Tag: PEM

Cardiovascular Considerations in the Management of People with Suspected Long COVID

Abstract:

Approximately 15% of adult Canadians with SARS-CoV-2 infection develop lingering symptoms beyond 12 weeks post-acute infection, known as post-COVID condition or long COVID. Some of the commonly reported long COVID cardiovascular symptoms include fatigue, shortness of breath, chest pain, and palpitations. Suspected long-term cardiovascular complications of SARS-CoV-2 infection may present as a constellation of symptoms that can be challenging for clinicians to diagnose and treat.

When assessing patients with these symptoms, clinicians need to keep in mind Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), post-exertional malaise and post-exertional symptom exacerbation (PEM/PESE), cardiac dysautonomia such as Inappropriate Sinus Tachycardia (IST), and Postural Orthostatic Tachycardia Syndrome (POTS), and occasionally Mast Cell Activation Syndrome (MCAS).

This paper summarizes the globally evolving evidence around management of cardiac sequelae of long COVID. In addition, this review includes a Canadian perspective, consisting of a panel of expert opinions from experienced clinicians across Canada who have been involved in management of long COVID. The objective of this review is to offer some practical guidance to cardiologists and generalist clinicians regarding diagnostic and treatment approaches for adult patients with suspected long COVID who continue to experience unexplained cardiac symptoms.

Source: Quinn KL, Lam GY, Walsh JF, Bhéreur A, Brown AD, Chow CW, Christie Chung KY, Cowan J, Crampton N, Décary S, Falcone EL, Graves L, Gross DP, Hanneman K, Harvey PJ, Holmes S, Katz GM, Parhizgar P, Sharkawy A, Tran KC, Waserman S, Zannella VE, Cheung AM. Cardiovascular Considerations in the Management of People with Suspected Long COVID. Can J Cardiol. 2023 Apr 6:S0828-282X(23)00303-3. doi: 10.1016/j.cjca.2023.04.003. Epub ahead of print. PMID: 37030518. Quinn KL, Lam GY, Walsh JF, Bhéreur A, Brown AD, Chow CW, Christie Chung KY, Cowan J, Crampton N, Décary S, Falcone EL, Graves L, Gross DP, Hanneman K, Harvey PJ, Holmes S, Katz GM, Parhizgar P, Sharkawy A, Tran KC, Waserman S, Zannella VE, Cheung AM. Cardiovascular Considerations in the Management of People with Suspected Long COVID. Can J Cardiol. 2023 Apr 6:S0828-282X(23)00303-3. doi: 10.1016/j.cjca.2023.04.003. Epub ahead of print. PMID: 37030518. https://www.onlinecjc.ca/article/S0828-282X(23)00303-3/fulltext (Full text)

Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

To assess biobehavioral sex differences in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) utilizing a low burden exercise protocol, 22 females and 15 males with ME/CFS and 14 healthy controls underwent two six-min walk tests.

Fifteen daily assessments were scheduled for fatigue and function ratings and heart monitoring. Six-min walk tests were conducted on days 8 and 9. The ME/CFS group showed high self-report fatigue and impaired physical function, whereas healthy controls did not show fatigue or function abnormalities.

In patients, no significant post-exercise changes were found for heart rate variability (HRV); however, heart rate decreased in ME/CFS males from Day 14 to Day 15 (p = 0.046). Female patients showed increased fatigue (p = 0.006) after the initial walk test, but a downward slope (p = 0.008) in fatigue following the second walk test. Male patients showed a decrease in self-report work limitation in the days after exercise (p = 0.046). The healthy control group evidenced a decrease in HRV after the walk tests from Day 9-14 (p = 0.038).

This pilot study did not confirm hypotheses that females as compared to males would show slower exercise recovery on autonomic or self-report (e.g. fatigue) measures. A more exertion-sensitive test may be required to document prolonged post-exertional abnormalities in ME/CFS.

Trial registration: NCT NCT03331419.

Source: Friedberg F, Adamowicz JL, Bruckenthal P, Milazzo M, Ramjan S, Zhang X, Yang J. Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome. Sci Rep. 2023 Apr 3;13(1):5442. doi: 10.1038/s41598-023-32581-w. PMID: 37012343. https://www.nature.com/articles/s41598-023-32581-w (Full text)

An international survey of experiences and attitudes towards pacing using a heart rate monitor for people with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic encephalomyelitis (ME) is a complex, multi-system neurological condition. The defining feature of ME is post-exertional malaise (PEM) with over 30 symptoms triggered by physical, cognitive, emotional and social activity.

The cause of PEM is unclear but one area of research using cardio-pulmonary exercise tests show a reduced ventilatory anaerobic threshold (VAT) with repeated tests leading to PEM.

Pacing with heart rate monitoring (HRM) provides feedback to maintain activity intensity below the VAT. There is only one piece of research investigating the use of HRM although a number of guidelines recommend it.

Objective: To identify the experiences and attitudes of people with ME towards HRM.

Methods: A 40 question online survey was devised and released on ME websites, Twitter and Facebook pages. People with ME read the information sheet and followed an online link to the survey. The survey was open for three weeks and all answers were anonymous.

Results: 488 people with ME completed the survey. Most participants were female, 35-50 years and with a reported illness of greater than 5 years. Over 100 types of HR monitor used. Over 30 benefits and over 30 negatives identified. HRM reduced severity of ME and severity and duration of PEM.

Conclusion: Although there are limitations, HRM has many benefits including helping PwME to understand and manage their PEM and support them to increase their activities, including work. There is a need for more research and education of healthcare professionals in the safe use of HRM.

Source: Clague-Baker N, Davenport TE, Madi M, Dickinson K, Leslie K, Bull M, Hilliard N. An international survey of experiences and attitudes towards pacing using a heart rate monitor for people with myalgic encephalomyelitis/chronic fatigue syndrome. Work. 2023 Mar 13. doi: 10.3233/WOR-220512. Epub ahead of print. PMID: 36938766. https://content.iospress.com/articles/work/wor220512 (Full text)

Development and measurement properties of the PEM/PESE activity questionnaire (PAQ)

Abstract:

Background: Existing instruments often are inappropriate to measure the effects of post-exertional malaise (PEM) and post-exertional symptom exacerbation (PESE) on activities of daily living (ADLs). A validated questionnaire to measure self-reported ability with ADLs would advance research and clinical practice in conditions like myalgic encephalomyelitis and Long Covid.

Objective: Determine the measurement properties of the PEM/PESE Activity Questionnaire (PAQ).

Methods: The PAQ is adapted from the Patient Specific Functional Scale. Respondents rated three self-selected ADLs on two 0-100 scales, including current performance compared to (1) a ‘good day’ and (2) before illness. Respondents provided a Burden of Functioning rating on a 0-100 scale, anchored at 0 being the activity took “No time, effort, and resources at all” and 10 being “All of my time, effort, and resources.” Respondents took the PAQ twice, completing a demographic questionnaire after the first PAQ and before the second PAQ. Descriptive statistics and intraclass correlation coefficients were calculated for each scale to assess test-retest reliability. Minimum detectable change outside the 95% confidence interval (MDC95) was calculated. Ceiling and floor effects were determined when the MDC95 for average and function scores crossed 0 and 100, respectively.

Results: n = 981 responses were recorded, including n = 675 complete surveys. Test-retest reliability was generally fair to excellent, depending on function and scale. MDC95 values generally indicated scale responsiveness. Ceiling and floor effects were noted infrequently for specific functions.

Conclusion: The PAQ is valid, reliable, and sensitive. Additional research may explore measurement properties involving functions that were infrequently selected in this sample.

Source: Davenport TE, Stevens SR, Stevens J, Snell CR, Van Ness JM. Development and measurement properties of the PEM/PESE activity questionnaire (PAQ). Work. 2023 Mar 13. doi: 10.3233/WOR-220553. Epub ahead of print. PMID: 36938768. https://content.iospress.com/articles/work/wor220553 (Full text)

Neuropathology and Neurological Manifestations in ME/CFS and Long COVID with focus on Post-Exertional Symptom Exacerbation: a Literature Review

Summary:

Many of the people that get infected with the Coronavirus develop long-lasting complaints and are diagnosed with Long COVID after the acute infection is gone. These complains can last several months or years and include fatigue, cognitive impairment, sleeping problems and post-exertional symptom exacerbation (PESE). Research shows that COVID-19 patients with an acute infection have abnormalities in their brain, which could potentially lead to long-lasting neurological problems and symptoms. However, although many researchers are trying to uncover the underlying mechanisms, Long COVID is still very new.
The underlying mechanisms causing and maintaining the disease are therefore unclear. A large group of Long COVID patients resembles patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in terms of symptoms and, in many cases, the viral trigger of the disease. A core symptom of ME/CFS is PESE, which is uncommon in other fatiguing illnesses, but frequently seen in Long COVID patients. PESE involves an abnormal worsening of symptoms and cognitive and physical functions after any type of normal activity. Because of the large symptom overlap and lack of knowledge regarding PESE, underlying brain-mechanisms associated with Long COVID and ME/CFS in general as well as after physical exertion were investigated.
The findings of this review indicate that ME/CFS is associated with several abnormalities in the brain which are also proposed to be present in Long COVID patients. Such abnormalities include inflammation of the brain, shrinkage of the brain and less blood flow to the brain. After physical exertion, these abnormalities might be exacerbated in ME/CFS patients. This results in a brain that needs to work harder than the healthy brain to complete a task. It is demonstrated by increased brain activity in several brain regions after physical exertion and general symptom exacerbation. Since the two diseases seem to have a large overlap in symptoms and underlying brain-mechanisms, this finding might apply to patients with long COVID as well. Importantly, Long COVID seems to consist of different subgroups of which a large part fulfills the criteria for ME/CFS.
Treatment and therapy for ME/CFS patients is therefore likely transferable to this subgroup of Long COVID patients, with explicit attention towards the PESE phenomenon. More research is needed to uncover the underlying mechanisms as well as correct treatment approach of these diseases. Future research should take subgroups of Long COVID into account.
Source: Rodenburg, Sanne. Neuropathology and Neurological Manifestations in ME/CFS and Long COVID with focus on Post-Exertional Symptom Exacerbation: a Literature Review. Master Thesis, Utrecht University. March 14, 2023. https://studenttheses.uu.nl/bitstream/handle/20.500.12932/43647/Rodenburg_7433050_Neuropathology%20and%20neurological%20manifestations%20in%20MECFS%20and%20Long%20COVID%20with%20focus%20on%20PESE.pdf (Full text)

Recovery from Exercise in Persons with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Background and Objectives: Post-exertional malaise (PEM) is the hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but there has been little effort to quantitate the duration of PEM symptoms following a known exertional stressor.

Using a Symptom Severity Scale (SSS) that includes nine common symptoms of ME/CFS, we sought to characterize the duration and severity of PEM symptoms following two cardiopulmonary exercise tests separated by 24 h (2-day CPET).

Materials and Methods: Eighty persons with ME/CFS and 64 controls (CTL) underwent a 2-day CPET. ME/CFS subjects met the Canadian Clinical Criteria for diagnosis of ME/CFS; controls were healthy but not participating in regular physical activity. All subjects who met maximal effort criteria on both CPETs were included.

SSS scores were obtained at baseline, immediately prior to both CPETs, the day after the second CPET, and every two days after the CPET-1 for 10 days.

Results: There was a highly significant difference in judged recovery time (ME/CFS = 12.7 ± 1.2 d; CTL = 2.1 ± 0.2 d, mean ± s.e.m., Chi2 = 90.1, p < 0.0001).

The range of ME/CFS patient recovery was 1–64 days, while the range in CTL was 1–10 days; one subject with ME/CFS had not recovered after one year and was not included in the analysis.

Less than 10% of subjects with ME/CFS took more than three weeks to recover. There was no difference in recovery time based on the level of pre-test symptoms prior to CPET-1 (F = 1.12, p = 0.33).

Mean SSS scores at baseline were significantly higher than at pre-CPET-1 (5.70 ± 0.16 vs. 4.02 ± 0.18, p < 0.0001). Pharmacokinetic models showed an extremely prolonged decay of the PEM response (Chi2 > 22, p < 0.0001) to the 2-day CPET.

Conclusions: ME/CFS subjects took an average of about two weeks to recover from a 2-day CPET, whereas sedentary controls needed only two days. These data quantitate the prolonged recovery time in ME/CFS and improve the ability to obtain well-informed consent prior to doing exercise testing in persons with ME/CFS. Quantitative monitoring of PEM symptoms may provide a method to help manage PEM.

Source: Moore GE, Keller BA, Stevens J, Mao X, Stevens SR, Chia JK, Levine SM, Franconi CJ, Hanson MR. Recovery from Exercise in Persons with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Medicina. 2023; 59(3):571. https://doi.org/10.3390/medicina59030571 (Full text)

A 2-day cardiopulmonary exercise test in chronic fatigue syndrome patients who were exposed to humidifier disinfectants

Abstract:

Some survivors of humidifier disinfectants (HDs) complain of chronic, inexplicable fatigue, and post-exertional malaise (PEM). Two-day cardiopulmonary exercise tests (CPETs) performed 24 hours apart (2-day CPET protocol) are increasingly employed to evaluate PEM and related disabilities among individuals with chronic fatigue syndrome (CFS). The purpose of this study was to assess the reproducibility of CPET variables in individuals who had been exposed to HD and to show that 2-day CPET is an objective means of differentiating between fatigue conditions in people with CFS symptoms who have been exposed to HDs.

Twenty-nine HD survivors with CFS symptoms were enrolled in this study. To document and assess PEM in CFS, a 2-day CPET was conducted to measure baseline functional capacity (CPET1) and provoke PEM. Twenty-four hours later, a second CPET assessed changes in related variables, focusing on PEM effects on functional capacity. This CPET also measured changes in energy production and physiological function, objectively documenting PEM effects.

In the 2-day CPET, the peak oxygen consumption (VO2peak), VO2 at ventilatory threshold (VO2@VT), time to reach VO2peak, and time to reach VO2@VT were significantly decreased (p<0.001). The peak O2 pulse and O2 pulse at VT also decreased significantly (p<0.001). A 6-minute walk test revealed significantly decreased distance (p<0.01). This is the first study to conduct a 2-day consecutive CPET in previously exposed HD participants with CFS symptoms.

Our results confirm previous work that demonstrated abnormal responses to PEM in CFS patients. Therefore, a 2-day CPET is an objective measure to differentiate fatigue conditions in people with CFS symptoms who have been exposed to HDs.

Source: Leem JH, Jeon HE, Nam H, Kim HC, Joa KL. A 2-day cardiopulmonary exercise test in chronic fatigue syndrome patients who were exposed to humidifier disinfectants. Environ Anal Health Toxicol. 2022 Dec;37(4):e2022033-0. doi: 10.5620/eaht.2022033. Epub 2022 Nov 3. PMID: 36916046; PMCID: PMC10014750. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014750/ (Full text)

Post-exertional malaise among people with long COVID compared to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Abstract:

Background: Long COVID describes a condition with symptoms that linger for months to years following acute COVID-19. Many of these Long COVID symptoms are like those experienced by patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Objective: We wanted to determine if people with Long COVID experienced post-exertional malaise (PEM), the hallmark symptom of ME/CFS, and if so, how it compared to PEM experienced by patients with ME/CFS.

Methods: A questionnaire that asked about the domains of PEM including triggers, experience, recovery, and prevention was administered to 80 people seeking care for Long COVID at Bateman Horne Center. Their responses were compared to responses about PEM given by 151 patients with ME/CFS using chi-square tests of independence.

Results: All but one Long COVID respondent reported having PEM. There were many significant differences in the types of PEM triggers, symptoms experienced during PEM, and ways to recover and prevent PEM between Long COVID and ME/CFS. Similarities between Long COVID and ME/CFS included low and medium physical and cognitive exertion to trigger PEM, symptoms of fatigue, pain, immune reaction, neurologic, orthostatic intolerance, and gastrointestinal symptoms during PEM, rest to recover from PEM, and pacing to prevent PEM.

Conclusion: People with Long COVID experience PEM. There were significant differences in PEM experienced by people with Long COVID compared to patients with ME/CFS. This may be due to the newness of Long COVID, not knowing what exertional intolerance is or how to manage it.

Source: Vernon SD, Hartle M, Sullivan K, Bell J, Abbaszadeh S, Unutmaz D, Bateman L. Post-exertional malaise among people with long COVID compared to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Work. 2023 Mar 7. doi: 10.3233/WOR-220581. Epub ahead of print. PMID: 36911963. https://content.iospress.com/articles/work/wor220581 (Full text)

A case of post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post-exertional malaise and low serum acylcarnitine level

Abstract:

COVID-19 afflicts patients with acute symptoms and longer term sequelae. One of the sequelae is myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is often difficult to diagnose, having no established tests. In this article, we synthesize information from literature reviews on patients with ME/CSF that developed after recovery from COVID-19.

Source: Jinushi R, Nishiguchi S, Masuda S, Sasaki A, Koizumi K, Ryozawa S. A case of post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post-exertional malaise and low serum acylcarnitine level. Clin Case Rep. 2023 Feb 10;11(2):e6930. doi: 10.1002/ccr3.6930. PMID: 36789311; PMCID: PMC9913186. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913186/ (Full text)

Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with unknown etiology or effective treatments. Post-exertional malaise (PEM) is a key symptom that distinguishes ME/CFS patients. Investigating changes in the urine metabolome between ME/CFS patients and healthy subjects following exertion may help us understand PEM.
The aim of this pilot study was to comprehensively characterize the urine metabolomes of eight female healthy sedentary control subjects and ten female ME/CFS patients in response to a maximal cardiopulmonary exercise test (CPET). Each subject provided urine samples at baseline and 24 h post-exercise. A total of 1403 metabolites were detected via LC-MS/MS by Metabolon® including amino acids, carbohydrates, lipids, nucleotides, cofactors and vitamins, xenobiotics, and unknown compounds.
Using a linear mixed effects model, pathway enrichment analysis, topology analysis, and correlations between urine and plasma metabolite levels, significant differences were discovered between controls and ME/CFS patients in many lipid (steroids, acyl carnitines and acyl glycines) and amino acid subpathways (cysteine, methionine, SAM, and taurine; leucine, isoleucine, and valine; polyamine; tryptophan; and urea cycle, arginine and proline).
Our most unanticipated discovery is the lack of changes in the urine metabolome of ME/CFS patients during recovery while significant changes are induced in controls after CPET, potentially demonstrating the lack of adaptation to a severe stress in ME/CFS patients.
Source: Glass KA, Germain A, Huang YV, Hanson MR. Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients. International Journal of Molecular Sciences. 2023; 24(4):3685. https://doi.org/10.3390/ijms24043685 https://www.mdpi.com/1422-0067/24/4/3685 (Full text available as PDF file)