Tag: post-exertional malaise

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/

Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS

Abstract:

Background: Skeletal muscle fatigue and post-exertional malaise are key symptoms of Myalgic Encephalomyelitis (ME/CFS). We have previously shown that AMPK activation and glucose uptake are impaired in primary human skeletal muscle cell cultures derived from patients with ME/CFS in response to electrical pulse stimulation, a method which induces contraction of muscle cells in vitro. The aim of this study was to assess if AMPK could be activated pharmacologically in ME/CFS.

Methods: Primary skeletal muscle cell cultures from patients with ME/CFS and healthy controls were treated with either metformin or 991. AMPK activation was assessed by Western blot and glucose uptake measured.

Results: Both metformin and 991 treatment significantly increased AMPK activation and glucose uptake in muscle cell cultures from both controls and ME/CFS. Cellular ATP content was unaffected by treatment although ATP content was significantly decreased in ME/CFS compared to controls.

Conclusions: Pharmacological activation of AMPK can improve glucose uptake in muscle cell cultures from patients with ME/CFS. This suggests that the failure of electrical pulse stimulation to activate AMPK in these muscle cultures is due to a defect proximal to AMPK. Further work is required to delineate the defect and determine whether pharmacological activation of AMPK improves muscle function in patients with ME/CFS.

Source: Brown AE, Dibnah B, Fisher E, Newton JL, Walker M. Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS. Biosci Rep. 2018 Apr 13. pii: BSR20180242. doi: 10.1042/BSR20180242. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29654166/

 

Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model

Abstract:

Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease.

A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension.

A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.

Source: Jonas Blomberg, Gerhard Gottfries, Amal Elfaitouri, Muhammad Rizwan and Anders Rosén. Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model. Hypothesis and Theory Article, Front. Immunol., 15 February 2018 | https://doi.org/10.3389/fimmu.2018.00229 (Full article)

Cerebral Blood Flow and Heart Rate Variability in Chronic Fatigue Syndrome: A Randomized Cross-Over Study

Abstract:

BACKGROUND: Pain, fatigue, and concentration difficulties are typical features of chronic fatigue syndrome (CFS). The exact underlying mechanisms of these symptoms are still unknown, but available evidence suggests an important role for impaired pain modulation. As evidence also suggests that pain modulation is related to cardiovascular mechanisms, it seems logical to investigate whether cerebral blood flow (CBF) and heart rate variability (HRV) are altered in these patients.

OBJECTIVES: We aimed to investigate the role of the cardiovascular system in pain modulation and symptoms of CFS; the response of CBF and HRV to physical stress and their relation to the change in temporal summation (TS) of pressure pain and self-reported symptoms was evaluated.

STUDY DESIGN: A controlled, randomized cross-over trial.

SETTING: University Hospital Brussels.

METHODS: Twenty CFS patients and 20 sedentary healthy controls were included in this study. In both of the groups, the change in TS of pressure pain, CBF (using transcranial Doppler), and HRV (using finger plethysmography) was examined during physical and emotional stress (to control for potential bias), as well as their association mutually and with self-reported symptoms of pain, fatigue, and concentrations difficulties.

RESULTS: There was no significant interaction or group (F-values ranging from .100 to 1.862, P-values ranging from .754 to .181) effect in CBF or HRV parameters. HRV and CBF did change during physical exercise, but the changes did not differ between patients and controls. While pain scores during TS at the trapezius site reduced in the control group after the physical exercise protocol (P = .037), they did not change in the CFS group (P = .108), suggesting impaired pain modulation. There were no significant correlations between CBF, HRV, TS, and self-reported symptoms (all P-values of correlation analyses > .01).

LIMITATIONS: Although effect sizes were medium to large, the study sample was relatively low. Also, the mild nature of the exercise bout is discussable. Nonetheless, this mild exercise was able to provoke endogenous pain modulation in the control group, which endorsed a proper execution of the cycling exercise. Moreover, mild exercises are more applicable to daily physical activities in CFS patients than vigorous exercises.

CONCLUSION: These results seem to refute the previously suggested alterations of CBF/HRV in CFS patients. These cardiovascular parameters appear not to explain pain before, during, and following exercise.

Source: Malfliet A, Pas R, Brouns R, De Win J, Hatem SM, Meeus M, Ickmans K, van Hooff RJ, Nijs J. Cerebral Blood Flow and Heart Rate Variability in Chronic Fatigue Syndrome: A Randomized Cross-Over Study. Pain Physician. 2018 Jan;21(1):E13-E24. https://www.ncbi.nlm.nih.gov/pubmed/29357332 Full article can be viewed as a PDF here: http://www.painphysicianjournal.com/current/pdf?article=NTAwOA%3D%3D&journal=109

Energy envelope maintenance among patients with myalgic encephalomyelitis and chronic fatigue syndrome: Implications of limited energy reserves

Abstract:

Objective: The Energy Envelope Theory of myalgic encephalomyelitis and chronic fatigue syndrome postulates that individuals with myalgic encephalomyelitis and chronic fatigue syndrome may experience some increase in functioning if their level of exertion consistently remains within the limits of their available energy. Findings of several studies support this theory; however, the current study is the first to explore how an individual’s initial level of available energy may influence the relation between energy envelope maintenance and level of functioning.

Method:The functioning, activity, and symptomatology of six groups of individuals with myalgic encephalomyelitis and chronic fatigue syndrome were compared. Groups were created based upon level of available energy (higher or lower) and energy envelope adherence (underextended, within, overextended).

Results: Results indicate that, as expected, individuals with myalgic encephalomyelitis and chronic fatigue syndrome who had higher available energy also had better functioning than individuals with lower available energy; however, this relation was less pronounced for individuals who were overexerting themselves.

Discussion: These results are consistent with the Energy Envelope Theory, and they suggest that overexertion was particularly impactful for individuals with higher levels of available energy.

Source: O’connor K, Sunnquist M, Nicholson L, Jason LA, Newton JL, Strand EB. Energy envelope maintenance among patients with myalgic encephalomyelitis and chronic fatigue syndrome: Implications of limited energy reserves. Chronic Illn. 2017 Jan 1:1742395317746470. doi: 10.1177/1742395317746470. [Epub ahead of print]

Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome

Abstract:

OBJECTIVE: To explore changes in autonomic functioning, sleep, and physical activity during a post-exertional symptom exacerbation induced by physical or cognitive challenge in participants with chronic fatigue syndrome (CFS).

METHODS: Thirty-five participants with CFS reported fatigue levels 24-h before, immediately before, immediately after, and 24-h after the completion of previously characterised physical (stationary cycling) or cognitive (simulated driving) challenges. Participants also provided ratings of their sleep quality and sleep duration for the night before, and after, the challenge. Continuous ambulatory electrocardiography (ECG) and physical activity was recorded from 24-h prior, until 24-h after, the challenge. Heart rate (HR) and HR variability (HRV, as high frequency power in normalized units) was derived from the ECG trace for periods of wake and sleep.

RESULTS: Both physical and cognitive challenges induced an immediate exacerbation of the fatigue state (p<0.001), which remained elevated 24-h post-challenge. After completing the challenges, participants spent a greater proportion of wakeful hours lying down (p=0.024), but did not experience significant changes in sleep quality or sleep duration. Although the normal changes in HR and HRV during the transition from wakefulness to sleep were evident, the magnitude of the increase in HRV was significantly lower after completing the challenge (p=0.016).

CONCLUSION: Preliminary evidence of reduced nocturnal parasympathetic activity, and increased periods of inactivity, were found during post-exertional fatigue in a well-defined group of participants with CFS. Larger studies employing challenge paradigms are warranted to further explore the underlying pathophysiological mechanisms of post-exertional fatigue in CFS.

Copyright © 2017 Elsevier Inc. All rights reserved.

Source: Cvejic E, Sandler CX, Keech A, Barry BK, Lloyd AR, Vollmer-Conna U.Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome. J Psychosom Res. 2017 Dec;103:91-94. doi: 10.1016/j.jpsychores.2017.10.010. Epub 2017 Oct 19. https://www.ncbi.nlm.nih.gov/pubmed/29167053

Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia

Abstract:

BACKGROUND: Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) share some similar symptoms with fibromyalgia (FM). Prior research has found increased illness severity when patients have FM that is comorbid with ME and CFS. For example, post-exertional malaise (PEM) has been shown to be more severe in those with comorbid FM. However, PEM can be separated into two factors, Muscle and General PEM. It is unknown if the more severe PEM findings in comorbid FM are due to the Muscle or General PEM factor.

PURPOSE:The purpose of this study was to determine if the PEM differences seen between patients with and without comorbid FM exist for the Muscle or General PEM factors.

METHOD: An international convenience sample was collected via an online questionnaire. The questionnaire assessed the frequency and severity of several PEM-related symptoms. Additionally, participants provided information regarding the course and characteristics of their illness.

RESULTS: Participants that indicated a comorbid diagnosis of FM displayed significantly more frequent and severe PEM symptoms in the Muscle and General PEM factors. The FM group also indicated significantly worse physical functioning compared to the group without comorbid FM.

DISCUSSION: The secondary diagnosis of FM in addition to ME and CFS appears to amplify the PEM symptomatology and worsen patients' physical functioning. The findings of this study have notable implications on the inclusion of patients with comorbid FM in ME and CFS research studies.

Source: McManimen SL, Jason LA. Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia. SRL Neurol Neurosurg. 2017;3(1):22-27. Epub 2017 Mar 10. https://www.ncbi.nlm.nih.gov/pubmed/28603794

Differences in ME and CFS Symptomology in Patients with Normal and Abnormal Exercise Test Results

Abstract:

Post-exertional malaise (PEM) is a cardinal symptom of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS), which often distinguishes patients with this illness from healthy controls or individuals with exclusionary illnesses such as depression. However, occurrence rates for PEM fluctuate from subject to how the symptom is operationalized. One commonly utilized method is exercise testing, maximal or submaximal. Many patients with ME and CFS experience PEM after participating in these tests, and often show abnormal results. However, some patients still exhibit normal results after participating in the exercise testing.

This study examined the differences between two patient groups with ME and CFS, those with normal results and those with abnormal results, on several PEM-related symptoms and illness characteristics. The results suggest those that displayed abnormal results following testing have more frequent and severe PEM, worse overall functioning, and are more likely to be bedbound than those that displayed normal results.

 

Source: Stephanie L McManimen and Leonard A Jason. Differences in ME and CFS Symptomology in Patients with Normal and Abnormal Exercise Test Results. Int J Neurol Neurother, IJNN-4-066, (Volume 4, Issue 1), Research Article; ISSN: 2378-3001 DOI: 10.23937/2378-3001/1410066 (Full article)

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. https://www.ncbi.nlm.nih.gov/pubmed/28339438

 

Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging.

Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30 minutes of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24 hours following exercise.

Functional brain images were obtained during performance of: 1) a fatiguing cognitive task – the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task – simple number recognition, and 3) a non-fatiguing motor task – finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05).

For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices.

Changes in brain activity were significantly related to symptoms for patients (p<0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients.

These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Published by Elsevier Inc.

 

Source: Cook DB, Light AR, Light KC, Broderick G, Shields MR, Dougherty RJ, Meyer JD, VanRiper S, Stegner AJ, Ellingson LD, Vernon SD. Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Brain Behav Immun. 2017 Feb 16. pii: S0889-1591(17)30051-X. doi: 10.1016/j.bbi.2017.02.009. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28216087