Unravelling ME/CFS: Gender‐specific changes in the microRNA expression profiling in ME/CFS

Posted on 04/23/2020 by wames

Unravelling ME/CFS: Gender‐specific changes in the microRNA expression profiling in ME/CFS by Amanpreet K Cheema, Leonor Sarria, Mina Bekheit, Fanny Collado, Eloy Almenar‐Pérez, Eva Martín‐Martínez, Jose Alegre, Jesus Castro‐Marrero, Mary A Fletcher, Nancy G Klimas,  Elisa Oltra, Lubov Nathanson in Journal of Cellular and Molecular Medicine 14 April 2020 [doi.org/10.1111/jcmm.15260]

 

Research abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by medically unexplained debilitating fatigue with suggested altered immunological state.

Our study aimed to explore peripheral blood mononuclear cells (PBMCs) for microRNAs (miRNAs) expression in ME/CFS subjects under an exercise challenge.

The findings highlight the immune response and inflammation links to differential miRNA expression in ME/CFS. The present study is particularly important in being the first to uncover the differences that exist in miRNA expression patterns in males and females with ME/CFS in response to exercise. This provides new evidence for the understanding of differential miRNA expression patterns and post‐exertional malaise in ME/CFS.

We also report miRNA expression pattern differences associating with the nutritional status in individuals with ME/CFS, highlighting the effect of subjects’ metabolic state on molecular changes to be considered in clinical research within the NINDS/CDC ME/CFS Common Data Elements. The identification of gender‐based miRNAs importantly provides new insights into gender‐specific ME/CFS susceptibility and demands exploration of sex‐suited ME/CFS therapeutics.

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Acupuncture for CFS: an overview of systematic reviews

Posted on 04/22/2020 by wames

Acupuncture for Chronic Fatigue Syndrome: an overview of systematic reviews, by Zi-han Yin, Lin-jia Wang, Ying Cheng, Jiao Chen, Xiao-juan Hong, Ling Zhao, Fan-rong Liang in Chin. J. Integr. Med. (2020). [https://doi.org/10.1007/s11655-020-3195-3]

 

Review abstract:

Objective

To evaluate the quality of the existing studies and summarize evidence of important outcomes of meta-analyses/systematic reviews (MAs/SRs) of CFS.

Methods

Potentially eligible studies were searched in the following electronic databases from inception to 1 September, 2019: Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), Web of Science, Embase, PubMed and Cochrane Library. Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence.

The methodological quality of the literature was evaluated by A Measure Tool to Assess Systematic Reviews-2 (AMSTAR-2) and the quality of the report was assessed by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The intra-class correlation coefficient was used to assess the consistency of the reviewers, with an overall intraclass correlation coefficient score of 0.967.

Results

Ten MAs/SRs were included. The overall conclusions were that acupuncture had good safety and efficacy in the treatment of CFS, but some of these results were contradictory. The GRADE indicated that out of the 17 outcomes, high-quality evidence was provided in 0 (0%), moderate in 3 (17.65%), low in 10 (58.82%), and very low in 4 (23.53%). The results of AMSTAR-2 showed that the methodological quality of all included studies was critically low. The PRISMA statement revealed that 8 articles (80%) were in line with 20 of the 27-item checklist, and 2 articles (20%) matched with 10–19 of the 27 items.

Conclusion

We found that acupuncture on treating CFS has the advantage for efficacy and safety, but the quality of SRs/MAs of acupuncture for CFS need to be improved

Read full paper

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Autoimmunity-related risk variants in PTPN22 & CTLA4 are associated with ME/CFS with infectious onset

Posted on 04/22/2020 by wames

Autoimmunity-related risk variants in PTPN22 and CTLA4 are associated with ME/CFS with infectious onset, by Sophie Steiner, Sonya C Becker, Jelka Hartwig, Franziska Sotzny, Sebastian Lorenz, Sandra Bauer, Madlen Löbel, Anna B Stittrich, Patricia Grabowski and Carmen Scheibenbogen in Front. Immunol., 09 April 2020[doi.org/10.3389/fimmu.2020.00578]

 

Research abstract:

SNP model by David Eccles, Wiki commons

Single nucleotide polymorphisms (SNP) in various genes have been described to be associated with susceptibility to autoimmune disease.

In this study, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients and controls were genotyped for five immune gene SNPs in tyrosine phosphatase non-receptor type 22 (PTPN22, rs2476601), cytotoxic T-lymphocyte-associated protein 4 (CTLA4, rs3087243), tumor necrosis factor (TNF, rs1800629 and rs1799724), and interferon regulatory factor 5 (IRF5, rs3807306), which are among the most important risk variants for autoimmune diseases.

Analysis of 305 ME/CFS patients and 201 healthy controls showed significant associations of the PTPN22 rs2476601 and CTLA4 rs3087243 autoimmunity-risk alleles with ME/CFS. The associations were only found in ME/CFS patients, who reported an acute onset of disease with an infection (PTPN22 rs2476601: OR 1.63, CI 1.04–2.55, p = 0.016; CTLA4 rs3087243: OR 1.53, CI 1.17–2.03, p = 0.001), but not in ME/CFS patients without infection-triggered onset (PTPN22 rs2476601: OR 1.09, CI 0.56–2.14, p = 0.398; CTLA4 rs3087243: OR 0.89, CI 0.61–1.30, p = 0.268).

This finding provides evidence that autoimmunity might play a role in ME/CFS with an infection-triggered onset. Both genes play a key role in regulating B and T cell activation.

Meet The Researchers: Carmen Scheibenbogen

 

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Processing of Laser-Evoked Potentials in patients with Chronic Whiplash-Associated Disorders, CFS & healthy controls: a case–control study

Posted on 04/20/2020 by wames

Processing of Laser-Evoked Potentials in patients with Chronic Whiplash-Associated Disorders, Chronic Fatigue Syndrome, and healthy controls: a case–control study, by Lisa Goudman, PhD, Liesbeth Daenen, PhD, Andre Mouraux, PhD, Jo Nijs, PhD, Patrick Cras, PhD, Nathalie Roussel, PhD, Maarten Moens, PhD, Iris Coppieters, PhD, Eva Huysmans, MSc, Margot De Kooning, PhD in Pain Medicine, 14 April 2020 [https://doi.org/10.1093/pm/pnaa068]

 

Research abstract:

Objective
Laser-evoked potentials (LEPs) are among the reliable neurophysiological tools to investigate patients with neuropathic pain, as they can provide an objective account of the functional status of thermo-nociceptive pathways. The goal of this study was to explore the functioning of the nociceptive afferent pathways by examining LEPs in patients with chronic whiplash-associated disorders (cWAD), patients with chronic fatigue syndrome (CFS), and healthy controls (HCs).

Design
Case–control study.

Setting
A single medical center in Belgium.

Subjects
The LEPs of 21 patients with cWAD, 19 patients with CFS, and 18 HCs were analyzed in this study.

Methods
All participants received brief nociceptive CO2 laser stimuli applied to the dorsum of the left hand and left foot while brain activity was recorded with a 32-channel electroencephalogram (EEG). LEP signals and transient power modulations were compared between patient groups and HCs.

Results
No between-group differences were found for stimulus intensity, which was supraliminal for Aδ fibers. The amplitudes and latencies of LEP wave components N1, N2, and P2 in patients with cWAD and CFS were statistically similar to those of HCs. There were no significant differences between the time–frequency maps of EEG oscillation amplitude between HCs and both patient populations.

Conclusions
EEG responses of heat-sensitive Aδ fibers in patients with cWAD and CFS revealed no significant differences from the responses of HCs. These findings thus do not support a state of generalized central nervous system hyperexcitability in those patients.

Read full paper

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Opposition to Oxford NHS Trust leaflet which confuses post Covid-19 fatigue with ME/CFS

Posted on 04/20/2020 by wames

The ME community requests Oxford NHS Trust leaflet be withdrawn

 

A collection of physicians, physiotherapists MPs and patient charities have written to Oxford Health NHS Foundation Trust to object to the content of a leaflet by their Psychosocial Response Group entitled Coping with the Coronavirus. It is one of a series of leaflets about Coronavirus and mental health, and has been adopted by other English NHS Trusts. (WAMES sincerely hopes no Welsh Trusts adopt it!)

“We, the undersigned, request immediate withdrawal of the Oxford Health NHS Foundation Trust leaflet “Coping with Coronavirus: Fatigue” for the following reasons:

  • The leaflet conflates post viral fatigue with myalgic encephalomyelitis (“ME”)
  • The leaflet purports to provide information for post-COVID-19 rehabilitation but is predominantly comprised of rehabilitation advice for ME / CFS
  • The information provided is incorrect or misleading
  • The advice provided is potentially detrimental to patients and may result in deterioration and exacerbation of disability”

The Oxford leaflet says this about recovering from Covid-19:

“Most of us will make a full recovery, but if you are still not back to your usual levels of energy, and you feel very tired and low, four months or more after you had the virus (or three months in children), then you may have post-viral fatigue.

Some people may go on to develop Chronic Fatigue Syndrome (CFS), sometimes also called Myalgic Encephalitis (ME), which is a condition which affects people in different ways. The main symptom is persistent fatigue (tiredness) and exhaustion which can be severe and disabling.”

It goes on to advise people not to rest too much and to avoid a ‘boom & bust’ approach to activity. The treatment for this? Pacing, activity management and Graded Exercise Therapy, and Cognitive Behavioural Therapy!

NB   The leaflet has now been removed from the Oxford site but is still online at another Trust site.

Why are patients and health professionals objecting?

The letter of objection asks for the withdrawal of the leaflet and offers an alternative, as soon as it is available, which would recommend:

“The emphasis should be on management of post Covid-19 fatigue and preventing the development of ME/CFS. This comes from effective management of post viral fatigue, in the form of paced activity, adequate sleep and nutrition. Inappropriate management may result in development of ME and reduces the likelihood of people being able to return to work36.

The recommended treatments of CBT and GET do not improve employment and illness benefit status. As a matter of fact, a systematic review of available data found that after CBT and GET more patients were unable to work and more were receiving illness benefits.

In brief, patients are advised to practice pacing techniques, which are a primary tool for managing energy and avoiding post exertional malaise. While some pacing guidance advocates a “quota-contingent” approach (undertaking activities according to an amount/distance/goal with the aim of improving function) for someone with ME, or recovering from a viral infection, this will ultimately push them beyond their limits and cause a symptom exacerbation and subsequent decline in abilities.”

Read the full letter 

Trial By Error: Oxford-NHS Recommends GET/CBT for Post-COVID “CFS” Patients

Dr David Tuller, a senior fellow in Public Health in Journalism at the University of Berkeley in the USA, and long time opponent of the discredited PACE trial, has announced his intention to challenge the Trust:

“I mean, really. Isn’t this 2020? The notion that there are “thoughts and beliefs” that “maintain” patients in a state of illness should have been discarded with the failure of PACE. I plan to ask the Oxford Health NHS Foundation Trust for references for the (mis)information provided in the pamphlet. I will also ask about  the role of the agency’s “psychosocial support group.”

Prof Tuller reports he has file a FOI request to find out more about the Psychosocial Response Group

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MCP-1 is increased in patients with CFS & FM, whilst several other immune markers are significantly lower than healthy controls

Posted on 04/20/2020 by wames

MCP-1 is increased in patients with CFS and FM, whilst several other immune markers are significantly lower than healthy controls, by Nina Groven, Egil Andreas Fors, Astrid Kamilla Stunes, Solveig Klæbo Reitan in Brain, Behavior, & Immunity – Health Vol 4, April 2020 [doi.org/10.1016/j.bbih.2020.100067]

 

Highlights:

  • MCP-1 is significantly increased in CFS and Fibromyalgia compared to controls.
  • CFS and Fibromyalgia share common features of inflammation.
  • Decreased IL-1β, IL-4, IL-6, TNF-α, TGF-β1, TGF-β2, TGF-β3, IL-10 and IL-17A are found in both CFS and Fibromyalgia.

Abstract:

The role of the immune system in the pathogenesis of Fibromyalgia (FM) and Chronic fatigue syndrome (CFS) is not clear. We have previously reported increased levels of C-reactive protein (CRP) in these patient groups compared to healthy controls and wanted to further explore the levels of circulating immune markers in these populations.

The population consisted of three groups, 58 patients with FM, 49 with CFS and 54 healthy controls. All participants were females aged 18–60. Patients were recruited from a specialised university hospital clinic and controls were recruited by advertisement among the staff and students at the hospital and university.

Plasma levels of Interferon (IFN)-γ, Interleukin (IL)-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-17, Interferon gamma-induced protein (IP)-10, Monocyte Chemoattractant Protein (MCP)-1, Transforming Growth Factor (TGF)-β1, TGF-β2, TGF-β3 and Tumour Necrosis Factor (TNF)-α were analysed by multiplex. Differences between the three groups CFS, FM and controls, were analysed by Kruskal Wallis tests.

MCP-1 was significantly increased in both patient groups compared to healthy controls. IL-1β, Il-4, IL-6, TNF-α, TGF-β1, TGF-β2, TGF-β3, IL-10 and IL17 all were significantly lower in the patient groups than healthy controls. IFN-γ was significantly lower in the FM group. For IL-8, IL-10 and IL-1ra there were no significant difference when controlled for multiple testing.

In conclusion, in our material MCP-1 seems to be increased in patients both with CFS and with FM, while several other immune markers are significantly lower in patients than controls.

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A unifying hypothesis of the pathophysiology of ME/CFS: recognitions from the finding of autoantibodies against ß2-adrenergic receptors

Posted on 04/17/2020 by wames

A unifying hypothesis of the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): recognitions from the finding of autoantibodies against ß2-adrenergic receptors, by Klaus Wirth, Carmen Scheibenbogen in Autoimmunity Reviews, online 1 April 2020 [doi.org/10.1016/j.autrev.2020.102527]

 

Research abstract:

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (CFS/ME) is a complex and severely disabling disease with a prevalence of 0.3% and no approved treatment and therefore a very high medical need. Following an infectious onset patients suffer from severe central and muscle fatigue, chronic pain, cognitive impairment, and immune and autonomic dysfunction. Although the etiology of CFS/ME is not solved yet, there is numerous evidence for an autoantibody mediated dysregulation of the immune and autonomic nervous system.

We found elevated ß2 adrenergic receptor (ß2AdR) and M3 acetylcholine receptor antibodies in a subset of CFS/ME patients. As both ß2AdR and M3 acetylcholine receptor are important vasodilators, we would expect their functional disturbance to result in vasoconstriction and hypoxemia. An impaired circulation and oxygen supply could result in many symptoms of ME/CFS. There are consistent reports of vascular dysfunction in ME/CFS. Muscular and cerebral hypoperfusion has been shown in ME/CFS in various studies and correlated with fatigue. Metabolic changes in ME/CFS are also in line with a concept of hypoxia and ischemia.

Here we try to develop a unifying working concept for the complex pathomechanism of ME/CFS based on the presence of dysfunctional autoantibodies against ß2AdR and M3 acetylcholine receptor and extrapolate it to the pathophysiology of ME/CFS without an autoimmune pathogenesis.

 

Health rising: Hypothesis predicts major failure point in Chronic Fatigue Syndrome (ME/CFS)

Simmaron Research: The blood vessel crunch: a unifying hypothesis for ME/CFS

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CFS – what nurses need to know (US)

Posted on 04/15/2020 by wames

Chronic Fatigue Syndrome – what nurses need to know, by Marianne Bush BS, RN in Nursing April 2020, vol 50 no. 4 – pp50-54 [doi:10.1097/01.NURSE.0000657068.67389.47]

Author information: Marianne Bush is an RN contractor for a national wellness company.

 

Article abstract: 

Chronic fatigue syndrome (CFS) is a long-term, often misunderstood disorder that involves the nervous, immune, metabolic, endocrine, and digestive systems. This article describes the pathophysiology of CFS, signs and symptoms of CFS in adults, diagnostic criteria for CFS, and nursing considerations for patients with CFS.

Nursing considerations
Nurses caring for patients with CFS should keep these points in mind:

  • Patients may need additional assistance with activities of daily living and take more time to recover from surgery and other medical procedures as well as any kind of emotional or mental stress.
  • Nurses should monitor patients for orthostatic intolerance and intervene appropriately; for example, by including standby assist with ambulation in the nursing plan of care.
  • Given the lack of standardized conventional treatments, patients may use alternative practitioners and therapies. During medication reconciliation, nurses should specifically inquire about vitamins and other supplements to avoid potential interactions with prescribed medications.
  • Remember that many patients with CFS do not look sick and have no outward sign of illness. This does not mean they are not experiencing symptoms. In severe cases, they may be more functionally impaired than those with heart failure, multiple sclerosis, or end-stage renal disease. These patients must not be dismissed because they “look” healthy.
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The effect of ME/CFS severity on cellular bioenergetic function

Posted on 04/14/2020 by wames

The effect of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function, by Cara Tomas, Joanna L Elson, Victoria Strassheim, Julia L Newton, Mark Walker in PLoS One vol 15, #4, e0231136, April 10, 2020

 

Research abstract:

Myalgic encephalomyelitis/ Chronic fatigue syndrome (ME/CFS) has been associated with abnormalities in mitochondrial function. In this study we have analysed previous bioenergetics data in peripheral blood mononuclear cells (PBMCs) using new techniques in order to further elucidate differences between ME/CFS and healthy control cohorts.

We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs.

Both  ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort. This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction.

Equations devised by another research group have enabled us to calculate ATP-linked respiration rates and glycolytic parameters. Parameters of glycolytic function were  calculated by taking into account respiratory acidification. This revealed severely affected ME/CFS patients to have higher rates of respiratory acidification and showed the importance of accounting for respiratory acidification when calculating parameters of glycolytic function. Analysis of previously published glycolysis data, after taking into account respiratory acidification, showed severely affected patients have reduced glycolysis compared to moderately affected patients and healthy controls. Rates of ATP-linked respiration were also calculated and shown to be lower in both ME/CFS cohorts.

This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotype.

ME Research UK explains:

In this latest study, the authors reanalysed some of the findings from their previous work, separating the ME/CFS patients into two groups: moderately affected (housebound) and severely affected (bedbound)…

In their previous study, the authors had found no difference in glycolysis between controls and ME/CFS patients. However, by separating out the patients into the two groups by disease severity, we can now see that the most severely affected patients do actually appear to have reduced glycolysis levels, while moderately affected patients do not…

The study also highlights the importance of conducting research into the most severely affected ME/CFS patients, where possible…

Potential next steps would be to test these methods in other diseases with symptoms of severe fatigue, to determine if the findings are a result of the symptoms (fatigue) or the underlying disease (ME/CFS).

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Emotional awareness correlated with number of awakenings from polysomnography in patients with ME/CFS – a pilot study

Posted on 04/14/2020 by wames

Emotional awareness correlated with number of awakenings from polysomnography in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—a pilot study, by Indre Bileviciute-Ljungar and Danielle Friberg in Front. Psychiatry, 26 March 2020 [https://doi.org/10.3389/fpsyt.2020.00222]

 

Research abstract:

Introduction:

Unrefreshing sleep is one of the diagnostic criteria in myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS), which could be explained by sleep disorders, for example obstructive sleep apnea, reported in our previous study with polysomnography. Our previous findings also indicate difficulties in emotional regulation when measuring alexithymia by TAS-20 (Toronto Alexithymia Scale) and level of emotional awareness by LEAS (Level of Emotional Awareness Scale) in ME/CFS patients. However, the reasons for this are unknown. The purpose of this study was to investigate correlations between data from subjective emotional regulation and polysomnography.

Methods:

Twenty-three ME/CFS patients (5 men and 18 women) of mean age 43, and 30 matched healthy controls (9 males and 21 women) of mean age 45, filled in TAS-20, LEAS, and Hospital Depression and Anxiety Scale (HADS). A polysomnography was performed on patients but not on healthy controls. Thus, values of normal population were used for sleep evaluation in ME/CFS patients.

Result:

There were significant differences between patients and controls in several aspects of emotional regulation, for example LEAS-self and LEAS-total. Seventy percent of the patients had increased numbers of awakenings (shifts from any sleep stage to awake), 22% had obstructive sleep apneas, and 27% had periodic limb movements. Correlation analysis showed that number of awakenings significantly correlated with LEAS-self and LEAS-total, p < 0.01, respectively. There were no other significant correlations.

Conclusion:

This pilot study demonstrated significant correlations between reduced emotional awareness and number of awakenings in polysomnography. Future studies with larger cohorts need to be conducted.

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