The ME Association End of Week Research Round-up

Charlotte Stephens, Research Correspondent, ME Association.

We show below brief summaries of the research studies about ME/CFS that have been published in the last week, followed by the abstracts from those studies.

All research relating to ME/CFS can be located in the Index of ME/CFS Published Research which is correct to the end of June 2020 and can be downloaded for free.

It is an A-Z of the most important published research studies and selected key documents and articles, listed by subject matter, on myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS).

You can use it to easily locate and read any research in a particular area that you might be interested in, e.g. epidemiology, infection, neurology, post-exertional malaise etc.

You can also find the Research Index in the Research section of the website together with a list of Research Summaries from the ME Association that provide lay explanations of the more important and interesting work that has been published to date.

ME/CFS Research Published 17 – 23 July 2020

This week, 5 new research studies have been published. Highlights include:

  • Researchers from the USA have found that there are protein markers associated with immune dysregulation that are in different levels in ME/CFS patients and can accurately predict ME/CFS cases, as well as specific markers that can distinguish between patients with and without IBS (Irritable bowel syndrome).
  • Dr. Nigel Speight, a Paediatrician from Durham and Hon. Medical advisor for the ME Association, has published a series of case reports on severe paediatric M.E., illustrating various points regarding clinical presentation, together with general principles of appropriate management and care.
  • A team of independent researchers with a specific interest in the mathematics and history of M.E. looked at a specific type of mathematical model used to classify infectious diseases. They may have shown that M.E. can be modelled as an infectious disease, using data from the Royal Free Hospital epidemic of 1955. This goes against a hypothesis that the outbreaks were psychosomatic in origin.

ME/CFS Research References and Abstracts

1. Campen CMC et al. (2020)
Cognitive Function Declines Following Orthostatic Stress in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
Frontiers in Neuroscience [Epub ahead of print].

Abstract
Introduction: Orthostatic intolerance (OI) is common among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Cognitive dysfunction has been demonstrated during head-up tilt testing (HUT) in those with ME/CFS: worse scores on cognitive tests occur with increasing tilt angles and increasing complexity of the cognitive challenge.

The aim of our study was to determine whether cognitive impairment persists after completion of HUT.

Methods and Results: Eligible participants were consecutive individuals satisfying criteria for ME/CFS who underwent HUT because of OI. The 2- and 3-back tests were performed before the start of HUT and within 5 min after completion of HUT. We measured the percentage of correct responses and raw reaction times before and after HUT for both the 2- and 3-back tests.

We studied 128 ME/CFS patients who underwent HUT and had a complete set of N-back data before and after HUT. Compared to pre-tilt responses, the percentage of correct responses on the 2-back test decreased post-HUT from 77(18) to 62(21) and of the 3-back test from 57(17) to 41(17) (both p < 0.0001).

The raw reaction time of the 2-back test increased post-HUT from 783(190) to 941(234) m/s and of the 3-back test from 950(170) to 1102(176) (both p < 0.0001).

There was no difference in the N-back test data for subgroups dichotomized based on disease severity, the presence of co-morbid fibromyalgia, or the presence of postural orthostatic tachycardia syndrome.

Conclusion: As measured by the N-back test, working memory remains impaired in adults with ME/CFS following a 30-min head-up tilt test.

2. Jacob L et al. (2020)
Associations of physical and psychiatric conditions with chronic fatigue syndrome in Germany: an exploratory case-control study.
Psychological Medicine 1-7.

Abstract
Background: Only a few studies have analyzed the effects of physical and psychiatric conditions on the risk of chronic fatigue syndrome (CFS).

Therefore, the goal of this exploratory case-control study was to investigate the associations of physical and psychiatric conditions with CFS in almost 19 800 adults from Germany.

Methods: This study included patients diagnosed for the first time with CFS in one of 1238 general practices in Germany between 2010 and 2017 (index date). Controls without CFS were matched (1:1) to cases with CFS by sex, age, index year, and practice.

Physical and psychiatric conditions diagnosed in the year prior to the index date were included if they were present in at least 3% of patients with CFS. Associations between physical and psychiatric conditions (33 potential independent variables) and CFS (dependent variable) were analyzed in an adjusted conditional logistic regression model, and physical and psychiatric disorders were included in the model using forward stepwise selection.

Results: This study included 9896 cases with CFS and 9896 controls without CFS [65.1% women; mean (standard deviation) age 49.5 (18.3) years]. Seven conditions were associated with CFS in the adjusted regression model.

The disorders displaying the strongest relationship with CFS were cancer [odds ratio (OR) = 2.57, 95% confidence interval (CI) = 2.24-2.95], sleep disorders (OR = 1.88, 95% CI = 1.66-2.12) and depression (OR = 1.77, 95% CI = 1.61-1.95).

Conclusions: Cancer, sleep disorders, and depression were strongly and positively associated with CFS. Additional studies are needed to gain a better understanding of the mechanisms underlying these relationships.

3. Milivojevic M et al. (2020)
Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS.
PLoS One 15 (7).

Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an unexplained chronic, debilitating illness characterized by fatigue, sleep disturbances, cognitive dysfunction, orthostatic intolerance and gastrointestinal problems.

Using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we analyzed the plasma proteomes of 39 ME/CFS patients and 41 healthy controls.

Logistic regression models, with both linear and quadratic terms of the protein levels as independent variables, revealed a significant association between ME/CFS and the immunoglobulin heavy variable (IGHV) region 3-23/30.

Stratifying the ME/CFS group based on self-reported irritable bowel syndrome (sr-IBS) status revealed a significant quadratic effect of immunoglobulin lambda constant region 7 on its association with ME/CFS with sr-IBS whilst IGHV3-23/30 and immunoglobulin kappa variable region 3-11 were significantly associated with ME/CFS without sr-IBS.

In addition, we were able to predict ME/CFS status with a high degree of accuracy (AUC = 0.774-0.838) using a panel of proteins selected by 3 different machine learning algorithms: Lasso, Random Forests, and XGBoost. These algorithms also identified proteomic profiles that predicted the status of ME/CFS patients with sr-IBS (AUC = 0.806-0.846) and ME/CFS without sr-IBS (AUC = 0.754-0.780).

Our findings are consistent with a significant association of ME/CFS with immune dysregulation and highlight the potential use of the plasma proteome as a source of biomarkers for disease.

4. Speight N (2020)
Severe ME in Children.
Healthcare 8 (3).

Abstract
A current problem regarding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is the large proportion of doctors that are either not trained or refuse to recognize ME/CFS as a genuine clinical entity, and as a result do not diagnose it.

An additional problem is that most of the clinical and research studies currently available on ME are focused on patients who are ambulant and able to attend clinics and there is very limited data on patients who are very severe (housebound or bedbound), despite the fact that they constitute an estimated 25% of all ME/CFS cases.

This author has personal experience of managing and advising on numerous cases of severe paediatric ME, and offers a series of case reports of individual cases as a means of illustrating various points regarding clinical presentation, together with general principles of appropriate management.

5. Waters FG et al. (2020)
Myalgic Encephalomyelitis (ME) outbreaks can be modelled as an infectious disease: a mathematical reconsideration of the Royal Free Epidemic of 1955.
Fatigue: Biomedicine, Health and Behaviour [Epub ahead of print].

Abstract
In 1970, two clinicians, McEvedy and Beard re-analysed some of the case notes, and hypothesised that the Royal Free outbreak was epidemic hysteria.

This hypothesis was the beginning of an entrenched belief that the disease at the Royal Free, and similar cluster outbreaks, were psychosomatic.

This was to have a profound effect on the interpretation of the same illness for nearly 50 years as a presumptive psychosomatic, an interpretation that has lasted nearly 50 years. 

Methods: The 1927 Susceptible Infected Recovered (SIR) mathematical model for the transmission of disease has been used to examine the published admission data from the Royal Free Hospital for the purpose of finding out if the disease had the characteristics of a contagious disease. Similar cluster outbreaks have also been modelled to assess whether they have similar characteristics to the Royal Free outbreak. 

Results: Using the 1927 Susceptible Infected Recovered (SIR) model for the transmission of disease, we show that the epidemic of a disease of an unknown aetiology at the Royal Free Hospital in 1955, and other similar twentieth-century outbreaks, have the characteristics of a communicable disease.

The disease causing the Royal Free outbreak was given the name ‘Benign Myalgic Encephalomyelitis’ by Acheson in 1956, now identified as ME. 

Conclusions: By showing that the Royal Free and other ME attributed outbreaks fit the SIR disease model, we demonstrate that the McEvedy and Beard hysteria hypothesis is mathematically incorrect.

The ensuing management of the treatment of ME/CFS-like conditions evolving from that, now mathematically improbable belief may need to be re-evaluated.

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