Chronic Fatigue Syndrome – A Medical Mystery

Medical mysteries pop up every now and then that are either misdiagnosed or dismissed as either a psychosomatic or a psychological disorder. Chronic fatigue syndrome (CFS) is one of these mysteries and identification of a cause, or even whether the disease actually exists, continues to elude scientists. My previous post focused upon my own personal experience with CFS; in this post I would like to turn the focus to a brief history of CFS and an exploration of current medical studies.

CFS was first described in 1984 when a cluster of people in Nevada and California presented with the classic symptoms of unrelenting and debilitating fatigue unrelieved by sleep that had lasted for six months or more. In addition, these people had symptoms of muscle and joint pain, headaches, stomach and intestinal upset, and problems with memory, attention, and concentration. A diagnosis is made by a process of elimination since there are no physical signs or medical tests currently available to diagnose CFS.

During the first few years following the identification of CFS, much of the medical community and scientists held the belief that CFS was a psychosomatic manifestation of an underlying psychological disorder. Symptoms of CFS are similar to the neurasthenia seen and described by scientists over the past 200 years; these disorders have also been called neuralgia, chronic mononucleosis, myalgic encephalomyelitis, and post-viral fatigue.

CFS has been linked to Epstein-Barr virus and human herpesvirus 6; however, study results have not been conclusive and the presence of these viruses does not always result in the development of CFS. Depression has been a common diagnosis, with as many as 80% of people affected with CFS misdiagnosed.

A very large number of studies have been performed since 1984; most with inconclusive results. There are four studies that have been conducted in the past four years that stand out from the rest of the crowd:

The first study found that perforin, a protein found in natural killer cells and T cells, was much lower in people with CFS. Perforin is necessary to maintain a healthy immune system; a deficiency may contribute to the development of CFS, and the measurement of perforin may turn out to be a biomarker that can be used to diagnose CFS.

The second study found that the volume of gray matter in the brain was significantly lower in people with CFS. A positive correlation was found between the level of physical activity and the amount of gray matter; the lower the level of activity, the lower the volume of gray matter. The researchers concluded that the debilitating fatigue and memory, attention, and concentration problems experienced by people with CFS may be due to this change within the central nervous system.  

The third study was also concerned with the memory, concentration, and attention problems, and explored the similarity of these symptoms to people affected with D-lactic acidosis. Anaerobic bacteria in the gut produce high levels of lactic acid; levels of these bacteria were significantly higher in people with CFS with the result of higher levels of D-lactic acid. The researchers concluded that high D-lactic acid levels may also explain why mitochondria (the ‘power-house’ of cells) have been found to not function correctly in people with CFS. Measurement of D-lactic acid levels may prove to be of use as a clinical lab test for the diagnosis of CFS.

The final study held the belief that CFS is a condition caused by many factors. Cytokines are produced as a response to inflammation and their levels affect natural killer cell activity. Researchers found that cytokine levels are higher in people with CFS. T cells, which are involved in the immune response, are activated in abnormally high numbers, but lower levels of immunity at the cellular level were seen. A number of biomarkers were identified that are positively related to CFS; these biomarkers may possibly be used as a diagnostic test.

Other diseases were considered to be psychosomatic in the past before sophisticated diagnostic testing was developed and the underlying cause of the disease could be identified. Diabetes mellitus was considered to be a psychosomatic illness prior to the discovery of blood glucose and insulin and the negative effects an alteration in their balance had upon the human body. Scientific understanding of this disease was only possible once medicine and science had progressed and were able to develop sophisticated diagnostic testing methods.

Over 800,000 people in the United States and around 240,000 people in the United Kingdom are affected with CFS. The majority of the scientific community now acknowledges that CFS does actually exist. While scientists have not yet identified the underlying cause of CFS or a definitive diagnostic test; and still cannot agree whether CFS is an illness state or disease entity, those of us who are affected with this mysterious disorder can take comfort in the fact that scientists continue to search for answers to this mystery.


Daugherty SA et al. Chronic fatigue syndrome in northern Nevada. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S39-44. PMID: 1850542

Floris P. de Langea, Joke S. Kalkmanb, Gijs Bleijenbergb, Peter Hagoorta, Jos W.M. van der Meerc, & Ivan Tonia (2005). Gray matter volume reduction in the chronic fatigue syndrome NeuroImage, 26 (3), 777-781 DOI: 10.1016/j.neuroimage.2005.02.037

Griffith JP et al. A Systematic Review of Chronic Fatigue Syndrome: Don’t Assume it’s Depression. Prim Care Companion J Clin Psychiatry. 2008;10(2):120-8. PMID: 18458765

Lorusso L et al. Immunological aspects of chronic fatigue syndrome. Autoimmun Rev. 2009 Feb;8(4):287-91. Epub 2008 Sep 16. [doi] 10.1016/j.autrev.2008.08.003

Maher KJ et al. Chronic fatigue syndrome is associated with diminished intracellular perforin. Clin Exp Immunol. 2005 Dec;142(3):505-11. [doi] 10.1111/j.1365-2249.2005.02935.x

Sheedy JR et al. Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome. In Vivo. 2009 Jul-Aug;23(4):621-8. PMID: 19567398

Carolyn Starner, RN, BSN

Carolyn Starner, RN, BSN, is a freelance researcher, registered nurse, and writer, focusing on medicine and health-related topics. Her main areas of interest are geriatrics and public health education.
See All Posts By The Author