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

  • William Lu

    I wonder if the sleep disturbances experienced by CFS patients contribute to their cognitive deficits and pain as well. It seems like CFS patients share similar symptoms to that of Fibromyalgia syndrome patients. An interesting study by Lentz, Landis, Rothermel, and Shaver (1999) found that disrupting SWS in healthy female subjects for several consecutive nights led to symptoms of FMS. Other studies have suggested an association between a good nights rest and cognitive performance.

    Lentz, M. J., Landis, C. A., Rothermel, J., & Shaver, J. F. L. (1999). Effects of selective slow-wave sleep stage disruption on musculoskeletal pain and fatigue in middle-aged women. The Journal of Rheumatology, 26, 1586-1592.

  • Annabelle

    A great synopsis of the history of CFS. It’s wonderful that people are being educated about this debilitating illness. Thank you for spreading the word.


  • Ken Davis

    Some good points but you really need to get up to speed on this. There’s a lot more to the history and the science than you have indicated. Read Osler’s Web by Hilary Johnson. Read the proceedings from the last IACFS conference. There’s a lot more than 4 studies. There are thousands where the results are NOT inconclusive. The ones where the results ARE inconclusive is the Psychosomatic guff. Most of them exclude subjects who drop out – which is very convenient when you are trying to prove it is psychosomatic 🙂

  • Very good summary. One view of CFS is that it’s a conglomeration of multiple diseases that have similar clinical features. Others are looking for that one gene, infection or biochemical imbalance that is the common pathway towards CFS.

    Here’s one more alternate perspective: All modern humans by definition are susceptible to breathing problems at while sleeping due to our unique upper airway anatomy. Because of our ability to have complex speech and language, our upper airway is unprotected. Due to the location of our voice box below the tongue (rather than behind the tongue), the tongue can fall back easily into the oropharynx.

    Dr. Weston Price, in his classic book, Nutrition and Physical Degeneration, showed that modern human’s jaws are much more narrow with dental crowding. This is thought to be due to a major change in our diets to processed foods and malnutrition. There’s also a pretty convincing theory that bottle-feeding (another modern, Western invention) can also cause malocclusion and dental crowding.

    By definition, this constricts the upper airway even more. In everyone, the tongue falls back to some degree due to gravity, but when the jaw is smaller, it takes up relatively more space and the tongue can obstruct breathing when in deeper levels of sleep due to muscle relaxation. This can cause various degrees micro-obstruction and arousals, preventing you from staying in deep sleep. These obstructions are not long enough to be classified as an apnea, since you need to stop breathing for more than 10 seconds for this definition. In theory, you can stop breathing 20 times every hour and still have an apnea-hypopnea index of 0.

    Ultimately, these multiple obstructions and arousals causes a physiologic stress response that can lead to a relative sympathetic hyperactivity, with resulting lowering of one’s thyroid and reproductive hormone function, weight gain, lowering of your pain thresholds, microscopic stokes and clotting anywhere in the body (even in the brain), amongst many others.

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  • It is possible to recover from this, I did but it took a good 3 years. My full story is on my website.

  • CSD

    I wonder how many people with CFS actually have an underlying problem with Celiac Disease. Debilitating fatigue, muscle and joint pain, headaches, stomach and intestinal upset, and problems with memory, attention, and concentration are some of the classic but varied trademarks of this treatable, underdiagnosed autoimmune disorder. It’s certainly not the cause of everyone’s problems, but I hope that more people with CFS will be screened, since almost 1% of Americans have Celiac, currently most of them don’t know it, and it can look just like CFS (

    For CFS symptoms, I hope it becomes standard practice by all physicians screen for Celiac.

    I developed CFS-type symptoms when I became ill with EBV mono – I was never the same in terms of energy levels, mood, and even clarity of thought. Years later, when I developed the severe GI symptoms accociated with more progressed Celiac Disease, I was tested and diagnosed. In my case, the stress on my body from EBV probably triggered the disease almost a decade before I was finally diagnosed. I would love to see others get faster treatment though better screening and diagnosis. Celiac Disease might not be everyone’s silver bullet diagnosis, but it’s definitley worth checking, as diagnosis and treatment could change (or save!) the life of those struggling with its vague but debilitating symptoms.

  • bradford

    Interesting information on CFS. I was diagnosed with CFS and Fibromyalgia both of which were “I don’t know what’s wrong with you” diagnosis as I didn’t believe they existed. I found the study on the gray matter of the brain interesting. The doctors never suggested or coorelated it but I had an MRI of the Brain that showed lessening of the gray matter of my brain which meant nothing to me but sure is addressed here. Maybe there is something to this study that needs to be investigated further. Thanks

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.

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