An Interesting Hypothesis

By Suzanne Vernon, PhD, Scientific Director

As scientists, we have the luxury and obligation to look at the world around us, contemplate, generate hypotheses and experiment. I particularly like this sequence of events because astute observations can be the foundation for some of the best experiments.

I never really appreciated the power of “observational science” until I worked with Dr. Elizabeth (Beth) Unger at the Centers for Disease Control and Prevention. Unger is a pathologist – a doctor who can make a diagnosis by looking at (observing) various body parts. Pathologists like Unger are a testament to the power of observational science. So it’s with interest that I read scientific publications like the journal Medical Hypothesis.

The April 2008 issue of Medical Hypotheses includes a paper by Dr. Bjorn Grinde titled “Is chronic fatigue syndrome caused by a rare brain infection of a common, normally benign virus?” Dr. Grinde is from the Institute of Public Health in Oslo, Norway. Many of his published work deals with infectious disease epidemiology, and it is likely that this experience—coupled with his interest in human and molecular evolution—inspired him to pose this particular hypothesis.

Dr. Grinde proposes that CFS is caused by an infection of the central nervous system (CNS) and that the infection is more likely from a virus rather than bacteria. He mentions how it has been difficult to distinguish between cause and effect in CFS, but that viral infection of the CNS offers a parsimonious explanation. Specifically, that viral infection causes CFS and results in immune and endocrine dysfunction, HPA disturbance, oxidative stress and other factors that can be ascribed as secondary effects of the viral infection.

Rather than the infection being from a novel virus, Dr. Grinde explains how the epidemiologic picture of CFS is more conducive to common viruses as the culprit. Herpesviruses, enteroviruses, parvoviruses, circoviruses and polyomaviruses are all common viruses present in healthy human and animal populations. It is important to note that most common viruses do not cause disease. Instead, infection is most often subclinical, with the body’s immune system either eliminating the pathogen or keeping it in check. Dr. Grinde hypothesizes that, occasionally, common viruses can breach the blood-brain barrier, infect the brain and cause CFS. The blood-brain barrier usually protects the brain from infection, but sometimes this barrier can be weakened and viruses not normally present in the CNS can gain entry.

Testing this hypothesis would involve looking for these viruses in cerebral spinal fluid—the liquid that bathes the CNS. Dr. Grinde contends that looking for these viruses in the blood is not worthwhile since they are common to most people, and it would be difficult to assign causality. If common viruses occasionally infect the brain and cause CFS, the suspect viruses would be detected in the cerebral spinal fluid. There are very sensitive molecular approaches that can be used to find and characterize viruses. The main hurdle to testing this hypothesis is getting cerebral spinal fluid, which requires a spinal tap—a very invasive and expensive procedure that is not without risk.

With the renewed interest and research into infectious and particularly viral causes of CFS, this is a timely and tantalizing hypothesis paper. Not all viruses are pathogens but with a certain combination of genetic vulnerability and environmental events, common viruses can become pathogenic. This paper provides a number of examples, observations and explanations of why virus infection of the brain is a plausible hypothesis in CFS.


Grinde B. Is chronic fatigue syndrome caused by a rare brain infection of a common, normally benign virus? Medical Hypotheses. 2008 Apr 24. [Epub ahead of print]

Disclaimer: This summary is intended to inform our readership of the latest in CFS research. Opinions, findings and conclusions reported in peer-reviewed articles are those of the authors and do not necessarily represent the views of the scientific director and the Solve ME/CFS Initiative .

Suzanne Vernon, PhD, is the Association’s scientific director. She has nearly two decades of experience as a microbiologist.

May 1, 2008