Tag: PEM

Mixed methods system for the assessment of post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an exploratory study

Abstract:

Background A central feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM), which is an acute worsening of symptoms after a physical, emotional and/or mental exertion. Dynamic measures of PEM have historically included scaled questionnaires, which have not been validated in ME/CFS. To enhance our understanding of PEM and how best to measure it, we conducted semistructured qualitative interviews (QIs) at the same intervals as visual analogue scale (VAS) measures after a cardiopulmonary exercise test (CPET).

Methods Ten ME/CFS and nine healthy volunteers participated in a CPET. For each volunteer, PEM symptom VAS (12 symptoms) and semistructured QIs were administered at six timepoints over 72 hours before and after a single CPET. QI data were used to plot the severity of PEM at each time point and identify the self-described most bothersome symptom for each ME/CFS volunteer. Performance of QI and VAS data was compared with each other using Spearman correlations.

Results Each ME/CFS volunteer had a unique PEM experience, with differences noted in the onset, severity, trajectory over time and most bothersome symptom. No healthy volunteers experienced PEM. QI and VAS fatigue data corresponded well an hour prior to exercise (pre-CPET, r=0.7) but poorly at peak PEM (r=0.28) and with the change from pre-CPET to peak (r=0.20). When the most bothersome symptom identified from QIs was used, these correlations improved (r=0.0.77, 0.42. and 0.54, respectively) and reduced the observed VAS scale ceiling effects.

Conclusion In this exploratory study, QIs were able to capture changes in PEM severity and symptom quality over time, even when VAS scales failed to do so. Measurement of PEM can be improved by using a quantitative–qualitative mixed model approach.

Source: Stussman B, Calco B, Norato G, et al. Mixed methods system for the assessment of post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an exploratory study. BMJ Neurology Open 2024;6:e000529. doi: 10.1136/bmjno-2023-000529  https://neurologyopen.bmj.com/content/6/1/e000529 (Full text)

Exploring the neurocognitive consequences of post-exertional malaise in myalgic encephalomyelitis

Background and aims:

Myalgic encephalomyelitis (ME) is a complex, debilitating and heterogeneous disorder. It affects over 500,000 people in Canada but remains poorly understood. People are affected with multi-systemic symptoms such as fatigue that is not alleviated by rest, pain, cognitive impairment and post-exertional malaise (PEM), which is considered as the hallmark symptom of ME. PEM is triggered by minimal mental or physical effort and exacerbates other symptoms. Our aim was to measure how individuals’ cognition can be impacted by the induction of PEM, and investigate the difference in cognitive response.

Section snippets:

Methods
A prospective cohort of people with ME (n = 42) and matched healthy controls (n = 15) was recruited and subjected to PEM induction through a 90-minutes mechanical arm stimulation. BrainCheck test (BrainCheck, Inc., TX, USA) was used at baseline (T0) and after 90 minutes of stimulation to evaluate six cognitive domains for which each participant received a score and a population percentile based on their performance.

Results
Comparison between both groups was significant (p < 0.05) at T90, but not at T0, in four out of six cognitive domains. We then classified our ME cohort in three clusters by k-means method based on the Δ percentile (T90-T0) for each cognitive task. This stratification allowed us to notice how some cognitive domains seem more affected depending on the cluster, namely memory and attention.

Conclusions
These results showed the impact of PEM on the disturbance of cognition in the context of ME as well as the variability of cognitive domains affected in people with ME.

Source: Corinne Leveau, Iurie Caraus, Anita Franco, Alain Moreau. Exploring the neurocognitive consequences of post-exertional malaise in myalgic encephalomyelitis. Journal of the Neurological Sciences, Volume 455, Supplement, December 2023, 122590. https://www.sciencedirect.com/science/article/abs/pii/S0022510X23020518

 

Muscle abnormalities worsen after post-exertional malaise in long COVID

Abstract:

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear.

With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

Source: Appelman, B., Charlton, B.T., Goulding, R.P. et al. Muscle abnormalities worsen after post-exertional malaise in long COVID. Nat Commun 15, 17 (2024). https://doi.org/10.1038/s41467-023-44432-3 https://www.nature.com/articles/s41467-023-44432-3 (Full text)

Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles

Abstract:

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also in many cases of post-infectious syndromes, colloquially referred to as “long COVID”. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms.

We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues.

In addition, complement system related proteins were more abundant in the serum of patients with PCS, matching observations on the transcriptomic level in the muscle tissue. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.

Source: Aschman, T., Wyler, E., Baum, O. et al. Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles. acta neuropathol commun 11, 193 (2023). https://doi.org/10.1186/s40478-023-01662-2 https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-023-01662-2 (Full text)

Post-exertional malaise in daily life and experimental exercise models in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Post-exertional malaise (PEM) is commonly recognized as a hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is often used as one of several criteria for diagnosing ME/CFS.

In this perspective paper we want to reflect on how PEM is understood, assessed, and evaluated in scientific literature, and to identify topics to be addressed in future research.

Studies show that patients use a wide variety of words and concepts to label their experience of PEM in everyday life, and they report physical or mental exertions as triggers of PEM. They also report that PEM may have an immediate or delayed onset and may last from a few days to several months.

When standardized exercise tests are used to trigger PEM experimentally, the exacerbation of symptoms has a more immediate onset but still shows a wide variability in duration.

There are indications of altered muscular metabolism and autonomic nervous responses if exercise is repeated on successive days in patients with ME/CFS. The decreased muscular capacity appears to be maintained over several days following such controlled exercise bouts. These responses may correspond to patients’ experiences of increased exertion.

Based on this background we argue that there is a need to look more closely into the processes occurring in the restitution period following exercise, as PEM reaches the peak in this phase.

Source: Nina K. Vøllestad, Anne Marit Mengshoel. Post-exertional malaise in daily life and experimental exercise models in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Frontiers in Physiology, Volume 14- 2023. https://www.frontiersin.org/articles/10.3389/fphys.2023.1257557/abstract

Focus on Post-Exertional Malaise when approaching ME/CFS in specialist healthcare improves satisfaction and reduces deteriorations

Abstract:

Background: Post-Exertional Malaise (PEM) is considered a hallmark characteristic of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). This may also apply to subgroups of patients with long COVID induced ME/CFS. However, it is uncertain to what extent PEM is acknowledged in routine specialist healthcare for ME/CFS patients, and how this affects patient outcomes.

Objective: This study aims to evaluate to what extent ME/CFS patients experienced focus on PEM in specialist healthcare practice and its significance for outcome and care quality.

Methods: Data from two online cross-sectional surveys covering specialist healthcare services for ME/CFS patients at rehabilitation institutes in Norway and at two regional hospitals respectively, were analyzed. Evaluations of 788 rehabilitation stays, 86 hospital consultations and 89 hospital interventions were included.

Logistic regression models and Mann-Whitney U tests were used to quantify the impact of addressing PEM on health and functioning, care satisfaction or benefit. Spearman’s rank correlation and Cronbach’s alpha of focus on PEM with the respondents’ perception of healthcare providers’ knowledge, symptom acknowledgement and suitability of intervention were assessed as measures for care quality and their internal consistency, respectively.

Results: PEM was addressed in 48% of the rehabilitation stays, 43% of the consultations and 65% of the hospital interventions. Failure to address PEM roughly doubled the risk of health deterioration following rehabilitation (OR=0.39, 95%CI 0.29-0.52; 40.1% vs 63.2% P= <.001) and hospital intervention (OR=0.34, 95%CI 0.13-0.89; 22.4% vs. 45.2%, P=.026).

PEM-focus during the clinical contact was associated with significantly higher scores on patients’ rated care satisfaction and benefit of both consultation and intervention. Furthermore, addressing PEM was (inter)related to positive views about healthcare providers’ level of knowledge of ME/CFS, their acknowledgment of symptoms, obtained knowledge, and the perceived suitability of intervention (Cronbach’s alpha ≥ 0.80).

Conclusion: PEM is still frequently not acknowledged in specialist healthcare practice for ME/CFS patients in Norway. Not addressing PEM substantially increased the probability of a decline in health and functioning following intervention and was strongly associated with reduced perceived care quality, satisfaction and benefit. These findings may be related to the applied explanatory models for ME/CFS and are most likely of relevance to long COVID.

Source: Marjon E. Wormgoor, Sanne C. Rodenburg. Focus on Post-Exertional Malaise when approaching ME/CFS in specialist healthcare improves satisfaction and reduces deteriorations. Frontiers in Neurology 14- 2023. https://www.frontiersin.org/articles/10.3389/fneur.2023.1247698/abstract

Physical exertion worsens symptoms in patients with post-COVID condition : Post-exertional malaise in patients with post-COVID condition

Abstract:

Patients with post-COVID condition suffer from fatigue, limited exercise capacity, and post-exertional malaise. Post-exertional malaise is the worsening of symptoms after physical or mental exertion, which reduces the efficacy of most forms of rehabilitation. This article presents the current understanding in the pathophysiology of post-COVID condition, particularly the underlying causes of post-exertional malaise.

Source: Ellen Breedveld, Braeden Charlton and Brent Appelman et al. Physical exertion worsens symptoms in patients with post-COVID condition. ScienceOpen Preprints. 2023. DOI: 10.14293/PR2199.000467.v1 https://www.scienceopen.com/document/read?vid=6ebbad1a-4c23-4323-b20c-e57a346ce9f9 (Full text)

Fatigue in post COVID-19 patients: the P4O2 COVID-19 study

Abstract:

Background: Some patients do not fully recover after COVID-19 and have symptoms occurring 3 months after acute illness, lasting for >2 months, defined as post COVID-19. Fatigue seems most present in post COVID-19 and part of the patients might develop symptoms similar to chronic fatigue syndrome.

Aim: To determine the occurrence of fatigue and other symptoms in post COVID-19 patients.

Methods: In the prospective P4O2 COVID-19 cohort, post COVID-19 patients aged 40-65 years were recruited from outpatient post-COVID clinics in 5 Dutch hospitals between May 2021-September 2022. At 3-6 months post-COVID, patients completed the Fatigue Severity Scale (FSS). If the FSS score was ≥4 (the cut-off for severe fatigue), patients also completed the DePaul Symptom Questionnaire version 2 (DSQ-2). The FSS ranges from 1-7 and a higher score means more fatigued. The DSQ-2 rates frequency and severity of 79 symptoms on a 5-point Likert scale. Binary thresholds (if scored ≥2 on both severity and frequency, the threshold is met and the symptom is present) were calculated.

Results: The mean age of the 78 included patients was 53.9±6.2 and 51.7% were male. Median (IQR) FSS score was 5.6 (4.2-6.3) and 66 patients (84.6%) had a score ≥4. According to the DSQ-2 (n=61), patients reported a median (IQR) of 16 (8-23) symptoms. The majority of the patients experienced fatigue (85%). Furthermore, post-exertional malaise (PEM) (40%), sleep-related problems (37%), pain (21%) and neurocognitive problems (23%) were frequently reported.

Conclusion: The occurrence of severe fatigue 3-6 months after COVID-19 was 84.6% in our cohort. Patients with severe fatigue also frequently reported PEM, sleep related problems, pain and neurocognitive problems.

Source: Merel E.B. Cornelissen, Lizan D. Bloemsma, Nadia Baalbaki, Somayeh Bazdar, Jelle M. Blankestijn, Inés Beekers, Rosanne J.H.C.G. Beijers, Joop P. Van Den Bergh, Debbie Gach, J.J. Miranda Geelhoed, Sebastiaan Holverda, Laura Houweling, John J. Jacobs, Renée Jonker, Ivo Van Der Lee, Paulien M.A. Linders, Lieke C.E. Noij, Esther J. Nossent, Marianne A. Van De Pol, Daphne W. Schaminee, Annemie M.W.J. Schols, Lisanne T. Schuurman, Brigitte Sondermeijer, Anouk W. Vaes, Els J.M. Weersink, Yolanda De Wit-Van Wijck, Martijn A. Spruit, Anke H. Maitland-Van Der Zee. Fatigue in post COVID-19 patients: the P4O2 COVID-19 study. European Respiratory Journal 2023 62: PA4574; DOI: 10.1183/13993003.congress-2023.PA4574 https://erj.ersjournals.com/content/62/suppl_67/PA4574.abstract

Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept

Abstract:

in English, German

Background: Multimodal pain therapy usually take place in the context of group therapy lasting several weeks and is based on a generally activating approach. Due to the specificity of stress intolerance with postexertional malaise (PEM) in patients with postviral syndromes, physical as well as psychological overload must be urgently avoided in these cases; however, these aspects can only be insufficiently considered in current medical pain therapy concepts.

Methods: Summary of the current literature and presentation of clinical characteristics as well as presentation of a model project for a multimodal pain therapy in postviral syndromes with PEM.

Model concept: The presented model project describes a day clinic treatment setting for interdisciplinary multimodal pain therapy adapted to the individual resilience with minimization of the risk of strain-induced deterioration of the condition.

Source: Luchting B, Behrends U, Eigner B, Stojanov S, Warlitz C, Haegele M, Neuwirth E, Mihatsch L, Richter HP. Interdisziplinäre multimodale Schmerztherapie bei postviralen Syndromen und ME/CFS : Besonderheiten, Fallstricke und Modellkonzept [Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept]. Schmerz. 2023 Oct 20. German. doi: 10.1007/s00482-023-00761-2. Epub ahead of print. PMID: 37 https://pubmed.ncbi.nlm.nih.gov/37864020/864020.

Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome from Early Symptoms of COVID-19 Infection

Abstract:

It is still unclear why certain individuals after viral infections continue to have severe symptoms. We investigated if predicting myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) development after contracting COVID-19 is possible by analyzing symptoms from the first two weeks of COVID-19 infection.
Using participant responses to the 54-item DePaul Symptom Questionnaire, we built predictive models based on a random forest algorithm using the participants’ symptoms from the initial weeks of COVID-19 infection to predict if the participants would go on to meet the criteria for ME/CFS approximately 6 months later.
Early symptoms, particularly those assessing post-exertional malaise, did predict the development of ME/CFS, reaching an accuracy of 94.6%. We then investigated a minimal set of eight symptom features that could accurately predict ME/CFS. The feature reduced models reached an accuracy of 93.5%. Our findings indicated that several IOM diagnostic criteria for ME/CFS occurring during the initial weeks after COVID-19 infection predicted Long COVID and the diagnosis of ME/CFS after 6 months.
Source: Hua C, Schwabe J, Jason LA, Furst J, Raicu D. Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome from Early Symptoms of COVID-19 Infection. Psych. 2023; 5(4):1101-1108. https://doi.org/10.3390/psych5040073 https://www.mdpi.com/2624-8611/5/4/73