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 July.
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.
You can also find the index in the Research section of our website.
Research abstracts from studies published in July 2018
1. Blease C and Geraghty K. (2018)
Are ME/CFS Patient Organizations “Militant”? Patient Protest in a Medical Controversy.
Journal of Bioethical Inquires [Epub ahead of print]
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a contested illness category. This paper investigates the common claim that patients with ME/CFS-and by extension, ME/CFS patient organizations (POs)-exhibit “militant” social and political tendencies.
The paper opens with a history of the protracted scientific disagreement over ME/CFS. We observe that ME/CFS POs, medical doctors, and medical researchers exhibit clear differences in opinion over how to conceptualize this illness. However, we identify a common trope in the discourse over ME/CFS: the claim of “militant” patient activism.
Scrutinizing this charge, we find no compelling evidence that the vast majority of patients with ME/CFS, or the POs representing them, have adopted any such militant political policies or behaviours. Instead, we observe key strategic similarities between ME/CFS POs in the United Kingdom and the AIDs activist organizations of the mid-1980s in the United States which sought to engage scientists using the platform of public activism and via scientific publications.
Finally, we explore the contours of disagreement between POs and the medical community by drawing on the concept of epistemic injustice. We find that widespread negative stereotyping of patients and the marginalization and exclusion of patient voices by medical authorities provides a better explanation for expressions of frustration among patients with ME/CFS.
2. Campen C et al. (2018)
The Effect of Curcumin on Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An Open Label Study.
Scientific Research 9 (5) 356-366.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), recently renamed as systemic exertion intolerance disease (SEID), is a chronic and often disabling disease. Although the exact pathophysiological mechanism of ME/CFS is unknown, immunological abnormalities may play an important role.
Curcumin is a herb with powerful anti-oxidative, and anti-inflammatory properties. Therefore, we hypothesized that curcumin has favorable effects on symptomatology in ME/CFS patients.
In total 52 patients participated, nine stopped the use of curcumin because of side effects. All remaining patients (n = 43) met the criteria for CFS; 72% met the criteria for ME. Before and 8 weeks after the use of curcumin complexed with phosphatidyl choline, 500 mg bid, the CDC inventory for assessment of Chronic Fatigue Syndrome was filled in.
The CDC questions (n = 19) were scored and divided into 2 parts: the first being specific for CFS complaints (n = 9), the second being scores of less specific symptoms (n = 10); denoted as CDC rest score. Results showed that 8 weeks curcumin use significantly decreased the CFS related symptom scores, but not the CDC rest scores.
Analyzing the data separately for ME and CFS patients, the same significance for the CFS symptom scores was present.
Conclusion: in this open-labeled study, 8 weeks curcumin use in a phosphatidyl choline complex reduced ME/CFS symptomatology. Therefore, a randomized placebo controlled study is warranted to assess its efficacy in ME/CFS patients.
3. Davenport T, et al. (2018)
Checking our blind spots: current status of research evidence summaries in ME/CFS.
British Journal of Sports Medicine [Epub ahead of print].
The evidence-based practice (EBP) model hierarchically organises scientific information by level, from lowly case studies to lofty systematic reviews and clinical trials. Clinical trials best influence recommendations because they putatively have the greatest internal validity.1 This assumption is based on sound research ethics, such as scientific competence and good faith actors, as well as observed differences in outcomes.
An EBP blind spot emerges when fundamental assumptions are unmet. Based on findings of a 2018 PEDro evidence summary in BJSM 2 and elsewhere,3 it now seems clear that scientific research in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) resides in a blind spot.
4. Finkelmeyer A, et al. (2018)
Intracranial compliance is associated with symptoms of orthostatic intolerance in chronic fatigue syndrome.
PLoS One 13 (7): e0200068.
Symptoms of orthostatic intolerance (OI) are common in Chronic Fatigue Syndrome (CFS) and similar disorders. These symptoms may relate to individual differences in intracranial compliance and cerebral blood perfusion.
The present study used phase-contrast, quantitative flow magnetic resonance imaging (MRI) to determine intracranial compliance based on arterial inflow, venous outflow and cerebrospinal fluid flow along the spinal canal into and out of the cranial cavity. Flow-sensitive Alternating Inversion Recovery (FAIR) Arterial Spin Labelling was used to measure cerebral blood perfusion at rest.
Forty patients with CFS and 10 age and gender matched controls were scanned. Severity of symptoms of OI was determined from self-report using the Autonomic Symptom Profile. CFS patients reported significantly higher levels of OI (p < .001). Within the patient group, higher severity of OI symptoms were associated with lower intracranial compliance (r = -.346, p = .033) and higher resting perfusion (r = .337, p = .038). In both groups intracranial compliance was negatively correlated with cerebral perfusion. There were no significant differences between the groups in intracranial compliance or perfusion.
In patients with CFS, low intracranial compliance and high resting cerebral perfusion appear to be associated with an increased severity of symptoms of OI. This may signify alterations in the ability of the cerebral vasculature to cope with changes to systemic blood pressure due to orthostatic stress, but this may not be specific to CFS.
5. Huber K et al. (2018)
Latent class analysis of a heterogeneous international sample of patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Fatigue: Biomedicine, Health and Behaviour 6 (3).
Background: Individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) routinely display differences in symptomatology, as well as illness course, onset, duration, and functional disability. Given such diversity, previous work has attempted to identify symptom-based ME/CFS subtypes. However, results have been inconsistent.
Purpose: This study sought to elucidate potential subtypes of ME/CFS as well as explore the impact of subtype membership on health functioning.
Methods: Twelve non-core (i.e. less frequently endorsed) symptoms were included in a latent class analysis of 1,210 adults with ME/CFS. Demographic and illness-related predictors of class membership were evaluated with a multinomial logistic regression. ANOVAs were then performed to determine if there were significant differences across class on the eight subscales of the Short-Form Health Survey (SF-36).
Results: A six-class solution was selected, which consisted of one class that was likely to endorse all non-core symptoms, one class that was unlikely to endorse any non-core symptoms, and four classes that were likely to endorse either one or two non-core symptom domains (i.e. circulatory/neuroendocrine impairment, orthostatic intolerance, and gastro-intestinal distress). Significant functioning differences by class were present for all SF-36 subscales.
Conclusions: These results are suggestive of subtypes of ME/CFS and, if replicated, may assist physicians in providing tailored treatment to patients and allow researchers to form more homogeneous samples.
6. Macnamara C, et al. (2018)
Personalised relaxation practice to improve sleep and functioning in patients with chronic fatigue syndrome and depression: study protocol for a randomised controlled trial.
Trials 19 (1): 371.
Background: Chronic fatigue syndrome (CFS) and major depressive disorder (MDD) are both debilitating but heterogeneous conditions sharing core features of fatigue, unrefreshing sleep, and impaired functioning. The aetiology of these conditions is not fully understood, and ‘best-practice’ treatments are only moderately effective in relieving symptoms. Unrecognised individual differences in the response to such treatments are likely to underlie poor treatment outcomes.
Methods/Design: We are undertaking a two-group, parallel, randomised controlled trial (RCT) comparing the effects of a personalised relaxation intervention on sleep quality, daytime symptoms, and functioning in patients with CFS (n = 64) and MDD (n = 64).
Following identification of the method that best enhances autonomic responding (such as heart rate variability), participants randomised to the active intervention will practise their recommended method nightly for 4 weeks.
All participants will keep a sleep diary and monitor symptoms during the trial period, and they will complete two face-to-face assessments, one at baseline and one at 4 weeks, and a further online assessment to evaluate lasting effects of the intervention at 2 months.
Assessments include self-report measures of sleep, wellbeing, and function and monitoring of autonomic responses at rest, in response to the relaxation method and during nocturnal sleep. Treatment outcomes will be analysed using linear mixed modelling.
Discussion: This is the first RCT examining the effects of a personalised relaxation intervention, pre-tested to maximise the autonomic relaxation response, in patients with unrefreshing sleep and fatigue attributed to CFS or MDD. Detailed monitoring of sleep quality and symptoms will enable sensitive detection of improvements in the core symptoms of these debilitating conditions. In addition, repeated monitoring of autonomic functioning can elucidate mechanisms underlying potential benefits. The findings have translational potential, informing novel, personalised symptom management techniques for these conditions, with the potential for better clinical outcomes.
Trial Registration: Australian and New Zealand Clinical Trials Registry (ANZCTR), ACTRN12616001671459 . Registered on 5 December 2016.
7. Nagy-Szaki D, et al. (2018)
Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics.
Scientific Reports 8 (1): 10056.
The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood.
We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls.
We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide.
Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone.
Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.
8. Nguyen T, et al. (2018)
Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/chronic fatigue syndrome patients: A preliminary investigation.
Asian Pacific Journal of Allergy and Immunology [Epub ahead of print].
Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is medically unexplained post-exertional fatigue associated with significant reduction in natural killer cell (NK) cytotoxicity activity. Cytotoxic activity relies on glycolytic flux and mitochondrial respiration to fulfill energetic cellular demands. While mitochondrial dysfunction has been reported in ME/CFS patients, no previous investigation has examined the bioenergetic profile of isolated NK cells from ME/CFS patients.
Objective: This study was to determine the metabolic function in resting NK cells from ME/CFS patients.
Method: Six ME/CFS patients (aged 50.33±4.95) were age and sex-matched with non-fatigued healthy controls (aged 50.00±5.04). Mitochondrial stress tests measured parameters of mitochondrial function in the NK cells including basal respiration, ATP production, proton leak, maximal respiration, spare respiratory capacity and bioenergetic health index. Glycolytic stress tests measured parameters of glycolytic function such as glycolytic reserve, glycolysis and glycolytic capacity in isolated NK cells from ME/CFS patients and healthy controls using an extracellular flux analyzer, Seahorse XFp.
Result: There was a significant reduction of glycolytic reserve in resting NK cells from ME/CFS patients (0.6±0.07 mpH/ min) compared with healthy control (2.25±1.3 mpH/min). Mitochondrial respiration in resting NK cells did not approach statistical significance between ME/CFS patients and healthy controls.
Conclusion: These findings suggest resting NK cells from ME/CFS patients have reduced ability to increase glycolytic flux to respond to high energetic demands for ATP production. Hence, the reduced glycolytic reserves we have identified in isolated resting isolated NK cells should be further investigated to assist in understanding ME/CFS pathogenesis.
9. Trivedi M, et al. (2018)
Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns.
PLoS One 13 (7): e0201066.
Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition involving multiple organ systems and characterized by persistent/relapsing debilitating fatigue, immune dysfunction, neurological problems, and other symptoms not curable for at least 6 months.
Disruption of DNA methylation patterns has been tied to various immune and neurological diseases; however, its status in ME/CFS remains uncertain. Our study aimed at identifying changes in the DNA methylation patterns that associate with ME/CFS.
Methods: We extracted genomic DNA from peripheral blood mononuclear cells from 13 ME/CFS study subjects and 12 healthy controls and measured global DNA methylation by ELISA-like method and site-specific methylation status using Illumina MethylationEPIC microarrays. Pyrosequencing validation included 33 ME/CFS cases and 31 controls from two geographically distant cohorts.
Results: Global DNA methylation levels of ME/CFS cases were similar to those of controls. However, microarray-based approach allowed detection of 17,296 differentially methylated CpG sites in 6,368 genes across regulatory elements and within coding regions of genes.
Analysis of DNA methylation in promoter regions revealed 307 differentially methylated promoters. Ingenuity pathway analysis indicated that genes associated with differentially methylated promoters participated in at least 15 different pathways mostly related to cell signaling with a strong immune component.
Conclusions: This is the first study that has explored genome-wide epigenetic changes associated with ME/CFS using the advanced Illumina MethylationEPIC microarrays covering about 850,000 CpG sites in two geographically distant cohorts of ME/CFS cases and matched controls.
Our results are aligned with previous studies that indicate a dysregulation of the immune system in ME/CFS. They also suggest a potential role of epigenetic de-regulation in the pathobiology of ME/CFS.
We propose screening of larger cohorts of ME/CFS cases to determine the external validity of these epigenetic changes in order to implement them as possible diagnostic markers in clinical setting.
10. Twisk F and Corsius L (2018)
Cognitive-behavioural therapy for chronic fatigue syndrome: neither efficacious nor safe.
British Journal of Psychiatry 213 (2): 500-501.
11. Wostyn P and De Deyn P. (2018)
The putative glymphatic signature of chronic fatigue syndrome: A new view on the disease pathogenesis and therapy.
Medical Hypotheses 118: 142-145.
The underlying pathophysiology of chronic fatigue syndrome remains incompletely understood and there are no curative treatments for this disorder at present. However, increasing neuroimaging evidence indicates that functional and structural abnormalities exist in the brains of chronic fatigue syndrome patients, suggesting that the central nervous system is involved in this disorder and that at least some chronic fatigue syndrome patients may have an underlying neurological basis for their illness.
In the present paper, we speculate that glymphatic dysfunction, causing toxic build up within the central nervous system, may be responsible for at least some cases of chronic fatigue syndrome. We further postulate that cerebrospinal fluid diversion such as lumboperitoneal shunting may be beneficial to this subgroup of patients by restoring glymphatic transport and waste removal from the brain.
Although recent evidence indicates that at least some chronic fatigue syndrome patients may benefit from cerebrospinal fluid drainage, further studies are needed to confirm this finding and to determine whether this can be attributed to enhancement of glymphatic fluid flow and interstitial fluid clearance. If confirmed, this could offer promising avenues for the future treatment of chronic fatigue syndrome.
Clearly, given the relative invasive nature of cerebrospinal fluid diversion, such procedures should be reserved for chronic fatigue syndrome patients who are severely debilitated, or for those with severe headaches. Anyhow, it seems worthwhile to make every effort to identify new therapies for patients who suffer from this devastating disease, especially given that there are currently no effective treatments for this condition.
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