ME Association Index of Published ME/CFS Research
The Index of Published ME/CFS Research has now been updated.
This is an A-Z index of all the most important research studies (and selected key documents and articles), listed by subject matter, that have been published on ME/CFS and is correct to 31st March 2018.
You can also find the index in the Research section of our website.
Published ME/CFS Research Studies 1st – 31st March 2018
Comhaire F. (2018)
Treating patients suffering from myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) with sodium dichloroacetate: An open-label, proof-of-principle pilot trial.
Medical Hypotheses 114: 45-48.
Abstract
Twenty-two consecutive patients suffering from refractory myalgic encephalitis/chronic fatigue syndrome (ME/CFS) were treated with an innovative nutriceutical containing sodium dichloroacetate in a proof-of-principle, pilot, open-label prospective cohort trial.
Ten patients experienced significant improvement of their health condition with reduction to almost half of their score in the fatigue severity scale.
In twelve patients treatment failed to exert any beneficial effect. In the latter patients several other diseases have commonly been revealed by extensive biological and imaging investigations.
These preliminary findings sustain the hypothetical role of mitochondrial hypo-metabolism due to inhibition of the activity of the pyruvate dehydrogenase in the pathogenesis of primary ME/CFS and suggest a possible benefit of nutriceutical treatment by sodium dichloroacetate.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29602463
Eaton N, et al. (2018)
Rituximab impedes natural killer cell function in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients: A pilot in vitro investigation.
BMC Pharmacology and Toxicology 19 (1): 12.
Abstract
Background:
A recent in vitro pilot investigation reported Rituximab significantly reduced natural killer (NK) cell cytotoxicity in healthy donors.
Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown etiology. A consistent finding is a significant reduction in NK cell cytotoxicity.
Rituximab has been reported having questionable potential therapeutic benefits for the treatment of CFS/ME, however, the potential effects of Rituximab on NK cell cytotoxicity in CFS/ME patients are yet to be determined.
Method:
A total of eight CFS/ME patients (48.63 ± 15.69 years) and nine non-fatigued controls (NFC) (37.56 ± 11.06 years) were included using the Fukuda case definition.
Apoptotic function, lytic proteins and degranulation markers were measured on isolated NK cells using flow cytometry following overnight incubation with Rituximab at 10 μg/ml and 100 μg/ml.
Results:
There was a significant reduction in NK cell lysis between CFS/ME patients and NFC following incubation with Rituximab at 100 μg/ml at 12.5:1 and 6.25:1 effecter-target (E:T) ratios (p < 0.05). However, there was no significant difference for NFC following incubation with Rituximab at 10 μg/ml and 100 μg/ml.
There was no significant difference between CFS/ME patients and NFC for granzyme A and granzyme B prior to incubation with Rituximab and following overnight incubation with Rituximab at 10 μg/ml. There was a significant decrease in granzyme B in CFS/ME patients compared to NFC with 100 μg/ml of Rituximab prior to K562 cells stimulation (p < 0.05).
There was a significant increase in CD107a (p < 0.05) and CD107b expression (p < 0.01) in NFC after stimulation with K562 cells prior to incubation with Rituximab. There was a significant increase in CD107b expression between CFS/ME patients and NFC prior to incubation with Rituximab and without stimulation of K562 cells (p < 0.01).
Importantly, there was a significant increase in CD107b following overnight incubation with 100 μg/ml of Rituximab in NFC prior to K562 cells stimulation (p < 0.01).
Conclusion:
This study reports significant decreases in NK cell lysis and a significant increase in NK cell degranulation following Rituximab incubation in vitro in CFS/ME patients, suggesting Rituximab may be toxic for NK cells.
Caution should be observed in clinical trials until further investigations in a safe and controlled in vitro setting are completed.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29587879
Kingdon C, et al. (2018)
Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls.
Pharmacoecon Open [Epub ahead of print]
Abstract
Background:
People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continue to struggle to have their condition recognised as disabling in the face of public and professional prejudice and discrimination.
Objective:
The aim of this study was to compare the functional status and well-being of people with well-characterised ME/CFS with people with multiple sclerosis (PWMS), as well as healthy controls (HCs).
Method:
In this cross-sectional study, we used data collected as part of the UK ME/CFS Biobank to compare actual participant scores from the Medical Outcomes Survey Short Form-36 v2™ (SF-36v2™) between groups, as a proxy for impact of disability, and from a bespoke questionnaire seeking data on employment and income.
Results:
People with ME/CFS scored significantly lower than PWMS or HCs in almost all SF-36v2™ areas.
Prominent were lower scores for people with ME/CFS in the Physical Component Summary and Role Physical and Social Function domains, while the smallest differences were seen in the Mental Health domain.
Responses to the bespoke questionnaire indicated that people with ME/CFS in this study work fewer hours and have lower incomes compared with people in the other two groups.
Conclusion:
Using SF-36v2™ scores as a proxy, people with ME/CFS were measurably more disabled than PWMS or HCs in this study population. Furthermore, employment and income data are consistent with loss of functional status.
These findings should encourage the health community to recognise the disabling effects of ME/CFS, to advocate for the needs of people with ME/CFS, and to investigate strategies to address the cost of the disease to both individuals and society.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29536371
Litleskare S, et al. (2018)
Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years After Giardia Infection.
Clinical Gastroenterology and Hepatology [Epub ahead of print]
Abstract
Background and Aims:
Irritable bowel syndrome (IBS) is a complication that can follow gastrointestinal infection, but it is not clear if patients also develop chronic fatigue.
We investigated the prevalence and odds ratio of IBS and chronic fatigue 10 years after an outbreak of Giardia lamblia, compared with a control cohort, and changes in prevalence over time.
Methods:
We performed a prospective follow-up study of 1252 laboratory-confirmed cases of giardiasis (exposed), which developed in Bergen, Norway in 2004. Statistics Norway provided us with information from 2504 unexposed individuals from Bergen, matched by age and sex (controls).
Questionnaires were mailed to participants 3, 6, and 10 years after the outbreak. Results from the 3- and 6-year follow-up analyses have been published previously. We report the 10-year data and changes in prevalence among time points, determined by logistic regression using generalized estimating equations.
Results:
The prevalence of IBS 10 years after the outbreak was 43% (n = 248) among 576 exposed individuals and 14% (n = 94) among 685 controls (adjusted odds ratio for development of IBS in exposed individuals, 4.74; 95% CI, 3.61-6.23).
At this time point, the prevalence of chronic fatigue was 26% (n = 153) among 587 exposed individuals and 11% (n = 73) among 692 controls (adjusted odds ratio, 3.01; 95% CI, 2.22-4.08).
The prevalence of IBS among exposed persons did not change significantly from 6 years after infection (40%) to 10 years after infection (43%; adjusted odds ratio for the change 1.03; 95% CI, 0.87-1.22).
However, the prevalence of chronic fatigue decreased from 31% at 6 years after infection to 26% at 10 years after infection (adjusted odds ratio for the change 0.74; 95% CI, 0.61-0.90).
Conclusion:
The prevalence of IBS did not change significantly from 6 years after an outbreak of Giardia lamblia infection in Norway to 10 years after. However, the prevalence of chronic fatigue decreased significantly from 6 to 10 years afterward.
IBS and chronic fatigue were still associated with giardiasis 10 years after the outbreak.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29378314
Miwa K and Inoue Y. (2018)
The etiologic relation between disequilibrium and orthostatic intolerance in patients with myalgic encephalomyelitis (chronic fatigue syndrome).
Journal of Cardiology [Epub ahead of print]
Abstract
Background:
Orthostatic intolerance (OI) causes a marked reduction in the activities of daily living in patients with myalgic encephalomyelitis (ME) or chronic fatigue syndrome.
Most symptoms of OI are thought to be related to cerebral hypo-perfusion and sympathetic activation. Because postural stability is an essential element of orthostatic tolerance, disequilibrium may be involved in the etiology of OI.
Methods and Results:
The study comprised 44 patients with ME (men, 11 and women, 33; mean age, 37±9 years), who underwent neurological examinations and 10-min standing and sitting tests.
Symptoms of OI were detected in 40 (91%) patients and those of sitting intolerance were detected in 30 (68%). Among the 40 patients with OI, disequilibrium with instability on standing with their feet together and eyes shut, was detected in 13 (32.5%) patients and hemodynamic dysfunction during the standing test was detected in 19 (47.5%); both of these were detected in 7 (17.5%) patients.
Compared with 31 patients without disequilibrium, 13 (30%) patients with disequilibrium more prevalently reported symptoms during both standing (100% vs. 87%, p=0.43) and sitting (92% vs. 58%, p=0.06) tests. Several (46% vs. 3%, p<0.01) patients failed to complete the 10-min standing test, and some (15% vs. 0%, p=0.15) failed to complete the 10-min sitting test.
Among the seven patients with both hemodynamic dysfunction during the standing test and disequilibrium, three (43%) failed to complete the standing test. Among the 6 patients with disequilibrium only, 3 (50%) failed while among the 12 patients with hemodynamic dysfunction only, including 8 patients with postural orthostatic tachycardia, none (0%, p=0.02) failed.
Conclusion:
Patients with ME and disequilibrium reported not only OI but also sitting intolerance. Disequilibrium should be recognized as an important cause of OI and appears to be a more influential cause for OI than postural orthostatic tachycardia in patients with ME.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29588088
Newberry F, et al. (2018)
Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?
Clinical Science (London) 132 (5): 523-542
Abstract
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms.
Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome.
Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS.
Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes. However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases.
Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies.
This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29523751
Ruiz-Núñez B, et al. (2018)
Higher Prevalence of “Low T3 Syndrome” in Patients with Chronic Fatigue Syndrome: A Case–Control Study.
Frontiers in Endocrinology.
Abstract
Chronic fatigue syndrome (CFS) is a heterogeneous disease with unknown cause(s). CFS symptoms resemble a hypothyroid state, possibly secondary to chronic (low-grade) (metabolic) inflammation.
Methods:
We studied 98 CFS patients (21–69 years, 21 males) and 99 age- and sex-matched controls (19–65 years, 23 males). We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation.
Results:
Most remarkably, CFS patients exhibited similar thyrotropin, but lower free triiodothyronine (FT3) (difference of medians 0.1%), total thyroxine (TT4) (11.9%), total triiodothyronine (TT3) (12.5%), %TT3 (4.7%), sum activity of deiodinases (14.4%), secretory capacity of the thyroid gland (14.9%), 24-h urinary iodine (27.6%), and higher % reverse T3 (rT3) (13.3%).
FT3 below the reference range, consistent with the “low T3 syndrome,” was found in 16/98 CFS patients vs. 7/99 controls (OR 2.56; 95% confidence interval = 1.00–6.54). Most observations persisted in two sensitivity analyses with more stringent cut-off values for body mass index, high-sensitive C-reactive protein (hsCRP), and WBC.
We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C). FT3, TT3, TT4, and rT3 correlated positively with hsCRP in CFS patients and all subjects. TT3 and TT4 were positively related to hsCRP in controls. Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels.
Conclusion:
The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state. They resemble a mild form of “non-thyroidal illness syndrome” and “low T3 syndrome” experienced by a subgroup of hypothyroid patients receiving T4 monotherapy.
Our study needs confirmation and extension by others. If confirmed, trials with, e.g., T3 and iodide supplements might be indicated.
Link: https://www.frontiersin.org/articles/10.3389/fendo.2018.00097/full
Saunders R. (2018)
Chronic fatigue syndrome therapies grounded in science hold promise.
Correspondence Nature 555(7696):311
Link: https://www.nature.com/articles/d41586-018-03055-1
Scheibenbogen C, et al. (2018)
Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME.
PLoS One 13 (3): e0193672
Abstract
Introduction:
Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) point to an autoimmune disease directed against neurotransmitter receptors.
We had observed elevated autoantibodies against ß2 adrenergic receptors, and muscarinic 3 and 4 acetylcholine receptors in a subset of patients. Immunoadsorption (IA) was shown to be effective in removing autoantibodies and improve outcome in various autoimmune diseases.
Methods:
10 patients with post-infectious CFS/ME and elevated ß2 autoantibodies were treated with IA with an IgG-binding column for 5 days. We assessed severity of symptoms as outcome parameter by disease specific scores. Antibodies were determined by ELISA and B cell phenotype by flow cytometry.
Results:
IgG levels dropped to median 0.73 g/l (normal 7-16 g/l) after the 4th cycle of IA, while IgA and IgM levels remained unchanged. Similarly, elevated ß2 IgG antibodies rapidly decreased during IA in 9 of 10 patients. Also 6 months later ß2 autoantibodies were significantly lower compared to pre-treatment.
Frequency of memory B cells significantly decreased, and frequency of plasma cells increased after the 4th IA cycle. A rapid improvement of symptoms was reported by 7 patients during the IA. 3 of these patients had long lasting moderate to marked improvement for 6-12+ months, 2 patients had short improvement only and 2 patients improved for several months following initial worsening.
Conclusions:
IA can remove autoantibodies against ß2 adrenergic receptor and lead to clinical improvement. B cell phenotyping provides evidence for an effect of IA on memory B cell development.
Data from our pilot trial warrants further studies in CFS/ME.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29543914
Serrador JM, et al. (2018)
Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia.
Neurorehabilitation 42 (2): 235-246.
Abstract
Objective:
Chronic Fatigue Syndrome (CFS) is a disorder of unknown etiology associated with debilitating fatigue. One symptom commonly reported is disequilibrium.
The goal of this study was to determine if CFS patients demonstrated verified balance deficits and if this was effected by comorbid fibromyalgia (FM).
Methods:
Twenty-seven patients with CFS (12 with comorbid FM) and 22 age and gender matched controls performed posturography.
Results:
Balance scores were significantly correlated with physical functional status in the CFS group (R2 = 0.43, P < 0.001), which was not found for mental functional status (R2 = 0.06, P > 0.5).
CFS patients (regardless of FM) had significantly higher anxiety subscale of the vertigo symptom scale scores.
CFS patients, regardless of FM status, demonstrated significantly lower overall composite balance scores (Controls – 78.8±1.5; CFS – 69.0±1.4, P < 0.005) even when controlling for anxiety and also had worse preference scores, indicating they relied on visual information preferentially even when visual information was incorrect.
Interestingly, the CFS+FM group, not CFS only, demonstrated significantly worse vestibular scores (Controls – 70.2±2.4; CFS only – 67.9±3.8; CFS with FM – 55.4±4.6, P = 0.013).
Interpretation:
The major findings are that poor balance may be associated with poorer self-reported physical health.
In addition, CFS patients seemed to rely preferentially on visual inputs, regardless of whether it was correct.
The finding that vestibular function may be impaired in patients with CFS+FM but not in those with CFS alone suggests that the pathophysiology of CFS+FM may differ as has been suggested by some.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29562557
Uhde M, et al. (2018)
Markers of non-coeliac wheat sensitivity (NCWS) in patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Gut Postscript Letter [Epub ahead of print]
Results:
Our results suggest that there may be a subset of patients with ME/CFS who have sensitivity to wheat and related cereals in the absence of coeliac disease, with potential relevance to some of their symptoms.
ME/CFS is recognised as a condition with a spectrum of clinical phenotypes and underlying aetiologies. Characterisation of patients into subsets based on clinical and biological data is essential to gaining a better understanding of the condition and identifying useful biomarkers and therapeutic targets.
The results of this analysis provide a rationale for examining the clinical and therapeutic relevance of food sensitivity, particularly NCWS, in the context of ME/CFS in future studies.
Link: http://gut.bmj.com/content/early/2018/03/17/gutjnl-2018-316133.long
Wilshire CE, et al. (2018)
Rethinking the treatment of chronic fatigue syndrome-a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT.
BMC Psychology 6 (1): 6.
Abstract
Background:
The PACE trial was a well-powered randomised trial designed to examine the efficacy of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome.
Reports concluded that both treatments were moderately effective, each leading to recovery in over a fifth of patients. However, the reported analyses did not consistently follow the procedures set out in the published protocol, and it is unclear whether the conclusions are fully justified by the evidence.
Methods:
Here, we present results based on the original protocol-specified procedures. Data from a recent Freedom of Information request enabled us to closely approximate these procedures. We also evaluate the conclusions from the trial as a whole.
Results:
On the original protocol-specified primary outcome measure – overall improvement rates – there was a significant effect of treatment group. However, the groups receiving CBT or GET did not significantly outperform the Control group after correcting for the number of comparisons specified in the trial protocol.
Also, rates of recovery were consistently low and not significantly different across treatment groups. Finally, on secondary measures, significant effects were almost entirely confined to self-report measures. These effects did not endure beyond two years.
Conclusions:
These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29562932
ME Association Index of Published ME/CFS Research
The Index of Published ME/CFS Research has now been updated.
This is an A-Z index of all the most important research studies (and selected key documents and articles), listed by subject matter, that have been published on ME/CFS and is correct to 31st March 2018.
You can also find the index in the Research section of our website.