Tag: PEM

Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue and postexertional malaise. We developed a provocation paradigm with two submaximal bicycle exercise stress tests on consecutive days bracketed by magnetic resonance imaging, orthostatic intolerance, and symptom assessments before and after exercise in order to induce objective changes of exercise induced symptom exacerbation and cognitive dysfunction.

Method: Blood oxygenation level dependent (BOLD) scans were performed while at rest on the preexercise and postexercise days in 34 ME/CFS and 24 control subjects. Seed regions from the FSL data library with significant BOLD signals were nodes that clustered into networks using independent component analysis. Differences in signal amplitudes between groups on pre- and post-exercise days were determined by general linear model and ANOVA.

Results: The most striking exercise-induced effect in ME/CFS was the increased spontaneous activity in the medial prefrontal cortex that is the anterior node of the Default Mode Network (DMN). In contrast, this region had decreased activation for controls. Overall, controls had higher BOLD signals suggesting reduced global cerebral blood flow in ME/CFS.

Conclusion: The dynamic increase in activation of the anterior DMN node after exercise may be a biomarker of postexertional malaise and symptom exacerbation in CFS. The specificity of this postexertional finding in ME/CFS can now be assessed by comparison to post-COVID fatigue, Gulf War Illness, fibromyalgia, chronic idiopathic fatigue, and fatigue in systemic medical and psychiatric diseases.

Source: Rayhan RU, Baraniuk JN. Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Neurosci. 2021 Dec 15;15:748426. doi: 10.3389/fnins.2021.748426. PMID: 34975370; PMCID: PMC8714840. https://www.frontiersin.org/articles/10.3389/fnins.2021.748426/full  (Full text)

Pain-related post-exertional malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia: A systematic review and three-level meta-analysis

Abstract:

Objective: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic musculoskeletal pain symptoms are prevalent. These individuals can experience post-exertional malaise (PEM), a phenomenon where symptom severity is worsened 24hr or longer following physical stress, but the pain-related component of PEM is not well characterized.

Design: Systematic review and meta-analysis.

Methods: Case-control studies involving adults with ME/CFS or FM and measuring pain symptoms before and after exposure to a standardized aerobic exercise test were included. Hedges’ d effect sizes were aggregated using random effects models and potential moderators were explored with meta-regression analysis. Results were adjusted for nesting effects using three-level modeling.

Results: Forty-five effects were extracted from 15 studies involving 306 patients and 292 healthy controls. After adjusting for nesting effects, we observed a small-to-moderate effect indicating higher post-exercise pain in patients than controls (Hedges’ d=0.42; 95% CI: 0.16, 0.67). The mean effect was significantly moderated by pain measurement timepoint (b = -0.19, z = -2.57, P = 0.01) such that studies measuring pain 8-72hr post-exercise showed larger effects (d = 0.71, 95% CI = 0.28-1.14) than those measuring pain 0-2hr post-exercise (d = 0.32, 95% CI = 0.10-0.53).

Conclusions: People with ME/CFS and FM experience small-to-moderate increases in pain severity following exercise which confirms pain as a component of PEM and emphasizes its debilitating impact in ME/CFS and FM. Future directions include determining mechanisms of pain-related PEM and developing exercise prescriptions that minimize symptom exacerbation in these illnesses.

Source: Barhorst EE, Boruch AE, Cook DB, Lindheimer JB. Pain-related post-exertional malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia: A systematic review and three-level meta-analysis. Pain Med. 2021 Oct 20:pnab308. doi: 10.1093/pm/pnab308. Epub ahead of print. PMID: 34668532. https://pubmed.ncbi.nlm.nih.gov/34668532/

Fatigue and post-exertional symptom exacerbation in Covid

Long Covid rehabilitation should include educating people about resuming everyday activities conservatively: WHO

By SHAHISTHA HAQUE

Fatigue is a feeling of extreme exhaustion. One feels over tired, low level of energy and extreme urge to sleep. It is the most common symptom of long Covid. It is easily relieved by rest or sleep. It is not the result of usually difficult activity. It can limit functioning in day to day activities. It negatively impacts the quality of life.

Now talking about post-exertional symptom exacerbation (PESE), it is a disabling and often delayed exhaustion disproportionate to the effort made. It is something described as crash.
The activity that can trigger this worsening of symptoms can be something that was easily tolerated before such as a daily activity e.g., a shower, a social activity, walking, reading, writing or working at a desk, an emotionally charged conversation, being in a sensory environment e.g., loud music or flashing lights.
Many of the symptoms experienced by those living with long Covid are very similar to those of myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS).
According to WHO, long Covid rehabilitation should include educating people about resuming everyday activities conservatively, at an appropriate pace that is safe and manageable for energy levels within the limit of current symptoms and exertion should not be pushed to the point of fatigue or symptom exacerbation.
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Chronic Fatigue Syndrome and Cardiovascular Disease: JACC State-of-the-Art Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medically unexplained illness characterized by severe fatigue limiting normal daily activities for at least 6 months accompanied by problems with unrefreshing sleep, exacerbation of symptoms following physical or mental efforts (postexertional malaise [PEM]), and either cognitive reports or physiological evidence of orthostatic intolerance in the form of either orthostatic tachycardia and/or hypocapnia.

Although rarely considered to have cardiac dysfunction, ME/CFS patients frequently have reduced stroke volume with a significant inverse relation between cardiac output and PEM severity. Magnetic resonance imaging of ME/CFS patients compared with normal control subjects found significantly reduced stroke, end-systolic, and end-diastolic volumes together with reduced end-diastolic wall mass. Another cardiovascular abnormality is reduced nocturnal blood pressure assessed by 24-hour monitoring. Autonomic dysfunction is also frequently observed with postural orthostatic tachycardia and/or hypocapnia. Two consecutive cardiopulmonary stress tests may provide metabolic data substantiating PEM.

Source: Natelson BH, Brunjes DL, Mancini D. Chronic Fatigue Syndrome and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021 Sep 7;78(10):1056-1067. doi: 10.1016/j.jacc.2021.06.045. PMID: 34474739. https://pubmed.ncbi.nlm.nih.gov/34474739/

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/

Chronic fatigue and post-exertional malaise in people living with long COVID

Abstract:

Purpose People living with long COVID describe a high symptom burden, and a more detailed assessment of chronic fatigue and post-exertional malaise (PEM) may inform the development of rehabilitation recommendations. The aims of this study were to use validated questionnaires to measure the severity of fatigue and compare this with normative data and thresholds for clinical relevance in other diseases; measure and describe the impact of PEM; and describe symptoms of dysfunctional breathing, self-reported physical activity/sitting time, and health-related quality of life.

Methods This was an observational study involving an online survey for adults living with long COVID (data collection from February-April, 2021) following a confirmed or suspected SARS-CoV-2 infection. Questionnaires included the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) and DePaul Symptom Questionnaire-Post-Exertional Malaise.

Results After data cleaning, n=213 participants were included in the analysis. Participants primarily identified as women (85.5%), aged 40-59 (78.4%), who had been experiencing long COVID symptoms for ≥6 months (72.3%). The total FACIT-F score was 18±10 (where the score can range from 0-52, and a lower score indicates more severe fatigue), and 71.4% were experiencing chronic fatigue. Post-exertional symptom exacerbation affected most participants, and 58.7% met the scoring thresholds used in people living with myalgic encephalomyelitis/chronic fatigue syndrome. PEM occurred alongside a reduced capacity to work, be physically active, and function both physically and socially.

Conclusion Long COVID is characterized by chronic fatigue that is clinically relevant and is at least as severe as fatigue in several other clinical conditions, including cancer. PEM appears to be a common and significant challenge for the majority of this patient group. Patients, researchers, and allied health professionals are seeking information on safe rehabilitation for people living with long COVID, particularly regarding exercise. Fatigue and post-exertional symptom exacerbation must be monitored and reported in studies involving interventions for people with long COVID.

Source: Rosie Twomey, Jessica DeMars, Kelli Franklin, S. Nicole Culos-Reed, Jason Weatherald, James G. Wrightson. Chronic fatigue and post-exertional malaise in people living with long COVID. medRxiv 2021.06.11.21258564; doi: https://doi.org/10.1101/2021.06.11.21258564 https://www.medrxiv.org/content/10.1101/2021.06.11.21258564v1

Post-Exertional Malaise May Be Related to Central Blood Pressure, Sympathetic Activity and Mental Fatigue in Chronic Fatigue Syndrome Patients

Abstract:

Post-exertional malaise (PEM) is regarded as the hallmark symptom in chronic fatigue syndrome (CFS). The aim of the current study is to explore differences in CFS patients with and without PEM in indicators of aortic stiffness, autonomic nervous system function, and severity of fatigue. One-hundred and one patients met the Fukuda criteria.

A Chronic Fatigue Questionnaire (CFQ) and Fatigue Impact Scale (FIS) were used to assess the level of mental and physical fatigue. Aortic systolic blood pressure (sBPaortic) and the autonomic nervous system were measured with the arteriograph and Task Force Monitor, respectively. Eighty-two patients suffered prolonged PEM according to the Fukuda criteria, while 19 did not.

Patients with PEM had higher FIS scores (p = 0.02), lower central systolic blood pressure (p = 0.02) and higher mental fatigue (p = 0.03). For a one-point increase in the mental fatigue component of the CFQ scale, the risk of PEM increases by 34%. For an sBPaortic increase of 1 mmHg, the risk of PEM decreases by 5%. For a one unit increase in sympathovagal balance, the risk of PEM increases by 330%.

Higher mental fatigue and sympathetic activity in rest are related to an increased risk of PEM, while higher central systolic blood pressure is related to a reduced risk of PEM. However, none of the between group differences were significant after FDR correction, and therefore conclusions should be treated with caution and replicated in further studies.

Source: Kujawski S, Słomko J, Hodges L, Pheby DFH, Murovska M, Newton JL, Zalewski P. Post-Exertional Malaise May Be Related to Central Blood Pressure, Sympathetic Activity and Mental Fatigue in Chronic Fatigue Syndrome Patients. J Clin Med. 2021 May 26;10(11):2327. doi: 10.3390/jcm10112327. PMID: 34073494. https://pubmed.ncbi.nlm.nih.gov/34073494/

Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and debilitating disease accompanied by muscular fatigue and pain. A functional measure to assess muscle fatigability of ME/CFS patients is, however, not established in clinical routine. The aim of this study is to evaluate by assessing repeat maximum handgrip strength (HGS), muscle fatigability as a diagnostic tool and its correlation with clinical parameters.

Methods: We assessed the HGS of 105 patients with ME/CFS, 18 patients with Cancer related fatigue (CRF) and 66 healthy controls (HC) using an electric dynamometer assessing maximal (Fmax) and mean force (Fmean) of ten repetitive measurements. Results were correlated with clinical parameters, creatinine kinase (CK) and lactate dehydrogenase (LDH). Further, maximum isometric quadriceps strength measurement was conducted in eight ME/CFS patients and eight HC.

Results: ME/CFS patients have a significantly lower Fmax and Fmean HGS compared to HC (p < 0.0001). Further, Fatigue Ratio assessing decline in strength during repeat maximal HGS measurement (Fmax/Fmean) was higher (p ≤ 0.0012). The Recovery Ratio after an identical second testing 60 min later was significantly lower in ME/CFS compared to HC (Fmean2/Fmean1; p ≤ 0.0020). Lower HGS parameters correlated with severity of disease, post-exertional malaise and muscle pain and with higher CK and LDH levels after exertion.

Conclusion: Repeat HGS assessment is a sensitive diagnostic test to assess muscular fatigue and fatigability and an objective measure to assess disease severity in ME/CFS.

Source: Jäkel B, Kedor C, Grabowski P, Wittke K, Thiel S, Scherbakov N, Doehner W, Scheibenbogen C, Freitag H. Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS. J Transl Med. 2021 Apr 19;19(1):159. doi: 10.1186/s12967-021-02774-w. PMID: 33874961. https://pubmed.ncbi.nlm.nih.gov/33874961/

Dissecting the nature of post-exertional malaise

Abstract:

Background: Post-exertional malaise (PEM) is a defining characteristic of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) but there is insufficient research dissecting the nature of PEM from the patients’ perspective.

Methods: A PEM questionnaire administered to 150 ME/CFS patients. It included open-ended questions about triggers, experiences, recovery, and prevention. Responses were re-coded into concise, representative topics. Chi-Square tests of independence were then used to test for differences and relationships between duration of ME/CFS illness (<4 years and >10 years), PEM onset and duration, and gender with PEM trigger, experience, recovery, and prevention.

Results: Physical exertion was the most common trigger of PEM. The onset of PEM occurred within minutes after physical exertion compared to within hours after cognitive exertion (<0.05). ME/CFS patients sick for <4 years reported stress as a trigger significantly more often than those sick for >10 years (<0.001). ME/CFS patients sick for <4 years experienced more orthostatic symptoms during PEM than those sick for >10 years. ME/CFS patients sick for >10 years reported using medications to recover from PEM significantly more that those sick for <4 years (<0.01). Pacing and avoiding specific triggers were common approaches to prevent PEM.

Conclusions: There are differences in PEM triggers, experiences and recovery based on duration of illness. Asking about PEM is important for diagnosis and to understand how to manage PEM. Given that PEM occurs more quickly after physical versus cognitive exertion, these results should instigate research on the relationship of upright posture, hypoperfusion and PEM.

Source: Megan Hartle, Lucinda Bateman & Suzanne D. Vernon (2021) Dissecting the nature of post-exertional malaise, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2021.1905415 https://www.tandfonline.com/doi/full/10.1080/21641846.2021.1905415 (Full text)

Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Introduction: Muscle pain, fatigue, and concentration problems are common among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These symptoms are commonly increased as part of the phenomenon of postexertional malaise (PEM). An increase in the severity of these symptoms is described following physical or mental exercise in ME/CFS patients. Another important symptom of ME/CFS is orthostatic intolerance, which can be detected by head-up tilt testing (HUT). The effect of HUT on PEM has not been studied extensively. For this purpose, we assessed numeric rating scales (NRS) for pain, fatigue, and concentration pre- and post-HUT. As pain is a core symptom in fibromyalgia (FM), we subgrouped ME/CFS patients by the presence or absence of FM.

Methods and Results: In eligible ME/CFS patients who underwent HUT, NRS of pain, fatigue, and concentration were obtained pre-HUT, immediately after HUT, at 24 and 48 h, and at 7 days posttest. We studied 174 ME/CFS patients with FM, 104 without FM, and 30 healthy controls (HC). Values for all symptoms were unchanged for HC pre- and post-HUT. Compared with pre-HUT, the three NRS post-HUT were significantly elevated in both ME/CFS patient groups even after 7 days. NRS pain was significantly higher at all time points measured in the ME/CFS patients with FM compared with those without FM. In ME/CFS patients, the maximum fatigue and concentration scores occurred directly post-HUT, whereas pain perception reached the maximum 24 h post-HUT.

Conclusion: NRS scores of pain, fatigue, and concentration were significantly increased even at 7 days post-HUT compared with pre-HUT in ME/CFS patients with and without FM, suggesting that orthostatic stress is an important determinant of PEM.

Source: C (Linda) M. C. van Campen, Peter C. Rowe, Freek W. A. Verheugt and Frans C. Visser. Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front. Med., 27 January 2021 | https://doi.org/10.3389/fmed.2020.602894 https://www.frontiersin.org/articles/10.3389/fmed.2020.602894/full  (Full text)