Copyright © by Jodi Bassett February 2006 on www.ahummingbirdsguide.com
This version updated January 2007

The reality is that objective evidence of quantifiable organic abnormalities in Myalgic Encephalomyelitis patients has existed since the 1950’s. Not only are there a series of tests which readily allow a M.E. diagnosis to be confirmed, but more than 1000 medical studies have shown a variety of measurable and in some cases extremely severe abnormalities in many different bodily systems of M.E. (or ICD-CFS) patients. Abnormalities are also visible on physical exam. Tests will only all be normal in M.E. patients – as with all illnesses – if completely the wrong tests are done, or if those tested do not in fact have M.E. in the first place.

This text will now focus on the series of tests which can be used to confirm a M.E. diagnosis as well as detailing some of physical signs common in M.E. patients which may also be useful for diagnosis. (Some of the tests listed may however also be useful in proving illness for the benefit of social security or insurance company entitlements, or may be used to determine appropriate treatments in patients who have already been diagnosed with M.E. References useful in providing further information about exclusionary tests – and all other aspects of diagnosis – are provided at the end of this text.)

• For more information see M.E. Is Not Fatigue, Fatigue Schmatigue and ME and CFS, The Definitions. Many of the worlds leading M.E. experts have spoken out strongly against ‘fatigue’ being the defining symptom of M.E. click here to read some of their comments. For more on the symptomatology of M.E. see: The Clinical and Scientific Basis of M.E. and The Ultra-comprehensive Myalgic Encephalomyelitis Symptom List.

As M.E. expert of more than twenty years Dr Byron Hyde MD explains: ‘The one essential characteristic of M.E. is acquired CNS dysfunction, [not] chronic fatigue. A patient with M.E. is a patient whose primary disease is CNS change, and this is measurable. We have excellent tools for measuring these physiological and neuropsychological CNS changes: SPECT, xenon SPECT, PET, and neuropsychological testing.’ (2003) Thus it is these tests which are therefore most critical in the diagnosis of M.E., although various other types of tests are also useful.

Some of the series of tests which can (in combination) help to confirm a suspected M.E. diagnosis include:

SPECT and xenon SPECT scans of the brain

SPECT scans have demonstrated decreased cerebral blood flow most frequently in the frontal, parietal, temporal, occipital and brain stem areas of the brain. This decrease in cerebral blood flow has also found to be worsened further still 24 - 48 hours post-exertion. These abnormalities have also been shown to correlate with clinical status. (Carruthers et al. 2003) Dr Byron Hyde MD adds that, ‘I do not describe a patient as having M.E. unless there is an abnormal SPECT. If the SPECT is normal, I often repeat it along with xenon SPECT. If the brain scans remain normal, I conclude that it is unlikely to be M.E.’ (Hyde, 2003)

MRI scans have shown the presence of small white matter lesions predominantly in the frontal lobes. Punctate, subcortical areas of high signal intensity consistent with edema or demyelination were identified by MRI in 78% of M.E. patients (similar to those seen in MS). The abnormalities in M.E. patients most closely resemble those seen in AIDS encephalopathy. Research has shown that an estimated 80% of M.E. patients will have abnormal MRI scans. (Hyde, 2003) (Carruthers et al. 2003) M.E. 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 M.E. 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)

MRI scans are also not recommended however for those patients which relapse when exposed to loud noises (a common symptom of M.E.); an MRI scan can cause severe and extended relapse in such patients. Dr Byron Hyde MD 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. (2003)

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 in the brain stem. (Carruthers et al. 2003)

Of the CNS dysfunctions that make up M.E., cognitive dysfunction is easily one of the most disabling characteristics of the illness. The cognitive dysfunction in M.E. can be extremely severe. (Hyde, 1992) Neuropsychological testing can be used to identify cognitive dysfunction and/or to confirm a M.E. diagnosis. It should focus on the abnormalities known to differentiate M.E. from other causes of organic brain dysfunctions. (Carruthers et al. 2003) Dr Sheila Bastien PhD. is easily the expert in this field with over 20 years experience in neuropsychological testing and more than 6 years experience in applying these tests to M.E. patients. She explains that:

Deterioration of IQ levels, as well as cognitive and motor dysfunction in these patients, suggest a pathological process in the brain. The pattern of focal and lateral impairments is consistent with patients who have this particular neurologic dysfunction. The impairment pattern is consistent across the study group [of M.E. patients] although impairment levels vary. This pattern is not seen in other diseases or injuries, such as Alzheimers, stroke, head injuries, multiple sclerosis, systemic lupus erythematosis, personality disorders, depression, psychosis, malingering, anxiety or panic disorders, somatisation or situational stress disorders. The pattern of impairment is one of focal and lateral deficits, consistent with a multi-focal organic brain syndrome. Tests suggest that the most impaired focal areas are the left temporal, right paretal, and left temporal lobes; although there are lesser bilateral impairments in the opposite lobes as well. (1992, pp. 453 - 454)

Dr Byron Hyde MD adds that: ‘This is a complex type of testing, and a physician should attempt to locate an experienced neuropsychologist without ties to the insurance industry. Most neuropsychologists today are employed by the insurance industry, and if they find too much pathology, I suspect that they are no longer engaged. Do not be fooled by a negative insurance-paid neuropsychological report; psychologists whose primary training is not neuropsychology prepare many of these reports.’ (2003)

• One of the most useful texts on neuropsychological testing in M.E. is chapter 51 of the book ‘The Clinical and Scientific Basis of ME’ written by Dr Sheila Bastien Ph.D. Several other chapters of this book also describe the various cognitive effects of M.E. in detail. (Details of this book are given below.) See also The Ultra-comprehensive Myalgic Encephalomyelitis Symptom List for more information about the specific cognitive deficits commonly seen in M.E.

95% of M.E. patients have been found to have abnormal cognitive-evoked EEG brain maps (Hooper, 2001 [Online]). But Dr Byron Hyde MD 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)

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, ‘In his 1995 Australian Workshop, M.E. expert Dr Paul Cheney said that more than 90% of patients have an abnormal Romberg versus 0% of controls.’ (Hooper et al. 2001 [Online.])

Most M.E. patients have abnormal neurological examination. (Hooper et al. 2001 [Online.])

The immune system abnormalities in M.E. patients mimic the immune pattern seen in viral infections. Specific findings include (but are not limited to):

• Increased numbers of activated cytotoxic T cells (most patients have evidence of T-cell activation)
• 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
• Elevations of circulating cytokines
• Immunoglobulin deficiencies (most often IgG 1 and IgG 3)

(McLaughlin, 2004 [Online]) (Carruthers et al. 2003) (Hooper et al. 2001 [Online.])

One doctor commented (in a presentation on the immunological markers in M.E.) that:

The NK (natural killer) cell is a very critical cell in [M.E. equivalent] CFS because it is clearly negatively impacted. The most compelling finding was that the NK cell cytotoxicity in CFS was as low as we have ever seen it in any disease. This is very, very significant data. [In CFS] the actual function was very, very low -- 9% cytotoxicity: the mean for the controls was 25, In early HIV and even well into ARC (AIDS related complex, which often precedes the fully developed condition), NK cytotoxicity might be around 13 or 14 percent. (ME)CFS patients represent the lowest cytotoxicity of all populations we've studied. (Klimas, 1990)

Professor Malcolm Hooper adds that: ‘There is mounting international evidence that M.E. is an autoimmune disorder, with similarities to systemic lupus erythematosus. Evidence of antilamin antibodies has been found in the blood of M.E. patients: antibodies against this protein are proof of autoimmunity and of damage to brain cells.’ (2001 [Online.])

A more specific immune system abnormality has been discovered in ICD-CFS 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 - 94.7% of M.E. patients have evidence of an up-regulated 2-5A antiviral pathway; are so positive for this marker. The degree of elevation of 37 kDa Rnase L has also been shown to correlate with symptom severity. This test is as yet not widely available but may be one of the most useful tests in helping to diagnose ICD-CFS in the future. (See Red Labs for more information.) (Carruthers et al. 2003)

An unusually low sedimentation rate of less than 5mm/hr is common in M.E. (although there may also be brief periods where there is an elevated rate >20mm/hr). (Hooper et al. 2001 [Online.]) ESR rates as low as 0 have been documented in M.E. patients.

Derangement of insulin response and insulin levels is a frequent finding in M.E. patients. Glucose tolerance curves are often abnormal. (Hooper et al. 2001 [Online.])

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 [Online.]) 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 MD explains that:

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 M.E.]. However, read the lowest heart rate at night, and note that it sometimes falls to the low 40’s. Though this may be normal in an athlete, it is not in a sedentary M.E. 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 MD and the Canadian Guidelines both recommend 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) (Carruthers et al. 2003)

Tilt Table Examination

The Canadian Guidelines explain that:

Investigation by tilt test is indicated if there is a fall in blood pressure and/or excessive rapidity of heart beat upon standing, which improves when sitting or lying down. Patients often report that they experience dizziness, feeling light-headed or ‘woozy’ upon standing, or feeling faint when they stand up or are standing motionless such as in a store checkout line. Patients may exhibit pallor and mottling of the extremities. These historical symptoms and signs are sufficient for the initial diagnosis. As [M.E.] patients often have a delayed form of orthostatic intolerance, taking the blood pressure after standing may not be effective in diagnosis. Rather than having the patient stand for a period of time where there is a risk of him/her falling, we recommend using the tilt test where the patient is strapped down. The tilt test involves the patient lying horizontally on a table and then tilting the table upright to a 60°-70° angle for approximately 45 minutes during which time blood pressure and heart rate are monitored.’ (2003)

Orthostatic intolerance is very common in M.E. 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.
• 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 2005, [Online])

Dr Byron Hyde MD warns about tilt table testing in M.E. patients however that:

I frequently find gross abnormalities in M.E. patients with this test. [But] a circulating blood volume and a complete cardiac investigation should be done first. This is not a test to undertake lightly since the patient's heart sometimes stops and may have to be restarted. This test should only be done in major hospital centers in the presence of an appropriate physician where such emergency capabilities can be instituted.’ (Hyde, 2003)

Cardiopulmonary exercise testing (CPX) is widely used for the diagnosis (and functional assessment) of various cardiac and metabolic disorders and can also be used in the diagnostic evaluation of M.E. patients. 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)

Many more severely affected M.E. patients however 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). In addition to the risk of relapse, there have also been reports of sudden deaths in M.E. patients following exercise as M.E. expert Dr Elizabeth Dowsett explains: ‘Some 20% [of M.E. patients] have progressive and frequently undiagnosed degeneration of cardiac muscle which has led, in several cases, to sudden death following exercise.’ (2000 [Online]) As exercise tests are not appropriate for many M.E. sufferers, Dr Byron Hyde MD writes:

Patients with ME frequently cannot do exercise tests, and so I then do chemical testing as a second best. 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)

Cholesterol (high), cortisol (low), thyroid stimulating hormone (TSH) (low), potassium (low), prolactin (high).

There are also abnormalities visible on physical exam in M.E. patients. These abnormalities are not usual in healthy patients but they are also found in people with other illnesses (so they are not specific to M.E.). In cases of severe or acute M.E. there are always definite physical signs indicative of physical illness but virtually all patients will have some abnormality on physical exam. Not all patients will have all signs and along with a fluctuating course of the illness from hour to hour and from day to day being one of the key characteristics of M.E., signs of the illness may also change or fluctuate during the course of a day. As M.E. expert Professor Malcolm Hooper explains: ‘a patient examined in the morning might have nystagmus, which would disappear at midday, recur later, disappear and recur the next day; thus a once-only cursory examination could be misleading.’ (Hooper et al. 2001 [Online.]) Physical signs of illness commonly observed in M.E. patients include:

• Nystagmus; nystagmus is jelly-like and variable (15% of M.E. patients will have nystagmus)
• Sluggish visual accommodation
• Unequal pupils and contrary pupil reaction to light
• A labile blood pressure (sometimes as low as 84/48 in an adult at rest)
• Shortness of breath (particularly on exertion)
• Sometimes marked falling pulse pressure in arterial pressures taken first when prone, then sitting, then standing
• Rapid heart rate on minor activity such as standing
• Subnormal temperature
• Patients show significant reduction in all lung function parameters tested
• Liver involvement (an enlarged liver or spleen)
• Abnormal tandem or augmented tandem stance
• Abnormal gait
• Hand tremor
• Incoordination
• Cogwheel movement of the leg on testing
• Muscular twitching or fasciculation
• Hyper-reflexia without clonus
• Facial vasculoid rash
• Vascular demarcation which can cross dermatomes with evidence of Raynaud's syndrome and / or vasculitis and spontaneous periarticular bleeds in the digits
• Mouth ulcers
• Hair loss
• Destruction of fingerprints is sometimes seen (atrophy of fingerprints is due to perilymphocytic vasculitis and vacuolisation of fibroblasts)
• Ghastly pallor of face with frequent lupus-like submaxillary mask
• Parkinsonian rigidity of facial expression
• Scanning, disjointed speech, or speech reversals
• Nasal passage obstruction and inflamed areas around tonsillar pillars
• Sicca syndrome of conjunctiva and mucous membranes
• Frequent equivocal Babinski/plantar reflex on one side
• Unusual sensitivity of cervical vertebrae area
• Nodular thyroid

(Hooper et al. 2001 [Online.]) (Hyde, 2003)

In addition, the diagnosis of M.E. should never be made without the post-exertional paralytic muscle weakness which is unique to M.E. being present. M.E. authority Dr Melvin Ramsay explains that this unique symptom: ‘is virtually a sheet-anchor in the diagnosis of Myalgic Encephalomyelitis and without it a diagnosis should not be made.’ Muscles may function normally to begin with but there is a continued loss of post-exertional muscle power after even a minor degree of physical effort; three, four or five days, or longer, elapse before full muscle power is restored. ([Online]) (In sedentary controls full muscle power is restored after just 200 minutes.) All muscles are affected, including the heart. (Hooper et al. 2001 [Online.])

Thus a patient may be easily able to lift/push/squeeze something with close to normal strength several times, or for a short period; but be unable to complete the same task (or even a trivial task) repeatedly (such as lifting a soup spoon many times for example). Professor Malcolm Hooper recommends testing for this by observing the patient repeatedly lifting something weighing around 2 pounds for a period of time. He explains that, ‘M.E. patients can often manage a small number of repeats but performance rapidly falls off and recovery is very slow compared to healthy controls. More sophisticated treadmill tests will also show the same effect.’ This sudden onset muscle weakness (or paralysis) and very slow recovery is uniquely characteristic of M.E. patients. (2003)

For more information on diagnosing M.E.; from lists of exclusionary tests, to alternative diagnosis that should be considered, to discussions of the hallmark symptoms and characteristics of M.E., to more information about many of the tests listed above; the following resources are highly recommended and are easily some of the best sources of information on M.E. available. Each of these texts has been produced primarily for doctors – but may also be accessible by less severely affected sufferers (and their families or carers).

This textbook is essential reading for anyone with an interest in M.E. as it contains the accumulated knowledge of 80 of the worlds leading M.E. experts in one 725-page encyclopedia. This book is a comprehensive account of current knowledge concerning the history, epidemiology, issues of diagnosis, children with M.E., investigation, virology, immunology, muscle pathology, host response, food intolerance, brain mapping, neurophysiology, neuropsychology, sleep dysfunction, treatment and management.

This is not simply theory, but is based upon an enormous body of clinical information collected over the last 50 years from many thousands of M.E. patients. Confirmation of this hypothesis is supported by electrical tests of muscle and of brain function (including the subsequent development of PET and SPECT scans) and by a variety of biochemical and hormonal assays. Newer scientific evidence continues to strengthen this hypothesis. (Bassett 2005, [Online].)

As The M.E. Society of America writes: ‘Unlike somatisation disorder, M.E. is not ‘medically unexplained.’ M.E. is a disease which, like lupus, has no single marker. M.E. is a multi-system disease with many organ and bodily systems affected, producing a myriad of symptoms [and] many aspects of the pathophysiology of the disease have, indeed, been medically explained in volumes of research. These are well-documented, scientifically sound explanations for why patients are often bedridden and unable to maintain an upright posture.’ ([Online.])

M.E. is a distinct neurological illness which has a well-documented and unique set of characteristics, symptoms, physical signs and diagnostic (and other) abnormalities which may be tested for. As M.E. authors Verillo and Gellman explain: ‘Contrary to popular belief, M.E. is a distinct, recognisable entity that can be diagnosed relatively early in the course of the disease, providing the physician has some experience with the illness.’ (1997 p. 21) The new non-fatigue-based clinical definition of the illness the Canadian Guidelines (although far from perfect) now also make diagnosis easier than ever before; even for those with no experience with the illness, as do the excellent papers on diagnosis and testing compiled by M.E. expert of more than 20 years Dr Byron Hyde M.D.

Whilst various ‘fatiguing conditions’ with a variety of different aetiology’s may be made up of vague and mild ‘everyday’ type symptoms, have no physical signs and no tests which have shown abnormalities or that can aid diagnosis; Myalgic Encephalomyelitis shares none of these characteristics. Myalgic Encephalomyelitis is a distinct organic neurological disorder (which can occur in both epidemic and sporadic forms) that has been recognised as such by the World Health Organisation in their International Classification of Diseases since 1969 with the code G93.3. It bears no relationship to any unrelated, vague and hard to diagnose ‘fatiguing illnesses.’