Fort Lauderdale, FL — New research focused on the phenomenon of postexertional malaise (PEM) is shedding light on the etiology of the illness that has been known as chronic fatigue syndrome, but is now increasingly termed myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
A growing body of evidence, including new findings presented here at the recent International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFSME) research and clinical conference, suggests ME/CFS arises from a complex neuroinflammatory process affecting the brain, autonomic nervous system, and energy metabolism, involving oxidative and nitrosative stress.
The name "chronic fatigue syndrome" is being phased out not just because it is viewed as trivializing a condition that renders many patients completely or nearly bedbound but also because it gives the misleading impression that the illness is characterized simply by prolonged unexplained fatigue. In fact, ME/CFS is characterized by multiple heterogeneous symptoms, with PEM, often described as a "crash" or a significant worsening of already-present symptoms, being a near-universal experience.
"Many studies show that physical exertion can help with insomnia in healthy people, and even people with other medical conditions such as depression, anxiety, or even heart failure. But in ME/CFS patients, physical exertion exacerbates their symptoms," conference cochair Lily Chu, MD, from Stanford University, Palo Alto, California, told Medscape Medical News.
"The way these patients present is very different from healthy people or people with other medical conditions."
Indeed, recent diagnostic criteria for the illness, including the February 2015 Institute of Medicine report, require PEM among other symptoms to make the diagnosis of ME or ME/CFS as opposed to older definitions of CFS. However, the Centers for Disease Control and Prevention continues to endorse a 1994 CFS definition that lists PEM as an optional criterion, but does not make it mandatory for the diagnosis.
What Is PEM?
At the IACFSME conference, Dr Chu presented findings from her group's study of 150 patients diagnosed with the 1994 criteria who completed a survey about their symptoms after physical or cognitive exertion or emotional distress.
The majority (89%) reported experiencing PEM after both types of triggers, but 10% reported no effect after emotional distress, whereas overall physical exertion elicited significantly more symptoms than did emotional distress (seven vs five; P < .001).
Although fatigue was the most commonly exacerbated symptom, more than 30% of patients also reported cognitive difficulties, sleep disturbance, headache, muscle pain, and influenza-like feelings. Some also reported gastrointestinal, orthostatic, and mood-related exacerbations.
Timing and duration of symptoms varied among respondents and per respondent, but 11% reported a consistent posttrigger delay of at least 24 hours, whereas 23% said that their symptoms typically lasted for 3 or more days.
"PEM consists of more than just fatigue and pain. It's an exacerbation of multiple symptoms, some of which are atypically associated with exertion," Dr Chu told Medscape Medical News.
She added, "PEM can be difficult for clinicians and patients to identify. We suggest patients keep a diary for a week or two, documenting symptoms and activity so we can look at and see relationship of activity and timing, duration, and intensity of symptoms."
Studies Document Biological Correlates of PEM
Not surprisingly, much of the clinical research into ME/CFS has focused on provocation studies, in which patients exercise or are subjected to other stressors in a laboratory setting and various biological responses are measured. The following were among such research papers presented at the IACFSME conference:
Jose Montoya, MD, professor of medicine at Stanford University, reported identifying a set of 15 cytokines and growth factors that changed significantly 24 hours after maximal ergo cycle exercise testing in 25 patients with ME/CFS compared with in 25 healthy volunteers. The groups were matched for baseline sedentary behavior, age, and body mass index. The cytokines that most differed between the patients and controls were interleukin 1-beta, platelet activator inhibitor 1, CD-40 ligand, MIP-1alpha, and interferon-gamma.
Dane B. Cook, PhD, professor of kinesiology at the University of Wisconsin in Madison, compared functional brain imaging performed during fatiguing and nonfatiguing cognitive and motor tasks in 15 patients with ME/CFS and 15 sedentary matched control participants. The patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain compared with control participants (P < .05). And although those in the control group improved on cognitive performance after exercise compared with before, the opposite occurred among those in the patient group (P < .05). For the fatiguing cognitive task, the patients exhibited increased brain activity from pretask to posttask compared with control participants, and changes in brain activity significantly correlated with reported symptoms (P < .05).
"These converging results, linking symptom exacerbation with brain function, illustrate some of the potential detrimental effects of PEM for ME/CFS patients," Dr Cook said.Katarina Lien, MD, PhD, a research fellow at the University of Oslo in Norway, presented data for 18 female patients with ME/CFS and 15 healthy sedentary control participants, all aged 18 to 50 years, who performed two cardiopulmonary exercise testing sessions 24 hours apart. Arterial blood lactate levels per work rate were higher in the patients than in the controls on both test days (Pinteraction < .001).
Lactate accumulation on test day 2 occurred earlier in the patients than on day 1, whereas the opposite was the case for the controls (P interaction < .001). At test 1, mean peak VO2 was lower in patients than in control participants (24.2 vs 36.6 mL/kg/minute; P < .001). Mean difference in test–retest peak VO2 was −1.4 among the patients (P < .001), whereas there was no significant change in the controls (−0.9; P = .07).J. Mark Van Ness, PhD, a scientific advisory committee member at the Workwell Foundation in Ripon, California, presented a study of 39 patients with ME/CFS and 39 control participants who performed a graded exercise test to volitional fatigue on a cycle ergometer. A subset of 17 patients and 18 control participants performed a second exercise test 24 hours later. Heart rate, measured continuously throughout both tests, did not differ between the two groups after the first test, or between the first and second tests in the control group. However, peak heart rate was significantly lower on test 2 compared with on test 1 in the ME/CFS group (P < .05).
"Patients with ME/CFS appear to display postexertional reductions in the peak heart rate response to exercise, which could contribute to exercise intolerance and observed reductions in oxygen consumption during [PEM]. The combination of elevation in heart rate and reduction in peak exercise heart rate may contribute to impaired quality of life," Dr Van Ness concluded.
The presenters have disclosed no relevant financial relationships.
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Cite this: Postexertion 'Crash,' not Fatigue per se, Marks Syndrome - Medscape - Nov 04, 2016.
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