Warning Signals of Post-Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Retrospective Analysis of 197 Patients

Abstract:

Post-exertional malaise (PEM), the key feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is characterized by baseline symptom exacerbation after exposure to a stressor, and some patients can experience new or non-typical symptoms. We hypothesized that new or non-typical symptoms occurring long enough before onset of baseline symptom exacerbation could be warning signals predicting PEM.

Adult ME/CFS patients who attended the internal medicine department of Angers University Hospital (France) between October 2011 and December 2019 were included in a retrospective medical records review. Patients who experienced one or more new or non-typical symptoms before baseline symptom exacerbation were compared with the rest of the study population for PEM features, epidemiological characteristics, fatigue features, and comorbidities. New or non-typical symptoms preceded baseline symptom exacerbation in 27/197 (13.7%) patients, and the most frequent ones were mood disorders (37%). When compared to the rest of the study population, only PEM intensity was significantly lower in these patients (p = 0.004), even after adjustment for sex and age at disease onset (p = 0.007).

New or non-typical symptoms preceding baseline symptom exacerbation in some ME/CFS patients could be warning signals for PEM. Their identification could help preventing PEM occurrences or reducing their intensity leading to improving disease prognosis.

Source: Ghali A, Lacout C, Ghali M, Gury A, Delattre E, Lavigne C, Urbanski G. Warning Signals of Post-Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Retrospective Analysis of 197 Patients. J Clin Med. 2021 Jun 7;10(11):2517. doi: 10.3390/jcm10112517. PMID: 34200126. https://pubmed.ncbi.nlm.nih.gov/34200126/

The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

Post-exertional malaise, or a variation of this term, is a key symptom of myalgic encephalomyelitis and chronic fatigue syndrome, as this symptom is mentioned in almost all myalgic encephalomyelitis and chronic fatigue syndrome case definitions. Until now there has not been a comprehensive questionnaire to assess post-exertional malaise. To rectify this situation, in this article we describe the development of a new questionnaire, called the DePaul Post-Exertional Malaise Questionnaire, which was based on input from hundreds of patients. Preliminary validation was provided by the findings of significant and predictable relationships between different domains of this post-exertional malaise questionnaire and physical functioning.

Source: Jason LA, Holtzman CS, Sunnquist M, Cotler J. The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome. J Health Psychol. 2018 Oct 24:1359105318805819. doi: 10.1177/1359105318805819. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30354489

A Brief Questionnaire to Assess Post-Exertional Malaise

Abstract:

Post-exertional malaise (PEM) is a key symptom of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Currently, five PEM-items from the DePaul Symptom Questionnaire (DSQ) were recommended as a first step in measuring this symptom for patients with ME and CFS by the National Institutes of Health/Centers for Disease Control and Prevention (NIH/CDC) Common Data Elements’ (CDE) working group.

The second step in this process, as recommended by the NIH/CDC CDE working group, involves assembling information from various sources to confirm the presence of PEM. There have not been any efforts, to date, to standardize this second-step process in the assessment of PEM.

The current study examined whether five supplementary items on the DSQ could be used to operationalize the second step of the recommendations made by the NIH/CDC CDE working group. The five supplementary DSQ PEM duration items correctly categorized patients with ME or CFS 81.7% of the time, while incorrectly categorizing multiple sclerosis (MS) and post-polio syndrome (PPS) as ME or CFS only 16.6% of the time. The findings suggested that a PEM second-step process could be operationalized using supplementary DSQ items.

Source: Cotler J, Holtzman C, Dudun C, Jason LA. A Brief Questionnaire to Assess Post-Exertional Malaise. Diagnostics (Basel). 2018 Sep 11;8(3). pii: E66. doi: 10.3390/diagnostics8030066.

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/

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

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

 

Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To design and validate an instrument to capture the characteristic post-exertional exacerbation of fatigue in patients with chronic fatigue syndrome (CFS).

METHODS: Firstly, patients with CFS (N=19) participated in five focus group discussions to jointly explore the nature of fatigue and dynamic changes after activity, and inform development of a self-report instrument – the Fatigue and Energy Scale (FES). The psychometric properties of the FES were then examined in two case-control challenge studies: a physically-demanding challenge (moderate-intensity aerobic exercise; N=10 patients), and a cognitively-demanding challenge (simulated driving; N=11 patients). Finally, ecological validity was evaluated by recording in association with tasks of daily living (N=9).

RESULTS: Common descriptors for fatigue included ‘exhaustion’, ‘tiredness’, ‘drained of energy’, ‘heaviness in the limbs’, and ‘foggy in the head’. Based on the qualitative data, fatigue was conceptualised as consisting of ‘physical’ and ‘cognitive’ dimensions. Analysis of the psychometric properties of the FES showed good sensitivity to the changing symptoms during a post-exertional exacerbation of fatigue following both physical exercise and driving simulation challenges, as well as tasks of daily living.

CONCLUSION: The ‘fatigue’ experienced by patients with CFS covers both physical and cognitive components. The FES captured the phenomenon of a post-exertional exacerbation of fatigue commonly reported by patients with CFS. The characteristics of the symptom response to physical and cognitive challenges were similar. Both the FES and the challenge paradigms offer key tools to reliably investigate biological correlates of the dynamic changes in fatigue.

Copyright © 2015 Elsevier Inc. All rights reserved.

 

Source: Keech A, Sandler CX, Vollmer-Conna U, Cvejic E, Lloyd AR, Barry BK. Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome. J Psychosom Res. 2015 Dec;79(6):537-49. doi: 10.1016/j.jpsychores.2015.08.008. Epub 2015 Sep 2. https://www.ncbi.nlm.nih.gov/pubmed/26359713

 

Problems in defining post-exertional malaise

Abstract:

Post-exertional malaise (PEM) is a cardinal symptom of the illnesses referred to as Myalgic Encephalomyelitis (ME), Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS), and chronic fatigue syndrome (CFS). PEM is reported to occur in many of these patients, and with several criteria (e.g., ME and ME/CFS), this symptom is mandatory (Carruthers et al., 2003 , 2011 ).

In the present study, 32 participants diagnosed with CFS (Fukuda et al., 1994 ) were examined on their responses to self-report items that were developed to capture the characteristics and patterns of PEM. As shown in the results, the slight differences in wording for various items may affect whether one is determined to have PEM according to currently used self-report criteria to assess CFS. Better understanding of how this symptom is assessed might help improve the diagnostic reliability and validity of ME, ME/CFS, and CFS.

 

Source: Jason LA, Evans M, So S, Scott J, Brown A. Problems in defining post-exertional malaise. J Prev Interv Community. 2015;43(1):20-31. doi: 10.1080/10852352.2014.973239. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295644/ (Full article)