Comparing Post-Exertional Symptoms following serial exercise tests

Abstract/Artist Statement:

Post-exertional malaise (PEM) is an exacerbation of symptoms that leads to a reduction in functional ability. Recognizing the triggers, onset, symptoms and duration of PEM is important for the diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). PEM following serial exercise tests has not been examined.

PURPOSE: To compare descriptions of symptoms by ME/CFS and control subjects after two maximal exercise tests, each separated by 24 hours.

METHODS: Open-ended questionnaires were provided to 10 control subjects and 49 ME/CFS patients who underwent two maximal exercise tests, 24 hours apart. Each subject evaluated how they felt immediately after the first exercise test, before and immediately after the second exercise test, 24 hours after the second exercise test and in the week following the tests. Responses were analyzed and categorized by two reviewers, blinded to subject diagnosis.

RESULTS: Over the two days of testing, ME/CFS subjects reported an average of 15.4±7.7 symptoms compared to 5.5±1.8 in the control group. Following the tests, ME/CFS subjects reported an average of 5.0±2.8 symptoms compared to 0.1±0.3 in the control group. Among the ME/CFS subjects, fatigue, cognitive dysfunction, and sleep problems were reported with the greatest frequency. Out of the eighteen symptom categories, ME/CFS subjects reported seventeen at a higher frequency than control subjects. The largest differences were observed in cognitive dysfunction, headache, light-headedness, muscle/joint pain and weakness. Other symptoms included decreased function, pain, flu-like and gastrointestinal symptoms. Forty-nine percent of ME/CFS subjects recovered within an average of 4.5 days while fifty-one percent had not recovered by day seven. In contrast, all but one control subject recovered within 1 day.

CONCLUSION: A standardized exertional stimulus produces prolonged and more diverse symptoms in ME/CFS subjects compared with those seen in control subjects. Understanding PEM more comprehensively may provide clues to the underlying pathophysiology of ME/CFS and lead to improved diagnosis and treatment.

Source: Lariel J. Mateo, University of the Pacific. Comparing Post-Exertional Symptoms following serial exercise tests. Poster presentation, April 4, 2018. https://scholarlycommons.pacific.edu/purcc/2018/events/87/

A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition

Abstract:

BACKGROUND: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with profound fatigue, flu-like symptoms, pain, cognitive impairment, orthostatic intolerance, and post-exertional malaise (PEM), and exacerbation of some or all of the baseline symptoms.

CASE REPORT: We report on a pair of 34-year-old monozygotic twins discordant for ME/CFS, with WELL, the non-affected twin, and ILL, the affected twin. Both twins performed a two-day cardiopulmonary exercise test (CPET), pre- and post-exercise blood samples were drawn, and both provided stool samples for biochemical and molecular analysis. At peak exertion for both CPETs, ILL presented lower VO2peak and peak workload compared to WELL.

WELL demonstrated normal reproducibility of VO2@ventilatory/anaerobic threshold (VAT) during  CPET2, whereas ILL experienced an abnormal reduction of 13% in VAT during  CPET2. A normal rise in lactate dehydrogenase (LDH), creatine kinase (CK), adrenocorticotropic hormone (ACTH), cortisol, creatinine, and ferritin content was observed following exercise for both WELL and ILL at each CPET.

ILL showed higher increases of resistin, soluble CD40 ligand (sCD40L), and soluble Fas ligand (sFasL) after exercise compared to WELL. The gut bacterial microbiome and virome were examined and revealed a lower microbial diversity in ILL compared to WELL, with fewer beneficial bacteria such as Faecalibacterium and Bifidobacterium, and an expansion of bacteriophages belonging to the tailed dsDNA Caudovirales order.

CONCLUSIONS: Results suggest dysfunctional immune activation in ILL following exercise and that prokaryotic viruses may contribute to mucosal inflammation and bacterial dysbiosis. Therefore, a two-day CPET and molecular analysis of blood and microbiomes could provide valuable information about ME/CFS, particularly if applied to a larger cohort of monozygotic twins.

 

Source: Giloteaux L, Hanson MR, Keller BA. A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition. Am J Case Rep. 2016 Oct 10;17:720-729. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058431/ (Full article)

 

Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment

Abstract:

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multi-system illness characterized, in part, by increased fatigue following minimal exertion, cognitive impairment, poor recovery to physical and other stressors, in addition to other symptoms. Unlike healthy subjects and other diseased populations who reproduce objective physiological measures during repeat cardiopulmonary exercise tests (CPETs), ME/CFS patients have been reported to fail to reproduce results in a second CPET performed one day after an initial CPET. If confirmed, a disparity between a first and second CPET could serve to identify individuals with ME/CFS, would be able to document their extent of disability, and could also provide a physiological basis for prescribing physical activity as well as a metric of functional impairment.

METHODS: 22 subjects diagnosed with ME/CFS completed two repeat CPETs separated by 24 h. Measures of oxygen consumption (VO₂), heart rate (HR), minute ventilation (Ve), workload (Work), and respiratory exchange ratio (RER) were made at maximal (peak) and ventilatory threshold (VT) intensities. Data were analyzed using ANOVA and Wilcoxon’s Signed-Rank Test (for RER).

RESULTS: ME/CFS patients showed significant decreases from CPET1 to CPET2 in VO₂peak (13.8%), HRpeak (9 bpm), Ve peak (14.7%), and Work@peak (12.5%). Decreases in VT measures included VO₂@VT (15.8%), Ve@VT (7.4%), and Work@VT (21.3%). Peak RER was high (≥1.1) and did not differ between tests, indicating maximum effort by participants during both CPETs. If data from only a single CPET test is used, a standard classification of functional impairment based on VO₂peak or VO₂@VT results in over-estimation of functional ability for 50% of ME/CFS participants in this study.

CONCLUSION: ME/CFS participants were unable to reproduce most physiological measures at both maximal and ventilatory threshold intensities during a CPET performed 24 hours after a prior maximal exercise test. Our work confirms that repeated CPETs warrant consideration as a clinical indicator for diagnosing ME/CFS. Furthermore, if based on only one CPET, functional impairment classification will be mis-identified in many ME/CFS participants.

 

Source: Keller BA, Pryor JL, Giloteaux L. Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment. J Transl Med. 2014 Apr 23;12:104. doi: 10.1186/1479-5876-12-104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004422/ (Full article)

 

Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome

Abstract:

BACKGROUND: Reduced functional capacity and postexertion fatigue after physical activity are hallmark symptoms of chronic fatigue syndrome (CFS) and may even qualify for biomarker status. That these symptoms are often delayed may explain the equivocal results for clinical cardiopulmonary exercise testing in people with CFS. Test reproducibility in people who are healthy is well documented. Test reproducibility may not be achievable in people with CFS because of delayed symptoms.

OBJECTIVE: The objective of this study was to determine the discriminative validity of objective measurements obtained during cardiopulmonary exercise testing to distinguish participants with CFS from participants who did not have a disability but were sedentary.

DESIGN: A prospective cohort study was conducted.

METHODS: Gas exchange data, workloads, and related physiological parameters were compared in 51 participants with CFS and 10 control participants, all women, for 2 maximal exercise tests separated by 24 hours.

RESULTS: Multivariate analysis showed no significant differences between control participants and participants with CFS for test 1. However, for test 2, participants with CFS achieved significantly lower values for oxygen consumption and workload at peak exercise and at the ventilatory or anaerobic threshold. Follow-up classification analysis differentiated between groups with an overall accuracy of 95.1%.

LIMITATIONS: Only individuals with CFS who were able to undergo exercise testing were included in this study. Individuals who were unable to meet the criteria for maximal effort during both tests, were unable to complete the 2-day protocol, or displayed overt cardiovascular abnormalities were excluded from the analysis.

CONCLUSIONS: The lack of any significant differences between groups for the first exercise test would appear to support a deconditioning hypothesis for CFS symptoms. However, the results from the second test indicated the presence of CFS-related postexertion fatigue. It might be concluded that a single exercise test is insufficient to reliably demonstrate functional impairment in people with CFS. A second test might be necessary to document the atypical recovery response and protracted fatigue possibly unique to CFS, which can severely limit productivity in the home and workplace.

 

Source: Snell CR, Stevens SR, Davenport TE, Van Ness JM.Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome. Phys Ther. 2013 Nov;93(11):1484-92. doi: 10.2522/ptj.20110368. Epub 2013 Jun 27. https://academic.oup.com/ptj/article/93/11/1484/2735315/Discriminative-Validity-of-Metabolic-and-Workload?searchresult=1 (Full article)