Richard A. Feely, D.O. FAAO, FCA, FAAMA

Chronic fatigue syndrome (CFS) is a disorder characterized by debilitating fatigue for at least six months duration, accompanied by a multitude of other symptoms. These symptoms are highly variable but often include a low grade fever, sore throat, tender lymph nodes, muscle pain, joint pain, headaches, sleep disturbance, depression, anxiety and cognitive dysfunction, impaired memory and/or concentration.

Objective findings are absent or insufficient to explain all these symptoms. CFS often begins after an acute flu-like respiratory or gastrointestinal illness or it may be preceded by other physical and emotional stress. In some cases, no initiating event can be identified. The symptoms are aggravated by stress and exertion.

Section A | Causes

A variety of possible explanations have been composed including chronic infection and metabolic disorder and toxic exposure. No endocrine dysfunction and psychological disturbance. Currently we do not know whether CFS is a distinct disorder or a multi-factorial origin or a nonspecific condition, infection.

About 50% of the CFS cases appear to be triggered by an acute respiratory, gastrointestinal illness. Viral infections have most often been implicated including epstein-barr virus (chronic mononucleosis), herpes virus and entero viruses. The epstein-barr virus (EBV) is the cause of infectious mononucleosis. CFS frequently begins after acute mononucleosis.

Current evidence does not support EBV as the cause of CFS. Increasing antibody titers of other viruses are also common in CFS suggesting that no single virus is responsible. Human herpesvirus-6 is currently being studies. HHV-6 was cultured in about 70% of the cases of CFS patient. Enteroviruses, especially coxsackie B virus is also being investigated for their possible role in CFS. The one study in enteroviral RNA was detected in muscle biopsies specimens of 20% of the CFS patients but none of the controlled subjects.

Exposure to certain toxins can produce multiple symptoms including fatigue. There may be a single high level or repeated low level exposure. The symptoms often improve after removal from exposure.

Immune Dysfunction

Laboratory abnormalities of the immune deficiencies and impaired T-cell function have been reported in CFS patients. There is no consistent pattern of these findings. Nevertheless, they do suggest that CFS involves immune disregulation within an activation of some immune function and an inactivation of others. With this immune dysfunction, this could explain the variety of positive viral cultures and antibody titers seen in many CFS patients.

Metabolic Disorder

Some symptoms of CFS resemble those of carnitine deficiency. Carnitine is a substance which plays an important role in energy metabolism primarily in the muscle but also in other tissues and cells including the brain and the immune system. Carnitine transports long chain fatty acid into the mitochondria and organals which are responsible for cellular energy production. In small studies, CFS patients were shown to have low serum levels of acylcarnitine compared with the normal. These acylcarnitine levels correlated with the patients waxing and waning of functional symptoms and suggest the possible mitochondria abnormality. Electrophysiolgoical abnormalities have been reported in a series of CFS patient using single fiber EMG testing. The results suggest an abnormality of muscle cell membrane. It has been proposed that CFS may involve the generalized cell membrane dysfunction effecting not only the muscle but also other cell type. The above abnormalities could theoretically be triggered by viral infections.

CFS symptoms resemble those of magnesium deficiency although serum magnesium levels are normal in CFS patients. Low red blood cell magnesium has been reported. In one study, symptoms improved with the administration of magnesium but not with the placebo. Moreover, more studies showed no improvement with magnesium. The vitamins B12 and folate deficiency have also been proposed, as causes of CFS. There have been anecdotal reports of dramatic improvement after administration of these vitamins. However in controlled trial, this treatment was no more effective than a placebo.

Neuroendocrine Dysfunction

Neural transmitters are chemical messengers that transmit nerve impulses from one neuron from another. Chemical imbalances of neural transmitters have been implicated in fatigue, sleep disturbance, depression, anxiety, cognitive dysfunction, and chronic pain. It has been proposed that CFS is a disorder of brain chemistry. Specifically, it has been suggested that CFS may result from a deficiency of cortisoltropin releasing hormone which would lead to a cortisol deficiency. Some symptoms of CFS resemble those of cortisol deficiency and a decrease level of cortisol has been observed in the blood and urine of CFS patients. Cortitropin releasing hormones (CRH) deficiency could also theoretically lead to immune disregulation.

Further study is needed to determine whether or not CFS have low levels of CRH. The ananomic nervous nervous regulates involuntary reflexes including heart rate and blood pressure. There is evidence that at least some CFS cases may result from autonomic dysfunction but disregulation of blood pressure, a condition known as neurally mediated hypotension. With this condition, the blood pressure drops after the patient has been in an upright position for some time. Fainting may occur but even if it doesn’t the hypotensive periods are followed by prolonged fatigue.

Several studies have documented neurally mediated hypertension in a significant percentage of CFS patients. Some of these patient recovered when the hypotension was treated. Further research is needed to determine whether neurally mediated hypotension is a consistent feature of CFS.

Psychological Disturbance

CFS have few or no objective findings in routine physical examinations or diagnostic test. High percentages of them have psychological symptoms and many of these meet criteria for psychiatric disorders. For these reasons, some authorities consider CFS a primary psychiatric disturbance. It has been suggested that CFS is identical to neurasthenia, a psychiatric diagnosis first discovered in the 1860’s. In contemporary terms CFS has been regarded as depression/anxiety or somatoform disorder. On the other hand, it can be argued that the psychological disturbance of CFS is an effect of chronic of illness and not the cause. The stress of chronic illness may lead to exaggerated perception of symptoms, somatoization which occurs even in patients with cardiac, orthopedic or other clearly organic diseases. Prolonged illness may lead to anxiety and depression.

Controlled studies have been performed to attempt to clarify the relationship between CFS and psychotherapy. It has been consistently been found that CFS patient have a higher prevalence of psychiatric disorder than the general population. Studies comparing CFS and other chronic disabling conditions have also shown a higher prevalence of psychiatric disorders in CFS patients. Furthermore, several studies suggesting that the psychiatric disorders more often predate CFS than vice versa.

Nevertheless, some CFS patients do not meet the criteria of any psychiatric disorders past or present. Thus the evidence suggests that CFS involves both physiological and organic mechanisms each contributing in varying degrees in different individuals. Regardless of the primary cause CFS seems to become a self perpetuating cycle. Fatigue leads to inactivity, deconditioning and more fatigue. Disability and psychological symptoms also can be mutually exacerbating.

Section B | Diagnosis

In 1988, the Centers For Disease Control (CDC) issued criteria for diagnosis of CFS. In 1994, a revised criteria was published which is as follows:

Unexplained persistent, recurrent fatigue with all the following characteristics: (1) at least six month duration (2) definite onset (3) resulting in a significant decrease from previous activity (4) not due to ongoing exertion (5) not substantially relieved by rest (6) headaches of a new type, pattern or severity (7) unrefreshed sleep (8) post exertional malaise lasting longer than 24 hours.

Other causes for fatigue: In order to diagnose CFS, the symptoms must be unexplained. Other symptoms for chronic fatigue must ruled out. The cause of chronic fatigue are numerous. Major categories are chronic infarction, metabolic nutritional disorder including severe obesity, endocrine disorders, immune and inflammatory disease, neuromuscular disorders, malignancy, drugs and toxins, primary sleep disorders, other chronic organic diseases such as cardiac pulmonary renal or lymphatic and many psychiatric disorders including major depression with psychotic features, bipolar disorders, schizophrenia, delusional disorders, dementia and dementia of any cause, anorexia, bulimia and nervosa.

The history is the primary importance in diagnosis of fatigue since it determines the focus of further evaluations. Included is the onset, circumstances associated with the onset, toxics or infectious exposures, duration, course, any previous episodes of unexplained symptoms. Included in the history is the past medical history, current medications, use of nutritional supplements, alcohol, tobacco, caffeine, occupation, psychosocial and psychiatric history.

Physical Examination

CFS patients either have no objective findings or minor abnormalities that insufficient to diagnosis an exclusionary condition. A mental status exam is usually integrated into the interview in the physical examination. The purpose is to screen for psychological and cognitive dysfunction. If significant abnormalities are found a referral to psychiatric and neurological evaluation is done.

Diagnostic Tests

There are no diagnostic tests for CFS. However a minimal battery of test are required in all cases to rule out other diseases as recommended by the CDC. These include complete blood count, sedimentation rate, blood chemistry including electrolytes, glucose, blood nitrogen, creatinine, calcium, phosphorus, liver enzymes, muscle enzymes, and serum protein, thyroid function and urinalysis. Testing for lyme disease is indicated where the disease is prevalent. HIV and viral hepatitis are indicated when there is a history of exposure or high risk life style. Further testing may be performed selectively based upon the history including serological test for viruses for candida, a test for immune function and brain imaging studies.

Symptom relief is important. The main goal of treatment is to minimize disability. This is best accomplished through a multidimensional approach including Osteopathic structural evaluation and manipulation, modifying the autonomic nervous system thereby improving and restoring health. Nutritional supplementation, acupuncture and neurological stimulation through the use of manipulation maybe helpful to improve the patients well being. Consideration for herbal remedies are based upon a Chinese diagnosis may also be used based. Until we have more research verifying the exact cause and effect of treatment, we must focus on the aforementioned therapies to improve health.

Page modified on 5/15/2011