Symptoms and diagnosis of ME/CFS
The following is provided for your information only. The diagnosis of ME/CFS should be determined only by a suitably qualified medical professional.
Despite the fact that the Department of Health now accepts ME/CFS as a genuine medical condition, diagnosis can still pose a problem because ME/CFS symptoms are similar to those present in a number of other medical conditions. In addition, there are no examination findings which can confirm the diagnosis. This means there has to be a process of elimination (the exclusion of other conditions) before a diagnosis of ME/CFS can be made.
Several different diagnostic criteria have now been published in the UK, USA and Australia. The CDC criteria (reference: Annals of Internal Medicine, 1994, 121, 953-959) are frequently used when selecting ME/CFS patients for research studies.
However, these criteria have a number of defects (e.g. you have to have been ill for at least six months before ME/CFS is confirmed) and anecdotal reports suggest there are a significant minority of people with genuine ME/CFS who do not have a sufficient number of different symptoms to fulfil the strict CDC definition. Such conditions may have a relevance when selecting people for research studies, but delaying or withholding a diagnosis on these grounds is not helpful. It can cause problems with employers, schools, benefit claims etc.It can also affect the individual’s recovery if they are unable take sufficient rest early on and manage their condition sensibly, rather than having to ‘soldier on’. It is known that stress exacerbates the condition.
The typical features of ME/CFS
Commonly, a previously fit and active person finds their illness triggered by an infection. Less common triggers include toxins, organophosphate pesticides, vaccinations, major trauma or stress (e.g. a road traffic accident), pregnancy and surgical operations.
In some cases there is no obvious precipitating event and the person reports a gradual decline in health over a period of months or even years.
The predominant symptom of ME/CFS is usually severe fatigue and malaise following mental or physical activity. The full extent of this exhaustion often becomes apparent only 24 to 48 hours after the activity (assuming, of course, the person was not already in a ‘recovery period’ from a previous activity).
The other main symptoms are:
- Muscle symptoms include exercise intolerance and post-exertional malaise (i.e. feeling shattered the day after undue physical activity), pain/myalgia (present in around 75% of people) and fasciculations (visible twitching of the muscles which sometimes includes blepharospasm/eyelid twitching).
- Brain and Central Nervous System symptoms include cognitive dysfunction (problems with short-term memory, concentration and maintaining attention), clumsiness, disequilibrium likened to ‘walking on rubber’, and word finding abilities. Problems with control of the autonomic nervous system results in palpitations, sweating episodes and symptoms associated with low blood pressure/postural hypotension (e.g. fainting).
- Symptoms which suggest on-going abnormalities in immune system function include sore throats, enlarged glands, joint pains, headaches, problems with temperature control and intermittent flu-like feelings.
- Other symptoms which frequently occur in ME/CFS include sleep disturbances (often increased requirements at the onset followed by an inability to maintain a full night’s sleep), alcohol intolerance (a very characteristic feature, particularly in the early period of illness) and irritable bowel symptomatology.
- Some people also develop emotional lability or mood swings and features of clinical depression as time goes on.
- Besides these more obvious and wide-spread symptoms there are also myriad “minor” ones. Not everyone experiences all of them and often they are not mentioned when patients describe their illness; however there is often very visible relief when they find others, too, have similar experiences.
ME/CFS symptoms tend to fluctuate in severity throughout the course of a day and people often report that they have both ‘good days’ and ‘bad days’, although the term ‘good’ is often used in a relative sense. The illness nearly always results in a severe reduction in a person’s ability to cope with all aspects of normal daily living (i.e. social and sporting activities, employment, household tasks). Relapses or exacerbations are often precipitated by infections, excessive physical or mental stress, general anaesthetics and surgical operations, and extremes of temperature.
There are a variety of hormonal (e.g. hypothyroidism), rheumatological (e.g. lupus/SLE), neurological (e.g. multiple sclerosis), infective (e.g. Lyme disease and hepatitis B/C virus) and gastrointestinal (e.g. coeliac disease) conditions which can all produce very similar symptoms to those found in ME/CFS. This is why it is so important for doctors to take a detailed clinical history from anyone suspected of having ME/CFS (especially when there are atypical features present) and arrange appropriate investigations if the diagnosis is in doubt.
The main value of blood tests in the assessment of someone with possible ME/CFS is to exclude other common conditions which produce fatigue as a principle symptom. This means the following tests should always be considered before a diagnosis is confirmed; these can be arranged by your GP if she/he is agreeable:
People with ME/CFS do not have anaemia as part of this illness. If the haemoglobin level is reduced, then an alternative explanation should always be pursued.
- white cell count
A measurement of the number of cells which fight off infection. This count is often increased during the early stages of an infection but as ME/CFS becomes chronic, the level usually starts to return to normal. Some people with ME/CFS have abnormally shaped white cells (atypical lymphocytes), particularly following glandular fever. A raised level of a type of white cell known as eosinophils can occur with allergies or when infection with toxocara is present (the latter should always be queried when a child has eosinophilia).
- ESR or acute phase protein changes (e.g.CRP)
The ESR test is a useful indicator of general health. If raised, this suggests some form of chronic infection or inflammation is present. The vast majority of people with ME/CFS have a normal ESR.
- liver, thyroid and kidney function tests
Liver function tests are sometimes abnormal in ME/CFS. This may be due to the precipitating infection causing liver inflammation or the effects of antidepressant drugs. There is also a condition called Gilbert’s disease which seems to be more common in people with ME/CFS (ref: Lancet, 1993, 341, 842 and 1162-1163). If liver tests remain abnormal then further investigation may be warranted. There is no evidence that hormonal disturbances in ME/CFS involve the thyroid gland: the results of thyroid function tests should always be normal.
- routine biochemistry (urea, electrolytes, calcium etc.)
results should all be within the normal range. A raised level of blood calcium could be due to sarcoidosis. A lowered level may indicate osteomalacia (a bone disease causing fatigue and bone pain). Research from Australia indicates that the total amount of body potassium may be lowered in ME/CFS (ref: Medical Journal of Australia, 1996, 164, 384). A raised level of potassium can occur in Addison’s disease.
- creatine kinase
- urine tests for sugar/protein
- hormone levels
In some cases, investigations should also include checking female hormone levels (serum oestradiol) and adrenal gland function.
Other blood tests which could be considered will depend on specific symptoms. For example, if irritable bowel symptoms are experienced then checking for adult-onset coeliac disease would be worthwhile, particularly if the symptoms appear to be relieved by a wheat-free diet.
A number of research studies have now reported on characteristic abnormalities in certain hormones (e.g. cortisol, prolactin and arginine vasopressin) which come under the control of a part of the brain known as the hypothalamus. However, these results are not consistently abnormal in all ME/CFS patients. Neither are the tests readily available outside research units.
Blood flow scans of the brain (SPECT scans) have produced interesting results (i.e. brain stem hypoperfusion) which appear to be almost unique to ME/CFS, but these are not widely available. Blood flow abnormalities in the brain stem will need to be confirmed by other research groups before they can be considered as a useful diagnostic aid.
The clinical features of ME were first clearly described by the late Dr. Melvin Ramsay MA MD (a physician at the Royal Free Hospital in London during an epidemic outbreak in 1955, and The ME Association’s first President). Since then, in the light of there being no diagnostic tests, there have been several more attempts to define the illness by way of its symptoms, although never with all-round agreement.
In recent years there have been the American Center for Disease Control (CDC) definition, the “Oxford Criteria” and more recently the “Canadian Guidelines”. Although the first two criteria tend to be used as a diagnostic aid by many clinicians, they were compiled primarily for researchers to identify particular sets of people for their studies. These earlier definitions (of “CFS” as opposed to “ME”) give various physical and neurological symptoms; however, in these definitions, the cardinal features of “ME” – the muscle fatigability and pain, and post-exertional malaise – do not have to be present for such a diagnosis. This suggests that nowadays, not everyone with a diagnosis of “Chronic Fatigue Syndrome” necessarily has the disease “ME” as described by Dr Ramsay. It also seems that CFS can cover a spectrum of fatigue-prominent diseases, possibly including illness based in depression, stress or ‘burn-out’. However the Canadian Guidelines were developed with clinicians more in mind.
Two other features of ME are first the fluctuation of symptoms from day to day, or within the day; and secondly the tendency for the condition to persist for several years.
Dr Ramsay’s description included the following:
The onset of the disease may be sudden and without apparent cause… but usually there is a history of infection of the upper respiratory tract or, occasionally, the gastrointestinal tract with nausea and/or vomiting. Instead of an uneventful recovery, the patient is dogged by persistent and profound fatigue accompanied by a medley of symptoms such as headache, giddiness, muscle pain, cramps or twitchings, muscle tenderness and weakness, paraesthesiae, frequency of micturition, blurred vision and/or diplopia, hyperacusis, tinnitus and a general feeling of ‘feeling awful’… the phenomenon of muscle fatigability is the dominant and most persistent feature of the disease and in my opinion a diagnosis should never be made without it. …If muscle power is found to be satisfactory, a re-examination should be made after exercise; a walk of half a mile is sufficient, as very few ME cases can manage more… Restoration of muscle power can take three to five days or even longer.
From Post-viral Fatigue Syndrome by A. Melvin Ramsay MA MD.
The CDC criteria are broadly as follows:
- Clinically evaluated, unexplained persistent or relapsing chronic fatigue that is of new or definite onset (i.e., not lifelong), is not the result of ongoing exertion, is not substantially alleviated by rest, and results in substantial reduction in previous levels of occupational, educational, social, or personal activities.
- The concurrent occurrence of four or more of the following symptoms: substantial impairment in short-term memory or concentration; sore throat; tender lymph nodes; muscle pain; multi-joint pain without swelling or redness; headaches of a new type, pattern, or severity; unrefreshing sleep; and post-exertional malaise lasting more than 24 hours. These symptoms must have persisted or recurred during 6 or more consecutive months of illness and must not have predated the fatigue.
(Note that although post-exertional malaise is listed, it does not have to be present for this diagnosis to be given.)
The CDC’s own website gives further details of the CDC definition.
The Oxford criteria identify two broad syndromes (remember these definitions are primarily for research purposes):
1. Chronic Fatigue Syndrome
- fatigue is the principal symptom: it is severe, disabling and affects physical and mental functioning; it should have been present for a minimum of 6 months during which it was present for more than 50% of the time.
- other symptoms may be present: particularly myalgia, mood swings and sleep disturbances.
- definite onset of symptoms, not life-long.
- exceptions: patients with established medical conditions known to produce chronic fatigue; also patients with a current diagnosis of schizophrenia, manic depressive illness, substance abuse, eating disorder or proven organic brain disease.
2. Post-infectious Fatigue Syndrome (PIFS)
- A sub-type of CFS which either follows an infection or is associated with a current infection (although whether such associated infection is of aetiological significance (i.e. whether it is the cause of the symptoms) is a topic for research).
- To meet the research criteria for PIFS patients must:
- i. fulfil the criteria for CFS as defined above (i.e. the Oxford definition)
- ii. should also fulfil the following additional criteria:
- (a) There is definite evidence of infection at onset or presentation (a patient’s self-report is unlikely to be sufficiently reliable).
- (b) the syndrome is present for a minimum of 6 months after onset of infection.
- (c) the infection has been corroborated by laboratory evidence.
The Canadian guidelines
The new Canadian Clinical Case Definition was written by U.S. and Canadian ME/CFS researchers.
In contrast to the 1994 CDC criteria, which make “fatigue” a compulsory symptom but downplay and make optional post-exertional sickness and other cardinal symptoms, the Canadian clinical case definition specifically selects patients whose condition gets worse with exercise. The clinical definition makes it clear that in order to meet the diagnostic criteria, the patient must become symptomatically ill after exercise, and must also have neurological, neurocognitive, neuroendocrine, dysautonomic (for example, orthostatic intolerance), and immune manifestations. So symptoms other than fatigue, must be present for a patient to meet the diagnostic criteria.
This case definition helps to distinguish ME/CFS patients from chronic fatigue patients, depressed patients, somatization, fibromyalgia, and other diseases with which ME/CFS has been confused, including those that improve with exercise. The Canadian definition specifically states that patients “become worse after exercise rather than better.” The new case definition, much of which is backed by research and hard science, is a strong counterstatement to the view held by many psychologists and psychiatrists.
Several books on the subject of ME/CFS are available from the ME Association.
In particular there is a very useful booklet called “ME/CFS/PVFS – An Exploration of the Key Clinical Issues” which is a booklet prepared for health professionals by Dr. Charles Shepherd MB BS and Dr. Abhit Chaudhuri DM MD MRCP and which is available from the ME Association.