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Chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a condition of excessive fatigue, cognitive impairment and other varied symptoms. Classified by the World Health Organisation (WHO) as a disease of the nervous system, it is of unknown etiology and may last months or years, causing severe disability.



In strict medical terms, the name chronic fatigue syndrome refers only to a pattern of symptoms (see below), and may in fact reflect several different disorders causing similar symptoms. While it can certainly be classified as a disease, there are no investigations that can confirm or rule out the diagnosis. Certain scoring systems have been designed to classify symptoms.


There are a number of different syndromes which have been at various times identified with CFS.

  • Chronic Fatigue Syndrome (CFS); this name was introduced in 1988 by a group of researchers, given that most other names were inaccurate.
  • Chronic Fatigue Immune Dysfunction Syndrome (CFIDS); many people, especially patients in the United States, use the term CFIDS (pronouced [See-Fids]), which was originally an acronym for " or "Chronic Fatigue & Immune Dysregulation Syndrome". These terms were based on the belief that the illness is caused by problems with the immune system. Although this view is less prevalent, the acronym CFIDS is still used.
  • Myalgic Encephalomyelitis Myalgic Encephalitis (ME); outside the United States, "ME" is in common use, meaning "infection and swelling of the brain with muscle pain" or "infection of the brain with muscle pain" respectively. Like CFIDS, the term ME is often used although its original meaning is inaccurate.
  • Post-viral (fatigue) syndrome (PVS or PVFS); this is a slightly more general and therefore more accurate equivalent of ME.
  • Chronic Epstein-Barr Virus (CEBV) or Chronic Mononucleosis; this name was in common use before CFS became more prevalent. The Epstein-Barr virus, a virus that commonly causes mononucleosis, was thought to be the cause of CFS. This has proven not to be true (see etiology below), although the symptoms develop in some people after contracting mononucleosis.
  • Low Natural Killer Cell Disease; This name is used widely in Japan; it reflects the belief that CFS is related to the number of natural killer cells the patient has.
  • Yuppie Flu; this was a nickname for CFS, especially in the 1980s. It reflects the belief that CFS mainly affects the affluent ("yuppies"), and implies that it is a form of malingering or burnout. CFS, however, affects people of all races, genders, and social standings, and this name is inaccurate.
  • Akureyri Disease
  • Iceland Disease: A name given in Iceland.
  • Raphe Nucleus Encephalopathy
  • Tapanui Flu; this is after the New Zealand town Tapanui where a doctor who investigated the disease lived.
  • Da Costa syndrome (The Netherlands)

Symptoms and course

Central features

There are six main categories of symptoms in CFS:

  • Fatigue: People with CFS experience profound, overwhelming exhaustion, which gets worse after exertion and can never be fully relieved by sleep.
  • Pain: Pain in CFS includes muscle pain, joint pain , headaches, abdominal pain, lymph node pain, and sore throats.
  • Cognitive and neurological problems:
    • Cognitive problems: people with CFS may have trouble remembering words, names, and places, find it hard to concentrate, and have trouble thinking straight.
    • Neurological problems include dizziness and light-headedness, especially when standing up quickly .
  • Hypersensitivity: people with CFS are often sensitive to light, sound, and some chemicals and foods.
  • Poor temperature control: people with CFS often report either running too hot or too cold, possible due to involvement of the hypothalamus, which regulates body temperature.
  • Sleep problems: many sufferers find going to sleep at night at the normal time very difficult and have to resort to medication in order to sleep properly. Also vivid dreams are a symptom in many people with CFS leading to disturbed sleep patterns and the ability to recall dream moments many months later, because of their intensity.

Some cases of CFS start gradually, but the majority start suddenly, often triggered by the flu or some other illness. People with CFS may get better after a few years or many years or may not get better at all. No one is sure whether anybody is truly cured or whether their illness has just subsided enough for them to live a more normal life.

Sudden onset

Most people with CFS report a sudden, drastic start to their illness. Sometimes people can remember a specific day or even hour when they first got sick.

Often, the illness starts with, or is triggered by, another illness. Many people report getting a case of the flu which slowly evolves into CFS. Other people have had a case of Lyme disease which has been treated adequately, but the symptoms change from those of Lyme to those of CFS. Other triggers include car accidents, moving house, and stressful life situations. Some patients say they felt unusual or uneasy for a short period (days or weeks) before the onset.

Gradual onset

The other cases have a very slow, gradual onset, sometimes spread over years. People with gradual onsets often don't realize there is anything wrong for years because it happens so slowly.

There is no standard course for CFS. Everyone diagnosed with CFS has had it for at least six months; they would not be diagnosed otherwise. It is possible that not all cases of CFS are chronic: some people may have CFS for four months and never get diagnosed. It's also possible that there are people who have CFS whose level of disability is so low they never get diagnosed.

People with CFS may get better after a few years or after many years, or never at all. They may reach a plateau at some constant level of health or may progressively decline. Often, the most prominent symptoms change over time or cycle through time. No one is sure whether anybody is truly cured or whether their illness has just subsided enough for them to live a more normal life. Relapses are common, especially after stressful life events.

Activity levels

Some people are more limited than others. The sickest are bedbound, while some people are self-reliant, and some are able to work or attend school. Some people with CFS can push themselves to do extraordinary things but feel much worse afterward. One notable CFS sufferer is soccer legend Michelle Akers, who reported struggling with the illness for much of the later years of her career. However, extreme sufferers like those confined to bed felt that an active professional athlete "poster child" like Akers only helped to trivialize the syndrome in the eyes of the public (the infamous "Michelle Akers has it and she plays soccer, so why are you complaining?" reaction), and thereby made it much more difficult for those who are highly incapacitated to be taken seriously.

Payback effect

One of the most common and recognizable aspects of CFS is what is called "post-exertional malaise," or, more colloquially, the "Payback Effect." When people with CFS exert themselves, their symptoms get worse afterward. Exertion could be physical or mental exercise, doing routine tasks, such as driving, cleaning, or eating, or handling a stressful situation. The harder the exertion and the longer it lasts, the worse the symptoms will be afterward. The payback effect leads to a few typical patterns, sometimes called "The Yo-Yo Pattern" and "The Downward Spiral."

The Yo-Yo pattern

The Yo-Yo Pattern happens when people work very hard at some activity, but only on good days. This leads to worse symptoms which prevents them from working for the next few days. When they feel better, they work extra hard to make up for the bad days — or just because they're so excited to feel good — but this leads to them feeling bad again...

The downward spiral

The Downward Spiral happens whenever feeling bad puts a patient in a situation that makes them feel worse. This is similar to the yo-yo, but in the downward spriral, people don't have time to recover on bad days. Here are some examples:

  • A person works very hard one day at work. This makes them feel worse, which leads to them not working as effectively. In order to catch up, they work harder, which leads to them feeling worse...
  • A person loses their appetite when they don't sleep well because they're so tired, they don't realize they're hungry. Then, they don't sleep well at night because they wake up very hungry...
  • A person does not feel well, and therefore cancels a date with a friend. This leads to them feeling depressed and sleeping poorly, which leads to them cancelling more dates...


These patterns can happen over days, weeks, or longer periods. They can happen together (over different periods of time) or alone.


Diagnosing CFS is very difficult. There is no conclusive test for CFS, so doctors must rely on their experience and intuition. Once a doctor suspects CFS in a patient who meets the general diagnostic criteria, the doctor must successively eliminate all other potential testable causes of their set of symptoms. CFS, therefore, is what is called an exclusionary diagnosis.

Historically, many doctors have been unfamiliar with CFS, and some have refused to diagnose it. This situation is rapidly changing, with more doctors willing to diagnose it and more diagnoses each year. In the UK, the Chief Medical Officer's report stated that all doctors should consider CFS as a serious chronic illness and treat patients accordingly. Unfortunately there appears to be considerable skepticism amongst doctors about the existence of CFS, which has led to frustration in some patients, who feel strongly that their disability is not psychological in origin but has a biochemical substrate. Some more vocal patients' groups maintain that research into CFS (ME) in the UK has been mostly hijacked by the psychologists/psychiatric lobby, who they claim hold significant power within the medical fraternity, with a resultant "abuse of patients' rights".

Some scoring systems, while being considered imperfect, have been proposed to quantify CFS symptoms for research purposes. These include the Holmes et al (1988) and the Fukuda et al (1994) scoring systems.


Due to problems with the definition of CFS, estimates of its prevalence vary widely. Studies in the United States have found between 75 and 420 cases of CFS for every 100,000 adults.

Far more women than men get CFS — between 60 and 85% of cases are women. Minorities and low income people are slightly more likely to have CFS. Though people of all ages can get CFS, and precise statistics are not available, the prevalence among children and adolescents appears to be lower than for adults. Among minors with CFS, about half are boys and half girls.

CFS occurs both in isolated cases and large-scale outbreaks. Blood relatives of people who have CFS appear to be more predisposed.

Disease associations

Some diseases show a considerable overlap with CFS, and it may be hard to distinguish between them. People with fibromyalgia have muscle pain and sleep disturbances. Those with multiple chemical sensitivities (MCS) are sensitive to chemicals and have sleep disturbances. Many veterans with Gulf War syndrome (GWI) have symptoms almost identical to CFS. Post-polio syndrome also bears remarkable resemblance to CFS. Some researchers maintain these disorders are all expressions of a general, yet undefined, syndrome with protean symptoms.

Other disorders with known causes and treatments that may produce CFS-like symptoms are Lyme disease, gluten intolerance (Celiac disease and related disorders), and vitamin B12 deficiency.


Proposed causes

The cause of CFS is unknown, although a large number of causes have been proposed, and several proposed causes have very vocal and partisan advocates. Among proposed causes:

  • Infectious agents: This includes several viruses (see below), Lyme and related bacteria, mycoplasma, and yeast and other fungi.
  • Toxic agents: Mercury, particularly from dental amalgams and vaccines, various organic solvents, herbicides, and several other chemical compounds are often named. The artificial sweetener aspartame is also often blamed.
  • Immune dysfunction: Both autoimmune disorders (representing a hyperactive immune system) and immunodeficiency (representing an underactive one) have been suggested.
  • Hormonal dysfunction: Thyroid disorders can cause CFS-like symptoms, as can several other known endocrine disorders. It's possible that disruption of the hormonal "master control" in the hypothalamus somehow causes CFS by upsetting the body's hormone balance.
  • Dysautonomia: Dysautonomia is the disruption of the function of the autonomic nervous system (ANS). The ANS is tightly tied to the body's endocrine system and also directly controls some aspects of blood pressure control and metabolism. The dysautonomia that evidences itself in CFS shows up mostly in problems of orthostatic intolerance - the inability to stand up without feeling dizzy, faint, nauseous etc. Research into the orthostatic intolerance found in CFS indicates it is very similar to that found in postural tachycardia syndrome (POTS). POTS and CFS patient exhibit reduced blood flows to the heart upon standing that result in reduced blood flow to the brain. The reduced blood flows to the heart are believed to originate in blood pooling in the lower body upon standing.
  • Chiari malformation and other spinal problems: Arnold-Chiari malformation is constriction where the cerebellum meets the spinal cord. This area can become constricted due to a portion of the cerebellum sagging too low or problems with the bone structure of the lower skull or upper spinal column. The constriction can impede the flow of cerebrospinal fluid between brain and spinal column, and can also compress some nerves in the area. This may cause paralysis or hydrocephalus in extreme cases, but this or other spinal problems may cause autonomic nervous system problems in less severe cases.
  • Metabolic disorders: Metabolic disorders such as McArdle's disease , CPT II deficiency , myoadenylate deaminase deficiency, and mitochondrial disorder can cause symptoms that strongly resemble CFS.
  • Nutritional deficiency or imbalance: Certain dietary practices, particularly the consumption of large amounts of carbohydrates, are sometimes blamed for CFS. Celiac disease or gluten intolerance is known to cause CFS-like symptoms in some individuals, as is vitamin B12 deficiency. Other forms of food allergies are also often blamed, especially in cases of Leaky Gut Syndrome.
  • Malnutrition: In some cases, simple malnutrition may be responsible for CFS (or CFS-like symptoms). Particularly highly restrictive vegetarian diets could cause problems, even though they appear sufficient from the standpoint of calories and essential vitamins and amino acids. Most people cannot manufacture the entire amounts of ribose, carnitine, CoQ10, fatty acids, and several other "semi-essential" nutrients that are critical for cellular metabolism and for nervous system health. A diet deficient in these can lead to a form of malnutrition that results in the classical CFS symptoms.
  • Depression: Many cases of CFS are attributed to depression, and there is no doubt that severe depression can cause most of the symptoms of CFS. While depression is not uncommon among CFS patients, there are many CFS patients without depressive signs, suggesting that depression is not a direct cause of the symptoms. In contrast to depressed patients, CFS patients may have low rather than high cortisol levels. The depression in CFS patients could also be of the type that is not uncommon in people suffering from chronic and untreatable diseases.
  • Dental infections: Some have implicated focal infections from root canals and cavitations in tooth sockets where the periodontal ligament was not removed when a tooth was extracted. The theory is that anaerobic bacteria can exist inside a tooth with a root canal or a cavitation because of the lack of blood supply. The bacteria produce toxins that cause system wide problems. Some individuals with CFS like symptoms have seen great improvement after the removal of all root canals and/or cavitation surgery to clean out the sockets from tooth extraction sites.

Viral hypothesis

Many members of the Herpesvirus family have been implicated as causative agents in CFS. For many years the ubiquitous Epstein-Barr virus, present in 90% of the population, was the principal suspect. Other viruses implicated include cytomegalovirus, and human herpesvirus type-6 (HHV-6). The evidence has not been consistent with these hypotheses, however, and they are generally no longer believed to explain the etiology of CFS. (Soto & Straus, 2000)

More recently, however, similarities to post-polio syndrome have led to a reexamination of the viral link. A number of viruses of the enterovirus family, notably the Coxsackie virus, can produce an infection of the nervous system similar to that caused by the poliovirus, and an even wider range of viruses have been shown capable of triggering an autoimmune reaction that attacks the nervous system. It is believed by some that one of these mechanisms causes damage to areas of the brain responsible for alertness and metabolism, resulting in many of the symptoms of CFS.

The role of the ascending reticular activating system

The ascending reticular activating system (ARAS) that extends upward from the reticular formation has been known since the early part of the 20th century to be associated with sleep function, and research since roughly 1950 has greatly extended this knowledge. Postmortem examination of the brains of polio patients and imaging studies of the brains of people with post-polio syndrome have shown lesions in the area of the ARAS and reticular formation. Other imaging studies of the brains of CFS patients have shown metabolic abnormalities in this area, though the results have often been equivocal.

It seems likely, however, that damage to the ARAS may be reponsible for at least some cases of CFS. Such damage could arise from direct viral damage to the area (most likely from an enterovirus similar to those that cause polio), or from an autoimmune attack on the region.

Studies with animal models (primarily cats) have shown that a malfunction of the ARAS is capable of causing behaviors similar to those of CFS patients.


The treatments that are proposed and often attempted for CFS are as varied as the suggested causes, and can generally be classified according to the specific cause that they presume. Unfortunately, since CFS symptoms tend to vary over time and will usually get gradually better once the initial crisis is past, it is very easy for someone to become convinced that a particular treatment has helped them (or not), regardless of its true effectiveness. Alternative medicine is often used for CFS, especially when conventional treatments are too toxic, ineffective or otherwise poorly tolerated.

  • Antibiotics: Antibiotics are commonly used to treat Lyme disease and mycoplasma infections. Both of these infections can be hard to eradicate, so often when an antibiotic cure fails it is claimed that the duration of treatment was insufficient or the wrong antibiotic was used. Another view is that some antibiotics have specific immuno-modulating side effects, quite separately from their antibiotic action. In the MedLine database, ciprofloxacine, doxycycline and the penicillines are reported to be of significant (albeit temporary) effect in some patients. It's worth noting that an even larger group of patients may have adverse effects, and a third group no effect at all.
  • Antifungals: Antifungal drugs are used to treat yeast and fungus infections. Proponents of the yeast hypothesis for CFS claim, however, that the drugs are largely useless unless combined with a low-carbohydrate diet that effectively "starves" the fungus at the same time.
  • Immune enhancers: These are generally "food supplements" of various types that are claimed to enhance the immune system, although they can include various antiviral drugs. They are often proposed either to treat some presumed viral infection or to treat a presumed general immune deficiency.
  • Detoxifiers': Various detoxification agents are often advocated, from simple intestinal purgatives to "liver cleanses" to various types of chelating agents for the removal of mercury and other heavy metals.
  • Hormones: Various hormones have been tried from time to time, including specifically steroids(cortisol) and thyroid hormones. Though steroids may produce some short-term pain relief, they have not been shown to be of any general benefit. Thyroid hormones occasionally are effective for certain people who may either have a thyroid hormone deficiency or lack an enzyme that allows them to effectively use thyroid hormones.
  • Antidepressants: Antidepressants are often given to CFS patients, for a number of reasons:
    • On the asumption that the illness is caused by depression
    • Because the illness often causes depression, and the patient may experience some overall improvement if this symptom is treated
    • Because tricyclic antidepressants often give pain relief without resorting to stronger pain killers such as codeine.
    • Because tricyclic antidepressants can help correct a drifting sleeping pattern.
    • Because sometimes certain antidepressants appear to help CFS symptoms, even when depression isn't present
    • To be doing "something" (out of therapeutic embarassment)
  • Sleep aids: Sleep aids are often given to CFS patients, either on the assumption that lack of restful sleep is causing the CFS symptoms, or because CFS disrupts restful sleep.
  • Pain relievers: Many CFS patients experience significant amounts of pain, and various narcotic and non-narcotic pain relievers are often given for symptomatic relief.
  • Mito cocktail: Given that the symptoms of CFS generally resemble those of metabolic disorders, a combination of supplements often known as a mito cocktail is sometimes used to treat the disorder. This "cocktail" consists of relatively large amounts of l-carnitine and CoQ10, and possibly d-ribose, vitamin B12, biotin, and several other nutrients. As with mitochondrial disorder, it is believed that large amounts (eg, 2-10g/day l-carnitine) are necessary to have a significant effect, and smaller amounts of these nutrients will not generally be helpful.
  • ANS stimulants: Drugs such as atomoxetine (Strattera®), which stimulate the autonomic nervous system, appear to have significant positive effects in some people with CFS symptoms.
  • Surgery: For Chiari malformation and some other disorders (eg, thoracic outlet syndrome) that are occasionally blamed for CFS symptoms, surgery to release trapped nerves or otherwise correct neurological problems may be helpful.
  • Location: Many CFS patients find relief in moving to warmer climes.
  • Dental cleanup: Some individuals suffering from CFS have reported a major reduction of symptoms and improvement in health after the removal of teeth with root canals. Cavitation surgery to clean up the sockets of sites where the periodontal ligament was not removed after a tooth extraction has also been helpful to some.
  • Graded exercise: A monitored 'self-developed' gradual exercise program to increase strength and cardiovascular health has proven helpful to some patients. However, the risks of post-exertional malaise, which can cause significant, if usually temporary, worsening of symptoms, make this a difficult regimen to implement successfully. Some studies which have suggested that graded exercise can improve the condition of sufferers have been criticized for ignoring individuals who fall out of the trials because they can't cope with the exercise program required. Indeed, in the UK, rigid enforcement of GE by medical professionals on people seriously ill with CFS may have led to many becoming much more ill than before.
  • Self-controlled exercise, "pacing": although accepting the above conclusions about 'graded exercise,' some exercise, however, is absolutely necessary in order to make any progress at all. "Pacing" is being advocated by a large number of patients as one of the few really effective means of improvement. The principles are: 1. Accept your limitations. 2. "Listen" to the first body signals of fatigue, and stop any exercise before becoming noticeably tired. Rule of thumb: dont exert more than 70% of your capacity. 3. rest. Shift between limited exercise/ rest, etc. "Body signals of fatigue" are individual. An understanding nurse, doctor or therapist may be of help.
  • Cognitive behavioural therapy: Cognitive therapy may benefit up to 25% of sufferers. This does not imply that CFS is a primary psychiatric condition, but rather that the protracted course of the illness may cause depression, anxiety and misinterpretations. In addition, CBT may teach patients various "coping strategies" to help them deal with cognitive impairments such as a deterioration of short-term memory or abbreviated attention span.
  • Legal advice, economic counselling: Many CFS patients face the stress of economic and legal problems, which can cause a serious deterioration and paralysis of the patient.

As there is no one identifiable cause or falsifiable diagnosis for CFS, there is also no one treatment protocol or "magic bullet". Due to the multi-systemic nature of the illness, and others like it, an emerging branch of medical science called psychoneuroimmunology is looking into how all the various theories fit together.

Social issues

Chronic fatigue syndrome suffers a considerable stigma and has been lumped together with various factitious diseases by some, both healthcare professionals and laypeople. As there is no objective measure of the condition, many argue that it is easy to "invent" CFS-like symptoms for financial, social or emotional benefits, adding to the stigma. This has contributed to a distorted picture of the average CFS patient as a resentful, claiming and depressed person. Cross-sectional studies disprove this picture.

Notable sufferers

Some notable sufferers of CFS are:


  • Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 1994;121:953-9. PMID 7978722.
  • Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med 1988;108:387-9. PMID 2829679.
  • Soto NE, Straus SE. Chronic Fatigue Syndrome and Herpesviruses: the Fading Evidence. Herpes 2000;7:46-50. PDF full text. PMID 11867001.

External links

Last updated: 08-11-2005 17:21:34
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