Chronic fatigue syndrome: Encyclopedia II - Chronic fatigue syndrome - Proposed etiologies and corresponding treatments

Chronic fatigue syndrome - Proposed etiologies and corresponding treatments

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.

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 exploring how all the various theories fit together.

The treatments that are proposed and often attempted for CFS are as varied as the suggested causes, and can generally be classified either according to the cause that they presume, or the symptom they propose to treat. Unfortunately, since CFS symptoms tend to vary over time, 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 proposed for CFS, especially when conventional treatments are too toxic or otherwise poorly tolerated, or simply fail to relieve symptoms. Alternative treatments may also be more affordable or accessible to patients with limited funds or health care coverage.

Chronic fatigue syndrome - Allergies

• Allergies: Similarly to the theory of immune dysfunction, some doctors believe that CFS patients suffer from immune dysfunction caused by exposure to allergens, ranging from food allergies or intolerances (see below) to pollen and dander allergies.

• TREATMENT: Allergy identification and treatment: In cases where CFS-like symptoms may be being caused by gluten intolerance, celiac disease, or chronic sinusitis, allergy testing, treatments, or elimination diets may prove beneficial. Since some CFS patients show decreased immune response or symptoms of MLS, pre-existing mild allergies may increase to harmful levels after CFS onset. Some studies suggest that a form of CFS may be triggered by a rare reaction to dental metals. Tests in Sweden showed that 76% of CFS patients who tested positive to metal allergy and swapped metal fillings for ceramic substitute achieved partial or full health improvement. Metal allergy can be detected by a blood test named MELISA [1].

Chronic fatigue syndrome - Autonomic nervous system disruption

• 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, nauseated, 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 patients exhibit reduced blood flows to the heart upon standing that result in reduced blood flow to the brain (though this reduced blood flow by itself does not account for the symptoms of CFS). The reduced blood flows to the heart are believed to originate in blood pooling in the lower body upon standing. Many CFS patients report symptoms of orthostatic intolerance and low or lowered blood pressure.

• TREATMENT: 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. Amphetamines and amphetamine analogs such as methylphenidate (Ritalin®) also seem to help some patients. Interestingly, at least some of those who experience improvement on stimulant drugs do not experience significant "payback effect", suggesting that the drug is to some degree acting to correct the underlying neurological problem rather than simply masking symptoms. Modafinil (Provigil®), a medication designed to aid in maintaining wakefulness, has had some positive effect on individuals with CFS, but has not been properly studied.

Chronic fatigue syndrome - Damage to ascending reticular activating system

• The ascending reticular activating system (ARAS) is an area in the brain that extends upward from the reticular formation. It 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 responsible 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.

Chronic fatigue syndrome - Depression

• 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. There also patients with pre-existing depression which responded to treatment, but whose CFS symptoms did not improve; and treatment for depression is not particularly effective on CFS patients without depression. While depression may occur in CFS patients, it may be a result of living with CFS rather than the cause. Depression sufferers have been shown to have lowered immune system responses in some cases, which may explain the slight correspondence between pre-existing depression and CFS.

• TREATMENT: Antidepressants: Antidepressants are often prescribed to CFS patients, for a number of reasons: the doctor may believe depression is the cause of the symptoms, or to treat co-existing depression caused by CFS. Tricyclics may also help adjust sleep cycles. For patients with muscle or joint pain, or co-existing fibromyalgia, tricyclic antidepressants (prescribed at much lower doses than are usual for depression) have been shown to be effective for neuralgic pain in fibromyalgia sufferers, and persons with diabetic myalgia.

Chronic fatigue syndrome - Hormonal dysfunction

• Hormonal dysfunction: thyroid and adrenal 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. This theory is supported by changes in cortisol response in some CFS patients.

• TREATMENT: Hormones: Various hormones have been tried from time to time, including specifically steroids (such as cortisol) and thyroid hormones. Though conventional steroidal treatment may produce short-term pain relief, it has not been shown to be of any general benefit. Studies performed by Dr. Jacob Teitelbaum incorporating low-dose cortisol therapy in a holistic approach have demonstrated positive results, but other studies have shown little benefit from cortisol itself. (Dr. Teitelbaum argues that the approach taken in those studies is flawed.) 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 (though one could question whether the disorder in such a case is correctly classified as CFS).

Chronic fatigue syndrome - Immune dysfunction

• Autoimmune disorders (representing a hyperactive immune system) have been suggested.

• White Blood Cells: In July 2005, researchers in the UK reported significant gene changes in the white blood cells in CFS patients consistent with the theory of immune system activation, possibly by a virus triggering a constant immune fatigue state.

• Immunodeficiency disorders (representing an underactive immune system) have been suggested.

• Some theories propose that an infection with one of the below-listed disease agents somehow leads to immune dysfunction and chronic fatigue in cases of CFS. This is partly supported by test results indicating lowered or changed immune responses in some patients, as well as elevated levels of infectious agents in some patients' blood.

• TREATMENT: 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.

Chronic fatigue syndrome - Infectious agents

• 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.

• TREATMENT: 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.

• Lyme and related tick-borne bacteria

• Bacterial respiratory infections such as mycoplasmic bronchitis/pneumonia, Legionnaire's disease, and possibly other bacteria associated with bacterial pneumonia.

• Sinusitis: Sinusitis is a chronic infection of the sinuses which can be difficult to diagnose, and can cause symptoms similar to those of CFS. Sinusitis can occur after dental surgeries or infections, and thus may be related to reaction to mercury in dental amalgams as above, or dental infections, as below.

• TREATMENT: Antibiotics: Antibiotics are commonly used to treat Lyme disease, sinusitis and bacterial infections. 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. While many patients still show evidence of the infectious agent in their system after antibiotic treatments, these levels are generally too low to qqualify for a diagnosis of an infection; that is, a patient with Lyme who has received Lyme antibiotic treatment will be pronounced 'cured' of Lyme disease when their blood levels of Lyme are at or below those found in healthy persons, although a Lyme-CFS case may still have CFS symptoms after treatment. Some patients may receive antibiotic treatment for the causative infection, and recover from the original infection, but still have CFS. High doses of antibiotics (sometimes intravenous doses) over longer than generally prescribed courses are recommended by some physicians in these cases of "late Lyme", and have had some beneficial effect for some sufferers, but this treatment remains highly controversial.

• yeast and other fungi. Some nutritionists believe that CFS is caused by an overgrowth of yeast, known as "candidiasis", but treatment of candidiasis has not helped all CFS patients.

• TREATMENT: 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.

• Brainstem Damage: Dissection studies of the brains of persons with post-polio syndrome have shown microscopic damage to areas of the brain responsible for alertness and metabolism, and possibly other motor functions, consistent with the symptoms of both CFS and post-polio syndrome. It is theorized that an infectious agent could cause similar damage in CFS cases, but no post-mortem studies on CFS patients have been done at this time. (See "viral hypothesis", below.)

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.

Chronic fatigue syndrome - Inner-ear disorders

• Inner-ear disorders: Problems such as Meniere's, tumor in the inner ear, or Benign Paroxysmal Positional Vertigo (BPPV) can cause dizziness, vertigo, and fatigue.

Chronic fatigue syndrome - Metabolic disorders

• Metabolic disorders: Metabolic disorders such as McArdle disease, CPT II deficiency, myoadenylate deaminase deficiency, and mitochondrial disorders can cause symptoms that strongly resemble CFS. Mitochondrial disturbances have recently been discovered in some CFS patients.

• TREATMENT: Mito cocktail: Given that the symptoms of CFS generally resemble those of metabolic and mitochondrial 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.

Chronic fatigue syndrome - Nutritional deficiency or imbalance

• Nutritional deficiency or imbalance: certain dietary practices, particularly the consumption of large amounts of carbohydrates, or poorly nutritive vegan diets (see below, 'malnutrition'), are sometimes blamed for CFS. Celiac disease or gluten intolerance is known to cause CFS-like symptoms in some individuals, as is vitamin B12 or vitamin D deficiency. Other forms of food allergies are also often blamed, especially in cases of leaky gut syndrome. While many nutritional supplements are touted as cures or palliatives for CFS, research on these is scattered and inconclusive.

• Malnutrition: In some cases, simple malnutrition may be responsible for CFS (or CFS-like symptoms). Particularly highly restrictive vegetarian or vegan diets could cause problems, even though they appear sufficient from the standpoint of food energy 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.

Chronic fatigue syndrome - Psychosomatic causes

• Psychosomatic causes: many doctors and researchers believe that CFS is a complex psychosomatic disorder caused by chronic stress. Patients generally disagree with this theory, believing their disorder to have organic components, and to date, psychological treatment alone has not been shown to be particularly effective in treating CFS. (See Chronic_fatigue_syndrome#Controversies, above)

Chronic fatigue syndrome - Spinal problems

• Arnold-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. This can be determined via an MRI, which may also be valuable in ruling out inner-ear conditions, or chronic sinusitis (see below).

• TREATMENT: Surgery: For Chiari malformation and some other disorders (e.g., thoracic outlet syndrome) that are occasionally blamed for CFS symptoms, surgery to release trapped nerves or otherwise correct neurological problems may be helpful.

Chronic fatigue syndrome - Toxic agents

• 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. In the cases of mercury and aspartame, this suspicion is not borne out by available evidence.

• TREATMENT: 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.

Chronic fatigue syndrome - Other treatments

• TREATMENT: Sleep aids: Sleep aids may be prescribed when a patient complains of poor or irregular sleep, or excessive fatigue. Some patients find sleep aids, whether over-the-counter or prescription, to help greatly in maintaining a sleep cycle or getting "better", more restful sleep.

• TREATMENT: Pain relievers: Many CFS patients experience significant amounts of physical, neuralgic pain. This "nerve pain", like that of phantom limb, diabetic neuralgia and fibromyalgia, does not generally respond well to NSAIDS. although some patients report that naprosyn or naproxen provides some relief due to its muscle relaxant properties. Tricyclic antidepressants, as above, offer better relief for some cases of nerve pain. Other pain relievers may have uses as well. Patients experiencing "other" pain (such as headache or migraine) should receive appropriate pain management for those symptoms. Hot water bathing has also been noted as relieving fibromyalgia or neuralgic pain, but patients with low blood pressure and dizziness are advised to be cautious about the use of hot tubs or baths. Acupuncture has also been shown to relieve pain in fibromyalgia cases, and may be beneficial to CFS sufferers as well.

• TREATMENT: Lifestyle Adjustments: Many CFIDS authorities recommend making use of medical treatments where appropriate, but focusing on minimizing symptoms through lifestyle adjustments such as pacing, control of stress, and good support. Importantly, acceptance rather than "fighting" to be as healthy as the patient was before CFS onset will lead to less frustration and fewer relapses. Adjustments to daily living - working less, making dietary changes, and more efficient use of time and energy can improve a patient's outlook, but more importantly, relieve some symptoms as well. This may also include the use of assistive devices; many CFS patients find that a cane, walker, wheelchair or power chair will greatly improve their ability to perform tasks. Simpler assistive devices - a kitchen stool rather than standing at the stove, a phone programmed to remember phone numbers - can also greatly improve the quality of life for CFS patients.

• TREATMENT: Location: Some CFS patients find relief in moving to warmer climes. This is a difficult and expensive treatment option, not always feasible or available.

• TREATMENT: 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. Patients and advocates strongly suggest that, where graded exercise is used, the patient be in control of the amount of increases, and allowed to set limits when those are recognized.

• TREATMENT: Self-controlled exercise, "pacing": although accepting the above conclusions about 'graded exercise,' some exercise, is necessary and beneficial to all persons. "Pacing" is being advocated by a large number of patients as one of the few really effective means of improvement. The principles involve: acceptance of the patient's limitations (by both the patient and any coaches), awareness of the early signals of physical fatigue, and stopping exercise before becoming noticeably tired. A good rule of thumb is to never exert more than 70% of capacity. An understanding nurse, doctor or physical therapist may be of help.

• TREATMENT: Other exercise: Most patients find health benefits and pain relief from gentle stretching, non-aerobic exercise, and gentle activity. More able persons may find gentle yoga, walking, or t'ai chi to be beneficial. Water-borne exercise and swimming is particularly beneficial for many CFS sufferers.

• TREATMENT: Cognitive behavioral therapy: Cognitive therapy may benefit up to 25% of CFS patients. This should not imply that CFS is a primary psychiatric condition, but rather that the protracted course of the illness may cause depression, anxiety and mental distress. In addition, CBT can teach patients various "coping strategies" to help them deal with cognitive impairments such as a deterioration of short-term memory or abbreviated attention span. CBT should always be used in conjunction with medical care and treatment, as it is not a substitute for such, and cannot fully treat the physical aspects of CFS.

• TREATMENT: Counselling, various: Many CFS patients face the stress of economic and legal problems, which can cause a serious deterioration and paralysis of the patient. CFS sufferers may lose jobs, marriages, and the ability to work at all, causing severe financial loss and distress. A lawyer, social worker or counselor can be beneficial in helping the patient determine their best course, and may assist the patient with applying for work-related disability, social programs, and other aid.

Adapted from the Wikipedia article "Proposed etiologies and corresponding treatments", under the G.N U Free Docmentation License. Please also see http://en.wikipedia.org/wiki