scholarly journals 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

2021 ◽  
Vol 15 ◽  
Author(s):  
Rakib U. Rayhan ◽  
James N. Baraniuk

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.

Healthcare ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1546
Author(s):  
Helen Brownlie ◽  
Nigel Speight

The findings of controlled trials on use of intravenous immunoglobulin G (IV IgG) to treat myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are generally viewed as representing mixed results. On detailed review, a clearer picture emerges, which suggests that the potential therapeutic value of this intervention has been underestimated. Our analysis is consistent with the propositions that: (1) IgG is highly effective for a proportion of patients with severe and well-characterised ME/CFS; (2) responders can be predicted with a high degree of accuracy based on markers of immune dysfunction. Rigorous steps were taken in the research trials to record adverse events, with transient symptom exacerbation commonly experienced in both intervention and placebo control groups, suggesting that this reflected the impact of participation on people with an illness characterised by post-exertional symptom exacerbation. Worsening of certain specific symptoms, notably headache, did occur more commonly with IgG and may have been concomitant to effective treatment, being associated with clinical improvement. The findings emerging from this review are supported by clinical observations relating to treatment of patients with severe and very severe ME/CFS, for whom intramuscular and subcutaneous administration provide alternative options. We conclude that: (1) there is a strong case for this area of research to be revived; (2) pending further research, clinicians would be justified in offering a course of IgG to selected ME/CFS patients at the more severe end of the spectrum. As the majority of trial participants had experienced an acute viral or viral-like onset, we further suggest that IgG treatment may be pertinent to the care of some patients who remain ill following infection with SARS-CoV-2 virus.


PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244116
Author(s):  
James N. Baraniuk ◽  
Grant Kern ◽  
Vaishnavi Narayan ◽  
Amrita Cheema

Myalgic encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) share many symptoms of fatigue, pain, and cognitive dysfunction that are not relieved by rest. Patterns of serum metabolites in ME/CFS and GWI are different from control groups and suggest potential dysfunction of energy and lipid metabolism. The metabolomics of cerebrospinal fluid was contrasted between ME/CFS, GWI and sedentary controls in 2 sets of subjects who had lumbar punctures after either (a) rest or (b) submaximal exercise stress tests. Postexercise GWI and control subjects were subdivided according to acquired transient postexertional postural tachycardia. Banked cerebrospinal fluid specimens were assayed using Biocrates AbsoluteIDQ® p180 kits for quantitative targeted metabolomics studies of amino acids, amines, acylcarnitines, sphingolipids, lysophospholipids, alkyl and ether phosphocholines. Glutamate was significantly higher in the subgroup of postexercise GWI subjects who did not develop postural tachycardia after exercise compared to nonexercise and other postexercise groups. The only difference between nonexercise groups was higher lysoPC a C28:0 in GWI than ME/CFS suggesting this biochemical or phospholipase activities may have potential as a biomarker to distinguish between the 2 diseases. Exercise effects were suggested by elevation of short chain acylcarnitine C5-OH (C3-DC-M) in postexercise controls compared to nonexercise ME/CFS. Limitations include small subgroup sample sizes and absence of postexercise ME/CFS specimens. Mechanisms of glutamate neuroexcitotoxicity may contribute to neuropathology and “neuroinflammation” in the GWI subset who did not develop postural tachycardia after exercise. Dysfunctional lipid metabolism may distinguish the predominantly female ME/CFS group from predominantly male GWI subjects.


2021 ◽  
Vol 3 (2) ◽  
pp. 33-39
Author(s):  
Jo Cossington ◽  
◽  
Dr. Shelly Coe ◽  
Yaomeng Liu ◽  
Helen Dawes ◽  
...  

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) affects approximately 250,000 people in the UK. The condition varies in severity causing long-term physical and cognitive fatigue which is not alleviated by rest. Whilst the pathology is not understood, recent evidence suggests metabolic abnormalities may be associated with the manifestation of symptoms, particularly involving the metabolism of glucose and energy production. The use of ketone bodies as an alternative energy substrate may be beneficial to people with ME/CFS, in order to by-pass the glycolytic pathway, enhance energy production and reduce fatiguing outcomes. Study Design and Methods: Using a pragmatic collective case study with repeated measures methodology we investigated the feasibility of following a ketogenic diet and potential effects of the high fat, low carbohydrate diet on response to physical activity in people with ME/CFS (n=3) and healthy controls (n=3) using a submaximal exercise stress test both with and without dietary intervention. Exercise tolerance (mins), rate of oxygen consumption (VO2) to workload (75W), respiratory exchange ratio (RER), rate of perceived effort (RPE) and lactate response were measured throughout and descriptive statistics performed. Results: We found that the ketogenic diet was followed, with compliance higher in the pwME/CFS. Variations in response following the ketogenic diet was observed across individuals in minutes performed, VO2, HR, RER, and RPE post diet but the KD only limited exercise capacity in the control individuals. Individuals responded differently to the KD but group trends have been reported as means and standard deviation. The KD resulted in a decrease in RER at submax in the controls with a mean change of 0.07 from baseline (0.86 ± 0.1) to post intervention (0.79 ± 0.1) compared to a mean change of 0.02 in the ME/CFS from baseline (1.03 ± 0.1) to post intervention (1.01 ± 0.1). A decrease in VO2 (L/min) at submax showed a mean change of 0.06 (L/min) in the pwME/CFS at baseline (1.34 ± 0.1) to post intervention (1.27 ± 0.2) compared to a mean change of 0.07 (L/min) in the controls at baseline (1.40 ± 0.3) to post intervention (1.33 ± 0.2). HR (bpm) at submax decreased in all individuals, with a mean change of 4 (bpm), with pwME/CFS at baseline (139 ± 8.2) to post intervention (135 ± 14) and control individuals at baseline (107 ± 7.8) to intervention (103 ± 3.2). RPE at submax decreased in the pwME/CFS from baseline (6 ± 1.0) to post intervention (5 ± 2.1) whereas the controls increased from baseline (2 ± 1.0) to post intervention (3 ± 1.5). Conclusion: Our observations suggest individualised but metabolic flexibility in healthy individuals is achievable via dietary manipulation showing the ability to switch from glucose to fats under controlled conditions. The different response in substrate utilisation in individuals with ME/CFS suggests that potential metabolic abnormalities may be present in ME/CFS. Further investigation is now warranted in order to assess whether the KD is beneficial for people with ME/CFS


2015 ◽  
Vol 16 (4) ◽  
pp. S54 ◽  
Author(s):  
C. Gay ◽  
A. O'Shea ◽  
M. Robinson ◽  
J. Craggs ◽  
R. Staud

2021 ◽  
Vol 10 (11) ◽  
pp. 2517
Author(s):  
Alaa Ghali ◽  
Carole Lacout ◽  
Maria Ghali ◽  
Aline Gury ◽  
Estelle Delattre ◽  
...  

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.


Medicina ◽  
2021 ◽  
Vol 57 (1) ◽  
pp. 43
Author(s):  
Esme Brittain ◽  
Nina Muirhead ◽  
Andrew Y. Finlay ◽  
Jui Vyas

Background and objectives: To explore the impacts that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has on the patient and their family members using the WHOQOL-BREF (Abbreviated World Health Organisation Quality of Life questionnaire) and FROM-16 (Family Reported Outcome Measure-16) quality of life assessments. Materials and Methods: A quantitative research study using postal questionnaires was conducted. A total of 39 adult volunteers expressed an interest in participating in the study: 24 returned appropriately completed questionnaires. Patients with ME/CFS completed the WHOQOL-BREF and up to four of their family members completed the FROM-16 questionnaire. Results: ME/CFS negatively affects the quality of life of the patient (median scores WHOQOL-BREF: Physical health = 19, Psychological = 44, Social relationships = 37.5, Environment = 56, n = 24) and their family members’ quality of life (FROM-16: Emotional = 9.5, Personal and social = 11.5, Overall = 20.5, n = 42). There was a significant correlation between the patient’s reported quality of life scores and their family members’ mean FROM-16 total scores. Conclusions: This study identifies the major impact that having an adult family member with ME/CFS has on the lives of partners and of other family members. Quality of life of ME/CFS patients was reduced most by physical health compared to the other domains. Quality of life of family members was particularly impacted by worry, family activities, frustration and sadness. This highlights the importance of measuring the impact on the lives of family members using tools such as the FROM-16 in the ME/CFS clinical encounter and ensuring appropriate support is widely available to family members.


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