Index

In Search of a Cause
Brain Abnormalities
CFS Cause Still a Mystery
Possible Causes
Hormones and CFS
Numerous Factors
New Possible Causes

In Search of A Cause

It took years to discover what was disrupting the immune system of AIDS patients, but it is taking even longer to identify what is wreaking havoc on the bodies and the brains of those with CFS (chronic fatigue syndrome). Although the cause has not been determined, medical authorities are able to present convincing evidence of physical abnormalities in patients. In fact, such evidence has been used in court.

Canada's Medical Post reported that in a controversial case, medical experts presented testimony to support the defense's claim that the patient's ability to make judgments had been impaired by his illness. Justice William G N. Egbert was thus moved to conclude: "The disease affects every area of judgment. . . . Small areas of the brain are injured." Is there truth to this?

Medical research supports the contention that the brain of CFS patients is affected. The New York Times of January 16, 1992, carried the headline: "Study Detects Brain Abnormality in Patients With Chronic Fatigue." The article, based on a report published the day before in Annals of Internal Medicine, observed:

"The largest study yet of chronic fatigue syndrome has found evidence of inflammation in the brains of patients, the first documentation of a neurological abnormality connected with the mysterious ailment." The article added: "The study is the latest of a recent series showing immunologic and hormonal differences between those with the syndrome and healthy people.

Another study that drew wide attention was reported in the December 1991 issue of the Journal of Clinical Endocrinology and Metabolism. It found indications of hormonal deficiencies in the endocrine glands and brains of people with CFS. The study thus added to evidence that biochemical and immunological factors produce the symptoms of CFS."

Dr. Walter Gunn, while serving at the CDC (U.S. Centers for Disease Control), monitored many studies of CFS patients. He noted that "some good scientists are beginning to get involved in CFS research." Although the findings of these researchers often pointed to different possible causes, Dr. Gunn emphasized: "The one thing that is consistent is that nobody is reporting there are no abnormalities."

What possible agent or agents are responsible for CFS? Is a virus involved, or viruses? If so, in what way? How is the immune system adversely affected? How could its dysfunction cause the symptoms manifest in CFS patients? See Memory Loss and M.E. and Research on Memory Loss

Studies are under way investigating causes, possible treatments and duration of CFS. At this time, reports show the syndrome can last for months to a lifetime. Currently there are no cures and most treatment is confined to combatting the array of symptoms associated with the disease. Research is increasing and new information should be generating during the next four years.

CFS has gone through an evolution of descriptive terms, but there is reason to believe that the disease has been around for years. Symptoms and charactertistics assigned to CFS, at that time called neurasthenia, were described in 1750 by Sir Richard Manningham. There are also claims that descriptions of a similar disease were found in Hippocrates writings.

Hormones and CFS

The hormones produced by the hypthalamus, pituitary gland and adrenal glands may play a major role in Chronic Fatigue Syndrome.

Normally, stress such as a virus, bacterium, environmental toxin or psychological event produces a series of physical responses.

1) The hypothalamus secretes corticotropin-releasing hormone (CRH)

2) This activates the pituitary gland to secrete adrenocorticotropin hormone (ACTH).

3) ACTH stimulates the adrenal glands to produce cortisol.

If something goes wrong with this chain of events, the symptoms of CFS can result. People with CFS often have CRH deficiency, which leads to a reduction of cortisol, which is known to be associated with lethargy and fatigue. But it's not known whether the deficiency is a cause or an effect of the disease - or neither.
See Research on Fatigue on Hormonal Deficiencies Found in CFS

Possible Causes

Research indicates that viruses are involved. But what viruses? Many have been implicated by researchers. "Retroviruses, spuma or 'foamy' viruses, enteroviruses, Epstein-Barr virus, and human herpesvirus type 6 are all among the popular and highly controversial contenders," observed The Journal of the American Medical Association last November.

In what way may viruses cause CFS? That is unknown. However, Dr. Anthony L. Komaroff, a leading CFS researcher, noted: "The pattern that is emerging is a chronically activated immune system, an immune system engaged in some kind of chronic war against some kind of thing that it perceives as foreign."

A healthy immune system responds to an enemy virus, or viruses, by releasing chemicals, called cytokines, to fight the invaders. However, when the emergency is taken care of, the production of cytokines normally ceases. But in CFS patients the immune system apparently fails to shut off. Significantly, a consistent finding in people with CFS is an increased production of cytokines.

This is important, since it is not the virus that makes a person feel sick when it invades his body. He feels ill because his body cells are producing cytokines, which cause the fever, achiness, and fatigue. Dr. William Carter, a U.S. medical professor, noted: "The cytokines remain and begin to damage the host until ultimately we see the profoundly bedridden patient who can barely move."

However, what causes the immune system to keep producing cytokines when it should have ceased production?" "A latent virus is activated by some sort of trigger," according to Dr. Jay A. Goldstein, "which makes the cells of the immune system produce [cytokines] in abnormal amounts.

Additionally, it appears that natural killer cells and macrophages, which are frontline defenses against invading organisms, are reduced in either number or function in CFS patients, further weakening the immune system. The significant thing is that the immune system of CFS patients seems to malfunction, although opinions vary as to why it does.

As noted in the previous article, doctors often observe that in many patients depression is not the cause of CFS. However, in other patients some doctors feel that psychological problems, such as depression, may be a causative factor. Interestingly, research has revealed that depression can damage the immune system. "Psychological distress itself can produce disturbances in neurohormonal and immunologic function," writes Dr. Kurt Kroenke, of the Walter Reed Army Medical Center in Washington, D.C.

Thus, in some instances depression may trigger changes in the immune system that may contribute to CFS. Yet, many other factors that can weaken the immune system are probably also involved.

New Possible Causes

New Possible causes of chronic fatigue syndrome (found on the CFS Home Page)

Q: What causes CFS?

A: The cause of CFS has not been identified, but there are several theories. Numerous well-characterized viruses are known to cause severe fatigue during acute infection. While some viruses, such as Epstein-Barr virus (EBV), occasionally establish a chronic active infection that results in persistent fatigue, no virus has been firmly associated with CFS. One hypothesis is that a virus, stress, or other transient traumatic condition may chronically activate the immune system. According to this hypothesis the immune system, which ordinarily gears down after an infection has been eliminated, remains activated after the initiating condition has passed. The result is that unusually high concentrations of immune activating factors, some of which are known to cause fatigue at high doses, persist in the bloodstream. Other theories involve proposed disturbances in the hormonal (endocrine) system, and some fatigue may be induced by psychological conditions. Another possibility is that a single causative agent, as yet unidentified, results in CFS.

Q: Is CFS caused by an uncharacterized human retrovirus?

A: One report in the scientific literature described possible retrovirus DNA sequences in lymphocytes from CFS patients that were absent in healthy controls. Despite intensive efforts, several laboratories could not confirm the results of this study. Anecdotal reports that CFS is caused by a human spuma virus are unsubstantiated. In addition, CFS does not have any relationship to a recently reported rare disease, HIV-negative AIDS. There is also no evidence to suggest that CFS is caused by HIV-1, the virus that causes AIDS. Reduced CD4 counts are rarely observed in CFS patients. There is no evidence of life-threatening or clinically noteworthy compromise of the immune system in CFS patients. Retrovirus involvement in CFS is unlikely, although it continues to be investigated.

Q: Does human herpesvirus type 6 (HHV-6) cause CFS?

A: HHV-6 is an extremely common herpesvirus infection that causes roseola in children and infects at least 95% of persons older than 1 year. Like all herpesviruses, HHV-6 normally remains latent within infected persons but can be reactivated periodically. Some studies have reported inconclusive evidence of HHV-6 reactivation in CFS patients; others have found no correlation between HHV-6 infection and CFS. However, since it is virtually ubiquitous in the general population, HHV-6 infection cannot be used to diagnose CFS.

Q: Do enteroviruses cause CFS?

A: Like herpesviruses, some enteroviruses are known to cause severe fatigue and muscle weakness. Enteroviruses have been studied by several groups for their involvement in CFS. As with other potential viral causes, no strong associations can be made between recent infection by enteroviruses and CFS.

Numerous Factors

Most investigators agree that it is very unlikely that one thing is causing CFS. "Instead, CFS probably is an illness that occurs in a vulnerable individual in whom depression, [allergies], viral infections, or other factors have resulted in some degree of immune compromise," explained the medical journal Cortlandt Forum.

A doctor, writing in Canada's Medical Post, noted: "There might be a hereditary susceptibility required and an overused body might be another predisposition. Then an acute event, most often an acute viral infection, hits the strained individual. The combination of all these factors probably induces damage to the immune system.

"Stress is one of the biggest triggers we see," said Dr. Charles Lapp. "Sometimes we have seen certain chemicals play a role. . . . And curiously a number of my patients (although we ve never done a study) have mentioned that insecticides, paints, and varnishes seemed to have been involved when their disease was triggered off."

Never in history have people been exposed to greater assaults on their bodies by environmental pollution. Food additives and drugs may also harm the body and adversely affect the immune system. Certain doctors even claim that long courses of antibiotics depress the immune system.

Other factors too may be involved in the suffering seen in thousands of CFS patients. But while there are tantalizing clues and intriguing possibilities, the cause of CFS is still unknown.


See Research on Memory Loss and Fatigue.

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