exercise – Page 5 – American ME and CFS Society

Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue and postexertional malaise. We developed a provocation paradigm with two submaximal bicycle exercise stress tests on consecutive days bracketed by magnetic resonance imaging, orthostatic intolerance, and symptom assessments before and after exercise in order to induce objective changes of exercise induced symptom exacerbation and cognitive dysfunction.

Method: Blood oxygenation level dependent (BOLD) scans were performed while at rest on the preexercise and postexercise days in 34 ME/CFS and 24 control subjects. Seed regions from the FSL data library with significant BOLD signals were nodes that clustered into networks using independent component analysis. Differences in signal amplitudes between groups on pre- and post-exercise days were determined by general linear model and ANOVA.

Results: The most striking exercise-induced effect in ME/CFS was the increased spontaneous activity in the medial prefrontal cortex that is the anterior node of the Default Mode Network (DMN). In contrast, this region had decreased activation for controls. Overall, controls had higher BOLD signals suggesting reduced global cerebral blood flow in ME/CFS.

Conclusion: The dynamic increase in activation of the anterior DMN node after exercise may be a biomarker of postexertional malaise and symptom exacerbation in CFS. The specificity of this postexertional finding in ME/CFS can now be assessed by comparison to post-COVID fatigue, Gulf War Illness, fibromyalgia, chronic idiopathic fatigue, and fatigue in systemic medical and psychiatric diseases.

Source: Rayhan RU, Baraniuk JN. Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Neurosci. 2021 Dec 15;15:748426. doi: 10.3389/fnins.2021.748426. PMID: 34975370; PMCID: PMC8714840. https://www.frontiersin.org/articles/10.3389/fnins.2021.748426/full (Full text)

Markers of Cardiac Autonomic Function During Consecutive Day Peak Exercise Tests in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have been shown to exhibit altered ventilatory characteristics on the second of two progressive maximal cardiopulmonary exercise tests (CPET) performed on consecutive days. However, maximal exercise can exacerbate symptoms for ME/CFS patients and cause significant post-exertional malaise. Assessment of heart rate (HR) parameters known to track post-exertional fatigue may represent more effective physiological markers of the condition and could potentially negate the need for maximal exercise testing.

Sixteen ME/CFS patients and 10 healthy controls underwent a sub-maximal warm-up followed by CPET on two consecutive days. Ventilation, ratings of perceived exertion, work rate (WR) and HR parameters were assessed throughout on both days. During sub-maximal warm-up, a time effect was identified for the ratio of low frequency to high frequency power of HR variability (p=0.02) during sub-maximal warm-up, and for HR at ventilatory threshold (p=0.03), with both being higher on Day Two of testing. A significant group (p<0.01) effect was identified for a lower post-exercise HR recovery (HRR) in ME/CFS patients. Receiver operator characteristic curve analysis of HRR revealed an area under the curve of 74.8% (p=0.02) on Day One of testing, with a HRR of 34.5bpm maximising sensitivity (63%) and specificity (40%) suggesting while HRR values are altered in ME/CFS patients, low sensitivity and specificity limit its potential usefulness as a biomarker of the condition.

Source: Nelson MJ, Buckley JD, Thomson RL, Bellenger CR, Davison K. Markers of Cardiac Autonomic Function During Consecutive Day Peak Exercise Tests in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Physiol. 2021 Dec 14;12:771899. doi: 10.3389/fphys.2021.771899. PMID: 34970156; PMCID: PMC8713453. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8713453/ (Full text)

Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients. Although severe exercise intolerance is one of the core features of ME/CFS, little attempts have been made to study ANS responses to physical exercise. Therefore, impairments in ANS activation at rest and following exercise were examined using a case-control study in 20 ME/CFS patients and 20 healthy people.

Different autonomous variables, including cardiac, respiratory, and electrodermal responses were assessed at rest and following an acute exercise bout. At rest, parameters in the time-domain represented normal autonomic function in ME/CFS, while frequency-domain parameters indicated the possible presence of diminished (para)sympathetic activation. Reduced parasympathetic reactivation during recovery from exercise was observed in ME/CFS.

This is the first study showing reduced parasympathetic reactivation during recovery from physical exercise in ME/CFS. Delayed HR recovery and/or a reduced HRV as seen in ME/CFS have been associated with poor disease prognosis, high risk for adverse cardiac events, and morbidity in other pathologies, implying that future studies should examine whether this is also the case in ME/CFS and how to safely improve HR recovery in this population.

Source: Van Oosterwijck J, Marusic U, De Wandele I, Meeus M, Paul L, Lambrecht L, Moorkens G, Danneels L, Nijs J. Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Clin Med. 2021 Sep 30;10(19):4527. doi: 10.3390/jcm10194527. PMID: 34640544; PMCID: PMC8509376. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509376/ (Full text)

The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People

Abstract:

Background: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are unable to activate brain-orchestrated endogenous analgesia (or descending inhibition) in response to exercise. This physiological impairment is currently regarded as one factor explaining post-exertional malaise in these patients. Autonomic dysfunction is also a feature of ME/CFS.

Objectives: This study aims to examine the role of the autonomic nervous system in exercise-induced analgesia in healthy people and those with ME/CFS, by studying the recovery of autonomic parameters following aerobic exercise and the relation to changes in self-reported pain intensity.

Study design: A controlled experimental study.

Setting: The study was conducted at the Human Physiology lab of a University.

Methods: Twenty women with ME/CFS- and 20 healthy, sedentary controls performed a submaximal bicycle exercise test known as the Aerobic Power Index with continuous cardiorespiratory monitoring. Before and after the exercise, measures of autonomic function (i.e., heart rate variability, blood pressure, and respiration rate) were performed continuously for 10 minutes and self-reported pain levels were registered. The relation between autonomous parameters and self-reported pain parameters was examined using correlation analysis.

Results: Some relationships of moderate strength between autonomic and pain measures were found. The change (post-exercise minus pre-exercise score) in pain severity was correlated (r = .580, P = .007) with the change in diastolic blood pressure in the healthy group. In the ME/CFS group, positive correlations between the changes in pain severity and low frequency (r = .552, P = .014), and between the changes in bodily pain and diastolic blood pressure (r = .472, P = .036), were seen. In addition, in ME/CHFS the change in headache severity was inversely correlated (r = -.480, P = .038) with the change in high frequency heart rate variability.

Limitations: Based on the cross-sectional design of the study, no firm conclusions can be drawn on the causality of the relations.

Conclusions: Reduced parasympathetic reactivation during recovery from exercise is associated with the dysfunctional exercise-induced analgesia in ME/CFS. Poor recovery of diastolic blood pressure in response to exercise, with blood pressure remaining elevated, is associated with reductions of pain following exercise in ME/CFS, suggesting a role for the arterial baroreceptors in explaining dysfunctional exercise-induced analgesia in ME/CFS patients.

Source: Oosterwijck JV, Marusic U, De Wandele I, Paul L, Meeus M, Moorkens G, Lambrecht L, Danneels L, Nijs J. The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People. Pain Physician. 2017 Mar;20(3):E389-E399. PMID: 28339438. https://www.painphysicianjournal.com/linkout?issn=&vol=20&page=E389 (Full text)

Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study in Patients and Healthy Subjects

Abstract:

Purpose: Oxidative stress has been proposed as a contributor to pain in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). During incremental exercise in patients with ME/CFS, oxidative stress enhances sooner and antioxidant response is delayed. We explored whether oxidative stress is associated with pain symptoms or pain changes following exercise, and the possible relationships between oxidative stress and parasympathetic vagal nerve activity in patients with ME/CFS versus healthy, inactive controls.

Methods: The present study reports secondary outcomes from a previous work. Data from 36 participants were studied (women with ME/CFS and healthy controls). Subjects performed a submaximal exercise test with continuous cardiorespiratory monitoring. Levels of thiobarbituric acid–reactive substances (TBARSs) were used as a measure of oxidative stress, and heart rate variability was used to assess vagal activity. Before and after the exercise, subjects were asked to rate their pain using a visual analogic scale.

Findings: Significant between-group differences in pain at both baseline and following exercise were found (both, P < 0.007). In healthy controls, pain was significantly improved following exercise (P = 0.002). No change in oxidative stress level after exercise was found. Significant correlation between TBARS levels and pain was found at baseline (r = 0.540; P = 0.021) and after exercise (r = 0.524; P = 0.024) in patients only. No significant correlation between TBARS and heart rate variability at baseline or following exercise was found in either group. However, a significant correlation was found between exercise-induced changes in HRV and TBARS in healthy controls (r = −0.720; P = 0.001).

Implications: Oxidative stress showed an association with pain symptoms in people with ME/CFS, but no exercise-induced changes in oxidative stress were found. In addition, the change in parasympathetic activity following exercise partially accounted for the change in oxidative stress in healthy controls. More research is required to further explore this link.

Source: Andrea Polli, MSc, Jessica Van Oosterwijck, PhD, Jo Nijs, PhD, Greta Moorkens, PhD, Luc Lambrecht, MD, Kelly Ickmans, PhD. Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study in Patients and Healthy Subjects. Clinical Therapeutics. ORIGINAL RESEARCH| VOLUME 41, ISSUE 4, P641-655, APRIL 01, 2019. Published online: January 18, 2019. Accepted: December 14, 2018. DOI: https://doi.org/10.1016/j.clinthera.2018.12.012 https://www.clinicaltherapeutics.com/article/S0149-2918(18)30611-8/fulltext#secsectitle0010 (Full article)

Pain-related post-exertional malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia: A systematic review and three-level meta-analysis

Abstract:

Objective: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic musculoskeletal pain symptoms are prevalent. These individuals can experience post-exertional malaise (PEM), a phenomenon where symptom severity is worsened 24hr or longer following physical stress, but the pain-related component of PEM is not well characterized.

Design: Systematic review and meta-analysis.

Methods: Case-control studies involving adults with ME/CFS or FM and measuring pain symptoms before and after exposure to a standardized aerobic exercise test were included. Hedges’ d effect sizes were aggregated using random effects models and potential moderators were explored with meta-regression analysis. Results were adjusted for nesting effects using three-level modeling.

Results: Forty-five effects were extracted from 15 studies involving 306 patients and 292 healthy controls. After adjusting for nesting effects, we observed a small-to-moderate effect indicating higher post-exercise pain in patients than controls (Hedges’ d=0.42; 95% CI: 0.16, 0.67). The mean effect was significantly moderated by pain measurement timepoint (b = -0.19, z = -2.57, P = 0.01) such that studies measuring pain 8-72hr post-exercise showed larger effects (d = 0.71, 95% CI = 0.28-1.14) than those measuring pain 0-2hr post-exercise (d = 0.32, 95% CI = 0.10-0.53).

Conclusions: People with ME/CFS and FM experience small-to-moderate increases in pain severity following exercise which confirms pain as a component of PEM and emphasizes its debilitating impact in ME/CFS and FM. Future directions include determining mechanisms of pain-related PEM and developing exercise prescriptions that minimize symptom exacerbation in these illnesses.

Source: Barhorst EE, Boruch AE, Cook DB, Lindheimer JB. Pain-related post-exertional malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia: A systematic review and three-level meta-analysis. Pain Med. 2021 Oct 20:pnab308. doi: 10.1093/pm/pnab308. Epub ahead of print. PMID: 34668532. https://pubmed.ncbi.nlm.nih.gov/34668532/

Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Humility and Acceptance: Working Within Our Limits With Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Synopsis:
The term long COVID was coined by patients to describe the long-term consequences of COVID-19. One year into the pandemic, it was clear that all patients—those hospitalized with COVID-19 and those who lived with the disease in the community—were at risk of developing debilitating sequelae that would impact their quality of life. Patients with long COVID asked for rehabilitation. Many of them, including previously healthy and fit clinicians, tried to fight postviral fatigue with exercise-based rehabilitation. We observed a growing number of patients with long COVID who experienced adverse effects from exercise therapy and symptoms strikingly similar to those of myalgic encephalomyelitis (ME). Community-based physical therapists, including those in private practice, unaware of safety issues, are preparing to help an influx of patients with long COVID. In this editorial, we expose growing concerns about long COVID and ME. We issue safety recommendations for rehabilitation and share resources to improve care for those with postviral illnesses. J Orthop Sports Phys Ther 2021;51(5):197–200. doi:10.2519/jospt.2021.0106

Source: Simon Décary, Isabelle Gaboury, Sabrina Poirier, Christiane Garcia, Scott Simpson, Michelle Bull, Darren Brown, and Frédérique Daigle. Humility and Acceptance: Working Within Our Limits With Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Orthopaedic & Sports Physical Therapy 2021 51:5, 197-200. https://www.jospt.org/doi/10.2519/jospt.2021.0106

Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Evidence is emerging that individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may suffer from chronic vascular dysfunction as a result of illness-related oxidative stress and vascular inflammation. The study aimed to examine the impact of maximal-intensity aerobic exercise on vascular function 48 and 72 h into recovery.

Methods: ME/CFS (n = 11) with gender and age-matched controls (n = 11) were randomly assigned to either a 48 h or 72 h protocol. Each participant had measures of brachial blood pressure, augmentation index (AIx75, standardized to 75 bpm) and carotid-radial pulse wave velocity (crPWV) taken. This was followed by a maximal incremental cycle exercise test. Resting measures were repeated 48 or 72 h later (depending on group allocation).

Results: No significant differences were found when ME/CFS were directly compared to controls at baseline. During recovery, the 48 h control group experienced a significant 7.2% reduction in AIx75 from baseline measures (p < 0.05), while the matched ME/CFS experienced no change in AIx75. The 72 h ME/CFS group experienced a non-significant increase of 1.4% from baseline measures. The 48 h and 72 h ME/CFS groups both experienced non-significant improvements in crPWV (0.56 ms−1 and 1.55 ms−1, respectively).

Conclusions: The findings suggest that those with ME/CFS may not experience exercise-induced vasodilation due to chronic vascular damage, which may be a contributor to the onset of post-exertional malaise (PEM).

Source: Bond J, Nielsen T, Hodges L. Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. International Journal of Environmental Research and Public Health. 2021; 18(5):2366. https://doi.org/10.3390/ijerph18052366 https://www.mdpi.com/1660-4601/18/5/2366/htm (Full text)

Exercise modifies glutamate and other metabolic biomarkers in cerebrospinal fluid from Gulf War Illness and Myalgic encephalomyelitis / Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) share many symptoms of fatigue, pain, and cognitive dysfunction that are not relieved by rest. Patterns of serum metabolites in ME/CFS and GWI are different from control groups and suggest potential dysfunction of energy and lipid metabolism. The metabolomics of cerebrospinal fluid was contrasted between ME/CFS, GWI and sedentary controls in 2 sets of subjects who had lumbar punctures after either (a) rest or (b) submaximal exercise stress tests. Postexercise GWI and control subjects were subdivided according to acquired transient postexertional postural tachycardia. Banked cerebrospinal fluid specimens were assayed using Biocrates AbsoluteIDQ® p180 kits for quantitative targeted metabolomics studies of amino acids, amines, acylcarnitines, sphingolipids, lysophospholipids, alkyl and ether phosphocholines.

Glutamate was significantly higher in the subgroup of postexercise GWI subjects who did not develop postural tachycardia after exercise compared to nonexercise and other postexercise groups. The only difference between nonexercise groups was higher lysoPC a C28:0 in GWI than ME/CFS suggesting this biochemical or phospholipase activities may have potential as a biomarker to distinguish between the 2 diseases. Exercise effects were suggested by elevation of short chain acylcarnitine C5-OH (C3-DC-M) in postexercise controls compared to nonexercise ME/CFS. Limitations include small subgroup sample sizes and absence of postexercise ME/CFS specimens. Mechanisms of glutamate neuroexcitotoxicity may contribute to neuropathology and “neuroinflammation” in the GWI subset who did not develop postural tachycardia after exercise. Dysfunctional lipid metabolism may distinguish the predominantly female ME/CFS group from predominantly male GWI subjects.

Source: Baraniuk JN, Kern G, Narayan V, Cheema A. Exercise modifies glutamate and other metabolic biomarkers in cerebrospinal fluid from Gulf War Illness and Myalgic encephalomyelitis / Chronic Fatigue Syndrome. PLoS One. 2021 Jan 13;16(1):e0244116. doi: 10.1371/journal.pone.0244116. PMID: 33440400. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244116 (Full text)