It is with regret that we have heard of the death of Judy Turner from Wrexham, on 1 January 2019, aged 82.
Judy was a prolific and successful author, person with ME and long time supporter of the Clwyd ME support group. She wrote historical and romantic fiction under the pseudonyms of Katie Flynn and Judith Saxton.
In 2013 Judy kindly contributed to an article in me voice, hoping to encourage other people affected by ME not to give up on their dream of writing.
We send our sympathy and best wishes to Judy’s husband Brian, daughter Holly and the rest of her family .
To evaluate the magnitude of the difference in VO2peak between patients with Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) and apparently healthy controls, 7 databases (Cochrane, PubMed, PsycINFO, Web of Knowledge, Embase, Scopus, Medline) were searched for articles published up to March 2018.
Search terms included ‘chronic fatigue syndrom*’AND (‘peak’ OR ‘maxim*’ OR ‘max’) AND (‘oxygen uptake’ OR ‘oxygen consumption’ OR ‘VO2peak’ or ‘VO2max’. Eligibility criteria were adults>18 y with clinically diagnosed CFS/ME, with VO2peak measured in a maximal test and compared against an apparently healthy control group.
The methodological quality of included studies was assessed using a modified Systematic Appraisal of Quality for Observational Research critical appraisal framework. A random effects meta-analysis was conducted on 32 cross-sectional studies (effects). Pooled mean VO2peak was 5.2 (95% CI: 3.8-6.6) ml.kg-1min-1 lower in CFS/ME patients vs. healthy controls. Between-study variability (Tau) was 3.4 (1.5-4.5) ml.kg-1min-1 indicating substantial heterogeneity. The 95% prediction interval was -1.9 to 12.2 ml.kg-1min-1.
The probability that the effect in a future study would be>the minimum clinically important difference of 1.1 ml.kg-1min-1 (in favour of controls) was 0.88 – likely to be clinically relevant.
Synthesis of the available evidence indicates that CFS/ME patients have a substantially reduced VO2peak compared to controls.
Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome, by Amit K Saha, Brendan R Schmidt, Julie Wilhelmy, Vy Nguyen, Justin Do, Vineeth C Suja, Mohsen Nemat-Gorgani, Ronald W Davis and Anand K Ramasubramanian inClinical Hemorheology and Microcirculation, Pre-press, pp. 1-4, 28 Dec 2018, [Epub ahead of print]
Research abstract:
BACKGROUND: Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a poorly understood disease. Amongst others symptoms, the disease is associated with profound fatigue, cognitive dysfunction, sleep abnormalities, and other symptoms that are made worse by physical or mental exertion. While the etiology of the disease is still debated, evidence suggests oxidative damage to immune and hematological systems as one of the pathophysiological mechanisms of the disease. Since red blood cells (RBCs) are well-known scavengers of oxidative stress, and are critical in microvascular perfusion and tissue oxygenation, we hypothesized that RBC deformability is adversely affected in ME/CFS.
METHODS: We used a custom microfluidic platform and high-speed microscopy to assess the difference in deformability of RBCs obtained from ME/CFS patients and age-matched healthy controls.
RESULTS AND CONCLUSION: We observed from various measures of deformability that the RBCs isolated from ME/CFS patients were significantly stiffer than those from healthy controls. Our observations suggest that RBC transport through microcapillaries may explain, at least in part, the ME/CFS phenotype, and promises to be a novel first-pass diagnostic test.
One of the researchers Prof Ronald W. Davis comments on an earlier paper on this topic:
This paper documents that red blood cells are less deformable in ME/CFS patients compared to healthy controls. It potentially could be a biomarker, and we are proceeding to design new devices that will make a clear distinction between patients and healthy controls. These devices will be hand-held and easy to use by doctors in their offices, or in clinical testing labs.
Past work has looked primarily at the shape of red blood cells, which is difficult to quantitate. Our approach will give a clear quantitative number. It measures the ability of red blood cells to deform while squeezing into a capillary, something that blood cells must do for healthy flow. We measure hundreds of cells from each patient, so, because of this, even though the number of patients is low, we get a very statistically significant distinction between patient and healthy cells’ deformability. We are putting our energy into developing the new devices as soon as possible.
This critical study has been fully funded by Open Medicine Foundation (OMF) through the support of our generous donors.
With regret we start the new year with sad news about the passing of Barbara Turnbull, who will be remembered for her tireless campaigning for ME services in North Wales and her kindness and support to many families. We send our condolences to her family.
“On behalf of Barbara Turnbull’s family I am sorry to have to tell you that Barbara passed away peacefully on Wednesday 12th December with her son by her bedside. The funeral takes place at 12 noon on Friday 4th January at the new crematorium in Northop / Connah’s Quay.
The family have few records from the Clwyd ME Support Group which Barbara founded and ran for many years, and have asked me to contact people who knew her. Barbara was a great support to many many pwme in North Wales for many years and I’m sure there will be many who will be saddened by her passing.
Yours, Anne Cutress
(friend and one time Trustee of the Clwyd ME Support Group)”
New research from King’s College London finds that an exaggerated immune response can trigger long-lasting fatigue, potentially explaining how chronic fatigue syndrome (CFS) begins. The study is the most in-depth biological investigation yet into the role of the immune system in lasting symptoms of fatigue.
CFS, also known as myalgic encephalomyelitis (ME), is a long-term illness which is characterised by extreme tiredness. The underlying biology of CFS has remained a mystery, hampering the search for treatments. There is some evidence that the immune system plays a role in triggering CFS and many patients report their illness starting with a challenge to the immune system such as a viral illness.
By the time patients are diagnosed it is too late to catch CFS in its earliest stages, and it is impossible to assess the biology of patients before the illness develops. To get around this problem, researchers from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) used a model for CFS based on a treatment for hepatitis C called interferon-alpha.
IL-13 is a cytokine that plays a central regulator role in IgE synthesis, goblet cell hyperplasia, mucus hypersecretion, airway hyperresponsiveness, fibrosis, It is a mediator of allergic inflammation and different diseases including asthma.
Interferon-alpha activates the immune system in the same way as a powerful infection. A lot of patients develop acute fatigue during treatment with interferon-alpha and a minority go on to have a CFS-like illness, where fatigue lasts for more than six months after the treatment ends. The researchers measured fatigue and immune system markers in 55 patients before, during and after treatment with interferon-alpha, tracking which people developed the persistent CFS-like illness.
The team found differences in the immune systems of 18 patients who developed lasting fatigue compared to those who recovered as normal. During treatment with interferon-alpha there was a much bigger immune response among those who developed the CFS-like illness, with a doubling in the levels of immune system ‘messenger’ molecules interleukin-10 and interleukin-6.
Importantly, even before treatment started, levels of interleukin-10 were higher among those who went on to have lasting fatigue, suggesting the immune system may have been ‘primed’ to over-respond.
Lead researcher Dr Alice Russell from the IoPPN says:
‘For the first time, we have shown that people who are prone to develop a CFS-like illness have an overactive immune system, both before and during a challenge to the immune system. Our findings suggest that people who have an exaggerated immune response to a trigger may be more at risk of developing CFS.’
By the time the CFS-like illness developed, however, there was no longer any detectable difference in the immune system of patients compared to those who recovered as normal. As well as looking at people having interferon-alpha treatment, the researchers also found no difference in immune activation between 54 people with diagnosed CFS and 57 healthy controls.
Alongside the overactive immune response, those people who developed the CFS-like illness had more acute fatigue during treatment with interferon-alpha than people who recovered as normal. Yet before treatment there was no difference between the groups in their levels of fatigue or in any psychiatric symptoms like depression or recent stressful life-events.
Senior researcher Professor Carmine Pariante from the IoPPN says:
‘A better understanding of the biology underlying the development of CFS is needed to help patients suffering with this debilitating condition. Although screening tests are a long way off, our results are the first step in identifying those at risk and catching the illness in its crucial early stages.’
Confirmation is needed that the findings from people treated with interferon-alpha apply to people with CFS, and future work to better understand the factors that may be driving an exaggerated immune response is required.
Dr Neha Issar-Brown, Head of Population and Systems Medicine at the Medical Research Council, which funded the research, said:
‘CFS/ME is a serious condition and its underpinning biology is poorly understood. Encouragingly, this work sheds light on potential mechanisms of immune dysregulation underlying early stages of chronic fatigue syndrome. The MRC strongly encourages more research to better understand this condition in order to address an area of unmet clinical need.’
Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of Chronic Fatigue Syndrome, by Alice Russell, Nilay Hepgul, Naghmeh Nikkheslat, Alessandra Borsini, Zuzanna Zajkowska, Natalie Moll, Daniel Forton, Kosh Agarwal, Trudie Chalder, Valeria Mondelli, Matthew Hotopf, Anthony Cleare, Gabrielle Murphy, Graham Foster, Terry Wong, Gregor A. Schutzb, Markus J. Schwarzb, Neil Harrison, Patricia A. Zunszain, Carmine M. Pariante inPsychoneuroendocrinology 17 Dec 2018
Highlights • Baseline fatigue is not associated with the development of persistent fatigue after IFN-α. • IFN-α-induced persistent fatigue is associated with increased baseline IL-10. • Patients who develop persistent fatigue experience greater increases in IL-6 and 10 in response to IFN-α. • Persistently fatigued patients recover at a similar rate, but from a more severe acute response to the initial trigger. • Once established, neither the persistent fatigue phenotype, nor CFS, are associated with peripheral immune activation.
Adolescent’s descriptions of fatigue, fluctuation and payback in chronic fatigue syndrome/myalgic encephalopathy (CFS/ME): Interviews with adolescents and parents, by Roxanne M Parslow, Nina Anderson, Danielle Byrne, Alison Shaw, Kirstie L Haywood, Esther Crawley inBMJ Paediatrics Open Vol 2, #1, December 4, 2018
What this study hopes to add?
All adolescents describe unique aspects of fatigue in CFS/ME; how it fluctuates naturally day to day but can also get worse following activity (payback).
The individual experience of fatigue varies in severity, frequency, the amount of activity taken to cause payback as well as the resulting impact on function.
The variation in the experience of fatigue needs to be taken into account in treatment.
Research abstract:
Objective:
As part of a larger qualitative study to explore outcomes important in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) and what improvements in fatigue and disability are key, interviews were undertaken with adolescents and their parents. This paper focuses on their descriptions of fatigue, fluctuation of symptoms and payback.
Design and setting:
Semistructured qualitative interviews were undertaken between December 2014 and February 2015. Adolescents and parents were interviewed separately. Participants were recruited from a single specialist paediatric chronic fatigue service. Interviews were audio recorded, transcribed verbatim and analysed using thematic analysis.
Participants:
We interviewed 21 adolescents and their parents (20 mothers and 2 fathers). The adolescents were aged between 12 and 17 years of age (mean age 14.4 years), mild to moderately affected by CFS/ME (not housebound) and the majority were female (16/21).
Results
All adolescents with CFS/ME reported fatigue, a natural fluctuation of the condition, with good days and bad days as well as an increase in symptoms after activity (payback). However, adolescent’s descriptions of fatigue, symptoms and the associated impact on their daily lives differed. The variations included: fatigue versus a collection of symptoms, constant versus variable symptoms and variable symptom severity. There were differences between participants in the amount of activity taken to cause payback. The impact of fatigue and symptoms on function ranged from: limiting the duration and amount of leisure activities, struggling with daily activities (eg, self-care) to no activity (sedentary).
Conclusions
Fatigue, fluctuation of the condition and payback after activity are described by all adolescents with CFS/ME in this study. However, the individual experience in terms of how they describe it and the degree and impact varies.
Fatigue is commonly reported in a variety of illnesses and has major impact on quality of life. Chronic fatigue syndrome (CFS) is a debilitating syndrome of unknown etiology. The clinical symptoms include problems in neuroendocrine, autonomic, and immune systems. It is becoming clear that the brain is the central regulator of CFS. For example, neuroinflammation, especially induced by activation of microglia and astrocytes, may play a prominent role in the development of CFS, though little is known about molecular mechanisms.
image description
Many possible causes of CFS have been proposed. However, in this mini-review, we summarize evidence for a role for microglia and astrocytes in the onset and the maintenance of immunologically induced CFS.
In a model using virus mimicking synthetic double-stranded RNA, infection causes sequential signaling such as increased blood brain barrier (BBB) permeability, microglia/macrophage activation through Toll-like receptor 3 (TLR3) signaling, secretion of IL-1β, upregulation of the serotonin transporter (5-HTT) in astrocytes, reducing extracellular serotonin (5-HT) levels and hence reduced activation of 5-HT1A receptor subtype.
Hopefully, drug discovery targeting these pathways may be effective for CFS therapy.
The International Alliance for Myalgic Encephalomyelitis (IAFME) has produced a trans-national consensus document covering Myalgic Encephalomyelitis (M.E.). Recognition, research and respect: An agenda for change in M.E. has the support of over 60 clinicians, researchers, and non-governmental organisations from 28 different countries.
As a member of IAFME, WAMES supports the sending of this document to the World Health Organisation by the Chair of the IAFME and Chief Executive of Action for M.E., Sonya Chowdhury, and the Executive Director of IAFME, Alexandra Heumber, requesting a meeting with representatives to discuss how they can work together to achieve the aims.
The IAFME is calling on the World Health Organisations (WHO) to take leadership for people living with ME worldwide who continue to face poor access to healthcare and support. Recognition, research and respect – an agenda for change in ME 25.11
WHO Headquarters in Geneva, Switzerland
This consensus document has three aims:
To provide an overview of ME and the disease burden
To highlight barriers to progressing research in the ME field
To propose an agenda for change
Dr Heidi Nicholl, CEO Emerge Australia and Vice-Chair IAFME said,
“This consensus document is a result of collaborative work from international experts, academics and researchers. It represents an important step forward that will underpin the global advocacy led by the IAFME, and has the broad support from stakeholders around the world. We look forward to hearing from the World Health Organisation in response to the Alliance’s request that they co-ordinate a global public health response to ME”
For more information: Alexandra Heumber aheumber@iafme.org, Executive Director IAFME.
