Paediatric patients with ME/CFS value understanding & help to move on with their lives

Posted on 01/13/2020 by wames

Paediatric patients with myalgic encephalomyelitis/chronic fatigue syndrome value understanding and help to move on with their lives, by Katherine Rowe in Acta Paediatrica, First published: 18 December 2019 [https://doi.org/10.1111/apa.15054]

 

Abstract:

Aim:
The aim of this study was to document qualitative questionnaire feedback regarding management from a cohort observational study of young people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Methods:
Between 1991 and 2009, 784 paediatric patients, age 6‐18 years, were diagnosed with ME/CFS following referral to a specialised clinic at the Royal Children’s Hospital, Melbourne. Over a 14‐year period, feedback was requested on up to seven occasions.

Management included the following: symptom management and a self‐management lifestyle plan that included social, educational, physical and a pleasurable activity outside of home. They adjusted it by severity of illness, stage of education, family circumstances and life interests.

Results:
Questionnaires were returned from 626 (80%) with 44% providing feedback more than once. They reported that their management plan allowed them to regain control over their lives. They cited early diagnosis, empathetic, informed physicians, self‐management strategies and educational liaison as helping them to function and remain socially engaged. Ongoing support, particularly assistance to navigate the education system, was essential for general well‐being and ability to cope.

Conclusion:
Young people valued regaining the control over their lives that was lost through illness, support to maintain social contacts and assistance to achieve educational and/or life goals.

Key Notes:

  • A cohort observational study of 784 young people with myalgic encephalomyelitis/chronic fatigue syndrome provided feedback across a 14‐year period regarding helpful strategies and ways to improve management.
  • Early diagnosis, empathetic informed physicians, assistance with symptom control, self‐management strategies, educational liaison and advocacy enabled them to regain control, remain socially engaged and function optimally.
  • Doctors and teachers awareness of helpful strategies could significantly reduce distress with this illness.

Comment in Arch Dis Child 2020;105:451. doi:10.1136/archdischild-2020-319237

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The role of low-grade inflammation in ME/CFS – associations with symptoms

Posted on 01/13/2020 by wames

The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) – associations with symptoms, by Martin A Jonsjö, Gunnar L Olsson, Rikard K Wicksell, Kjell Alving, Linda Holmström, Anna Andreasson in Psychoneuroendocrinology Vol 113, March 2020, 104578 [https://doi.org/10.1016/j.psyneuen.2019.104578]

 

Highlights

  • Associations between inflammatory markers and common symptoms in ME/CFS.
  • Higher levels of markers were significantly associated with higher levels of symptoms.
  • Biological sex moderated several associations.

Abstract

Background:
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often present with a range of flu-like symptoms resembling sickness behavior as well as widespread pain and concentration deficits. The aim of this study was to explore the association between inflammatory markers previously shown to be related to fatigue severity in ME/CFS and common ME/CFS symptoms post-exertional fatigue, impaired cognitive processing, musculoskeletal pain and recurrent flu-like symptoms, and the moderating effect of sex on these associations.

Methods:
53 adult patients diagnosed with ME/CFS at a specialist clinic were included in the study. Fasting blood plasma was analyzed using the Olink Proseek Multiplex Inflammation panel (β-NGF, CCL11, CXCL1, CXCL10, IL-6, IL-7, IL-8, IL-10, IL-18, TGF-α, TGF-β-1 and SCF) and BioRad Human Cytokine Type 1 assay (TNF-α). Participants rated the average severity of symptoms (0–10) based on the 2011 International Consensus Criteria of ME/CFS during a structured clinical interview. Associations between inflammatory markers and symptom severity were analyzed using bivariate correlations and moderated regression analyses bootstrapped with 5000 repetitions.

Results and conclusions:
Only β-NGF was associated with the fatigue severity measure. However, higher levels of CCL11, CXCL10, IL-7, TNF-α and TGF-β-1 were significantly associated with higher levels of impaired cognitive processing and musculoskeletal pain, and sex was a significant moderator for CXCL10, IL-7 and TGF-β-1. Future studies should investigate the relationship between inflammatory markers and key symptoms in ME/CFS in a longitudinal design in order to explore if and for whom low-grade inflammation may contribute to illness development.

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The All-Party Parliamentary Group on ME to re-convene – Please invite your MP to attend!

Posted on 01/09/2020 by wames

ME Association blog post: The All-Party Parliamentary Group on ME to Re-Convene – Please Invite Your MP to Attend! by Dr Charles Shepherd, 9 January 2020

 

 

Carol Monaghan MP has decided that the time is right to re-establish the APPG on ME.

Following the election, it was decided to hold an inaugural APPG meeting as soon as possible after members returned to Westminster, and this will now take place on Tuesday 14th January.

Invite Your MP to the Meeting

We now want people to contact their MPs, especially if they are known to be already interested in ME and invite them to attend.

FIND YOUR MP
For further information on the time and location of the meeting, your MP can contact Carol Monaghan via House of Commons email/telephone or consult the All-Party Notices.

More info on MEA website

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Perturbation of effector & regulatory T cell subsets in ME/CFS

Posted on 01/09/2020 by wames

Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS), by Ece Karhan, Courtney Gunter, Vida Ravanmehr, Meghan Horne, Lina Kozhaya, Stephanie Renzullo, Lindsey Placek, Joshy George, Peter N Robinson, Suzannne D Vernon, Lucinda Bateman, Derya Unutmaz in bioRxiv  2019.12.23. 887505

 

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder of unknown etiology, and diagnosis of the disease is largely based on clinical symptoms. We hypothesized that immunological disruption is the major driver of this disease and analyzed a large cohort of ME/CFS patient or control blood samples for differences in T cell subset frequencies and functions. We found that the ratio of CD4+ to CD8+ T cells and the proportion of CD8+ effector memory T cells were increased, whereas NK cells were reduced in ME/CFS patients younger than 50 years old compared to a healthy control group.

Remarkably, major differences were observed in Th1, Th2, Th17 and mucosal-associated invariant T (MAIT) T cell subset functions across all ages of patients compared to healthy subjects. While CCR6+ Th17 cells in ME/CFS secreted less IL-17 compared to controls, their overall frequency was higher. Similarly, MAIT cells from patients secreted lower IFNgamma;, GranzymeA and IL-17 upon activation. Together, these findings suggest chronic stimulation of these T cell populations in ME/CFS patients.

In contrast, the frequency of regulatory T cells (Tregs), which control excessive immune activation, was higher in ME/CFS patients. Finally, using a machine learning algorithm called random forest, we determined that the set of T cell parameters analyzed could identify more than 90% of the subjects in the ME/CFS cohort as patients (93% true positive rate or sensitivity).

In conclusion, these multiple and major perturbations or dysfunctions in T cell subsets in ME/CFS patients suggest potential chronic infections or microbiome dysbiosis.

These findings also have implications for development of ME/CFS specific immune biomarkers and reveal potential targets for novel therapeutic interventions.

 

Press release: JAX Research on Immune Profiles in ME/CFS is now Available Online, 27 Dec 2019

…In this detailed study, we analyzed the immunological differences between ME/CFS patients and healthy controls within a large cohort and found several major differences in T cell subset frequencies and functions between the two groups.

… the ratio of two major subsets of T cells, namely the CD4+ to CD8+ T cell ratio, was increased in ME/CFS patients compared to healthy controls.

… There was also a major difference seen between healthy controls and ME/CFS patients in the Th17 cell subset, which is involved in responding to bacteria and is also a culprit in several autoimmune and chronic inflammatory conditions… we think this suggests a chronic activation of Th17 cells in ME/CFS which induces an ‘exhausted’ state where the cells are more dysfunctional due to their chronic stimulation.

…There was also a major difference seen in the mucosal-associated invariant T (MAIT) cells in ME/CFS patients compared to healthy controls…  It is possible that these changes in Th17 and MAIT cells are associated with differences in the composition of the microbiota of the ME/CFS patients, and that a disruption in the microbiota causes chronic activation of these subsets and an exhausted state in ME/CFS patients.

Interestingly, we also noted that regulatory T cells (Tregs) were increased in ME/CFS patients compared to controls. Tregs function to suppress excessive chronic immune responses, so this is consistent with our finding that there appears to be chronic activation of major T cell subsets in ME/CFS patients.

Finally and importantly, we utilized these immune profiling parameters in a machine learning classifier and were able to correctly identify ME/CFS patients from healthy controls with high sensitivity and accuracy. As patients often wait years to receive an ME/CFS diagnosis since there are currently no clear diagnostic tools to identify the disease, the development of an immune profile classier could aid as a biomarker to diagnose the disease.

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Autonomic markers, CFS & post-exertion states

Posted on 01/08/2020 by wames

Autonomic markers, chronic fatigue syndrome, and post-exertion states, by Fred Friedberg in Journal of Psychosomatic Research Vol 127, Dec 2019, [https://doi.org/10.1016/j.jpsychores.2019.109845]

 

Article extracts:

A large body of evidence suggests that autonomic imbalance, i.e., hyperactive sympathetic nervous system and hypoactive parasympathetic nervous system, is associated with a number of pathological conditions and diseases, and may be a final common pathway to increased morbidity and mortality [1].

Heart rate variability (HRV), a measure of inter-beat interval fluctuations and more broadly of parasympathetic (vagal) activity has been successfully used to index autonomic imbalances.

…In conclusion, reduced HRV may be a sensitive (and conveniently assessed) autonomic indicator of post-exertional worsening and a correlate of activity and fatigue that may differentiate CFS from healthy controls. If negative changes in HRV are uniquely associated with greater PEM and day-to-day illness fluctuations in CFS, then its potential as an illness marker can be productively tested in exertional challenge designs that amplify PEM-related symptom exacerbations.

Read full paper

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Patients with ME/CFS & chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation

Posted on 01/07/2020 by wames

Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation, by Martin A Jonsjö, Jenny Åström, Michael P Jones, Bianka Karshikoff, KarinLodin, Linda Holmström, Lars Agréus, Rikard K Wicksell, John Axelsson, Mats Lekander, Gunnar L Olsson, Mike Kemani, Anna Andreasson in Brain, Behavior, & Immunity – Health 17 December 2019 [https://doi.org/10.1016/j.bbih.2019.100028]

 

Highlights:

  • Investigation of the level of subjective sickness behavior, assessed with a validated questionnaire, in patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and in patients with chronic pain compared to clinical, non-clinical and experimental groups.
  • The level of sickness behavior is similarly high in ME/CFS and chronic pain, and equal to the level in experimentally induced inflammation via injection of bacterial endotoxin.
  • Higher levels of sickness behavior showed significant associations with lower levels of self-rated health and functioning.

Abstract:

Background:
Chronic sickness behavior is implicated in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain but the level of subjective sickness behavior in these conditions has not been investigated or compared to other clinical and non-clinical samples, or to the level in experimental inflammation. Furthermore, the relationship between sickness behavior and self-rated health and functioning is not known in patients with ME/CFS and chronic pain.

The aim of the present study was to investigate how sickness behavior in patients with chronic conditions differs from that in individuals with experimental acute sickness, primary care patients, the general population and healthy subjects. In addition, we wanted to explore how sickness behavior is related to self-rated health and health-related functioning.

Methods:
Sickness behavior was quantified using the sickness questionnaire (SicknessQ). Self-ratings were collected at one time-point in 6 different samples. Levels of sickness behavior in patients with ME/CFS (n ​= ​38) and patients with chronic pain (n ​= ​190) were compared to healthy subjects with lipopolysaccharide(LPS)-induced inflammation (n ​= ​29), primary care patients (n ​= ​163), individuals from the general population (n ​= ​155) and healthy subjects (n ​= ​48), using linear regression. Correlations and moderated regression analyses were used to investigate associations between sickness behavior and self-rated health and health-related functioning in ME/CFS, chronic pain and the general population.

Results:
LPS-injected individuals (M ​= ​16.3), patients with ME/CFS (M ​= ​16.1), chronic pain (M ​= ​16.1) and primary care patients (M ​= ​10.7) reported significantly higher SicknessQ scores than individuals from the general population (M ​= ​5.4) and healthy subjects (M ​= ​3.6) all p’s ​< ​0.001). In turn, LPS-injected individuals, patients with ME/CFS and chronic pain reported significantly higher SicknessQ scores than primary care patients (p’s ​< ​0.01). Higher levels of sickness behavior were associated with poorer self-rated health and health-related functioning (p’s ​< ​0.01), but less so in patients with ME/CFS and chronic pain than in individuals from the general population.

Conclusions:
Patients with ME/CFS and chronic pain report similar high levels of sickness behavior; higher than primary care patients, and comparable to levels in experimental inflammation. Further study of sickness behavior in ME/CFS and chronic pain populations is warranted as immune-to-brain interactions and sickness behavior may be of importance for functioning as well as in core pathophysiological processes in subsets of patients.

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Central sensitization: a pathogenic mechanism in complex undefined diseases

Posted on 01/07/2020 by wames

Central sensitization: A pathogenic mechanism in complex undefined diseases, by Joaquim Fernández-Solà, in Neuropsychiatry (London) 2019: 9(6), 2485–2490

 

Abstract:

There is a common perception that complex undefined diseases manifested with diverse combination of symptoms and a difficult clinical diagnosis have a possible common physiological mechanism of disease production.

Physical or cognitive fatigue, widespread pain without arthritis, sleep, mood and autonomic disturbances as well as multiple intolerance involving drug, food, chemical agents, electromagnetic fields or other environmental factors may be included in this category.

Along last three decades, the existence of central sensitivity as a well established common pathogenic mechanism involved in abnormal symptom development emerged in diverse areas as pain, fatigue, food and environmental intolerance, as well as in the global chronic disease epidemic. The common fact of all of these disorders is a deregulation of the central control mechanisms at the limbic brain system. This may relate to amplification of pain and fatigue perception and disturbance of environmental tolerance and control of circadian rhythms and mood.

This deregulation causes amplification of central somatosensory perception, but also a decrease of nociceptive inhibitory outputs. The final result is a chronic condition with central hyperexcitability and systemic disabling symptoms highly difficult to manage.

This article comments on the current significance to evaluate central sensitization symptoms and to consider these mechanisms in the development of complex diseases, as well as in the global chronic disease epidemic. We propose to include central sensitization to structuring a multidisciplinary concept addressed to improve scientific comprehension and clinical management of diseases, as well as future research directions on this field.

Read the full paper

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An investigation into the modulation of T cell phenotypes by amitriptyline & nortriptyline

Posted on 12/28/2019 by wames

An investigation into the modulation of T cell phenotypes by amitriptyline and nortriptyline, by JonathanRoyds, Melissa J Conroy, Margaret R Dunne, Connail McCrory, Joanne Lysaght in European Neuropsychopharmacology, Dec 2019[doi.org/10.1016/j.euroneuro.2019.12.106]

 

Research abstract:
Amitriptyline is prescribed for treating the symptoms of neuroinflammatory disorders including neuropathic pain and fibromyalgia. As amitriptyline has evidence of modulating the neuroimmune interface; the effects of amitriptyline treatment on T-cell phenotype and function were examined in vitro. Peripheral blood mononuclear cells (PBMCs) were isolated and treated with amitriptyline, nortriptyline and a combination of both drugs. Toxicity for T-cells was assessed by Annexin V/Propidium Iodide staining. Activation status and cytokine expression by T-cells post treatment was assessed by flow cytometry.

The levels of secreted cytokines, chemokines and neurotrophins were measured by ELISA in the supernatants. There was no significant increase in T-cell death following 24 or 48 h compared to controls. There were significantly lower frequencies of CD8+ T-cells after treatment with amitriptyline, nortriptyline and a combination of both compared to a Vehicle Control(VC)(p<0.001). The frequencies of naive CD8+CD45RA+ cells were significantly lower after amitriptyline, nortriptyline and a combination of both (p<0001).

The frequencies of CD27+CD4+(p<0.05) and CD27+CD8+(p<0.01) T-cells were also significantly lower following combination drug treatment. Significantly lower frequencies of IFN-γ-producing CD8+ T-cells were observed with all treatment combinations(p<0.05) and frequencies of IL-17-producing CD4+ and CD8+ T-cells were significantly lower following amitriptyline treatment (p<0.05).

Frequencies of Natural Killer T-cells were significantly higher following treatment with nortriptyline (p<0.05). Significantly higher levels of IL-16 (p<0.001) and lower levels of TNF-β (p<0.05) were observed in supernatants. This data indicates that both amitriptyline and nortriptyline modulate the phenotype and function of T-cells and this may have clinical relevance in the pathologies of its off-label applications.

Read full paper

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Register your interest today in taking part in ME/CFS genome-wide research!

Posted on 12/23/2019 by wames

The ME/CFS Biomedical Partnership Genome-wide association study

The ME/CFS Biomedical Partnership is working on a funding application to be made in early 2020 to the MRC/NIHR for a genome-wide association study.

 

How can we help?

They need to demonstrate to the funders that they can recruit 20,000 people to participate so they are asking people to sign up to a mailing list to keep updated on the application progress. Additionally, UK residents can log their potential interest in being involved in the research itself and they need as many people as possible to do this.

Sign up here: https://mebiomed.org.uk/get-involved/

What is a genome-wide association study?

A genome-wide association study (GWAS) is a very large genetic study that seeks to uncover some of the biological roots of ME/CFS. By probing small DNA differences among people, a GWAS can help to pinpoint the genetic causes of disease and then can help to guide drug development.

This design has previously provided helpful in identifying genes together with molecular and cellular pathways to contribute to disease risk. Read more about the science of GWAS.

The ME/CFS Biomedical Partnership website: https://mebiomed.org.uk/

More information: https://mecfsresearchreview.me/2020/01/08/sign-up-your-support-could-help-win-funding-for-a-game-changing-me-cfs-study/

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WAMES helpline holiday hours 2019-2020

Posted on 12/22/2019 by wames

WAMES helpline hours

The WAMES helpline is run by volunteers and will be closed over the festive period.

 

Support bricksWe apologise that due to extra pressures on the team in January, the closure will last longer than usual. Feel free to email queries and we will reply as soon as possible.

helpline@wames.org.uk  0290 2051 5061

  • 23 December – 12 January  closed
  • 13 January onwards 10-7pm

 

For emotional support, the Samaritans can be contacted 24 hours a day, 7 days a week.

English – 116 123 – free number (24 hours a day, 7 days a week)

Cymraeg – 0808 164 0123 – free number (check times on the website)

 

Children and young people up to age 25 can also contact Meic by phone, email, SMS text and instant messaging.

  • 8am to midnight, 7 days a week
  • FREEPHONE: 0808 80 23456
  • SMS TEXT: 84001
  • IM/Webchat: www.meic.cymru
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