Journal

Tests That Can Aid Diagnosis Some of the series of tests which can (in combination) help to confirm a suspected ME diagnosis include: n 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. Eighty percent of ME/ICD-CFS patients will have abnormal SPECT scans. These abnormalities have also been shown to correlate with clinical status. Dr. Hyde adds that “I do not describe a patient as having ME 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 ME.” n MRI scans of the brain Punctate, subcortical areas of high signal intensity consistent with edema or demyelination were identified by MRI in 78 percent of ME/ICD-CFS patients (similar to those seen in MS). Research has shown that 50 percent to 80 percent of ME/ICD-CFS patients will have abnormal MRI scans. ME patients with abnormalities on MRI have been reported as being more severely impaired than those without such abnormalities. n PET scans of the brain PET scans have shown decreased metabolism of glucose in the right mediofrontal cortex and generalized hypoperfusion of the brain with a particular pattern of decreased neuronal metabolism in the brain stem. n Neuropsychological testing Of the CNS dysfunctions that make up ME, cognitive dysfunction is easily one of the most disabling characteristics of the illness. Neuropsychological testing can be used to identify cognitive dysfunction and/or to confirm a ME/ICD-CFS diagnosis. It should focus on the abnormalities known to differentiate ME/ICD-CFS from other causes of organic brain dysfunctions. n EEG brain maps and QEEG brain maps Ninety-five percent of ME/ICD-CFS patients have been found to have abnormal cognitive-evoked EEG brain maps. But Dr. Hyde argues that QEEG brain maps are far more accurate, and that they “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.” n Neurological examination and the Romberg or tandem Romberg test Most ME patients have abnormal neurological examination. The Romberg test is a useful test of brain stem function. [It involves standing with eyes open and then with eyes closed with feet together or one behind the other for a minute or more. A patient tests positive for “Romberg’s sign,” or abnormal, if he or she can stand with the eyes open but falls when the eyes are closed.] Professor Malcolm Hooper [a CFS/FM specialist at the University of Sunderland, England], explains that “In his 1995 Australian Workshop, [CFS expert Dr. Paul] Cheney said that more than 90 percent of [CFS] patients have an abnormal Romberg, versus 0 percent of controls.” n Tests of the immune system The immune system abnormalities in ME 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). n RNase L A more specific immune system abnormality has been discovered in ME/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 80.0 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. This test is as yet not widely available but will be one of the most useful tests in helping to diagnose ME/ICD-CFS in the future. [See also the related article, “Dr. Kenny De Meirleir’s Breakthrough Research and Recommendations for CFS Testing & Treatment,” in this newsletter. Dr. De Meirleir’s lab, at www.redlabsusa.com, offers RNase L testing information.] n 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 ESR of <5mm/hr is common in ME/ICD-CFS. n Insulin levels and glucose tolerance tests Derangement of insulin response is a frequent finding in ME patients. Glucose tolerance curves are often abnormal. n 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. 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. Heart rates as low as 40 beats per minute may also be observed (during sleep). n Tilt table examination Orthostatic intolerance is very common in ME/ICD-CFS patients, and may manifest as one of, or a combination of, the following: neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), or delayed postural hypotension. n Exercise testing and chemical stress tests 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 ME/ICD-CFS 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. As exercise tests are not appropriate for many ME 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.” n Physical exam There are also a variety of abnormalities visible on physical exam in ME patients. These abnormalities are not usual in healthy patients, but they are also found in people with other organic illnesses (so they are not specific to ME/ICD-CFS). The post-exertional paralytic muscle weakness unique to ME should also be tested for; a diagnosis of ME should never be made without this characteristic being present. * * * * Contrary to popular belief, ME/ICD-CFS is a distinct, recognizable entity that can be diagnosed relatively early in the course of the disease, providing the physician has some experience with the illness. The new non-fatigue-based clinical definition of the illness in the Canadian Guidelines [see the Expert Consensus Panel Clinical Case Definition for ME/CFS at http://www.cfids-cab.org/MESA/ccpc.html] now also makes diagnosis easier than ever before, even for those with no experience with ME. While various “fatiguing conditions” with a variety of different etiologies 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 (and ME equivalent CFS) shares none of these characteristics. ME is a distinct organic neurological disorder (which can occur in both epidemic and sporadic forms) that has been recognized as such by the World Health Organization (WHO) 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.” As the ME Society of America explains: “Unlike somatization disorder, ME is not ‘medically unexplained.’ ME is a disease which, like lupus, has no single marker. ME 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.” _______ 1. See the full-length, fully-sourced article, “Testing for ME,” at Jodi Bassett’s Australia-based Web site, A Hummingbirds’ Guide to ME, at www.ahummingbirdsguide.com. It provides more information on the tests listed here as well as on many other aspects of diagnosis, plus a list of references. 2. ME/ICD-CFS refers to the disease’s classification as a neurological disorder in the World Health Organization’s International Classification of Diseases (ICD G93.3). Also see the article, “What is ME?” for more information on medical and political aspects of ME/ICD-CFS. 3. Dr. Byron Hyde, MD, is an internationally recognized CFS specialist, and chairman of the Nightingale Research Foundation for the study and treatment of ME/CFS, in Ontario, Canada. ______ Note: This summary is reproduced with permission of the author. The information provided here is not intended to diagnose, treat, cure, mitigate, or prevent any disease.

Myalgic Encephalomyelitis (abbreviated ME) is a chronic, inflammatory, primarily neurological disease that is multisystemic, affecting the central nervous system (CNS), immune system and cardiovascular system, the endocrinological system and musculoskeletal system. ME can cause a wide variety of symptoms, including changes in sensory tolerance, visual problems, exertional muscle weakness, difficulties with coordination and speech, severe fatigability, cognitive impairment, problems with balance, subnormal or poor body temperature control (due to circulation issues) and severe pain. ME will cause a degree of impaired mobility and disability in all cases. The degree of impairment and complexity depends on the degree of diffuse brain injury and end organ involvement.

Myalgic Encephalomyelitis affects the brain and spinal cord which control the body, allow thought and sensory processing, causing dysautonomia, impaired thinking and loss of internal homeostasis, the process whereby the body maintains a consistent internal environment in response to external stressors. Cellular metabolism and communication is disrupted, causing inefficiency in all biological processes. This includes the cellular mitochondria which process fuel to make energy, resulting in a deficiency of adenosine-triphosphate ATP with a chronic, severe, measurable loss of sustainable strength on exertion. A hallmark of ME is intolerance to previously trivial effort and deterioration through persistent or repeated exertion (often resulting in relapse).

Current theory suggests ME results from a persistent viral infection and/or attacks by an individual's immune system on the nervous system, musculoskeletal system, and blood vessels. It has been classified by the World Health Organisation as an organic brain disease since 1969. There is a controversial view that ME is not a chronic infectious or autoimmune disease, but rather a illness triggered by infection along with stress. Usually proponents of this school disdain the term ME, claiming it to be inaccurate. Although more than 50 years of research and clinical observation informs knowledge of ME pathology, its exact cause remains unknown and more research is required particularly for treatment.

ME patients are barred from donating blood or organs in the United Kingdom.

Myalgic encephalomyelitis is a relapse-remitting disease with new symptoms occurring either in discrete relapses (or "crashes") or slowly accruing over time. Between relapses, symptoms may resolve completely with sufficient rest, BUT permanent neurologic problems usually persist, especially as the disease advances. ME currently does not have a cure, though some treatments such as antivirals are being trailed which may at least slow the appearance of new symptoms.

ME affects all ages, with peak incidence typically between 20 and 40 years, and is more common in women than in men.

1 Terminology 2 Signs and symptoms 3 Diagnosis 3.1 Differential Diagnosis 4 Disease course and clinical subtypes 4.1 Severity 5 Comorbid Illnesses 6 Factors triggering a relapse 7 Pathophysiology 8 Causes 8.1 Environmental 9 Treatment 10 Prognosis 11 Epidemiology 12 History 12.1 The Formative Years 12.2 WHO Classification and Disgrace 12.3 CDC Intervention 12.4 Villified but Vindicated 12.5 ME Redux 13 References 13.1 External links 13.2 Organizations [edit] Terminology

The name Myalgic Encephalomyelitis refers to the inflammation of the brain and spinal cord accompanied by muscle pain.

In 1988 The US Centers for Disease Control (CDC) for reasons best known to them dismissed fifty years of research and decided to treat the Lake Tahoe outbreak as a new illness, which they christened chronic fatigue syndrome (CFS). CFS is a highly contentious concept to patients and specialists alike. Because of the similarity in terminology, CFS is often confused with "chronic fatigue". A study found that while most medical trainees consider the symptom complex of CFS to be a serious illness resulting in poor quality of life, the "chronic fatigue syndrome" name may be regarded less seriously than the name "myalgic encephalopathy".[] Another study found that nurses and physician assistants viewed a patient's CFS symptoms as more severe and disabling if they were told the patient had a more medical sounding accurate diagnosis of "chronic neuroendocrineimmune dysfunction syndrome".[]

Patients and specialists alike had long lobbied for a name and definition change or reversal of "CFS". In January 2007 The American "CFS Name Change Advisory Board" consisting of doctors Bateman, Bell, Cheney, Jason, Klimas, Lapp, and Peterson agreed that ""CFS downplays the severity of the disease and is hurtful to patients" and publicised their deliberation that CFS should now be termed ME.

[edit] Signs and symptoms

The core symptom of ME is muscle fatigability following minimal exertion plus delayed recovery of muscle power. Ramsay, a world authority on ME referred to a diagnostic triad of muscle fatigability, central nervous system involvement and impaired circulation. However, ME affects many bodily systems and other symptoms include increased sensitivity to light and sound (photosensitivity, hyperacusis) and general migraine-like sensory intolerance, changes in sensation (hypoesthesia), muscle spasms (myclonus or fasciculation), or difficulty initiating movement (transient paralysis); difficulties with coordination and balance (ataxia); problems in speech and verbalisation (Dysarthria, Dysphasia), visual problems (Nystagmus (involuntary twitching or rolling of the eyes), blurred vision), and acute or chronic pain, difficulty standing (orthostatic intolerance), cardiopulmonary symptoms (palpitations, dysrhythmia and dyspnea), sleep dysregulation (hypersomnia, insomnia or sleep reversal), gastroenteric difficulties, cognitive impairment, or emotional symptomatology (emotional lability or depression). Side effects much like that seen in polio, M.S., or A.I.D.S. What differentiates ME from similar conditions is the close link with exertion and the variability, not only from day to day, but from hour to hour.

[edit] Diagnosis

ME is diagnosed definitively using case history to look for a distinctive pattern and type of symptoms and signs. Diagnosis necessitates involvement of the CNS and muscoskeletal symptomology.

There are no accepted clinical criteria for ME but all descriptions tend to emphasize muscle fatigability and central nervous system involvement. The Canadian Consensus criteria represents international efforts to standardize the diagnosis of ME using clinical data and laboratory data but are controversial. The list of symptoms is long and there is therefore a danger of misdiagnosis. Research criteria based on Ramsay's descriptions have been used in various studies e.g. Costa et al, 1995.

Generally consistent findings of a novel low molecular weight antiviral protein (Rnase-L) have shown promise as a potential diagnostic test for CFS and may be relevant to ME. Another test which may become important in the future is an assay of genes for the immune system and mitochondria, however, these tests are so far seen as discretionary. Without research criteria for ME, it is not possible to confirm that abnormalities found in people with chronic fatigue syndrome are also generalizable to ME.

[edit] Differential Diagnosis

The signs and symptoms of ME can be similar to other medical problems, such as multiple sclerosis, Lyme disease, lupus, anemia, cancers, and other autoimmune problems, such as lupus, sarcoidosis. Additional testing may be needed to help distinguish ME from these other problems.

[edit] Disease course and clinical subtypes