The Hallmark of CFS

By Suzanne D. Vernon, PhD, Scientific Director

Over the years, there have been at least six published definitions for CFS. For research, the 1994 definition by Fukuda et al. is presently the “standard.” The 2003 Canadian Clinical Definition for ME/CFS was the first one written specifically for use by practicing health care professionals seeing patients. Both require a thorough clinical evaluation and medical history to rule out possible conditions that could explain the patient’s symptoms. Both require a disabling degree of fatigue that substantially reduces the patient’s ability to do physical and mental activity. A key difference between these two definitions is that the Canadian definition identifies post-exertional malaise/fatigue (PEM) as a required symptom, whereas the Fukuda definition makes PEM “optional,” as one of eight case-identifying symptoms. Four of those eight symptoms must be present for a case to be considered CFS under the Fukuda research criteria.

Why this distinction? The authors of the Canadian clinical definition describe post-exertional malaise in detail, emphasizing the long recovery period ME/CFS patients require. They include a chart showing the response to exercise of healthy people compared to ME/CFS patients. Few diseases have the characteristic post-exertion “crash” that CFS does, making it a hallmark symptom. Indeed, studies by the Pacific Fatigue Laboratory at the University of the Pacific have shown that the exercise physiology of CFS patients is quite different from and, in many ways, worse than people with cardiovascular disease. In a paper published in the Journal of Women’s Health, the Pacific Fatigue Laboratory and collaborators examine the perceptions of CFS patients following exercise. Dr. Mark VanNess and colleagues determined that the post-exertional malaise was both real and incapacitating for the women with CFS whom they studied and that it was not attributed to fear of exercise or deconditioning. This is not surprising to those of you who experience post-exertional malaise, but (believe it or not) this has been a controversial topic in the medical and research world. Let’s look more closely at what this group of researchers did.


This study included 25 women with CFS and 23 age-matched sedentary controls. There were no significant differences in the age, weight and height between CFS patients and controls. Each participated in an exercise test where they pedaled a bicycle ergometer until voluntary exhaustion and met criterion for maximal effort. For seven days following the exercise challenge, participants were asked to describe their symptoms in writing and to complete a survey called the Short Form-36 (SF-36) to measure self-perceived health status. Responses revealed that zero CFS patients recovered within 24 hours after the exercise challenge, compared to 85 percent of the sedentary controls. Forty-eight hours later, one CFS patient and the remaining controls reported complete recovery. Fifteen of the 25 CFS patients took more than five days to recover. The control subjects reported feeling energized and revitalized from the exercise. The CFS patients described extreme fatigue, pain, weakness and dizziness. The CFS patients reported lower SF-36 health status on physical and mental scales, but the mental assessments of emotion and mental health were not significantly different from controls. CFS subjects’ written descriptions indicated physiologic, rather than psychologic, effects of the exercise challenge. This post-exercise physiology is an indicator of the pathology of CFS and the authors suggest caution with exercise so that exercise benefits rather than harms.

Exercise challenge is a powerful paradigm for studying CFS because the exertion induces the hallmark post-exertion symptoms. While exercise studies are very difficult for CFS patients to participate in, it is an important study method that “levels the field.” Using an exercise challenge can effectively “calibrate” CFS subjects to the same degree of illness severity as one another and usually provoke differences between healthy and disease group controls that aren’t as easily seen under normal “at-rest” conditions. This increases the chance of identifying markers or causes – not only for the induced state of post-exertional malaise, but of CFS itself.

In addition to providing funding for the VanNess study described above (in an earlier grants cycle), the Solve ME/CFS Initiative currently funds two other studies that use an exercise challenge to identify objective markers for CFS diagnosis and treatment. Kathy Light, PhD, of the University of Utah Health Sciences Centers uses a moderate exercise challenge to identify specific CFS markers on the blood that can be used for objective diagnosis and to evaluate effectiveness of treatment. Sanjay Shukla, PhD, a microbiologist at the Marshfield Clinic Research Foundation, uses an exercise challenge to determine if gut bacteria are different in CFS patients compared to normal controls and if they cross the gut into the blood stream to cause post-exertional malaise. These are all examples of the mission-oriented research the Solve ME/CFS Initiative supports to accelerate progress toward objective diagnosis and effective treatments for CFS.


Vanness JM, Stevens SR, Bateman L, Stiles TL, Snell CR.  Postexertional Malaise in Women with Chronic Fatigue Syndrome.  J Womens Health (Larchmt). 2010 Jan 24. [Epub ahead of print]

Note: Dr. VanNess and colleagues collected a considerable amount of data during the study; this is just one publication arising from it. One of the study’s aims was to “characterize the physical, cognitive, immune, metabolic, cardiovascular, and neuroendocrine profiles of CFIDS patients during conditions of post-exertional malaise,” and they are working on other manuscripts for publication.

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

February 3, 2010