The Physical Basis of CFS
Anthony L. Komaroff MD, Harvard Medical School
when people hear that there is no known test or cause for chronic fatigue
syndrome (CFS), they mistakenly understand that to mean that the illness
is not real. This is incorrect.
Over the past 15 years, scientists have identified numerous biological abnormalities that provide evidence for the reality and seriousness of CFS, even though the cause of CFS and diagnostic tests for it are still unknown. (1) These biological abnormalities have given researchers clues to the cause of the illness. In particular, they have provided evidence that the illness involves both the brain and the immune system.
There are no diagnostic tests yet for CFS because none of the biological abnormalities clearly distinguishes patients with CFS from other individuals. In reality, there are no perfect biological tests (see sidebar at end) for any illness. When a test gets close enough to perfect, clinicians use it to help confirm or refute their clinical judgment. Testing in CFS has primarily been used to rule out other illnesses that also can cause chronic fatigue.
What is the cause
This immune system activation could theoretically result in brain dysfunction: when the immune system is activated, it makes chemical messages. Brain cells as well as other immune system cells can receive these messages. This could lead to fatigue, cognitive dysfunction, enhanced sense of pain, hormonal dysregulation and other features of CFS. (4)
However, some of the most interesting research in recent years involves studies that did document an infection at the start of the illness. For example, CFS has been reported following acute mononucleosis (5,6) (a viral infection), Lyme disease (7-9) (a bacterial infection) and Q fever (10) (an infection with a different kind of infectious agent). These studies prove that CFS can indeed follow in the wake of a well-documented infection.
This research indicates that no single infectious agent is likely to be the cause of CFS. Instead, CFS is likely to be caused by some abnormality in the bodys response to any of several different infectious agents. The studies of infectious agents in CFS are complicated.
One reason is that the symptoms of CFS almost surely arise from the brain, yet it is very hard for scientists to study infectious agents in the human brain: that requires taking brain tissue (biopsies), a potentially dangerous test.
Another reason is that some infectious agents permanently live in a dormant state inside our bodies. There is evidence that some of these infections, like infection with the virus HHV-6, (11-14) get reawakened in patients with CFS. The unanswered question is whether the reawakened virus is the cause of the bodily damage, and resulting symptoms, or whether it is result of the illness.
Immune system abnormalities
The most intriguing recent immunological finding in CFS is the discovery of a novel, low molecular weight protein in an antiviral pathway called the RNase-L pathway. (24-27) This novel protein is found much more often in CFS patients than in healthy people, or people with two other conditions that can cause fatigue: depression or fibromyalgia.(27)
Depending on demographic factorssuch as age, sex and ethnicitythe prevalence can range from 200 to 800 cases per l00,000. (38) This makes CFS more common than well-known illnesses such as multiple sclerosis (41) and systemic lupus erythematosus (42), which, like CFS, predominantly affect females.
CFS is real
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23. Suhadolnik RJ et al Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome. J Interferon Cytokine Res. 1997;17(7): 377-85.
24. Suhadolnik RJ et al. Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(I)poly(CI2U) in chronic fatigue syndrome. In Vivo. 1994; 8(4): 599-604.
25. Suhadolnik RJ et al. Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis. 1994;18(1):S96-104.
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29. Schwartz RB et al. SPECT imaging of the brain: comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex, and major unipolar depression. Am J Roentgenol. 1994; 162(4):943-51.
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31. Rowe PC et al. Is neurally mediated hypotension an unrecognized cause of chronic fatigue? Lancet. 1995;345:623-4.
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37. Reyes M et al. Wichita population-based study of a fatiguing illness. Presented at the American Association for Chronic Fatigue Syndrome Fourth International Research Conference. Cambridge, Mass., October 12, 1998. New England Med, in press.
38. Jason LA et al. A community-based study of chronic fatigue syndrome. Arch Int Med. 1999;159:2129-37.
39. Centers for Disease Control and Prevention: Chronic Fatigue Syndrome Program Review; Objective Surveillance. November 1999.
40. National Institute of Neurological Diseases and Stroke (NINDS): Multiple Sclerosis: Hope Through Research. National Institutes of Health, 1999 http://www.ninds.nih.gov/patients/Disorder/MS/MSTEXT1.HTM
41. National Institute of Allergy and Infectious Diseases (NIAID): Lupus Erythemafosus. National Institutes of Health, 1999: http://www.nih.gov/niarns/healthinfo/Iupusguide/chp1.htm
Dr. Komaroff is Professor of Medicine, Harvard Medical School, and Editor-in-Chief Harvard Health Publications, Boston, Mass.
This article appeared in the CFS Research Review, Spring 2000, Vol. 1 Issue 2, a quarterly newletter of the CFIDS Association of America. PO Box 220398, Charlotte, NC 28210. (704) 365-2343, and is copyright 2000 by the CFIDS Association of America.
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