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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Gravity-induced exercise intervention in an individual with CFS/ME & PTS: a case report

Posted on 04/10/2020 by wames

Gravity-induced exercise intervention in an individual with chronic fatigue syndrome/ myalgic encephalomyeltis and postural tachycardia syndrome: a case report, by Robert Ballantine, Victoria Strassheim, Julia Newton in International Journal of Therapy and Rehabilitation 2019 vol 26,#5

 

Abstract:

Background/Aims
Chronic fatigue syndrome/myalgic encephalomyeltis is a condition of complex nature, characterised by unexplained disabling fatigue and a combination of non-specific accompanying symptoms.

Individuals with chronic fatigue syndrome/myalgic encephalomyeltis frequently present
with debilitating orthostatic symptoms, which may fall under the umbrella of postural tachycardia syndrome. Postural tachycardia syndrome is underpinned by autonomic nervous system dysfunction. The gravitational deconditioning that occurs in those severely affected by chronic fatigue syndrome/myalgic encephalomyeltis alongside postural
tachycardia syndrome has been suggested as a key focus for interventions in this group.

This case report documents the evaluation and rationale behind a novel gravity-induced exercise intervention to improve the symptoms of a 44-year-old female severely affected by chronic fatigue syndrome/myalgic encephalomyeltis and postural tachycardia syndrome, who had been bedbound for 10-15 years.

Methods
An exercise intervention was designed to challenge and therefore improve key areas of autonomic nervous system regulation in the presence of gravity. It contained seven different exercises conducted once a month in a class over a 6-month period.

Results
Fatigue impact score, activity levels and heart rate upon standing, as detected by an active stand test, improved during the exercise intervention and at follow up.

Conclusions
Gravity-induced exercise intervention can have a positive effect on an individual severely affected by Chronic fatigue syndrome/myalgic encephalomyeltis alongside postural tachycardia syndrome.

Read full paper

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Chronic Fatigue Syndrome: progress & possibilities

Posted on 04/10/2020 by wames

Chronic Fatigue Syndrome: progress and possibilities, by Carolina X Sandler, Andrew R Lloyd in Medical Journal of Australia April 5, 2020

 

Review Summary

  • Chronic fatigue syndrome (CFS) is a prevalent condition affecting
    about one in 100 patients attending primary care.
  • There is no diagnostic test, validated biomarker, clear
    pathophysiology or curative treatment.
  • The core symptom of fatigue affects both physical and cognitive
    activities, and features a prolonged post‐activity exacerbation
    triggered by tasks previously achieved without difficulty.
  • Although several different diagnostic criteria are proposed, for
    clinical purposes only three elements are required: recognition of the
    typical fatigue; history and physical examination to exclude other
    medical or psychiatric conditions which may explain the symptoms; and a
    restricted set of laboratory investigations.
  • Studies of the underlying pathophysiology clearly implicate a range of
    different acute infections as a trigger for onset in a significant
    minority of cases, but no other medical or psychological factor has been
    reproducibly implicated.
  • There have been numerous small case-control studies seeking to
    identify the biological basis of the condition. These studies have
    largely resolved what the condition is not: ongoing infection,
    immunological disorder, endocrine disorder, primary sleep disorder, or
    simply attributable to a psychiatric condition.
  • A growing body of evidence suggests CFS arises from functional
    (non‐structural) changes in the brain, but of uncertain character and
    location. Further functional neuroimaging studies are needed.
  • There is clear evidence for a genetic contribution to CFS from family
    and twin studies, suggesting that a large scale genome‐wide association
    study is warranted.
  • Despite the many unknowns in relation to CFS, there is significant
    room for improvement in provision of the diagnosis and supportive care.
    This may be facilitated via clinician education.

Introduction

Chronic fatigue syndrome (CFS) is an enigmatic clinical entity which challenges patients, health care providers and researchers alike.1 The diagnosis is sometimes avoided by medical practitioners, leaving patients in diagnostic limbo andprone to non-evidence- based labels and potentially harmful treatments. This quandary reflects the lack of a diagnostic test, validated biomarker, clear pathophysiology or curative treatment.

We retrieved publications from MEDLINE, PsycINFO, EMBASE, Cochrane and PubMed databases from 1988 to 2019 to consider aspects of clinical decision making in the diagnosis, assessment of prognosis, and management of CFS; provide an update on understanding of CFS pathophysiology; and identify priorities for improved care of patients with CFS and for future research. This review focuses on adult populations, but the condition also affects children and adolescents (reviewed elsewhere).2

Read full paper

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Neural based assessment of mind wandering during a fatigue inducing motor task: is task failure due to fatigue or distraction?”

Posted on 04/08/2020 by wames

Neural based assessment of mind wandering during a fatigue inducing motor task: Is task failure due to fatigue or distraction? by Surbhi Hablani, Ciara Marie O’Higgins, Declan Walsh and Richard B Reilly in 9th International IEEE EMBS Conference on Neural Engineering (San Francisco, CA, USA) March 20 – 23 , 2019

 

Abstract:

This study developed a method for investigating mind wandering (MW) in a fatigue-inducing motor task. To develop research protocols to assess fatigue in clinical cohorts, it is important that participants perform the task at hand to the best of their ability and with their complete attention. Therefore, it is important to know if the participant fails in the task due to fatigue or lack of sustained attention as a result of MW.

Two cohorts of 12 healthy controls and Chronic Fatigue Syndrome (CFS) subjects performed a hand-grip fatigue-inducing motor task while EMG and EEG were simultaneously recorded. Frontal midline theta (FMT) and parietal alpha power were calculated throughout the task.

While no significant differences were obtained in the FMT power for both cohorts, significant differences in parietal alpha power for the healthy subjects across the task shows they may have experienced MW unlike CFS subjects, who had to put in consistent effort to sustain attention during the task, which could imply fewer MW events.

Assessing MW using EEG can serve as an objective marker for evaluating performance in a task and, for assessing the impact of fatigue on the ability to sustain attention.

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The development of a consistent Europe-wide approach to investigating the economic impact of ME/CFS

Posted on 04/08/2020 by wames

The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE) by Derek FH Pheby, Diana Araja,  Uldis Berkis, Elenka Brenna, John Cullinan, Jean-Dominique de Korwin, Lara Gitto, Dyfrig Hughes, Rachael M Hunter, Dominic Trépel, X Wang-Steverding in Healthcare 31 March 2020

 

Abstract:

We have developed a Europe-wide approach to investigating the economic impact of ME/CFS, facilitating acquisition of information on the economic burden of ME/CFS, and international comparisons of economic costs between countries.

The economic burden of ME/CFS in Europe appears large, with productivity losses most significant, giving scope for substantial savings through effective prevention and treatment. However, economic studies of ME/CFS, including cost-of-illness analyses and economic evaluations of interventions, are problematic due to different, arbitrary case definitions, and unwillingness of doctors to diagnose it. We therefore lack accurate incidence and prevalence data, with no obvious way to estimate costs incurred by undiagnosed patients.

Other problems include, as for other conditions, difficulties estimating direct and indirect costs incurred by healthcare systems, patients and families, and heterogeneous healthcare systems and patterns of economic development across countries.

We have made recommendations, including use of the Fukuda (CDC-1994) case definition and Canadian Consensus Criteria (CCC), a pan-European common symptom checklist, and implementation of prevalence-based cost-of-illness studies in different countries using an agreed data list.

We recommend using purchasing power parities (PPP) to facilitate international comparisons, and EuroQol-5D as a generic measure of health status and multi-attribute utility instrument to inform future economic evaluations in ME/CFS.

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Systemic hyperalgesia in females with Gulf War Illness, CFS & FM

Posted on 04/07/2020 by wames

Systemic hyperalgesia in females with Gulf War Illness, Chronic Fatigue Syndrome and Fibromyalgia, by Amber A Surian, James N Baraniuk in Scientific Reports vol 10, no. 5751 (2020)

 

Research abstract:

Pain is a diagnostic criterion for Gulf War Illness (GWI), Chronic Fatigue Syndrome (CFS), and fibromyalgia (FM). The physical sign of systemic hyperalgesia (tenderness) was assessed in 920 women who were stratified by 2000 Kansas GWI, 1994 CFS, and 1990 FM criteria.

Pressure was applied by dolorimetry at 18 traditional tender points and the average pressure causing pain determined. GWI women were the most tender (2.9 ± 1.6 kg, mean ± SD, n = 70), followed by CFS/FM (3.1 ± 1.4 kg, n = 196), FM (3.9 ± 1.4 kg, n = 56), and CFS (5.8 ± 2.1 kg, n = 170) compared to controls (7.2 ± 2.4 kg, significantly highest by Mann-Whitney tests p < 0.0001, n = 428).

Receiver operating characteristics set pressure thresholds of 4.0 kg to define GWI and CFS/FM (specificity 0.85, sensitivities 0.80 and 0.83, respectively), 4.5 kg for FM, and 6.0 kg for CFS.

Pain, fatigue, quality of life, and CFS symptoms were equivalent for GWI, CFS/FM and CFS. Dolorimetry correlated with symptoms in GWI but not CFS or FM. Therefore, women with GWI, CFS and FM have systemic hyperalgesia compared to sedentary controls.

The physical sign of tenderness may complement the symptoms of the Kansas criteria as a diagnostic criterion for GWI females, and aid in the diagnosis of CFS. Molecular mechanisms of systemic hyperalgesia may provide new insights into the neuropathology and treatments of these nociceptive, interoceptive and fatiguing illnesses.

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The presence of overlapping quality of life symptoms in primary antibody deficiency (PAD) & CFS

Posted on 04/05/2020 by wames

The presence of overlapping quality of life symptoms in primary antibody deficiency (PAD) and chronic fatigue syndrome (CFS), by Rhea A Bansal, Susan Tadros, Amolak S Bansal in Allergy, Asthma & Clinical Immunology Vol 16, no: 21 (2020), March 30, 2020

Research abstract:

Background:
Fatigue, sleep disturbance and altered mood are frequently reported in patients with primary antibody deficiency syndrome (PADS) on adequate immunoglobulin replacement therapy. This study aimed to determine the frequency of symptoms compatible with chronic fatigue syndrome (CFS) in patients with PADS.

Methods:
The study involved the distribution of 682 self-completed postal questionnaires to ascertain the presence and frequency of symptoms compatible with CFS in patients with PADS. The reporting of symptoms for each patient were scored against the CFS diagnostic criteria used within our own South London Chronic Fatigue service.

Results:
The frequency of symptoms compatible with CFS were evident in 26 of the 188 patients (16.25%) returning adequately completed questionnaires. We considered a bias in the return of questionnaires amongst PADS patients with fatigue to be likely. As such we estimated the minimum frequency of CFS in patients with PADS to be 4% based on the 682 PAD patients to whom the questionnaire was distributed. This was significantly higher than the 0.5% estimate of the prevalence of CFS in the community in western populations. While the presence of significant fatigue correlated with the presence of anxiety and depression, there was no association with self-reported lung damage. Sleep disturbance affected 60% of the PAD patients returning satisfactory questionnaires and as expected the CFS score was higher in those with greater physical limitation.

Conclusions:
We conclude that patients with PADS have a high frequency of fatigue, low mood and anxiety. We suggest routine questioning for the symptoms of fatigue, disturbed sleep and altered mood in patients with PADS. The use of several treatment strategies in CFS may prove beneficial in improving the quality of life of patients with PAD.

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