The Young ME Sufferers Trust: No Reported Harassment at Bristol University (Information Obtained Under FOI)

There has been no reported harassment of staff at Bristol University. Yes, you read that correctly.

We have all become accustomed to the increasingly shrill ‘harassment’ accusations against ME patients
and ‘activists’, both via the media and in lectures. This campaign appears to have originated at that now
infamous meeting of the Science Media Centre, revealed by our original 2014 Freedom of Information
Report, now updated under the title Shining a Light on the CMRC Setup (http://www.tymestrust.org/pdfs/ shiningalight.pdf). Members of the UK Research Collaborative have continued to spread these allegations ever since its launch.

In Shining a Light we stated: In the records of the meeting where ‘harassment’ of researchers was discussed, no mention was made of personal threats such as have been reported in the media. Freedom of Information (FOI) requests were listed as the most damaging type of ‘harassment’. The 2016 tribunal appeal Judgement ordering QMUL to release the PACE trial data highlights that Professor Trudie Chalder accepts that “no threats have been made either to researchers or participants”.

And yet the accusations persist and have even escalated. Tymes Trust has found this constant narrative so abhorrent that we have sought some answers. We have, once again, sought evidence.

You can read the rest of this report here: http://www.tymestrust.org/pdfs/noharassmentbristol.pdf

Neurometabolites in anterior cingulate cortex in chronic fatigue syndrome: A magnetic resonance spectroscopy study at 7 Tesla

Abstract:

Background: Chronic fatigue syndrome (CFS) is a disorder characterized by prolonged physical and mental fatigue that cannot be explained by another established medical diagnosis. The anterior cingulate cortex (ACC) and putamen are two regions involved in frontal-striatal neural circuitry, which may be related to the pathophysiology of CFS. The aim of this study was to investigate the concentrations of neurometabolites, including glutamate, gamma-aminobutyric acid (GABA) and glutathione, in the ACC and putamen, using magnetic resonance spectroscopy (MRS) at 7 Tesla (7T). In addition, this study also aimed to evaluate resting-state functional connectivity in CFS with functional magnetic resonance imaging (fMRI).

Methods: This study involved 12 patients who met the Oxford criteria for CFS and 25 healthy controls. Participants rated themselves on the Chalder Fatigue Questionnaire (CFQ) and the Beck Depression Inventory (BDI). All participants had a single proton (1H) MRS and resting-state fMRI scan with a 7T Siemens MAGNETOM scanner (Siemens, Erlangen, Germany) with a Nova Medical 32 channel receive array head coil. Spectra were measured from voxels in the ACC (20 × 20 × 20 mm), putamen (10 × 16 × 20 mm) and occipital cortex (20 × 20 × 20 mm). Spectra were analysed with LCModel to obtain absolute concentrations of the neurochemicals. Differences in functional connectivity between CFS and healthy participants were tested using multivariate exploratory linear optimized decomposition into independent components (MELODIC) and dual regression.

Results: Concentrations of putamen glutamate and glutamate+glutamine (Glx) were increased in CFS while that of ACC GABA was decreased. Putamen Glx and ACC glutamine were negatively associated with the severity of self-reported fatigue. There were main effects of CFS diagnosis on glutathione (GSH) and total creatine, indicating decreases of these neurometabolites in all the regions studied in CFS patients. In addition, the CFS patients demonstrated elevated functional connectivity between the default mode network and right supracalcarine cortex, precuneus cortex and dorsolateral prefrontal cortex.

Conclusions: The increased putamen glutamate, decreased ACC GABA and elevated resting state functional connectivity of the default mode network suggest a hyperactive brain status in CFS. The global decrease of GSH and total creatine also suggest that CFS patients may have an abnormal bioenergetic status with higher oxidative stress.

Source: Chi Chen. Neurometabolites in anterior cingulate cortex in chronic fatigue syndrome: A magnetic resonance spectroscopy study at 7 Tesla. Oxford University Research Archive. September 22, 2017. (Open access article) https://ora.ox.ac.uk/objects/uuid:60ff242e-2ccd-4f23-ac7d-16553d864e8b

Cytokine signature in chronic fatigue syndrome

Extract:

One of the major findings in the publication by Montoya et al. on cytokine signatures in chronic fatigue syndrome is elevation of circulating TGF-β in patients with chronic fatigue syndrome (CFS). Unfortunately, the materials and methods do not give much information on how the controls were recruited, and how the blood samples …

(This article is behind a paywall. You can address correspondence to jos.vandermeer@radboudumc.nl.)

Source: Megan E. Roerink, Matthew Buckland, Andrew R. Lloyd, and Jos W. M. van der Meer. Cytokine signature in chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2017 Oct 30. pii: 201714011. doi: 10.1073/pnas.1714011114. [Epub ahead of print] http://www.pnas.org/content/early/2017/10/26/1714011114.short?rss=1

Effect of Acupuncture on the Expression of Transcription Factor T-bet/GATA-3 in Plasma of Rats with Chronic Fatigue Syndrome

Abstract:

OBJECTIVE: To observe the effect of acupuncture on the expression of T-box expressed in T cell (T-bet)/GATA binding factor-3 (GATA-3) in plasma of rats with chronic fatigue syndrome (CFS) and explore the mechanism of acupuncture treatment for CFS.

METHODS: Forty-eight healthy male SD rats were randomly divided into blank control group, CFS model group, acupuncture group, and ginsenoside group (12 rats in each group). CFS rat model was established by combining restriction and cold water swimming. Acupuncture was applied to “Baihui”(GV 20), “Guanyuan” (CV 4) and “Zusanli” (ST 36, bilate-ral) acupoints, once a day for two weeks. The ginsenoside group was gavage administrated with ginsenoside, once a day for two weeks. After 14 days, behavioural changes were observed, and the expression levels of T-bet/GATA-3 genes in plasma were detected by RT-PCR.

RESULTS: Compared with the blank control group, the time for immobility of forced suspensory test was signi-ficantly longer (P<0.05) and the time for exhaustive swimming was significantly shortened (P<0.05) in the CFS model group. Compared with the model group, the two indexes above-mentioned were reversed (P<0.05) both in the acupuncture group and the ginsenoside group, and the effects in the acupuncture group were more significant than those in the ginsenoside group (P<0.05). Compared with the blank control group, the expression level of T-cell transcription factor T-bet gene in plasma was higher in the CFS model group (P<0.05), companied with lower GATA-3 gene expression (P<0.05). The ratio of T-bet/GATA-3 was higher in the model group than in the blank control group(P<0.05). Compared with the CFS model group, all the indexes above-mentioned were reversed (P<0.05) in the two treatment groups. Acupuncture group showed a better effect on reducing T-bet gene expression than the ginsenoside group (P<0.05).

CONCLUSIONS: Acupuncture can decrease the expression level of T-bet gene while increase the expression of GATA-3 gene, which may be associated with its role in treating CFS.

Source: Wang XY, Liu CZ, Lei B. Effect of Acupuncture on the Expression of Transcription Factor T-bet/GATA-3 in Plasma of Rats with Chronic Fatigue Syndrome. Zhen Ci Yan Jiu. 2017 Jun 25;42(3):246-8. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/29071982

MEA Review: Grey and white matter differences in chronic fatigue syndrome

The ME Association of Great Britain has provided an excellent review of a recent study on brain matter abnormalities in ME/CFS patients. The study, Grey and white matter differences in Chronic Fatigue Syndrome – A voxel-based morphometry study, was conducted by Julia Newton’s group at Newcastle University. Below is an excerpt from Dr. Shepherd’s summary of the study. To read a full discussion, along with an excellent overview of brain pathology and the implications of these brain abnormalities, go HERE. You can download the full review as a PDF file.

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Comment from Dr Charles Shepherd, Hon Medical Adviser, ME Association:

This study was carried out in Newcastle by Professor Julia Newton and colleagues – a team who have not only achieved a long and distinguished record in ME/CFS research but also have access to patients who have been very carefully assessed from a clinical point of view. So, the results should be taken seriously.

As has been pointed out in this review, three of the main criticisms of previous neuroimaging studies involving people with ME/CFS is that the numbers involved have often been far too small; there has been a lack of information from other control groups that would be relevant in addition to the use of healthy controls; and that different imaging techniques have been used.  So, not surprisingly, the results are not always consistent.

Despite these caveats, these results clearly add weight to the findings from previous neuroimaging studies describing white matter abnormalities in ME/CFS but also raise the possibility of grey matter involvement in ME/CFS.

There are several possible explanations for these findings but no clear answer has emerged in the paper.  Are they a primary feature of ME/CFS?  Or are they secondary to other factors – e.g. duration of illness, decrease in activity, severity of fatigue – that are related to having ME/CFS?  The only way to find out is through further research into what is clearly an interesting aspect of neuropathology in ME/CFS.

A fully referenced summary of all the key findings from both functional and structural neuroimaging studies in ME/CFS can be found in the Research section of the ME Association ‘An Exploration of the Key Clinical Issues’ available from our online shop.

You can read the rest of this brief summary HERE.

American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society Statement on the Graham-Cassidy Amendment

PRESS RELEASE AND PUBLIC COMMENT

September 23, 2017 – Between one and two million Americans suffer from Myalgic Encephalomyelitis (ME), a chronic disease that profoundly disrupts the immune and nervous systems of those who contract it. Twenty-five per cent of those affected are severely ill, and unable to meet their needs. These patients rely on Medicaid services not only for access to medical care but for home assistance as well. The American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society (AMMES) is deeply concerned about the effect the proposed Graham-Cassidy Amendment will have on patients with ME.

The proposed changes to Medicaid outlined in the Graham-Cassidy Amendment could have a drastic impact on patients. Community services would be cut, hospitalizations could be eliminated, pre-existing conditions – including ME – would be excluded from coverage. Laboratory services would also be curtailed, which would be devastating for ME patients, who frequently experience secondary infections as a result of immune dysfunction. Premiums would rise, resulting in a loss of insurance for a significant portion of those who have lost income as a result of ME.

We strongly urge Congress to reject the proposed Graham-Cassidy Amendment. Those living with this debilitating disease must have access to affordable, quality care, which is something the Graham-Cassidy Amendment cannot provide.

*The American ME and CFS Society, a national 501(c)(3) nonprofit, is dedicated to serving the needs of patients and caregivers through support, advocacy, and education.

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients.

A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls. These experiments investigated cellular patterns in oxidative phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls. Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency.

While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003). The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand.

Source: Cara Tomas, Audrey Brown, Victoria Strassheim, Joanna Elson, Julia Newton, Philip Manning. Cellular bioenergetics is impaired in patients with chronic fatigue syndrome. PLoS One. 2017 Oct 24;12(10):e0186802. doi: 10.1371/journal.pone.0186802. eCollection 2017. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186802 (Full article)

Are current chronic fatigue syndrome criteria diagnosing different disease phenotypes?

Abstract:

Importance: Chronic fatigue syndrome (CFS) is characterised by a constellation of symptoms diagnosed with a number of different polythetic criteria. Heterogeneity across these diagnostic criteria is likely to be confounding research into the as-yet-unknown pathophysiology underlying this stigmatised and debilitating condition and may diagnose a disease spectrum with significant implications for clinical management. No studies to date have objectively investigated this possibility using a validated measure of CFS symptoms–the DePaul Symptom Questionnaire (DSQ).

Objective: To examine whether current CFS diagnostic criteria are identifying different disease phenotypes using the DSQ.

Design: Case control study.

Setting: Clinical Research Facility of the Royal Victoria Infirmary, Newcastle upon Tyne, UK.

Participants: 49 CFS subjects and ten matched, sedentary community controls, excluded for co-morbid depression.

Main outcomes and measures: Self-reported autonomic and cognitive features were assessed with the Composite Autonomic Symptom Score (COMPASS) and Cognitive Failures Questionnaire (COGFAIL) respectively. Objective autonomic cardiovascular parameters were examined using the Task Force® Monitor and a battery of neuropsychological tests administered for objective cognitive assessment.

Results: Self-reported autonomic and cognitive symptoms were significantly greater in CFS subjects compared to controls. There were no statistically significant differences in objective autonomic measures between CFS and controls. There were clinically significant differences between DSQ subgroups on objective autonomic testing. Visuospatial memory, verbal memory and psychomotor speed were significantly different between DSQ subgroups.

Conclusions and relevance: The finding of no significant differences in objective autonomic testing between CFS and control subjects may reflect the inclusion of sedentary controls or exclusion for co-morbid depression. Consistent exclusion criteria would enable better delineation of these two conditions and their presenting symptoms. Findings across CFS subgroups suggest subjects have a different disease burden on subjective and objective measures of function, autonomic parameters and cognitive impairment when categorised using the DSQ. Different CFS criteria may at best be diagnosing a spectrum of disease severities and at worst different CFS phenotypes or even different diseases. This complicates research and disease management and may contribute to the significant stigma associated with the condition.

Source: Laura Maclachlan, Stuart Watson, Peter Gallagher, Andreas Finkelmeyer, Leonard A. Jason, Madison Sunnquist, Julia L. Newton. Are current chronic fatigue syndrome criteria diagnosing different disease phenotypes? PLoS ONE. Published: October 20, 2017https://doi.org/10.1371/journal.pone.0186885   http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186885 (Full article)

The importance of a research case definition

Abstract:

All scientific activities with diseases rely on the selection of reliable and valid case definitions in order to accurately estimate prevalence rates, to identify biological markers, and to understand the outcomes of treatment trials. The failure to develop a consensus on which research case definition to use for defining Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS) has had negative consequences for the scientific and patient community.

If case definition criteria inappropriately select patients with symptoms due to primary affective disorders, other fatiguing medical conditions, burnout, or over-committed lifestyle issues, the scientific consequences are serious. For example, a case definition that is too broad would include individuals with other illnesses and conditions, complicating the tasks of estimating prevalence rates or identifying effective treatment programs.

A consensus on a research case definition and its operationalization and assessment would enable investigators to select more homogenous samples that could expedite the identification of valid biological markers, and consequently reduce misperceptions regarding the role of psychogenic versus biomedical factors. Our editorial reviews the implications of previous research and clinical case definitions in CFS and ME domains.

Source: Leonard A. Jason, Pamela A. Fox & Kristen D. Gleason. The importance of a research case definition.  Fatigue: Biomedicine, Health & Behavior. Pages 1-7 | Received 01 Aug 2017, Accepted 04 Oct 2017, Published online: 12 Oct 2017.    http://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1389336?journalCode=rftg20 

Psychometric properties and factor structure of a shortened version of the Cognitive Behavioural Responses Questionnaire (CBRQ)

Abstract:

OBJECTIVE: Symptoms of chronic fatigue syndrome (CFS) can be perpetuated by cognitive and behavioural responses to the illness. We aimed to determine the factor structure, reliability and validity of the 40-item Cognitive Behavioural Responses Questionnaire (CBRQ) using data gathered from CFS patients. We also propose a short version CBRQ for greater clinical utility.

METHODS: The psychometric analysis was performed on datasets drawn from two sources: a clinical service for CFS patients (N=576) and the PACE randomised controlled trial (RCT) of CFS treatments (N=640). An exploratory factor analysis (EFA) was conducted on the clinical dataset and a confirmatory factor analysis (CFA) was performed on the RCT dataset. Using these results, a short version of the CBRQ was proposed. Reliability, metric invariance across age and sex, and construct validity were assessed.

RESULTS: The EFA (relative Chi-square 2.52; RMSEA 0.051; CFI 0.964; TLI 0.942) and CFA (relative Chi-square 4.029; RMSEA 0.069; CFI 0.901; TLI 0.892) revealed that eight factor models fitted the data well. Satisfactory Cronbach’s alpha values were obtained for the final subscales (≥0.76). The shortened CBRQ was obtained by removing items that cross-loaded onto other factors and/or were the lowest loading items in each factor. The shortened CBRQ contained 18 items which had high factor loadings, good face-validity and reliability (Cronbach’s alpha 0.67-0.88).

CONCLUSIONS: The CBRQ, long and short versions, are reliable and valid scales for measuring cognitive and behavioural responses of patients with CFS. Further research is needed to examine the utility of the CBRQ in other long-term conditions.

Source: Ryan EG, Vitoratou S, Goldsmith KA, Chalder T. Psychometric properties and factor structure of a shortened version of the Cognitive Behavioural Responses Questionnaire (CBRQ). Psychosom Med. 2017 Oct 10. doi: 10.1097/PSY.0000000000000536. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29023262