ME Association September Summary of ME/CFS Published Research | 03 October 2018

October 3, 2018


ME Association Index of Published ME/CFS Research

The Index of Published ME/CFS Research has now been updated to take account of the research that has been published during the month of September 2018.

The Index is a useful way to locate and then read all relevant research on ME/CFS. It’s free to download and comes with an interactive contents table.

This is an A-Z list of all the most important ME/CFS research studies (and selected key documents and articles), listed by subject matter and author with links to PubMed or to the Journal it was published in.

You can also find the index in the Research section of our website.

ME/CFS research abstracts from studies published in September 2018

1. Albrecht DS, et al. (2018)
Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation.
Brain, Behaviour and Immunity [Epub ahead of print].

Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM.

In this study, we conducted a Positron Emission Tomography (PET) study using [11C]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes.

To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [11C]-L-deprenyl-D2 PET, thought to primarily reflect astrocytic (but not microglial) signal.

Thirty-one FM patients and 27 healthy controls (HC) were examined using [11C]PBR28 PET. 11 FM patients and 11 HC were scanned using [11C]-L-deprenyl-D2 PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (VT) were computed from the [11C]PBR28 data. [11C]-L-deprenyl-D2 was quantified using λ k3. PET imaging metrics were compared across groups, and when differing across groups, against clinical variables.

Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [11C]PBR28 VTand SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes.

No regions showed significant group differences in [11C]-L-deprenyl-D2 signal, including those demonstrating elevated [11C]PBR28 signal in patients (p's ≥ 0.53, uncorrected). The elevations in [11C]PBR28 VT and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude.

In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [11C]PBR28 SUVR in the anterior and posterior middle cingulate cortices (p's < 0.03). SUVR was not significantly associated with any other clinical variable.

Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology.

Given that the elevations in [11C]PBR28 signal were not also accompanied by increased [11C]-L-deprenyl-D2 signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions.

Although [11C]-L-deprenyl-D2 signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.

2. Bram AD, et al. (2018)
Emotional Regulation in Women with Chronic Fatigue Syndrome and Depression: Internal Representations and Adaptive Defenses.
Journal of the American Psychoanalytic Association 66 (4): 701-741.

Chronic fatigue syndrome (CFS) presents challenges in differential diagnosis and treatment. Complicating diagnosis is that its symptoms overlap with those of depression. This study applies psychoanalytic concepts to understand emotional regulation (ER) in women with CFS and/or depression.

One hundred eighty-six women were assigned to four groups and compared: (a) CFS plus higher depression (CFS-HD); (b) CFS plus lower depression (CFS-LD); (c) depressive disorder (DD); and (d) healthy controls (HC). ER was operationalized by measures of capacity to form internal representations and adaptive defenses.

The study's premise was that difficulties metabolizing emotions psychologically would be associated with their greater somatic expression.

Some support was found for the hypothesis that CFS participants would exhibit more impairment in representing emotions and in adaptive defenses compared to the DD and HC groups, but this held only for the CFS-HD group.

Although CFS-LD participants were expected to be more purely somatizing than the CFS-HD group, they instead showed more sophisticated capacities for ER than that group and recalled less distressing early relationships, revealing more resilience.

Still, however, we found support for somatization in some CFS sufferers: Within both the CFS-HD and the CFS-LD groups, weaknesses in representing emotions and in defensive functioning were associated with more severe physical symptoms.

Clinically, the heterogeneity of CFS and those who suffer from it indicates the need for individual assessment and depression treatment.

3. Brigden A, et al. (2018)
Using the internet to cope with chronic fatigue syndrome/myalgic encephalomyelitis in adolescence: a qualitative study
BMJ Paediatrics Open 2 (1).

Background: Adolescents are increasingly using online resources for health purposes. Previous studies suggest that online provision of information about chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is neither balanced nor consistent with evidence-based practice. However, little is known about how adolescents with CFS/ME use the internet for their condition and whether this is helpful or harmful.

Methods: Nine indepth, semistructured, qualitative interviews were conducted with young people (aged 12–17) recruited from a specialist paediatric CFS/ME service. Interviews explored the types of online resources accessed, motivations for doing so and how resource use related to patterns of coping.

Results: Around the time of diagnosis, participants focused on gathering facts about CFS/ME and therefore used official resources (e.g., National Health Service sites) that were considered reliable. This transitioned to exploring patient-led and peer-led spaces: health forums, Facebook and YouTube.

Participants accessed these regularly, over the long term, and valued these sites for the personal stories, emotional content and interactive technology. Patient-led and peer-led sites supported coping, encouraging active behavioural management, providing social support and addressing stigmatised aspects of the condition. CFS/ME put a strain on normal adolescent life, such as identity and friendships.

Online resources allowed participants to adapt and maintain a sense of normality.

Conclusions: Adolescents who use the internet find online resources helpful in seeking information and social support for their condition.

Healthcare services should improve their online resources to meet the needs of younger users, providing evidence-based content in ways that are relevant to adolescents and that can meet the needs for social support, as well as providing information.

4. Espejo JA, et al. (2018)
Unraveling the Molecular Determinants of Manual Therapy: An Approach to Integrative Therapeutics for the Treatment of Fibromyalgia and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
International Journal of Molecular Science 19 (9).

Application of protocols without parameter standardization and appropriate controls has led manual therapy (MT) and other physiotherapy-based approaches to controversial outcomes.

Thus, there is an urgency to carefully define standard protocols that elevate physiotherapy treatments to rigorous scientific demands.

One way in which this can be achieved is by studying gene expression and physiological changes that associate to particular, parameter-controlled, treatments in animal models, and translating this knowledge to properly designed, objective, quantitatively-monitored clinical trials (CTs).

Here, we propose a molecular physiotherapy approach (MPTA) requiring multidisciplinary teams, to uncover the scientific reasons behind the numerous reports that historically attribute health benefits to MT-treatments.

The review focuses on the identification of MT-induced physiological and molecular responses that could be used for the treatment of fibromyalgia (FM) and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

The systemic effects associated to mechanical-load responses are considered of particular relevance, as they suggest that defined, low-pain anatomic areas can be selected for MT treatment and yet yield overall benefits, an aspect that might result in it being essential to treat FM.

Additionally, MT can provide muscle conditioning to sedentary patients without demanding strenuous physical effort, which is particularly detrimental for CFS/ME patients, placing MT as a real option for integrative medicine programs to improve FM and CFS/ME.

5. Estevez-Lopez F, et al. (2018)
Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe-the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review.
BMJ Open 8 (9): e020817.

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease involving central nervous system and immune system disorders, as well as cardiovascular abnormalities. ME/CFS is characterised by severe chronic fatigue lasting for at least 6 months, including clinical symptoms such as tender cervical or axillary lymph nodes, muscle pain, joint pain without swelling or redness, post-exertional malaise for more than 24 hours and unrefreshing sleep.

Studies on the epidemiology of ME/CFS in Europe only include single countries and, therefore, the prevalence and incidence of ME/CFS in Europe (as a whole) is unknown. One of the purposes of the European Network on ME/CFS (EUROMENE; European Union-funded COST Action; Reference number: 15111) is to address this gap in knowledge. We will systematically review the literature reporting figures from European countries to provide a robust summary and identify new challenges.

Methods and Analysis: We will systematically search the literature databases Scopus, PubMed and Web of Science for studies published in the last 10 years (ie, after 2007). No language restriction will be applied. Two independent reviewers will search, screen and select studies as well as extract data about their main characteristics and evaluate their methodological and reporting quality.

When disagreements emerge, the reviewers will discuss to reach a consensus. We plan to produce a narrative summary of our findings as we anticipate that studies are scarce and heterogeneous. The possibility of performing meta-analyses will be discussed in a EUROMENE meeting.

Ethics and Dissemination: Ethical approval is not required as only publicly available data will be included. Findings will be described in EUROMENE reports, published in peer-reviewed journal(s) and presented at conferences.

The findings will be also communicated to policy-makers, healthcare providers, people with ME/CFS and other sections of society through regular channels including the mass-media.

6. Friedman KJ, et al. (2018)
School Nurses Can Improve the Lives of Students with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
National Association of School Nurses [Epub ahead of print]

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness that is defined and diagnosed by its symptoms: extreme fatigue made worse by physical and mental activity, pain and decreased mental stamina, among others.

A long-held, erroneous belief that ME/CFS is not a physiological illness has persisted among some clinicians, leading to the denial of a patient's physical illness and attributing the symptoms to other causes.

The debilitating effects of ME/CFS in the pediatric population can affect all aspects of academic, social, emotional, and physical development. ME/CFS has been diagnosed in children younger than 10 years.

Therefore, the school nurse is likely to encounter one or more students in the various stages of this disease, putting the school nurse in a position to ameliorate the impact of this potentially devastating chronic condition.

7. Roerink ME, et al. (2018)
Pitfalls in cytokine measurements – Plasma TGF-β1 in chronic fatigue syndrome.
Netherlands Journal of Medicine 76 (7): 310-313.

Background: Serum TGF-β1 concentrations are reported to be elevated in chronic fatigue syndrome (CFS). However, measurement of circulating cytokines is a complex procedure and control of pre-analytical procedures is essential. The objective of the current study was to measure circulating TGF-β1 concentrations in CFS patients compared to healthy controls, taking into account differences in pre-analytical procedures.

Methods: Two cohorts of female CFS patients were included. In both studies patients were asked to bring a healthy, age-matched control. At baseline, TGF-β1 levels were measured in plasma and additionally P-selectin, a marker of platelet activity, was determined in a subgroup of participants.

Results: 50 patients and 48 controls were included in cohort I, and 90 patients and 29 controls in cohort II. Within the cohorts there were no differences in TGF-β1 concentrations.

However, between the cohorts there was a large discrepancy, which appeared to be caused by differences in g-force of the centrifuges used. The lower g-force used in cohort II (1361 g) caused more platelet activation, reflected by higher p-selectin concentrations, compared to cohort I (p < 0.0001), which was confirmed in a second independent experiment.

There was a correlation between TGF-β1 and p-selectin concentrations (r 0.79, p < 0.0001).

Conclusion: These results demonstrate that control of pre-analytical procedures is an essential aspect when measuring circulating cytokines. No evidence for enhanced TGF-β1 in patients with CFS was found.

8. Stevens S, et al. (2018)
Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Frontiers in Pediatrics 6:242.

Background: Concise methodological directions for administration of serial cardiopulmonary exercise testing (CPET) are needed for testing of patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Maximal CPET is used to evaluate the coordinated metabolic, muscular, respiratory and cardiac contributions to energy production in patients with ME/CFS. In this patient population, CPET also elicits a robust post-exertional symptom flare (termed, post-exertional malaise); a cardinal symptom of the disease. CPET measures are highly reliable and reproducible in both healthy and diseased populations.

However, evidence to date indicates that ME/CFS patients are uniquely unable to reproduce CPET measures during a second test, despite giving maximal effort during both tests, due to the effects of PEM on energy production.

Methodology: To document and assess functional impairment due to the effects of post-exertional malaise in ME/CFS, a 2-day CPET procedure (2-day CPET) has been used to first measure baseline functional capacity (CPET1) and provoke post-exertional malaise, then assess changes in CPET variables 24 h later with a second CPET to assess the effects of post-exertional malaise on functional capacity.

The second CPET measures changes in energy production and physiological function, objectively documenting the effects of post-exertional malaise. Use of CPET as a standardized stressor to induce post-exertional malaise and quantify impairment associated with post-exertional malaise has been employed to examine ME/CFS pathology in several studies.

This article discusses the results of those studies, as well as the standardized techniques and procedures for use of the 2-day CPET in ME/CFS patients, and potentially other fatiguing illnesses.

Conclusions: Basic concepts of CPET are summarized, and special considerations for performing CPET on ME/CFS patients are detailed to ensure a valid outcome. The 2-day CPET methodology is outlined, and the utility of the procedure is discussed for assessment of functional capacity and exertion intolerance in ME/CFS.

9. Strassheim VJ, et al. (2018)
Defining the prevalence and symptom burden of those with self-reported severe chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a two-phase community pilot study in the North East of England
BMJ Open 8 (9).

Objectives: Define the prevalence of severe chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and its clinical characteristics in a geographically defined area of Northern England. To understand the feasibility of a community-based research study in the severely affected CFS/ME group.

Design: A two-phase clinical cohort study to pilot a series of investigations in participants own homes.

Setting: Participants were community living from the area defined by the Northern clinical network of the UK.

Participants: Adults with either a medical or a self-reported diagnosis of CFS/ME. Phase 1 involved the creation of a database. Phase 2: five participants were selected from database, dependent on their proximity to Newcastle.

Interventions: The De Paul fatigue questionnaire itemised symptoms of CFS/ME, the Barthel Functional Outcome Measure and demographic questions were collected via postal return. For phase 2, five participants were subsequently invited to participate in the pilot study.

Results: 483 questionnaire packs were requested, 63 were returned in various stages of completion. 56 De Paul fatigue questionnaires were returned: all but 12 met one of the CFS/ME criteria, but 12 or 22% of individuals did not fulfil the Fukuda nor the Clinical Canadian Criteria CFS/ME diagnostic criteria (but 6 of them indicated that their fatigue was related to other causes and they barely had any symptoms). The five pilot participants completed 60% of the planned visits.

Conclusions: Severely affected CFS/ME individuals are keen to participate in research; however, their symptom burden is great, and quality of life is poor. These factors must be considered when planning research and methods of engaging with such a cohort.

10. Terman JM, et al. (2018)
Confirmatory factor analysis of a myalgic encephalomyelitis and chronic fatigue syndrome stigma scale.
Journal of Health Psychology [Epub ahead of print]

This study adapted a chronic illness stigma scale and explored its psychometric properties. The main purposes were to confirm the factor structure of the instrument with this population and address the previous factor intercorrelation discrepancies.

Five hundred and fifty-four individuals with myalgic encephalomyelitis or chronic fatigue syndrome completed the adapted stigma scale.

Results document the stigma experienced by an international sample of individuals with myalgic encephalomyelitis and chronic fatigue syndrome. Factors demonstrated good internal consistency, and a model fit was found in a confirmatory factor analysis.

Participants endorsed high levels of stigma, estrangement, and disclosure. Implications of these findings and future directions are discussed.

11. Twisk F (2018)
Myalgic Encephalomyelitis (ME) or What? An Operational Definition.
Diagnostics (Basel) 8 (3).

Myalgic encephalomyelitis (ME), identified as a new clinical entity with distinctive features in 1956, was originally considered as a neuromuscular disease. In 1988 the Centers for Disease Control and Prevention introduced the ill-defined concept of chronic fatigue syndrome (CFS). As predicted, CFS, unjustly considered to be a synonym for ME, pushed ME to the background.

To develop effective therapies for of ME and CFS, it is essential to investigate patients with ME specifically. For that reason, an operational definition of ME is indispensable. This article proposes an operational definition based on the most recent formal definitions and symptoms observed in ME.

ME is a multi-systemic illness, which (1) often has a sudden onset, in most cases a respiratory and/or gastro-intestinal infection, but a gradual or more dramatic onset is also possible; (2) has an epidemic and an endemic form; (3) has an unique clinical pattern deviating from other post-viral states; (4) is distinguished by muscle fatigability/prolonged muscle weakness after trivial exertion; (5) is accompanied by symptoms relating to neurological disturbance, especially of cognitive, autonomic, and sensory functions; (6) can be accompanied by symptoms associated with cardiac and other systems; (7) is characterized by fluctuation of symptoms (within and between “episodes”); (8) has a prolonged relapsing course; and (9) has a tendency to become chronic.

In conclusion, a discriminative definition for ME contains four mandatory elements: (1) muscle fatigability/post-exertional muscle weakness lasting for days; (2) operational criteria for “neurological disturbance, especially of cognitive, autonomic and sensory functions”; (3) fluctuation of symptoms; and (4) a prolonged relapsing course.

This tentative definition of ME justifies the qualification “neuromuscular disease”.

12. Wang T, et al. (2018)
Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function.
PLoS One 13 (9).

Host-microbe interactions have been implicated in the pathogenesis of chronic fatigue syndrome (CFS), but whether the oral microbiome is altered in CFS patients is unknown.

We explored alterations of the oral microbiome in Chinese Han CFS patients using 16S rRNA gene sequencing and alterations in the functional potential of the oral microbiome using PICRUSt.

We found that Shannon and Simpson diversity indices were not different in CFS patients compared to healthy controls, but the overall oral microbiome composition was different (MANOVA, p < 0.01).

CFS patients had a higher relative abundance of Fusobacteria compared with healthy controls. Further, the genera Leptotrichia, Prevotella, and Fusobacterium were enriched and Haemophilus, Veillonella, and Porphyromonas were depleted in CFS patients compared to healthy controls.

Functional analysis from inferred metagenomes showed that bacterial genera altered in CFS patients were primarily associated with amino acid and energy metabolism.

Our findings demonstrate that the oral microbiome in CFS patients is different from healthy controls, and these differences lead to shifts in functional pathways with implications for CFS pathogenesis.

These findings increase our understanding of the relationship between the oral microbiota and CFS, which will advance our understanding of CFS pathogenesis and may contribute to future improvements in treatment and diagnosis.

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