CDC's head of CFS research Dr. Beth Unger said at last month's Chronic Fatigue Syndrome Advisory Committee meeting that she couldn't figure out how to measure post-exertional malaise (PEM)--the hallmark of ME--and thus believes problems would ensue if PEM is a mandatory symptom.
"My concern about making post-exertional malaise an absolute criteria for diagnosis is if you don't have a consistent, validated way of measuring it that clinicians can use easily, it's big barrier," Unger explained at the meeting. A few minutes later, when committee member Donna Pearson asked again about PEM being included in the criteria, Unger replied, "I think everybody agrees that it's very characteristic and a very important symptom, and clinicians will tell you that they can recognize it, they can elicit this information from patients, but to make that quantifiable and to make it easily implementable is another question...."
"My concern about making post-exertional malaise an absolute criteria for diagnosis is if you don't have a consistent, validated way of measuring it that clinicians can use easily, it's big barrier," Unger explained at the meeting. A few minutes later, when committee member Donna Pearson asked again about PEM being included in the criteria, Unger replied, "I think everybody agrees that it's very characteristic and a very important symptom, and clinicians will tell you that they can recognize it, they can elicit this information from patients, but to make that quantifiable and to make it easily implementable is another question...."
Several researchers have shown how to measure PEM. Cardiac pulmonary testing used by Dr. Chris Snell is one way, gene expression testing devised by Drs. Alan and Kathleen Light is another, comprehensive patient history is yet another, and using a pedometer like the Fitbit would also work. Dr. Jose Montoya conducted VO2 max studies with patients on the antiviral Valcyte to determine if their exercise tolerance improved on the antiviral. Unger's familiar with all of this. In fact, Unger is one of the authors of a 2012 paper, "Minimum data elements for research reports on CFS," in which the authors discuss how to measure PEM:
"As post-exertional malaise is a key symptom of all CFS case
definitions, it would be appropriate to measure the extent of activity and how
such activity might result in symptoms of fatigue and malaise. Light et al.
(2009) found patients with CFS demonstrated increases after exercise that
reliably exceeded responses of control subjects in mRNA for genes receptors that can detect muscle
produced metabolites, genes that are essential for sympathetic nervous system
processes, and immune function genes. The researchers concluded that CFS
patients might have enhanced sensory signal for fatigue that is increased after
exercise. Activity, or in work performed is generally quantified in terms of
energy used, i.e., caloric expenditure. Because this is difficult to measure
during activity, total oxygen consumption which increases in a similar fashion,
is typically used in its place.
"Sometimes represented as METs or metabolic equivalents, oxygen consumption may be assessed directly using cardiopulmonary exercise testing with measured gas exchange (Milani et al., 2006), or estimated from heart rate or other indicators of effort such as time and/or distance travelled. Assessment of effort is critical when exercise is used as a physiological stressor to elicit symptoms in CFS patients or for assessments of functional capacity as part of clinical trials. Heart rate as a percentage of age-predicted maximum is the most recognized indicator of subject effort for both maximal and submaximal exercise protocols. However, the maximal heart rate response to exercise varies widely in the general population (Balady et al., 2010) and has been shown to be blunted in some subjects with CFS (e.g., VanNess et al., 2003) and also in fibromyalgia (Ribeiro et al., 2011).
"As an alternative to heart rate, the peak respiratory exchange ratio (RER) is acknowledged as the most valid and reliable gauge of subject effort (Balady et al., 2010). Because it can only be obtained from ventilatory expired gas analysis, RER may not be available in all exercise studies. Similarly, submaximal exercise protocols do not provide for the measurement of peak RER. In such instances selecting alternative measures that can accurately assess effort both within and across subjects is particularly important."
In addition, in Table 2 in the paper, the authors cite actigraphy and pedometers for activity assessments.
"Sometimes represented as METs or metabolic equivalents, oxygen consumption may be assessed directly using cardiopulmonary exercise testing with measured gas exchange (Milani et al., 2006), or estimated from heart rate or other indicators of effort such as time and/or distance travelled. Assessment of effort is critical when exercise is used as a physiological stressor to elicit symptoms in CFS patients or for assessments of functional capacity as part of clinical trials. Heart rate as a percentage of age-predicted maximum is the most recognized indicator of subject effort for both maximal and submaximal exercise protocols. However, the maximal heart rate response to exercise varies widely in the general population (Balady et al., 2010) and has been shown to be blunted in some subjects with CFS (e.g., VanNess et al., 2003) and also in fibromyalgia (Ribeiro et al., 2011).
"As an alternative to heart rate, the peak respiratory exchange ratio (RER) is acknowledged as the most valid and reliable gauge of subject effort (Balady et al., 2010). Because it can only be obtained from ventilatory expired gas analysis, RER may not be available in all exercise studies. Similarly, submaximal exercise protocols do not provide for the measurement of peak RER. In such instances selecting alternative measures that can accurately assess effort both within and across subjects is particularly important."
In addition, in Table 2 in the paper, the authors cite actigraphy and pedometers for activity assessments.
Thus, Unger knows how to measure PEM. So why is CDC trying to bury PEM? After all, PEM is the most important symptom of the disease--and PEM distinguishes ME patients from people diagnosed with CFS who in reality are just depressed. But maybe that's the point. To lump bona fide ME patients in with the depressed. That way you don't get meaningful data or treatment, and the band plays on.
First, Unger nixed a two-day exercise test in favor of a one-day test, even though Dr. Chris Snell has shown PEM isn't apparent until the second day of testing. And now Unger can't figure how to measure PEM. If Unger is hung up a "consistent, validated way" of measuring PEM, she only has herself to blame for not having done a two-day exercise test after all these years. Leaving off PEM in the definition is like omitting elevated blood sugar in diabetes or a depressed CD4 count in AIDS.
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