How is Chronic Fatigue Syndrome & Myalgic Encephalomyelitis Diagnosed?
Taking a careful history is essential for making a diagnosis, as is comparing the patient's symptoms with a case definition.
Currently, there are several case definitions for ME/CFS. Physicians who are not ME/CFS specialists rely on the CDC case definition (also known as the Fukuda definition) to make a diagnosis. Because the Fukuda definition is very broad, it often leads to misdiagnosis (De Becker, et al, Jason et al.). As a consequence, ME/CFS specialists prefer to use the more accurate Canadian Consensus Criteria (CCC), or the International Consensus Criteria (ICC) (Carruthers et al.).
You may be asked to fill out a questionnaire, such as the DePaul Symptom Questionnaire, prior to your visit, to help the physician assess the frequency and severity of your symptoms (Jason et al.)
In addition, the physician should take into account the type of onset (acute or insidious), triggering mechanisms (exposure to chemicals, viral infection, physical trauma), and any other factors that might influence the severity or persistence of the illness. Symptoms that develop quickly after an initial trigger are indicative of Chronic Fatigue Syndrome & ME. In adolescents, the initial trigger is frequently mononucleosis.
Most specialists question their patients carefully about the type of symptoms they are experiencing. ME/CFS is a syndrome, which means that multiple symptoms are present. Many of these symptoms are reflective of an autonomic nervous system disorder; others are indicative of a persistent viral infection. What is important to the doctor is not necessarily that you have all of the symptoms, or even a certain percentage, but that they cover a spectrum. The symptoms most doctors consider as particularly significant are the persistent loss of energy not relieved by rest, a worsening of symptoms after mild exertion (post-exertional malaise), pain, sleep disorders, and cognitive problems. Other symptoms can occur in an astonishing array.
Even if the patient does not have all of the symptoms, it is unlikely that a doctor will make diagnosis based strictly on fatigue. Fatigue is one of the primary symptoms of depression. However, unlike patients with ME/CFS, those with depression feel better after exercise. Any doctor familiar with Chronic Fatigue Syndrome & ME will ask the question, "How do you feel after exercise?" to rule out depression.
Conscientious physicians should order all the necessary tests to rule out illnesses that produce similar symptoms, as these may be treated with existing protocols. A significant percentage of patients who have rare or hard-to-detect diseases, such as Behçet's Disease, rare forms of leukemia, early MS, and empty sella (shrunken pituitary) have been erroneously diagnosed with chronic fatigue syndrome, because they initially present with fatigue. It is important for patients to mention symptoms other than fatigue in the initial interview to avoid misdiagnosis.
Any competent physician will also perform a physical exam. While ME/CFS is often called an "invisible illness," there are some distinctive features that are apparent during a routine examination.
Initial Office Observations
- Blood pressure: usually low (orthostatic hypotension)
- Temperature: low (97° F) or slightly elevated (<100° F) or, more commonly, both over the course of a day (excessive diurnal variation)
- Heartbeat: tachycardia (hard to detect in an office visit; Holter monitor is more efficient)
- Throat: irritated, crimson crescents
- Lymph nodes: tenderness in nodes of groin and neck, particularly on left side
- Pallor: usually present
- Positive Romberg test (tandem stance)
- Stiff, slow gait
- Nystagmus (involuntary eye movements)
- Photophobia (light sensitivity)
- Hyperreflexia (increased reflex reactions)
Common Findings on Routine Screening Tests
Physicians usually order routine screening tests, such as a complete blood count (CBC) with differential, a urinalysis, and liver function tests, as part of their initial examination. While these tests are useful to eliminate other possible diagnoses, there are also a few abnormalities that are typical of people with ME/CFS.
- Decreased number of white blood cells (leukopenia), also increased number of white blood cells
- Abnormal red blood cell membranes, elevated MCV (large red blood cells)
- Low concentrations of zinc and magnesium
- Low uric acid concentration (<3.5 mg/dl)
- Total cholesterol concentration slightly elevated
- Decreased potassium and sodium
- Sedimentation rate: Low (<5 mm/hr); sometimes brief periods of elevated rate (>20 mm/hr)
- Urinalysis: alkaline; mucus or blood, or both, without bacterial infection
- Positive ANA, speckled pattern
- Liver function tests: mildly elevated AST (SGOT) and ALT (SGPT)
What Tests Are Recommended for ME/CFS?
When a patient presents with debilitating fatigue as a primary symptom, physicians must perform a battery of tests to rule out other illnesses that produce chronic fatigue, including leukemia, MS, kidney disease, brain injury, liver disease, thyroid disease, infections such as Lyme, and autoimmune diseases.
In most instances, exclusionary tests are not expensive or difficult to perform. Depending on the symptoms, the physician may wish to rule out ongoing Lyme disease, lupus, rheumatoid arthritis or other autoimmune disorders, parasitic infections, heart disease, specific neurological disorders such as multiple sclerosis, endocrine disorders such as hypothyroidism, and systemic infections and inflammatory conditions (as indicated by a high erythrocyte sedimentation rate). In general, patients with ME/CFS test negative for other conditions. However, as many physicians have noted, nothing prevents a person from having two conditions simultaneously or developing one after the other. Thus a positive test result does not necessarily rule out a diagnosis of ME/CFS.
negative for lupus, rheumatoid arthritis, Hashimoto's disease. Note: Patients sometimes test positive on initial screening but not on more specific tests.
negative for Addison's disease, Cushing's disease, hypothyroidism, diabetes mellitus. Note: Although some patients with ME/CFS with enlarged thyroid gland test negative on standard tests, more refined tests may reveal secondary thyroid deficiencies. Many patients also develop co-morbidities such as Hashimoto's disease and diabetes.
negative for mitral valve prolapse. Note: Test is warranted if the patient reports tachycardia. Tests sometimes reveal elevated transaminase concentrations and angiotensin-converting enzyme.
negative for hepatitis
negative for multiple sclerosis (MS). Note: Test is warranted if patient shows severe neurological, cognitive, and muscle dysfunction. Although some patients with ME/CFS may test negative for MS, more specific testing (brain function) may reveal abnormalities.
negative for tuberculosis, brucellosis, Lyme disease
negative for lymphoma and leukemia
negative for toxoplasmosis, giardiasis, amoebiasis. Note: Patients with ME/CFS can have multiple parasitic infections as part of a prodromal illness.
Even though there is no single test that is universally accepted as a biomarker, there are some tests that are consistent with a positive diagnosis of ME/CFS. These tests are usually expensive, specialized, and, in most cases, cannot be performed locally. A diagnosis can be made without performing any of these tests, but if they are available, a positive result on two or more of these tests (especially exercise testing) would be strongly indicative of ME/CFS. Not all of these specialized tests are necessary to make a diagnosis, although someone applying for disability insurance may need some of them to file.
Decreased cortisol levels after exercise, decreased cerebral blood flow after exercise, inefficient glucose utilization, erratic breathing pattern. In Cardio-Pulmonary Exercise Testing with measurement of VO2 max, patients with ME/CFS score significantly lower than controls.
Positive for cytomegalovirus, Epstein-Barr virus, human herpesvirus 6 and 7, and Coxsackie virus; negative for hepatitis A or B virus
Low natural killer cell counts, elevated interferon alpha, tumor necrosis factor, interleukins 1 and 2; T cell activation, altered T4/T8 cell ratios, low T cell suppressor-cell (T8) count, fluctuating low and high T cell counts, low and high B cell counts, antinuclear antibodies, immunoglobin deficiency, sometimes antithyroid antibodies
SPECT brain scan:
Hypoperfusion in either right or left temporal lobe, particularly Wernicke's area, after exercise
MRI brain scans:
unexplained bright areas.
Magnetic resonance spectroscopy (MRS) bran scan:
abnormally high lactic acid spikes near or around the hippocampus (which indicates mitochondrial dysfunction).
abnormal impedance cardiography; repetitively oscillating T wave inversions and/or T wave flats during 24-hour Holter monitoring.
For those who can afford it, a single-photon emission computed tomography (SPECT) scan can reveal areas of the brain with reduced blood flow, a common finding in people with ME/CFS. MRIs of the brain often show small plaques, an indication of brain injury. For patients with severe cognitive impairment, IQ tests and other neurocognitive examinations may be recommended.
Immune system tests can be used to confirm a diagnosis of ME/CFS. Immune system testing is specialized, so results cannot be reliably interpreted by anyone other than an immunologist or ME/CFS physician. Even among specialists, there is tremendous dissent as to what these test results actually mean. The value of having these tests done is to determine whether the patterns seen in the test results are similar to those of other people with ME/CFS. Many (but not all) people with ME/CFS have reduced numbers of natural killer cells and increased numbers of circulating cytokines (such as alpha interferon and the interleukins). Immune cell function also may be measured. Patients with ME/CFS generally have diminished NK cell, T and B cell function. (Brenu et al.) Reaction to pokeweed mitogen, total immunoglobulin production (IgG, IgA, IgM), and demonstrable anergy (lack of immune response) when tested with foreign proteins can help determine immune cell responsiveness.
Along with immune system tests, most ME/CFS specialists look for evidence of viral reactivation. People with ME/CFS usually show evidence of reactivation of latent viruses, particularly in the herpesvirus family, such as Epstein-Barr virus, human herpesvirus 6 (HHV-6), and cytomegalovirus. Enteroviruses may also be present. Reactivation of latent viruses (as indicated by high titers) provides further proof of immune system dysfunction, because in a healthy person these viruses are controlled.
Research has shown that people with ME/CFS have inflammation in the brain, as well as a specific cytokine signature (Yasuhito Nakatomi et al., Brenu et al.). There are also distinct changes in spinal fluid proteins (Schutzer et al.) While most medical practitioners cannot order tests to confirm these findings, they may eventually lead to a biomarker - a single test to confirm a diagnosis.
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The first question patients ask after they are diagnosed is "When will I get better?" Will the illness last a year? Two years? Ten years? Or is it a life sentence? Unfortunately, this question does not have an easy answer, which is deeply frustrating to people who need to know when they can resume their lives.
ME/CFS is a notoriously unpredictable illness. Some people recover completely within one or two years and can return to their jobs and previous activities. Others improve sufficiently to return to work, but must make modifications of their lifestyles. The majority of those with this chronic illness learn to plan every aspect of their lives within the parameters of symptoms that wax and wane. A few must adjust to long periods of illness, or "plateaus," with little or no improvement, and, at the far end of the spectrum, there are those who do not show improvement and may even decline over time.
Recovery times vary from a few months (although these short-term cases go largely unreported and therefore never make it into statistical tables) to decades. Statistics reported by physicians are highly individualized, with the more renowned ME/CFS specialists, who see the most severe cases, giving the longest recovery rates, and GPs and family practitioners the shortest. However, most physicians tell their patients that ME/CFS, generally speaking, is a lengthy proposition, a matter of years, not months.
Significant improvement and functional recovery are possible even after many years of illness. By functional recovery, doctors mean a return to normal life with accommodations. While these patients may not return to lifestyles as active as those they enjoyed before becoming ill, they are able to work and engage in leisure activities. Andersen et al. found that patients who had adjusted their lifestyles by limiting exercise and by switching to less demanding jobs had the greatest degree of functionality.
Recovery does not necessarily correlate with duration of illness. Dr. Dedra Buchwald, a physician in Seattle, concluded, after a five-year study of local patients with ME/CFS, that duration of the illness does not correlate with outcome. There are even cases of long-term sufferers who have recovered completely. One ME/CFS patient from North Carolina reported full recovery after 19 years of illness. Dean Anderson, in a personal account, says he did not even begin to see an improvement until five years had passed (CFIDS Chronicle, Winter 1996).
While there are few reliable long-term studies of ME/CFS patients, those which have been completed are encouraging. In 2007 Matthews and Komaroff published a study in which 234 ME/CFS patients were assessed for physical and mental impairment between 1991 and 2002. This study found that physical function tended to improve for many patients over time, especially for patients between the ages of 18 and 60, and for women. Physical function did not deteriorate with time, despite the fact that they were aging. No deterioration of mental function was noted.
Although a lack of deterioration may seem cold comfort for those who are significantly disabled by the illness, for most people with ME/CFS, especially those with severe cases, the possibility of "substantial" or even "partial" recovery is cause for hope. The Komaroff study also addresses one of the primary concerns of those with ME/CFS, which is that simply having the illness will cause degeneration.
Who recovers? It is difficult to say, but those who have viral onset seem to experience the highest rate of recovery. In a study by Masuda et al, ME/CFS patients with viral onset had the best prognosis. After two years, eight out of nine viral onset patients had returned to work. Of the nine patients with non-infectious onset, only three had returned to work. All patients received the same treatments.
The best outcomes are seen in children and in those with milder cases. In a 13-year follow-up study of 35 children with ME/CFS, 80% reported full recovery. However, 20% of those children (7) were still chronically ill, a percentage that roughly parallels chronic, severe cases in the adult population (25%).
Those with early diagnoses and who seek appropriate treatment tend to improve more quickly. Dr. Lapp, Dr. Teitelbaum, Dr. Holtorf and Dr. De Meirleir all report that 80% or more of their patients see significant improvement over time, which is to be expected in a population of patients receiving aggressive treatment. (Cort Johnson
) The fact that early diagnosis and treatment seem to correlate with recovery rate should be sufficient motivation to seek the proper specialist. However, even those who spend years searching for a diagnosis should not lose heart. Proper diagnosis and treatment any time during the illness can bring substantial improvement, if not full recovery.
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Kenneth Casanova's story of illness and recovery
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