hospitals in Ireland

The information below is an idea of particular tests mentioned above, and the approximate cost of having those tests done privately. (Information and prices may have changed and need to be updated)
 

 

 - Hermitage Clinic - Blood Tests

Phone: (01) 6459181

Email: phlebotomy@hermitageclinic.ie

Hours: Mon-Fri, 9:30am to 4:30pm

 

Note: Call ahead to book an appt (not a walk-in service) and to ensure your request from GP or Consultant will be honored. Sample of costs for following sample of tests:

Reverse T3          €245

Free T3                  €39

Lyme Serology       €74

Free T4                   €27

ENA:                       

ENA Screen            €50

ENA Identity          €105

ANCA                      €48

ANTICCP                €84

DHEA                      €50

More here and here

 

 - St James Private Clinic - Blood Tests

Phone: (01) 4284291 

 

Email: privateclinicrecp@stjames.ie 

 

Website: https://www.stjamesprivateclinic.ie/blood-tests  

 

Hours: Mon-Fri, 8:00am - 2pm. 

 

The blood testing clinics are located off the main concourse of the hospital. Booking is essential. 

 

The price of the 6 below tests is approx. €325.00 in total. No breakdown available.

Magnesium

ENA

ANCA

ANTICCP

DHEA

Lyme Serology

Then the price of the Reverse T3 & Free T4 is approx €200, because they are sent to an external lab. 

 

Reverse T3 

 

Free T4

Note - Be aware there is also the separate “St James GP Clinic”, which takes appts but does not take requests from consultants. Information re GP Blood Testing here.

 - Online Labs

There are various labs accessible online who provide blood or saliva testing services. A pack is sent out and either saliva or blood* taken then returned by courier the same day. Then your results will be reviewed by one of the labs GPs and made available in your via email/other within approximately 1 - 5 working days after the lab receives your sample, depending on the test.The various labs usually advise customers on how to take tests and on how to return tests via the courier.
 

*  Blood tests are finger-prick blood testing you do at home

 

(B) You could then self refer to Allergy Counts e.g.the Charlemont Clinic Allergy Clinic or any other allergy clinic providing IgE skin prick tests and get a full panel of skin prick tests done to see if you have any allergies. Do not bother with IgG tests for intolerances (even if a doctor recommends them) as the research behind these is not robust enough.

(C) You could also seek the advice of a good properly qualified nutritionist to comprehensively investigate your diet and lifestyle and see if any of your symptoms could be a result dietary issues or a lack of supplementation or too much supplementation or innappropriate supplementation.
 

(D) In tandem with this you could get your 24hr sleep hormones & stress hormones checked privately using a private lab. If you have problems with your menstrual cycle you need to get a complete salivary panel of your female hormones - also from a private lab. 

 

 

'All the tests were negative' & 'everything has been tested' is probably not true in many cases. This assumption is what stops further investigations such as those outlined in the above list - and others (depending on case history)

 

 

 

Conditions to Rule Out When Testing or Confirming an ME Diagnosis

There is no diagnostic blood test for ME, but testing your blood and doing other tests is essential to rule out other illnesses that can cause similar symptoms. Diagnosis should also involve the exclusion of other possible causes of your symptoms. Too often patients discover after getting an ME diagnosis that a treatable illness had been overlooked. 

The ICP includes testing recommendations to rule out other diseases. As in exclusion of alternate explanatory diagnoses is achieved by the patient’s history, physical examination, and laboratory/biomarker testing as indicated. It is possible to have more than one disease but it is important that each one is identified and treated. 

It is common for people with ME to have other associated conditions. Co-morbid entities include Fibromyalgia, Myofascial Pain Syndrome, Temporomandibular Joint Syndrome (TMJ), Irritable Bowel Syndrome, Interstitial Cystitis, Raynaud’s Phenomenon, Prolapsed Mitral Valve, Migraines, Allergies, Multiple Chemical Sensitivities, Hashimoto’s Thyroiditis, Sicca Syndrome, Reactive Depression. Migraine and irritable bowel syndrome may precede ME but then become associated with it. Fibromyalgia overlaps.

There are many conditions that can be ruled out as seen in ME International's (MEI) handout: Conditions to Rule Out and here

Differential Diagnosis

When indicated on an individual basis, rule out other diseases that could plausibly simulate the widespread, complex, symptom pathophysiology defining ME. 

For Example: Infectious disorders: TB, AIDS, Lyme, chronic hepatitis, endocrine gland infections; Neurological: MS, myasthenia gravis, B12; Autoimmune disorders: polymyositis & polymyalgia rheumatica, rheumatoid arthritis; Endocrine: Addison’s, hypo & hyper thyroidism, Cushing’s Syndrome; cancers; anemias: iron deficiency, B12 [megaloblastic]; diabetes mellitus

Final Comments

ME patients reading the above information re testing should be aware that not all symptoms experienced may be due to ME and that ME does not mean that other illnesses which may need urgent investigation cannot develop.

All tests listed above are not suitable for all patients; the risk/benefit ratio must always be taken into account with each patient. 

Some people with ME, especially those with more severe ME will be too ill to undergo some tests.

The list of diagnostic tests given above are not exhaustive. 

There is further useful information on testing by Jodi Bassett in The Humming Bird's Foundation for M.E. pages on Testing for Myalgic Encephalomyelitis. 

(please note that some parts of the information on testing recommendations may have been updated elsewhere but in general this is a very good page)

Further Reading

Testing for ME summaries by The Hummingbird Foundation for ME here 

Acknowledgements

Thanks to Jodi Bassett for her information compiled in “Testing for ME,” at Jodi Bassett’s Australia-based web site, 'The Hummingbirds' Foundation ME', at https://www.hfme.org 

& 

Thanks to Dr. Byron Hyde, MD, an internationally recognized ME specialist, and chairman of the Nightingale Research Foundation for the study and treatment of ME in Ontario, Canada. 

&

Thanks to Lily Silver for her information on Cardio-Pulmonary Exercise Testing (CPET) via her blog 'How to Get On', https://howtogeton.wordpress.com 

|

Remembering Jodi Bassett & Lily Silver

(RIP)

Information above was compiled by ME Advocates Ireland (MEAI) to aid patients to communicate with their doctor and other healthcare practitioners

Disclaimer: The information in this post is for general information purposes only. While we endeavour to keep the information up to date and correct, we make no representations or warranties of any kind, express or implied, about the completeness, accuracy, reliability, suitability or availability with respect to the post or the information, products, services, etc contained in the post for any purpose. Any reliance you place on such information is therefore strictly at your own risk.The suitability of any solution is totally dependent on the individual. It is strongly recommended to seek professional advice and assistance.