Tag: PEM

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)

Homebound versus Bedridden Status among Those with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Persons living with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) vary widely in terms of the severity of their illness. It is estimated that of those living with ME/CFS in the United States, about 385,000 are homebound. There is a need to know more about different degrees of being homebound within this severely affected group. The current study examined an international sample of 2138 study participants with ME/CFS, of whom 549 were severely affected (operationalized as ‘Homebound’). A subsample of 89 very severely affected participants (operationalized as ‘Homebound-bedridden’) was also examined. The findings showed a significant association between severely and very severely affected participants within the post-exertional malaise (PEM) symptom domain. The implications of these findings are discussed.

Source: Conroy K, Bhatia S, Islam M, Jason LA. Homebound versus Bedridden Status among Those with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare (Basel). 2021 Jan 20;9(2):E106. doi: 10.3390/healthcare9020106. PMID: 33498489. https://pubmed.ncbi.nlm.nih.gov/33498489/

Modulatory effects of cognitive exertion on regional functional connectivity of the salience network in women with ME/CFS: A pilot study

Abstract:

Background: A common symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM). Various brain abnormalities have been observed in patients with ME/CFS, especially in insular and limbic areas, but their link with ME/CFS symptoms is still unclear. This pilot study aimed at investigating the association between PEM in ME/CFS and changes in functional connectivity (FC) of two main networks: the salience network (SN) and the default-mode network (DMN).

Methods: A total of 16 women, 6 with and 10 without ME/CFS, underwent clinical and MRI assessment before and after cognitive exertion. Resting-state FC maps of 7 seeds (3 for the SN and 4 for the DMN) and clinical measures of fatigue, pain and cognition were analysed with repeated-measure models. FC-symptom change associations were also investigated.

Results: Exertion induced increases in fatigue and pain in patients with ME/CFS, compared to the control group, while no changes were found in cognitive performance. At baseline, patients showed altered FC between some DMN seeds and frontal areas and stronger FC between all SN seeds and left temporal areas and the medulla. Significantly higher FC increases in patients than in controls were found only between the right insular seed and frontal and subcortical areas; these increases correlated with worsening of symptoms.

Conclusions: Cognitive exertion can induce worsening of ME/CFS-related symptoms. These changes were here associated with strengthening of FC of the right insula with areas involved in reward processing and cognitive control.

Source: Riccardo Manca, Katija Khan, Micaela Mitolo, Matteo DeMarco, Lynsey Grieveson, Rosemary Varley, Iain D. Wilkinson, Annalena Venneri. Journal of the Neurological Sciences Preprint. January 22, 2021. DOI:https://doi.org/10.1016/j.jns.2021.117326 https://www.jns-journal.com/article/S0022-510X(21)00019-8/fulltext#secst0005 

Exercise alters brain activation in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Gulf War Illness affects 25–30% of American veterans deployed to the 1990–91 Persian Gulf War and is characterized by cognitive post-exertional malaise following physical effort. Gulf War Illness remains controversial since cognitive post-exertional malaise is also present in the more common Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An objective dissociation between neural substrates for cognitive post-exertional malaise in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome would represent a biological basis for diagnostically distinguishing these two illnesses.

Here, we used functional magnetic resonance imaging to measure neural activity in healthy controls and patients with Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome during an N-back working memory task both before and after exercise. Whole brain activation during working memory (2-Back > 0-Back) was equal between groups prior to exercise. Exercise had no effect on neural activity in healthy controls yet caused deactivation within dorsal midbrain and cerebellar vermis in Gulf War Illness relative to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients.

Further, exercise caused increased activation among Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients within the dorsal midbrain, left operculo-insular cortex (Rolandic operculum) and right middle insula. These regions-of-interest underlie threat assessment, pain, interoception, negative emotion and vigilant attention. As they only emerge post-exercise, these regional differences likely represent neural substrates of cognitive post-exertional malaise useful for developing distinct diagnostic criteria for Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Source: Stuart D Washington, Rakib U Rayhan, Richard Garner, Destie Provenzano, Kristina Zajur, Florencia Martinez Addiego, John W VanMeter, James N Baraniuk, Exercise alters brain activation in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Brain Communications, Volume 2, Issue 2, 2020, fcaa070, https://doi.org/10.1093/braincomms/fcaa070 https://academic.oup.com/braincomms/article/2/2/fcaa070/5885074 (Full text)

Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome

Abstract:

Elevated blood lactate after moderate exercise was reported in some of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We hypothesised that blood lactate could be also elevated in resting conditions. We aimed investigating the frequency of elevated lactate at rest in ME/CFS patients, and comparing characteristics of ME/CFS patients with and without elevated lactate.

Patients fulfilling international consensus criteria for ME/CFS who attended the internal medicine department of University hospital Angers-France between October 2011 and December 2017 were included retrospectively. All patients were systematically hospitalised for an aetiological workup and overall assessment.

We reviewed their medical records for data related to the assessment: clinical characteristics, comorbidities, fatigue features, post-exertional malaise (PEM) severity, and results of 8 lactate measurements at rest. Patients having ≥1 lactate measurement ≥2 mmol/L defined elevated lactate group. The study included 123 patients. Elevated (n = 55; 44.7%) and normal (n = 68; 55.3%) lactate groups were comparable except for PEM, which was more severe in the elevated lactate group after adjusting for age at disease onset, sex, and comorbidities (OR 2.47, 95% CI: 1.10-5.55). ME/CFS patients with elevated blood lactate at rest may be at higher risk for more severe PEM. This finding may be of interest in ME/CFS management.

Source: Ghali A, Lacout C, Ghali M, Gury A, Beucher AB, Lozac’h P, Lavigne C, Urbanski G. Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome. Sci Rep. 2019 Dec 11;9(1):18817. doi: 10.1038/s41598-019-55473-4. ncbi.nlm.nih.gov/pubmed/31827223

Suggested pathology of systemic exertion intolerance disease: Impairment of the E3 subunit or crossover of swinging arms of the E2 subunit of the pyruvate dehydrogenase complex decreases regeneration of cofactor dihydrolipoic acid of the E2 subunit

Abstract:

Systemic Exertion Intolerance Disease (SEID) or myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) has an unknown aetiology, with no known treatment and a prevalence of approximately 22 million individuals (2%) in Western countries. Although strongly suspected, the role of lactate in pathology is unknown, nor has the nature of the two most central symptoms of the condition – post exertional malaise and fatigue. The proposed mechanism of action of pyruvate dehydrogenase complex (PDC) plays a central role in maintaining energy production with cofactors alpha-lipoic acid (LA) and its counterpart dihydrolipoic acid (DHLA), its regeneration suggested as the new rate limiting factor.

Decreased DHLA regeneration due to impairment of the E3 subunit or crossover of the swinging arms of the E2 subunit of PDC have been suggested as a cause of ME/CFS/SEID resulting in instantaneous fluctuations in lactate levels and instantaneous offset of the DHLA/LA ratio and defining the condition as an LA deficiency with chronic instantaneous hyperlactataemia with explicit stratification of symptoms. While instantaneous hyperlactataemia has been suggested to account for the PEM, the fatigue was explained by the downregulated throughput of pyruvate and consequently lower production of ATP with the residual enzymatic efficacy of the E3 subunit or crossover of the E2 as a proposed explanation of the fatigue severity. Functional diagnostics and visualization of instantaneous elevations of lactate and DHLA has been suggested.

Novel treatment strategies have been implicated to compensate for chronic PDC impairment and hyperlactataemia. This hypothesis potentially influences the current understanding and treatment methods for any type of hyperlactataemia, fatigue, ME/CFS/SEID, and conditions associated with PDC impairment.

Copyright © 2019. Published by Elsevier Ltd.

Source: Bohne VJB, Bohne Ø.Suggested pathology of systemic exertion intolerance disease: Impairment of the E3 subunit or crossover of swinging arms of the E2 subunit of the pyruvate dehydrogenase complex decreases regeneration of cofactor dihydrolipoic acid of the E2 subunit. Med Hypotheses. 2019 Sep;130:109260. doi: 10.1016/j.mehy.2019.109260. Epub 2019 Jun 14. https://www.ncbi.nlm.nih.gov/pubmed/31383326

Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing

Abstract:

Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes.

ME/CFS patients (n = 14) and matched sedentary controls (n = 11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing reduced oxygen consumption ([Formula: see text]) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points.

None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P = 0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes.

Source: Bouquet J, Li T, Gardy JL, Kang X, Stevens S, Stevens J, VanNess M, Snell C, Potts J, Miller RR, Morshed M, McCabe M, Parker S, Uyaguari M, Tang P, Steiner T, Chan WS, De Souza AM, Mattman A, Patrick DM, Chiu CY. Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing. PLoS One. 2019 Mar 21;14(3):e0212193. doi: 10.1371/journal.pone.0212193. eCollection 2019. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212193 (Full article)
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Chronotropic Intolerance: An Overlooked Determinant of Symptoms and Activity Limitation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Abstract:

Post-exertional malaise (PEM) is the hallmark clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). PEM involves a constellation of substantially disabling signs and symptoms that occur in response to physical, mental, emotional, and spiritual over-exertion. Because PEM occurs in response to over-exertion, physiological measurements obtained during standardized exertional paradigms hold promise to contribute greatly to our understanding of the cardiovascular, pulmonary, and metabolic states underlying PEM.

In turn, information from standardized exertional paradigms can inform patho-etiologic studies and analeptic management strategies in people with ME/CFS. Several studies have been published that describe physiologic responses to exercise in people with ME/CFS, using maximal cardiopulmonary testing (CPET) as a standardized physiologic stressor. In both non-disabled people and people with a wide range of health conditions, the relationship between exercise heart rate (HR) and exercise workload during maximal CPET are repeatable and demonstrate a positive linear relationship.

However, smaller or reduced increases in heart rate during CPET are consistently observed in ME/CFS. This blunted rise in heart rate is called chronotropic intolerance (CI). CI reflects an inability to appropriately increase cardiac output because of smaller than expected increases in heart rate. The purposes of this review are to (1) define CI and discuss its applications to clinical populations; (2) summarize existing data regarding heart rate responses to exercise obtained during maximal CPET in people with ME/CFS that have been published in the peer-reviewed literature through systematic review and meta-analysis; and (3) discuss how trends related to CI in ME/CFS observed in the literature should influence future patho-etiological research designs and clinical practice.

Source: Todd E. Davenport, Mary Lehnen, Staci R. Stevens, J. Mark VanNess, Jared Stevens and Christopher R. Snell. Chronotropic Intolerance: An Overlooked Determinant of Symptoms and Activity Limitation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Front. Pediatr., 22 March 2019 | https://doi.org/10.3389/fped.2019.00082 https://www.frontiersin.org/articles/10.3389/fped.2019.00082/full (Full article)

Assessment of Post-Exertional Malaise (PEM) in Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): A Patient-Driven Survey

Abstract:

Considerable controversy has existed with efforts to assess post-exertional malaise (PEM), which is one of the defining features of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). While a number of self-report questionnaires have been developed to assess this symptom, none have been comprehensive, and a recent federal government report has recommended the development of a new PEM measure.

The current study involved a community-based participatory research process in an effort to develop a comprehensive PEM instrument, with critical patient input shaping the item selection and overall design of the tool. A survey was ultimately developed and was subsequently completed by 1534 members of the patient community.

The findings of this survey suggest that there are key domains of this symptom, including triggers, symptom onset, and duration, which have often not been comprehensively assessed in a previous PEM instrument. This study indicates that there are unique benefits that can be derived from patients collaborating with researchers in the measurement of key symptoms defining ME and CFS.

Source: Carly S. Holtzman, Shaun Bhatia, Joseph Cotler and Leonard A. Jason. Assessment of Post-Exertional Malaise (PEM) in Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): A Patient-Driven Survey. Diagnostics 2019, 9(1), 26; doi:10.3390/diagnostics9010026 https://www.mdpi.com/2075-4418/9/1/26/htm (Full article)