Tag: PEM

Two-Day Cardiopulmonary Exercise Testing in Long COVID Post-Exertional Malaise Diagnosis

Abstract:

Background: Long COVID patients present with a myriad of symptoms that can include fatigue, exercise intolerance and post exertional malaise (PEM). Long COVID has been compared to other post viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), where a reduction in day 2 cardiopulmonary exercise test (CPET) performance of a two-day CPET protocol is suggested to be a result of PEM. We investigated cardiopulmonary and perceptual responses to a two-day CPET protocol in Long COVID patients.

Methods: 15 Long COVID patients [n=7 females; mean (SD) age: 53(11) yr; BMI = 32.2(8.5) kg/m2] performed a pulmonary function test and two ramp-incremental CPETs separated by 24hr. CPET variables included gas exchange threshold (GET), V̇O2peak and WRpeak. Ratings of perceived dyspnoea and leg effort were recorded at peak exercise using the modified 0-10 Borg Scale. PEM (past six months) was assessed using the modified DePaul Symptom Questionnaire (mDSQ). One-sample t-tests were used to test significance of mean difference between days (p<0.05).

Results: mDSQ revealed PEM in 80% of patients. Lung function was normal. Responses to day 1 CPET were consistent with the presence of aerobic deconditioning in 40% of patients (V̇O2peak <80% predicted, in the absence of evidence of cardiovascular and pulmonary limitations). There were no differences between day-1 and day-2 CPET responses (all p>0.05).

Conclusion: Post exertional malaise symptoms in Long COVID patients, in the absence of differences in two-day CPET responses separated by 24hours, suggests that post-exertional malaise is not due to impaired recovery of exercise capacity between days.

Source: Gattoni C, Abbasi A, Ferguson C, Lanks CW, Decato TW, Rossiter HB, Casaburi R, Stringer WW. Two-Day Cardiopulmonary Exercise Testing in Long COVID Post-Exertional Malaise Diagnosis. Respir Physiol Neurobiol. 2024 Oct 25:104362. doi: 10.1016/j.resp.2024.104362. Epub ahead of print. PMID: 39490617. https://www.sciencedirect.com/science/article/pii/S1569904824001551 (Full text)

The persistence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis

Highlights:

  • SARS-CoV-2 can trigger Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
  • 51% of Long COVID-19 patients have Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
  • Long COVID-19 is a new name for an old disease.

Abstract:

Objectives: Long COVID-19 (LC) patients experience a number of chronic idiopathic symptoms that are highly similar to those of post-viral Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We have therefore performed a systematic review and meta-analysis to determine the proportion of LC patients that satisfy ME/CFS diagnostic criteria.

Methods: Clinical studies published between January 2020 to May 2023 were identified using the PubMed, Web of Science, Embase and CINAHL databases. Publication inclusion/exclusion criteria were formulated using the global CoCoPop framework. Data were pooled using a random-effects model with a restricted maximum-likelihood estimator. Study quality was assessed using the Joanna Briggs Institute critical assessment tool.

Results: We identified 13 eligible studies that reported a total of 1,973 LC patients. Our meta-analysis indicated that 51% (95% CI, 42%-60%) of LC patients satisfied ME/CFS diagnostic criteria with fatigue, sleep disruption, and muscle/joint pain being the most common symptoms. Importantly, LC patients also experienced the ME/CFS hallmark symptom, post-exertional malaise.

Conclusions: Our study not only demonstrates that LC patients exhibit similar symptom clusters to ME/CFS, but that approximately half of LC patients satisfy a diagnosis of ME/CFS. Our findings suggest that current ME/CFS criteria could be adapted to the identification of a subset of LC patients that may facilitate the standardized diagnosis, management and the recruitment for clinical studies in the future.

Source: Ankush Dehlia, Mark A. Guthridge. The persistence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis. Journal of Infection, 2024, 106297, ISSN 0163-4453, https://doi.org/10.1016/j.jinf.2024.106297.
https://www.sciencedirect.com/science/article/pii/S0163445324002317 (Full text)

Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: A considerable number of patients who contracted SARS-CoV-2 are affected by persistent multi-systemic symptoms, referred to as Post-COVID Condition (PCC). Post-exertional malaise (PEM) has been recognized as one of the most frequent manifestations of PCC and is a diagnostic criterion of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Yet, its underlying pathomechanisms remain poorly elucidated.

Purpose and methods: In this review, we describe current evidence indicating that key pathophysiological features of PCC and ME/CFS are involved in physical activity-induced PEM.

Results: Upon physical activity, affected patients exhibit a reduced systemic oxygen extraction and oxidative phosphorylation capacity. Accumulating evidence suggests that these are mediated by dysfunctions in mitochondrial capacities and microcirculation that are maintained by latent immune activation, conjointly impairing peripheral bioenergetics. Aggravating deficits in tissue perfusion and oxygen utilization during activities cause exertional intolerance that are frequently accompanied by tachycardia, dyspnea, early cessation of activity and elicit downstream metabolic effects. The accumulation of molecules such as lactate, reactive oxygen species or prostaglandins might trigger local and systemic immune activation. Subsequent intensification of bioenergetic inflexibilities, muscular ionic disturbances and modulation of central nervous system functions can lead to an exacerbation of existing pathologies and symptoms.

Source: Haunhorst S, Dudziak D, Scheibenbogen C, Seifert M, Sotzny F, Finke C, Behrends U, Aden K, Schreiber S, Brockmann D, Burggraf P, Bloch W, Ellert C, Ramoji A, Popp J, Reuken P, Walter M, Stallmach A, Puta C. Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome. Infection. 2024 Sep 6. doi: 10.1007/s15010-024-02386-8. Epub ahead of print. PMID: 39240417. https://link.springer.com/article/10.1007/s15010-024-02386-8 (Full text)

Post-Exertional Malaise in Veterans with Gulf War Illness

Abstract:

Post-exertional malaise (PEM) is a potentially debilitating aspect of Gulf War Illness (GWI) that has received limited research attention. The purpose of the present investigation was to determine symptom severity changes following exercise in Veterans with GWI compared to control Veterans without GWI (CO).

Sixty-seven Veterans (n=39 GWI; n=28 CO) underwent a 30-minute submaximal exercise challenge at 70% of heart rate reserve. Symptom measurements (e.g. fatigue, pain) occurred pre-, immediately post-, and 24-hours post-exercise. Self-reported physical and mental health, and physiological and perceptual responses to exercise were compared between groups using descriptive statistics, independent samples t-tests and repeated measures Analysis of Variance (RM-ANOVA).

Post-exertional malaise was modeled using Group by Time (2 × 3) doubly-multivariate, RM-MANOVAs for (1) mood, (2) pain and (3) GWI-related symptoms, respectively (α=0.05). Data were analyzed for the full sample of Veterans with GWI (n=39) compared to CO (n=28) and a subsample of Veterans (n=18) who endorsed “feeling unwell after physical exercise or exertion” (“PEM endorsers”) during screening.

Veterans with GWI reported significantly lower physical and mental health. Groups exercised at similar relative exercise intensities, but GWI perceived exercise as more painful and fatiguing. Group-by-Time interactions were not significant for the entire sample for the three PEM models, however limiting the GWI sample to “PEM endorsers” resulted in significant interactions for Pain- and GWI-related PEM models.

These results indicate that not all GVs with GWI experience PEM 24 hr after exercise, and that more research is needed to determine the extent that exercise worsens symptoms in GWI.

Source: Lindheimer JB, Stegner AJ, Wylie GR, Klein-Adams JC, Almassi NE, Ninneman JV, Van Riper SM, Dougherty RJ, Falvo MJ, Cook DB. Post-exertional malaise in veterans with gulf war illness. Int J Psychophysiol. 2020 Jan;147:202-212. doi: 10.1016/j.ijpsycho.2019.11.008. Epub 2019 Nov 28. PMID: 31786249; PMCID: PMC6957714. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957714/ (Full text)

Assessing Functional Capacity in Myalgic Encephalopathy/Chronic Fatigue Syndrome: A Patient-Informed Questionnaire

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an acquired disease with significant morbidity that affects both children and adults. Post-exertional malaise is a cardinal symptom of ME/CFS and impacts a patient’s functional capacity (FC). The absence of effective tools to assess FC has significant consequences for timely diagnosis, clinical follow-up, assessments for patient disability benefits, and research studies. In interventional studies, the inability to assess FC can result in an incomplete assessment of the potential benefit of the intervention, leading to beneficial treatment outcomes being missed.
Methods: Using extensive, repeated patient feedback, we have developed a new questionnaire, FUNCAP, to accurately assess FC in ME/CFS patients. The questionnaire consists of eight domains divided by activity types: A. personal hygiene/basic functions, B. walking/movement, C. being upright, D. activities in the home, E. communication, F. activities outside the home, G. reactions to light and sound, and H. concentration.
Results: Through five rounds of anonymous web-based surveys and a further test–retest validation round, two versions of the questionnaire were developed: a longer version comprising 55 questions (FUNCAP55), developed for improved diagnostic and disability benefit/insurance FC assessments; and a shorter version (FUNCAP27) for clinical patient follow-up and potential use in research. Good reliability and validity and negligible floor and ceiling effects were found, with comparable findings in all aspects in both a large Norwegian (n = 1263) and a separate English-language international sample (n = 1387) demonstrating the validity and reliability of FUNCAP.
Conclusions: Our findings support the utility of FUNCAP as an effective, reliable and valid tool for assessing FC in ME/CFS patients.
Source: Sommerfelt K, Schei T, Seton KA, Carding SR. Assessing Functional Capacity in Myalgic Encephalopathy/Chronic Fatigue Syndrome: A Patient-Informed Questionnaire. Journal of Clinical Medicine. 2024; 13(12):3486. https://doi.org/10.3390/jcm13123486 https://www.mdpi.com/2077-0383/13/12/3486 (Full text)

Medical students highlight the importance of medical education, kindness, compassion and belief when learning about patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

‘Imagine my surprise to discover ME/CFS is definitely not rare, but inexplicably and infuriatingly unacknowledged’. Fifth year medical student, Scotland.
Earlier this year, medical students at Scottish medical schools were invited to take part in an essay competition, 500 words on the topic of ‘What is your most important learning point about myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)?’ This edition proudly features the first prize winning essay of the competition which was funded by the Scottish Government’s education project; Learn About ME.1
ME/CFS affects at least 280,000 people in the UK, including approximately 23,000 in Scotland. It is a neurological disease with multisystem symptoms, often triggered by a virus. People with ME/CFS may be left bedbound or housebound with a significantly reduced quality of life.2 Yet many healthcare professionals do not know how to diagnose or manage this devastating disease, nor do they know how, or what, to teach our next generation of doctors.3
People with ME/CFS, and a subset of those with long COVID, experience symptoms including post-exertional malaise (PEM), unrefreshing sleep, profound fatigue, brain fog and orthostatic intolerance.4
Patients can also present with sore throats, muscle aches, disrupted sleep, changes in bowel habit, joint and bone pain, problems with multitasking and short-term memory, word-finding difficulties, headaches, changes in smell and taste, tinnitus, disrupted menses, breathlessness, dizziness, skin rashes and hair loss.4
Research into underlying mechanisms has revealed key defects: an abnormal response to repeat exercise, gait and strength abnormalities, immune system dysfunction, neuroinflammation, altered blood cell morphology and clotting, problems with cellular-energy delivery, microbial gut dysbiosis and changes in metabolomics.5
The lack of medical education on this topic and resulting weak clinical knowledge of ME/CFS has resulted in delays to diagnosis, multiple clinic referrals and a huge cost to every taxpayer. ME/CFS costs the UK an estimated £3.3 billion a year6 and long COVID clinics cost millions, with funding being extended for this chronic condition. Yet Scottish services are struggling to find healthcare practitioners to deliver this care or worse, offering potentially harmful patient support workshops that are directly in conflict with the NICE (NG206) 2021 ME/CFS guidelines such as the highly criticised ‘Lightning Process’.7 Medical education on ME/CFS and post-acute infectious disease is urgently needed for earlier recognition and better management.
One student described the experience and delay in diagnosis for two of their family members: ‘. . .these young women were discarded as victims of teenage laziness or anxiety. They had to fight to gain support from their GP (General Practitioner) and their diagnosis took several second opinions and ultimately years’.
Outdated treatment using graded exercise, shown to harm ME/CFS patients, has been rebranded as ‘activity management’ in some services and offered to both ME/CFS and long COVID patients. Another medical student displayed incredible insight in recognising the deficiency of the current system, which relies largely on patient self-help: ‘the burden being placed on the patient to improve their condition through mental work’.
The key feature of ME/CFS is PEM. The most important thing to learn about PEM is that even trivial activity (whether physical, mental or emotional) can exacerbate symptoms, and that this exacerbation or flare can be delayed. A person with ME/CFS who can sit upright for five minutes on a given day could be too ill to sit up at all the next day due to PEM.8
A traditional rehabilitation programme led by a physiotherapist might include graded activity or exercise. For a non-ME/CFS person following a sports injury, orthopaedic surgery or intensive care, gently increasing activity for just a few minutes, or a few steps at a time is ideal. However, for ME/CFS patients, this approach could be incredibly harmful. People with ME/CFS need to conserve their energy and pace themselves to avoid a flare in symptoms.4
People who are only mildly affected still experience a major negative impact on their ability to work. They have very little energy for socialising, hobbies and housework. For those moderately affected, basic activities of normal daily living such as preparing food, washing and dressing can cause symptom exacerbation. Very severely affected individuals, who are often bedbound, can experience PEM from simply turning in bed, speaking and digesting food.9
ME/CFS also has a major impact on family members’ quality of life.2 Nearly a third of medical students responding commented on the impact on quality of life as being one of the most important things to learn about this disease.
Several students wrote about a family member, or friend, whom they knew with ME/CFS. Sadly, it was a recurring theme that the medical students explained they had not been taught about ME/CFS at medical school. One commented: ‘Alas, the only time in the last four years I have encountered the term ME/CFS at medical school was as a differential diagnosis for fibromyalgia’.
It is vital that this topic features more prominently in the medical curriculum, and in our medical textbooks, to avoid patient harm due to delayed or mis-diagnosis and mismanagement. There is a lot we can offer ME/CFS patients: an early and accurate diagnosis, medication for symptom control, practical support with disability applications and mobility aids, but above all, these medical students have reminded us that ME/CFS patients should be treated with kindness, compassion and belief.10
Source: Muirhead NL. Medical students highlight the importance of medical education, kindness, compassion and belief when learning about patients with myalgic encephalomyelitis/chronic fatigue syndrome. J R Coll Physicians Edinb. 2024 May 27:14782715241255977. doi: 10.1177/14782715241255977. Epub ahead of print. PMID: 38798174. https://journals.sagepub.com/doi/10.1177/14782715241255977 (Full text)

Interdisciplinary, collaborative D-A-CH (Germany, Austria and Switzerland) consensus statement concerning the diagnostic and treatment of myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

in English, German

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe, chronic multisystemic disease which, depending on its severity, can lead to considerable physical and cognitive impairment, loss of ability to work and the need for nursing care including artificial nutrition and, in very severe cases, even death.

The aim of this D-A-CH (Germany, Austria, Switzerland) consensus statement is 1) to summarize the current state of knowledge on ME/CFS, 2) to highlight the Canadian Consensus Criteria (CCC) as clinical criteria for diagnostics with a focus on the leading symptom post-exertional malaise (PEM) and 3) to provide an overview of current options and possible future developments, particularly with regard to diagnostics and therapy. The D-A-CH consensus statement is intended to support physicians, therapists and valuer in diagnosing patients with suspected ME/CFS by means of adequate anamnesis and clinical-physical examinations as well as the recommended clinical CCC, using the questionnaires and other examination methods presented.

The overview of the two pillars of therapy for ME/CFS, pacing and symptom-relieving therapy options, is intended not only to provide orientation for physicians and therapists, but also to support decision-makers from healthcare policy and insurance companies in determining which therapy options should already be reimbursable by them at this point in time for the indication ME/CFS.

Source: Hoffmann K, Hainzl A, Stingl M, Kurz K, Biesenbach B, Bammer C, Behrends U, Broxtermann W, Buchmayer F, Cavini AM, Fretz GS, Gole M, Grande B, Grande T, Habermann-Horstmeier L, Hackl V, Hamacher J, Hermisson J, King M, Kohl S, Leiss S, Litzlbauer D, Renz-Polster H, Ries W, Sagelsdorff J, Scheibenbogen C, Schieffer B, Schön L, Schreiner C, Thonhofer K, Strasser M, Weber T, Untersmayr E. Interdisziplinäres, kollaboratives D-A-CH Konsensus-Statement zur Diagnostik und Behandlung von Myalgischer Enzephalomyelitis/Chronischem Fatigue-Syndrom [Interdisciplinary, collaborative D-A-CH (Germany, Austria and Switzerland) consensus statement concerning the diagnostic and treatment of myalgic encephalomyelitis/chronic fatigue syndrome]. Wien Klin Wochenschr. 2024 Aug;136(Suppl 5):103-123. German. doi: 10.1007/s00508-024-02372-y. Epub 2024 May 14. PMID: 38743348. https://pubmed.ncbi.nlm.nih.gov/38743348/

Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19

Abstract:

Objectives: To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment.

Methods: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We collected demographics, symptoms, skin biopsy, iCPET testing, treatments, and clinical response to treatment or no intervention.

Results: Sixteen patients were diagnosed with SFN on skin biopsy (median age 47, 75% female, 75% White). 92% of patients reported postexertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and 7 patients underwent iCPET, which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Nine patients underwent treatment with IVIG, and 7 were not treated with IVIG. The IVIG group experienced significant clinical response in their neuropathic symptoms (9/9) compared with those who did not receive IVIG (3/7; p = 0.02).

Discussion: Here, we present preliminary evidence that after COVID-19, SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia on iCPET. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating postinfectious SFN.

Classification of evidence: This study provides Class III evidence. It is a retrospective cohort study.

Source: McAlpine L, Zubair AS, Joseph P, Spudich S. Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19. Neurol Neuroimmunol Neuroinflamm. 2024 May;11(3):e200244. doi: 10.1212/NXI.0000000000200244. Epub 2024 Apr 17. PMID: 38630952. https://www.neurology.org/doi/10.1212/NXI.0000000000200244 (Full text)

Impaired Hand Grip Strength Correlates with Greater Disability and Symptom Severity in Post-COVID Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Post-COVID syndrome (PCS) encompasses a diverse array of symptoms persisting beyond 3 months after acute SARS-CoV-2 infection, with mental as well as physical fatigue being the most frequent manifestations.
Methods: In 144 female patients with PCS, hand grip strength (HGS) parameters were assessed as an objective measure of muscle fatigue, with 78 meeting the Canadian Consensus Criteria for postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The severity of disability and key symptoms was evaluated using self-reported questionnaires.
Results: Patients with ME/CFS exhibited heightened overall symptom severity, including lower physical function (p < 0.001), a greater degree of disability (p < 0.001), more severe fatigue (p < 0.001), postexertional malaise (p < 0.001), and autonomic dysfunction (p = 0.004) compared to other patients with PCS. While HGS was impaired similarly in all patients with PCS and exhibited a significant correlation with physical function across the entire patient group, HGS of patients with ME/CFS uniquely demonstrated associations with key symptoms.
Conclusions: Thus, impaired HGS serves as an objective marker of physical function in patients with PCS. Only in patients meeting ME/CFS criteria is impaired HGS also associated with the severity of hallmark symptoms. This suggests a common mechanism for muscle fatigue and other symptoms in the ME/CFS subtype, distinct from that in other types of PCS.
Source: Paffrath A, Kim L, Kedor C, Stein E, Rust R, Freitag H, Hoppmann U, Hanitsch LG, Bellmann-Strobl J, Wittke K, et al. Impaired Hand Grip Strength Correlates with Greater Disability and Symptom Severity in Post-COVID Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Clinical Medicine. 2024; 13(7):2153. https://doi.org/10.3390/jcm13072153 https://www.mdpi.com/2077-0383/13/7/2153

Attenuating Post-exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long-COVID: Is Blood Lactate Monitoring the Answer?

Highlights:

  • Lactate monitoring has the potential to extend beyond applied sports settings and could be used to monitor the physiologic and pathophysiological responses to external and internal stimuli in chronic disease areas such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Covid syndrome or Long Covid.
  • It is applicable due to the recurrent, episodic and often disabling post-exertional symptom exacerbation (PESE) otherwise referred to as post-exertional malaise (PEM) which is a characteristic symptom of ME/CFS and Long Covid that can last for days and/or weeks.
  • Lactate monitoring presents an opportunity to support those living with ME/CFS and Long COVID, by allowing patients and practitioners to determine the intensity and anaerobic contribution to everyday tasks which could aid the development of pacing strategies that prevent PEM/PESE.

Source: Faghy PMA, Ashton DRE, McNeils MR, Arena R, Duncan DR. Attenuating Post-exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long-COVID: Is Blood Lactate Monitoring the Answer? Curr Probl Cardiol. 2024 Mar 30:102554. doi: 10.1016/j.cpcardiol.2024.102554. Epub ahead of print. PMID: 38561114. https://www.sciencedirect.com/science/article/abs/pii/S0146280624001932