ME Association August Summary of ME/CFS Published Research | 05 September 2018

September 5, 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 August.

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 August 2018

1. Barnden LR, et al. (2018)
Hyperintense sensorimotor T1 spin echo MRI is associated with brainstem abnormality in chronic fatigue syndrome
NeuroImage: Clinical 20; 102-109.

We recruited 43 Chronic Fatigue Syndrome (CFS) subjects who met Fukuda criteria and 27 healthy controls and performed 3T MRI T1 and T2 weighted spin-echo (T1wSE and T2wSE) scans. T1wSE signal follows T1 relaxation rate (1/T1 relaxation time) and responds to myelin and iron (ferritin) concentrations. We performed MRI signal level group comparisons with SPM12. Spatial normalization after segmentation was performed using T2wSE scans and applied to the coregistered T1wSE scans.

After global signal-level normalization of individual scans, the T1wSE group comparison detected decreased signal-levels in CFS in a brainstem region (cluster-based inference controlled for family wise error rate, PFWE= 0.002), and increased signal-levels in large bilateral clusters in sensorimotor cortex white matter (cluster PFWE < 0.0001). Moreover, the brainstem T1wSE values were negatively correlated with the sensorimotor values for both CFS (R2 = 0.31, P = 0.00007) and healthy controls (R2 = 0.34, P = 0.0009), and the regressions were co-linear.

This relationship, previously unreported in either healthy controls or CFS, in view of known thalamic projection-fibre plasticity, suggests brainstem conduction deficits in CFS may stimulate the upregulation of myelin in the sensorimotor cortex to maintain brainstem – sensorimotor connectivity. VBM did not find group differences in regional grey matter or white matter volumes.

We argued that increased T1wSE observed in sensorimotor WM in CFS indicates increased myelination which is a regulatory response to deficits in the brainstem although the causality cannot be tested in this study. Altered brainstem myelin may have broad consequences for cerebral function and should be a focus of future research.

2. Bram A, et al. (2018)
Chronic fatigue syndrome and the somatic expression of emotional distress: Applying the concept of illusory mental health to address the controversy
Journal of Clinical Psychology [epub ahead of print]

Objective: The process of somatization in chronic fatigue syndrome (CFS) was investigated using the concept of illusory mental health (IMH). IMH involves self-reporting low emotional distress alongside performance-based assessment of distress.

Method: We studied IHM and physical symptoms in 175 women across four groups: (a) CFS plus depression; (b) CFS with no depression (CFS-ND); (c) depressive disorder without CFS; and (d) healthy controls (HC). IMH was assessed using a self-report measure plus the performance-based Early Memory Index (EMI).

Results: CFS-NDs were no more likely to have IMH compared with HCs. Among the CFS-NDs, IMH was associated with more physical symptoms. For CFS-NDs, EMI added meaningfully beyond self-reported mental health in predicting physical symptoms.

Conclusion: Findings refute reducing CFS to somatization, but there is a subgroup of CFS whose lacking access to emotional distress is associated with heightened physical symptomatology.

3. Burgess M, et al. (2018)
Home-based family focused rehabilitation for adolescents with severe Chronic Fatigue Syndrome
Clinical Child Psychology and Psychiatry [Epub ahead or print].

Aims: The purpose of this article is to describe and evaluate a home based, family focused rehabilitative approach for severely affected housebound adolescents with Chronic Fatigue Syndrome (CFS). The main aims were to facilitate a return to school, improve physical functioning, reduce fatigue and assess any adverse effects of the intervention.

Methods: Six housebound adolescents aged 11-18, diagnosed with CFS by a paediatrician, were assessed and treated at home by an experienced cognitive behaviour therapist. Outcomes were assessed 12 months after discharge from treatment.

Results: At 12 months follow-up all patients had returned to either school or college, and physical functioning had improved in most of the patients. Fatigue had reduced in some. No adverse effects of the intervention were reported.

Conclusion: Severely affected adolescents with CFS showed improved physical functioning and social adjustment after a home-based rehabilitative approach. Although several patients showed improvements in physical functioning, they did not all show substantial improvements in fatigue. At this crucial stage of development, it is important to offer young people and their parents hope by stating that improvement is possible.

4. Hatziagelaki E, et al. (2018)
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Metabolic Disease or Disturbed Homeostasis?
Journal of Pharmacology and Experimental Therapeutics [Epub ahead of print].

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease characterized by debilitating fatigue, lasting for at least 6 months, with severe impairment of daily functioning and associated symptoms. A significant percentage of ME/CFS patients remains undiagnosed, mainly due to the complexity of the disease and the lack of reliable objective biomarkers.

ME/CFS patients display decreased metabolism and the severity of symptoms appears to be directly correlated to the degree of metabolic reduction that may be unique to each individual patient. However, the precise pathogenesis is still unknown preventing the development of effective treatments. The ME/CFS phenotype has been associated with abnormalities in energy metabolism, mostly with mitochondrial dysfunction, resulting in reduced oxidative metabolism.

Mitochondrial dysfunction may be further contributing to the ME/CSF symptomatology by extracellular secretion of mitochondrial DNA, which could create an “innate” inflammatory state in the hypothalamus, thus disrupting normal homeostasis. We propose that stimulation of hypothalamic mast cells activates microglia leading to focal inflammation in the brain and disturbed homeostasis.

5. Loades ME, et al. (2018)
Illness beliefs of adolescents with CFS and their parents: the perceived causes of illness and beliefs about recovery
International Journal of Adolescent Medicine and Health [Epub ahead of print].

The objective here was to explore beliefs about the causes of chronic fatigue syndrome (CFS) in a cohort of adolescents with CFS and their parents, and to explore the adolescent’s beliefs about recovery.

Questionnaires were administered to a clinical cohort of adolescents (n = 104) and their parents (n = 102 mothers and 63 fathers), presenting to a specialist CFS unit. These included a question about the causes of their illness. Adolescents were also asked about the projected timeline of their recovery from CFS.

The most commonly endorsed causes of CFS by adolescents and their parents were a virus and/or contextual factors and stress. Adolescents and their parents were in close agreement about the causes of CFS. Most adolescents said they did not know how long it would take them to recover from CFS.

Informing adolescents about the prognosis for CFS is an important aspect of treatment.

6. Naviaux RK. (2018)
Metabolic features and regulation of the healing cycle – A new model for chronic disease pathogenesis and treatment

Without healing, multicellular life on Earth would not exist. Without healing, one injury predisposes to another, leading to disability, chronic disease, accelerated aging, and death. Over 50% of adults and 30% of children and teens in the United States now live with a chronic illness. Advances in mass spectrometry and metabolomics have given scientists a new lens for studying health and disease.

This study defines the healing cycle in metabolic terms and reframes the pathophysiology of chronic illness as the result of metabolic signaling abnormalities that block healing and cause the normal stages of the cell danger response (CDR) to persist abnormally.

Once an injury occurs, active progress through the stages of healing is driven by sequential changes in cellular bioenergetics and the disposition of oxygen and carbon skeletons used for fuel, signaling, defense, repair, and recovery.

>100 chronic illnesses can be organized into three persistent stages of the CDR. One hundred and two targetable chemosensory G-protein coupled, and ionotropic receptors are presented that regulate the CDR and healing. Metabokines are signaling molecules derived from metabolism that regulate these receptors.

Reframing the pathogenesis of chronic illness in this way, as a systems problem that maintains disease, rather than focusing on remote trigger(s) that caused the initial injury, permits new research to focus on novel signaling therapies to unblock the healing cycle, and restore health when other approaches have failed.

7. Roberts D. (2018)
Chronic Fatigue Syndrome and Quality of Life
Patient Related Outcome Measures 9: 253-262.

Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a challenging long-term condition (LTC) with complex and fluctuating symptoms. It is heterogeneous in presentation without diagnostic indicators; therefore, in health care encounters, insight must be gained from the patient's perspective.

One indicator of impact can be gained by measuring quality of life (QoL). By applying a patient-reported outcome measure (PROM), professionals can gather insights with direct relevance to the patient questioned. Such a tool can act therapeutically to promote holistic and individualized professional interventions and interval measurement can inform commissioning of specialist services.

Standard practice appears not fully to capture the experience of CFS, while a search of the literature turned up QoL patient-reported outcome tools but failed to reveal a CFS/ME-specific measure.

The author explores a valid and reliable PROM that can monitor change and evaluate the UK National Institute of Clinical Excellence rehabilitation program, as delivered by specialist National Health Service units.

An alternative, the World Health Organization's quality-of life instrument (WHOQoL)-Bref26, is reviewed for relevance to the condition, measuring treatment outcomes and the wider debate of measuring QoL in LTCs.

8. Vink M and Vink-Niese A (2018)
Multidisciplinary rehabilitation treatment is not effective for myalgic encephalomyelitis/chronic fatigue syndrome: A review of the FatiGo trial
Health Psychology Open 5 (2): 2055102918792648.

The FatiGo trial concluded that multidisciplinary rehabilitation treatment is more effective for chronic fatigue syndrome/myalgic encephalomyelitis in the long term than cognitive behaviour therapy and that multidisciplinary rehabilitation treatment is more cost-effective for fatigue and cognitive behaviour therapy for quality of life.

However, FatiGo suffered from a number of serious methodological flaws. Moreover, it ignored the results of the activity metre, its only objective outcome. This jeopardizes the validity of FatiGo.

Its analysis shows that there was no statistically significant difference between multidisciplinary rehabilitation treatment and cognitive behaviour therapy and neither are (cost-)effective.

FatiGo's claims of efficacy of multidisciplinary rehabilitation treatment and cognitive behaviour therapy for chronic fatigue syndrome/myalgic encephalomyelitis are misleading and not justified by their results.

9. Xu J. et al. (2018)
A new approach to find biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) by single-cell Raman micro-spectroscopy
RSC, Analyst, 10.1039/C8AN01437J

Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME), is a debilitating disorder characterized by physical and mental exhaustion. Mitochondrial and energetic dysfunction has been investigated in CFS patients due to a hallmark relationship with fatigue, however, no consistent conclusion has yet been achieved.

Single-cell Raman spectra (SCRS) are label-free biochemical profiles, indicating phenotypic fingerprints of single cells. In this study, we applied a new approach using single-cell Raman microspectroscopy (SCRM) to examine r0 cells that lack mitochondrial DNA (mtDNA), and peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls.

The experimental results show that Raman bands associated with phenylalanine in r0 cells and CFS patient PBMCs were significantly higher than wild type model and healthy controls. Remarkably, an increase in intensities of Raman phenylalanine bands were also observed in CFS patients. As similar changes were observed in the r0 cell model with a known deficiency in the mitochondrial respiratory chain as well as in CFS patients, our results suggest that the increase in cellular phenylalanine may relate to mitochondrial/energetic dysfunction in both systems.

Interestingly, phenylalanine can be used as a potential biomarker for diagnosis of CFS by SCRM. A machine learning classification model achieved an accuracy rate of 98% correctly assigning Raman spectra to either the CFS group or the control group. SCRM combined with machine learning algorithm therefore has the potential to become a diagnostic tool for CFS.

This research comes from the Oxford university team and Dr Karl Morton as well as from researchers at Newcastle university, who are in receipt of ME Association grant funding. A summary review of this latest work will be published very soon.

10. Yang CA, et al. (2018)
The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome
Journal of Translational Medicine 16 (1): 231.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease with huge social-economic impact. It has been suggested that immune dysregulation, nitro oxidative stress, and metabolic impairment might contribute to disease pathogenesis.
However, the etiology of ME/CFS remains largely unclear, and diagnostic/prognostic disease markers are lacking. Several long noncoding RNAs (lncRNA, > 200 bp) have been reported to play roles in immunological diseases or in stress responses.

Methods: In our study, we examined the expression signature of 10 very long lncRNAs (> 5 kb, CR933609, His-RNA, AK124742, GNAS1-AS, EmX2OS, MIAT, TUG1, NEAT1, MALAT1, NTT) in the peripheral blood mononuclear cells of 44 ME/CFS patients.

Results: LncRNAs NTT, MIAT and EmX2OS levels were found to be significantly elevated in ME/CFS patients as compared with healthy controls. Furthermore, NTT and EmX2OS levels increased with disease severity. Stimulation of human monocytic cell line THP-1 and glioma cell line KALS1 with H2O2 (oxidative stress) and poly (I:C) (double strand RNA, representing viral activation) increased the expression levels of NTT and MIAT.

Conclusions: Our study revealed a ME/CFS-associated very long lncRNA expression signature, which might reflect the regulatory response in ME/CFS patients to oxidative stress, chronic viral infection and hypoxemia. Further investigations need to be done to uncover the functions and potential diagnostic value of these lncRNAs in ME/CFS.

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