The ME Association End of Week Research Round-up

August 17, 2020

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 ME Association: Index of ME/CFS Published Research.

This extensive library of research is updated at the end of every month, and is correct to the end of July 2020. It is a free resource available to anyone.

The Index provides an A-Z of published research studies and selected key documents and articles, listed by subject matter, on myalgic encephalomyelitis, myalgic encephalopathy, 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 that provide lay explanations of the more important and interesting work that has been published to date.

ME/CFS Research Published 07 – 13 August 2020

This week, 6 new research studies have been published. Highlights Include:

  1. A collaboration of researchers from the EUROMENE group, including Dr. Karl Morten at Oxford and Dr. Julia Newton from Newcastle University, looked at autonomic subgroups within ME/CFS.
    The study identified four autonomic profiles: 34% of patients had sympathetic symptoms with dysautonomia, 5% sympathetic alone, 21% parasympathetic and 40% had issues with sympathovagal balance.
    They found those with a sympathetic-dysautonomia phenotype were associated with more severe disease and had the lowest quality of life. The research group intend to carry out future studies in which they aim to design autonomic profile-specific treatment interventions.
  2. Researchers from Australia used a special type of MRI called T1w/T2w weighting that shows changes in the levels of myelin (insulating layer around nerves) and/or iron in different areas of the brain.
    The study found increased levels of myelin and/or iron in white matter and basal ganglia in ME/CFS.
  3. Researchers from the USA used functional magnetic resonance imaging (fMRI) to look at changes in brain activity during a memory task before and after exercise in patients with ME/CFS and patients with Gulf War Illness compared to healthy controls.
    The study found no differences before exercise between the groups and exercise had no effect on neural activity in healthy controls.
    In contrast, there were changes in neural activity in different areas of the brain in Gulf War Illness and ME/CFS. The brain regions that changed in the ME/CFS group are related to threat assessment, pain, and vigilant attention. The differences observed in changes in neural activity post-exercise could be useful for aiding in diagnosis.

ME/CFS Research References and Abstracts

1. Anderson E et al. (2020)
Recruiting Adolescents With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis to Internet-Delivered Therapy: Internal Pilot Within a Randomized Controlled Trial.
Journal of Medical Internet Research 22 (8): e17768.

Background: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adolescents is common and disabling. Teenagers in the United Kingdom are more likely to recover if they access specialist care, but most do not have access to a local specialist CFS/ME service. Delivering treatment remotely via the internet could improve access to treatment.

Objective: This study aims to assess (1) the feasibility of recruitment and retention into a trial of internet-delivered specialist treatment for adolescents with CFS/ME and (2) the acceptability of trial processes and 2 web-based treatments (to inform continuation to full trial).

Methods: This study is an internal pilot for the initial 12 months of a full randomized controlled trial (RCT), with integrated qualitative methods (analysis of recruitment consultations and participant and clinician interviews).
Recruitment and treatment were delivered remotely from a specialist pediatric CFS/ME treatment service within a hospital in South West United Kingdom. Adolescents (aged 11-17 years) from across the United Kingdom with a diagnosis of CFS/ME and no access to local specialist treatment were referred by their general practitioner to the treatment center.
Eligibility assessment and recruitment were conducted via remote methods (telephone and on the web), and participants were randomized (via a computer-automated system) to 1 of 2 web-based treatments.
The trial intervention was Fatigue in Teenagers on the InterNET in the National Health Service, a web-based modular CFS/ME-specific cognitive behavioral therapy program (designed to be used by young people and their parents or caregivers) supported by individualized clinical psychologist electronic consultations (regular, scheduled therapeutic message exchanges between participants and therapist within the platform).
The comparator was Skype-delivered activity management with a CFS/ME clinician (mainly a physiotherapist or occupational therapist). Both treatments were intended to last for up to 6 months.
The primary outcomes were (1) the number of participants recruited (per out-of-area referrals received between November 1, 2016, to October 31, 2017) and the proportion providing 6-month outcome data (web-based self-report questionnaire assessing functioning) and (2) the qualitative outcomes indicating the acceptability of trial processes and treatments.

Results: A total of 89 out of 150 (59.3% of potentially eligible referrals) young people and their parents or caregivers were recruited, with 75 out of 89 (84.2%) providing 6-month outcome data.
Overall, web-based treatment was acceptable; however, participants and clinicians described both the advantages and disadvantages of remote methods. No serious adverse events were reported.

Conclusions: Recruiting young people (and their parents or caregivers) into an RCT of web-based treatment via remote methods is feasible and acceptable.
Delivering specialist treatment at home via the internet is feasible and acceptable, although some families prefer to travel across the United Kingdom for face-to-face treatment.

2. Bjørklund G et al. (2020)
Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome.
Molecular Neurobiology [Epub ahead of print].

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS) is a complex, multisystem disease that is characterized by long-term fatigue, exhaustion, disabilities, pain, neurocognitive impairments, gastrointestinal symptoms, and post-exertional malaise, as well as lowered occupational, educational, and social functions.

The clinical and biomarker diagnosis of this disorder is hampered by the lack of validated diagnostic criteria and laboratory tests with adequate figures of merit, although there are now many disease biomarkers indicating the pathophysiology of CFS.

Here, we review multiple factors, such as immunological and environmental factors, which are associated with CFS and evaluate current concepts on the involvement of immune and environmental factors in the pathophysiology of CFS.

The most frequently reported immune dysregulations in CFS are modifications in immunoglobulin contents, changes in B and T cell phenotypes and cytokine profiles, and decreased cytotoxicity of natural killer cells. Some of these immune aberrations display a moderate diagnostic performance to externally validate the clinical diagnosis of CFS, including the expression of activation markers and protein kinase R (PKR) activity. Associated with the immune aberrations are activated nitro-oxidative pathways, which may explain the key symptoms of CFS.

This review shows that viral and bacterial infections, as well as nutritional deficiencies, may further aggravate the immune-oxidative pathophysiology of CFS. Targeted treatments with antioxidants and lipid replacement treatments may have some clinical efficacy in CFS. We conclude that complex interactions between immune and nitro-oxidative pathways, infectious agents, environmental factors, and nutritional deficiencies play a role in the pathophysiology of CFS.

3. Devendorf A et al. (2020)
Patients' hopes for recovery from myalgic encephalomyelitis and chronic fatigue syndrome: Toward a “recovery in” framework.
Chronic Illness 16 (4): 307-321.

Objective: There is no consensus on recovery from myalgic encephalomyelitis and chronic fatigue syndrome, which has spawned debates when interpreting outcome research. Within these debates, the patient voice is often neglected.

This study aimed to understand how patients conceptualize recovery – regarding the definition and possibility of recovery.

Method: We conducted in-depth, semi-structured interviews with 10 older (above age 50) female patients with myalgic encephalomyelitis or chronic fatigue syndrome. Data were analyzed using a deductive thematic analysis.

Results: Our sample viewed recovery as functioning without fear of relapse, returning to previous roles and identities, and achieving a sustained absence of symptoms. Participants expressed skepticism that reaching recovery from myalgic encephalomyelitis and chronic fatigue syndrome exists but working toward significant improvement through coping is a viable goal. Although many accepted they would never reclaim full functioning, participants continued to experience uncertainty about their future with unclear prognostic goals and limited treatment options.

Discussion: Recovery is more than just symptom reduction. Outcome research should incorporate well-being measures like identity, meaning and quality of life, and personal empowerment to enhance recovery definitions.

When communicating treatment goals, providers might convey cautious optimism for complete symptom remission, while emphasizing that living a fulfilling life through effective coping strategies is possible.

4. Słomko J et al. (2020)
Autonomic Phenotypes in Chronic Fatigue Syndrome (CFS) Are Associated with Illness Severity: A Cluster Analysis.
Journal of Clinical Medicine 9 (8).

In this study we set out to define the characteristics of autonomic subgroups of patients with Chronic Fatigue Syndrome (CFS).

The study included 131 patients with CFS (Fukuda criteria). Participants completed the following screening symptom assessment tools: Chalder Fatigue Scale, Fatigue Impact Scale, Fatigue Severity Scale, Epworth Sleepiness Scales, the self-reported Composite Autonomic Symptom Scale. Autonomic parameters were measured at rest with a Task Force Monitor (CNS Systems) and arterial stiffness using an Arteriograph (TensioMed Kft.).

Principal axis factor analysis yielded four factors: fatigue, subjective and objective autonomic dysfunction and arterial stiffness. Using cluster analyses, these factors were grouped in four autonomic profiles: 34% of patients had sympathetic symptoms with dysautonomia, 5% sympathetic alone, 21% parasympathetic and 40% had issues with sympathovagal balance.

Those with a sympathetic-dysautonomia phenotype were associated with more severe disease, reported greater subjective autonomic symptoms with sympathetic over-modulation and had the lowest quality of life. The highest quality of life was observed in the balance subtype where subjects were the youngest, had lower levels of fatigue and the lowest values for arterial stiffness.

Future studies will aim to design autonomic profile-specific treatment interventions to determine links between autonomic phenotypes CFS and a specific treatment.

5. Thapaliya K et al. (2020)
Mapping of pathological change in chronic fatigue syndrome using the ratio of T1- and T2-weighted MRI scans.
NeuroImage Clinical 28.


Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) subjects suffer from a variety of cognitive complaints indicating that the central nervous system plays a role in its pathophysiology.

Recently, the ratio T1w/T2w has been used to study changes in tissue myelin and/or iron levels in neurodegenerative diseases such as multiple sclerosis and schizophrenia. In this study, we applied the T1w/T2w method to detect changes in tissue microstructure in ME/CFS patients relative to healthy controls.

We mapped the T1w/T2w signal intensity values in the whole brain for forty-five ME/CFS patients who met Fukuda criteria and twenty-seven healthy controls and applied both region- and voxel-based quantification. We also performed interaction-with-group regressions with clinical measures to test for T1w/T2w relationships that are abnormal in ME/CFS at the population level.

Region-based analysis showed significantly elevated T1w/T2w values (increased myelin and/or iron) in ME/CFS in both white matter (WM) and subcortical grey matter.

The voxel-based group comparison with sub-millimetre resolution voxels detected very significant clusters with increased T1w/T2w in ME/CFS, mostly in subcortical grey matter, but also in brainstem and projection WM tracts.

No areas with decreased T1w/T2w were found in either analysis. ME/CFS T1w/T2w regressions with heart-rate variability, cognitive performance, respiration rate and physical well-being were abnormal in both gray and white matter foci.

Our study demonstrates that the T1w/T2w approach is very sensitive and shows increases in myelin and/or iron in WM and basal ganglia in ME/CFS.

6. Washington S et al. (2020)
Exercise alters brain activation in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Brain Communications 2 (2).

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.

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