Immunosignature analysis of ME/CFS – promising diagnostic biomarker

Posted on 10/15/2018 by wames

Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Oliver P Günther, Jennifer L Gardy, Phillip Stafford, Øystein Fluge, Olav Mella, Patrick Tang, Ruth R Miller, Shoshana M Parker, Stephen A Johnston, David M Patrick in Molecular Neurobiology (2018) pp 1-9 [Published online: 8 October 2018]

Research abstract:

A random-sequence peptide microarray can interrogate serum antibodies in a broad, unbiased fashion to generate disease-specific immunosignatures. This approach has been applied to cancer detection, diagnosis of infections, and interrogation of vaccine response.

We hypothesized that there is an immunosignature specific to ME/CFS and that this could aid in the diagnosis. We studied two subject groups meeting the Canadian Consensus Definition of ME/CFS. ME/CFS (n = 25) and matched control (n = 25) sera were obtained from a Canadian study.

ME/CFS (n = 25) sera were obtained from phase 1/2 Norwegian trials (NCT01156909). Sera from six healthy controls from the USA were included in the analysis. Canadian cases and controls were tested for a disease immunosignature.

By combining results from unsupervised and supervised analyses, a candidate immunosignature with 654 peptides was able to differentiate ME/CFS from controls. The immunosignature was tested and further refined using the Norwegian and USA samples. This resulted in a 256-peptide immunosignature with the ability to separate ME/CFS cases from controls in the international data sets.

We were able to identify a 256-peptide signature that separates ME/CFS samples from healthy controls, suggesting that the hit-and-run hypothesis of immune dysfunction merits further investigation. By extending testing of both our signature and one previously reported in the literature to larger cohorts, and further interrogating the specific peptides we and others have identified, we may deepen our understanding of the origins of ME/CFS and work towards a clinically meaningful diagnostic biomarker.

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GET for ME/CFS is not effective & unsafe – re-analysis of a Cochrane review

Posted on 10/10/2018 by wames

Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review, by Mark Vink & Alexandra Vink-Niese in Health Psychology Open, Vol 5, issue: 2 [First Published October 8, 2018]

 

Review article abstract:

The analysis of the 2017 Cochrane review reveals flaws, which means that contrary to its findings, there is no evidence that graded exercise therapy is effective.

Because of the failure to report harms adequately in the trials covered by the review, it cannot be said that graded exercise therapy is safe.

The analysis of the objective outcomes in the trials provides sufficient evidence to conclude that graded exercise therapy is an ineffective treatment for myalgic encephalomyelitis/chronic fatigue syndrome.

Article Conclusion:

The GET trials reviewed here are inherently biased: use of exercise may attract only the mildly affected and may deter the more disabled patients from participating. These trials go back for more than two decades, at the cost of considerable money and involving large numbers of patients. The flaws in the review and the trials, as discussed above, all created a bias in favour of the exercise intervention. Despite these flaws, they have found no significant evidence of objective improvement. The analysis of the objective outcomes in the trials provides sufficient evidence to conclude GET is an ineffective treatment for ME/CFS.

Most studies failed to report on safety or adverse reactions, and White et al. (2011), one of the two studies that did, used an unrealistic definition. ME is characterised by an abnormally delayed muscle recovery after trivial exertion (Ramsay, 1988), commonly referred to as PEM. Exercise physiology studies reveal abnormalities in patients’ responses to exertion.

Yet PEM is not a requirement for diagnosis according to the Oxford criteria, used by five of the studies, and only an optional criterion according to the Fukuda criteria, used by the other three studies in the review. If patients do not suffer from PEM, it is likely that they will have no problems exercising. This might be an important reason why outside of clinical trials things are different with many patients, who do suffer from PEM, reporting deterioration with GET. Given these considerations, one cannot conclude that GET is safe.

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School nurses can improve the lives of students with ME/CFS

Posted on 10/05/2018 by wames

School nurses can improve the lives of students with Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, by Kenneth J. Friedman, Beth Mattey, Faith Newton in NASN School Nurse  [First Published September 15, 2018]

Article abstract:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness that is defined and diagnosed by its symptoms: extreme fatigue made worse by physical and mental activity, pain and decreased mental stamina, among others.

A long-held, erroneous belief that ME/CFS is not a physiological illness has persisted among some clinicians, leading to the denial of a patient’s physical illness and attributing the symptoms to other causes.

The debilitating effects of ME/CFS in the pediatric population can affect all aspects of academic, social, emotional, and physical development. ME/CFS has been diagnosed in children younger than 10 years. Therefore, the school nurse is likely to encounter one or more students in the various stages of this disease, putting the school nurse in a position to ameliorate the impact of this potentially devastating chronic condition.

Read full article              Excerpt:

Role of the School Nurse
The role of the school nurse in assisting a student with ME/CFS falls into three main categories:

(1) being informed about the disease,

(2) recognizing the signs and symptoms of the disease in the student, and educating school staff and families about the disease and its impact, and

(3) advocating for accommodations and modifications in the school setting, and assisting the student in managing what is most likely to be a modified educational program on his or her return to school (Centers for Disease Control and Prevention [CDC], 2017b).

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Chronic viral infections in ME/CFS

Posted on 10/04/2018 by wames

Chronic viral infections in myalgic encephalomyelitis/ chronic fatigue syndrome  (ME/CFS), by Santa Rasa, Zaiga Nora-Krukle, Nina Henning, Eva Eliassen, Evelina Shikova, Thomas Harrer, Carmen Scheibenbogen, Modra Murovska, Bhupesh K Prusty and the European Network on ME/CFS (EUROMENE) in Journal of Translation Medicine 2018, #16 p 268, August 2, 2018 [Published: 1 October 2018]

Review abstract:

Background and main text:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals.

Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies.

Conclusions:
This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.

Review Conclusions:

Currently available data on the role of chronic viral infection with ME/CFS is still controversial, showing potential viral involvement for at least a subgroup of ME/CFS patients. Therefore, it is necessary to assess the presence and markers of viral activity at the initial stage of the disease to evaluate possible etiological factors and conduct longitudinal studies in order to assess active viral infection and symptom severity variations over time. Moreover, results should be compared not only between ME/CFS patients and controls, but also with other co-morbidities to assess specificity of suggested biomarkers.

Considering ME/CFS heterogeneity, the use of clinical characteristics and biomarkers to enable definition of the disease subtypes is crucial. In addition, longitudinal and standardized studies determining ME/CFS course and therapy effectiveness with follow-up measurements in dynamics should be accomplished. This will allow prognosis of the disease development and promote development of a specific definition for diagnostics and a treatment plan.

Future strategies for development of infection biomarkers in ME/CFS

  1. Use of quantitative assays rather than qualitative assays to assess the extent of the viral load instead of simple detection of presence or absence. This may facilitate monitoring of a response to treatment; however, diurnal variations and individual response on treatment should be taken into account. Further comprehensive serological testing may help to identify a signature of active infection.
  2. Use of additional biological samples together with blood and serum will be useful in determining the localization and distribution of biomarkers, as well as pathogenicity. Using hair follicles, virus integration can be detected. Similarly throat swab and stool samples can be used for detection of enteroviruses.
  3. Functional studies to compliment clinical biomarker studies in order to clarify functions and interactions of genes, transcripts, proteins, and immune cells and molecules in cases of ME/CFS. This will facilitate understanding of the disease aetiology as well as development and maintenance pathways, and thereby, potential prevention and treatment strategies. However, this strategy requires definition of ME/CFS subgroups.
  4. Use of high throughput methods to gain broader insight into potential biomarkers for infections by obtaining and analysing large-scale data, which will raise the quality and significance of the research.
  5. Confirmation of results by validation studies and multi-centre cohort studies to obtain generalizability of the study and promote implementation of credible biomarkers usable worldwide.
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Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?

Posted on 10/02/2018 by wames

Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?, by Frank Comhaire in Med Hypotheses 2018 Nov;120:65-67 [Epub 2018 Aug 25]

Research abstract:

Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is an enigmatic disease the pathogenesis of which remains elusive.

Pragmatic proof-of-principle of the hypothetical mechanisms causing the clinical symptoms has been delivered, but it is hard to explain why some patients do respond favourably to treatment with sodium dichloroacetate (DCA), which enhances the activity of the mitochondrial enzyme pyruvate dehydrogenase, but other patients experience no benefit from this substance.

In a prospective trial including 35 ME/CFS patients, logistic regression analysis with stepwise elimination has identified 6 pre-treatment characteristics allowing for the differentiation between responders (n = 13) and non-reponders (n = 22) with high accuracy (P < 0.0001; area under the ROC-curve = 0.92).

A formula was derived generating the probability of belonging to the group of responders. This finding may assist in selecting ME/CFS patients suitable for treatment with DCA, but requires further studies as to the predictive capacity of the derived formula.

Read full paper

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EUROMENE – European co-operation to address gaps in ME/CFS understanding

Posted on 09/27/2018 by wames

EUROMENE – the European Network on ME/CFS

Funded by COST – a European framework supporting trans-national cooperation among researchers, engineers and scholars across Europe – EUROMENE aims to create an integrated network of researchers on ME/CFS in Europe and beyond.

The network will promote multidisciplinarity in ME/CFS research and foster a full chain of translational research to further develop much-needed treatment and prevention strategies for improvement of patients’ quality of life.

  •  to develop strategies to collect population-based data on the prevalence of ME/CFS in Europe
  • to promote co-operation and involvement of research groups
  • to define a standardized clinical diagnosis for ME/CFS for clinicians and researchers
  • to coordinate efforts to determine the social impact of ME/CFS and to appraise the economic damage from the disease.
  • to establish communication links with industrial organisations
  • to develop strategies to collect population-based data on the prevalence of ME/CFS

CA COST Action CA15111 Grant period from 1st May 2018 – 30th April 2019

Recent events:

  • A seminar about “Diagnostics & Therapy in CFS” in Berlin, 26 Sep 2018
  • Call No 3 for Short Term Scientific Missions (STSM) Applications
  • Epidemiology & Socio-economics Working groups met in London 13 Sep
  • Summer school for translational research in ME/CFS June 2018, Berlin
  • Euromene meeting: Clinical research enablers and diagnostic criteria, Paris, April 2018

Dr Derek Pheby from Buckinghamshire New University in the UK is on the Socio-economics work group

Dr Luis Nacul from Cure ME and the ME/CFS Biobank in London is on the Clinical Research Working Group

Find out more: EUROMENE website

 

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The effects of warm water immersion on people with CFS

Posted on 09/27/2018 by wames

The effects of warm water immersion on blood pressure, heart rate and heart rate variability in people with chronic fatigue syndrome, by Romy Parker, Zeenath Higgins, Zandiswa N.P. Mlombile, Michaela J. Mohr, and Tarryn L Wagner in S Afr J Physiother. 2018; 74(1): 442. [Published online 2018 Aug 28]

Research abstract:

Background:
Chronic fatigue syndrome (CFS) is a central sensitisation syndrome with abnormalities in autonomic regulation of blood pressure (BP), heart rate (HR) and heart rate variability (HRV). Prior to exploring the effects of hydrotherapy as a treatment for this population, changes in BP, HR and HRV during warm water immersion need to be established.

Objectives:
The study aimed to determine the effects of warm water immersion on BP, HR and HRV in adults with CFS compared to matched-pair healthy adults.

Method:
A quasi-experimental, single-blinded study design was used with nine CFS participants and nine matched controls. Participants’ BP, HR and HRV were measured before, after 5 minutes and post warm water immersion at the depth of the fourth intercostal space, using the Ithlete® System and Dräger BP monitor.

Results:
There was a significant difference between groups in HRV prior to immersion (control group: 73 [55–74] vs. chronic fatigue syndrome group: 63 [50–70]; p = 0.04). There was no difference in HRV post-immersion. A significant difference in HR after immersion was recorded with the control group having a lower HR than those with CFS (78 [60–86] vs. 86 [65–112]; p = 0.03). The low HRV present in the CFS group prior to immersion suggests autonomic dysregulation. Individuals with CFS may have reduced vagal nerve activation post-immersion. During immersion, HRV of the CFS participants improved similar to that of the healthy controls.

Conclusion:
Prior to immersion, differences were present in the HRV of the participants with CFS compared to healthy controls. These differences were no longer present post-immersion.

Clinical implications:
Warm water immersion appears safe and may be beneficial in the management of individuals with CFS.

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A concurrent cognitive task does not perturb (i.e. alter) quiet standing in FM & CFS/ME

Posted on 09/26/2018 by wames

A Concurrent Cognitive Task Does Not Perturb Quiet Standing in Fibromyalgia and Chronic Fatigue Syndrome, by Omid Rasouli, Egil A Fors, Ottar Vasseljen and Ann-Katrin Stensdotter in Pain Research and Management Vol 2018, Article ID 9014232 [Published 7 August 2018]

Research abstract:

Background and Objectives:

Cognitive complaints are common in fibromyalgia (FM) and chronic fatigue syndrome (CFS). Fatigue as well as pain may require greater effort to perform cognitive tasks, thereby increasing the load on processing in the central nervous system and interfering with motor control.

Methods:

The effect of a concurrent arithmetic cognitive task on postural control during quiet standing was investigated in 75 women (aged 19–49 years) and compared between FM, CFS, and matched controls (/group). Quiet standing on a force plate was performed for 60 s/condition, with and without a concurrent cognitive task. The center of pressure data was decomposed into a slow component and a fast component representing postural sway and adjusting ankle torque.

Results:

Compared to controls, CFS and FM displayed lower frequency in the slow component (), and CFS displayed greater amplitude in the slow ( and ) and fast () components. There were no interactions indicating different responses to the added cognitive task between any of the three groups.

Conclusion:

Patients displayed insufficient postural control across both conditions, while the concurrent cognitive task did not perturb quiet standing. Fatigue but not pain correlated with postural control variables.

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Defining the prevalence & symptom burden of those with self-reported severe CFS/ME

Posted on 09/24/2018 by wames

Defining the prevalence and symptom burden of those with self-reported severe chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): A two-phase community pilot study in the North East of England, by Victoria Jane Strassheim,  Madison Sunnquist, Leonard A Jason, Julia L Newton in BMJ Open Vol 19, #8, p e020775 [Published: September 19, 2018]

Research abstract:

Objectives:
To define the prevalence of severe chronic fatigue syndrome/ myalgic  encephalomyelitis (CFS/ME) and its clinical characteristics in a geographically defined area of Northern England. To understand the feasibility of a community-based research study in the severely affected CFS/ME group.

Design:
A two-phase clinical cohort study to pilot a series of investigations in participants own homes.

Setting:
Participants were community living from the area defined by the Northern clinical network of the UK.

Participants:
Adults with either a medical or a self-reported diagnosis of CFS/ME.

Phase 1 involved the creation of a database.

Phase 2: five participants were selected from database, dependent on their proximity to Newcastle.

Interventions:
The De Paul fatigue questionnaire itemised symptoms of CFS/ME, the Barthel Functional Outcome Measure and demographic questions were collected via postal return. For phase 2, five participants were subsequently invited to participate in the pilot study.

Results: 
483 questionnaire packs were requested, 63 were returned in various stages of completion. 56 De Paul fatigue questionnaires were returned: all but 12 met one of the CFS/ME criteria, but 12 or 22% of individuals did not fulfil the Fukuda nor the Clinical Canadian Criteria CFS/ME diagnostic criteria but 6 of them indicated that their fatigue was related to other causes and they barely had any symptoms. The five pilot participants completed 60% of the planned visits.

Conclusions:
Severely affected CFS/ME individuals are keen to participate in research, however, their symptom burden is great and quality of life is poor. These factors must be considered when planning research and methods of engaging with such a cohort.

Strengths and limitations of this study

  • Two-phase pilot study with severe chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) individuals in the community, to understand the feasibility of engaging those with severe CFS/ME with research.
  • Phase 1 consisted of postal questionnaires including demographic data, Barthel Functional Outcome Score and De Paul fatigue questionnaire.
  • Effort was taken to engage with this severely symptom burdened group in their own environment.
  • The postal questionnaires sent to return ratio was poor; feedback from the local support group suggests in part due to the severity of impairment experienced by this group of individuals.
  • This pilot study can only give an indication of possible people with severe CFS/ME presentation in a specific, geographically defined area.
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Near-infrared spectroscopy screening to allow detection of pathogenic mitochondrial DNA variants in individuals with unexplained abnormal fatigue

Posted on 09/21/2018 by wames

Near-infrared spectroscopy screening to allow detection of pathogenic mitochondrial DNA variants in individuals with unexplained abnormal fatigue: A preliminary study, by Bert M Celie, An Mariman, Jan Boone, Liesbeth Delesie, Els Tobback, Sara Seneca, Boel De Paepe, Dirk Vogelaers, Rudy N Van Coster, Jan G Bourgois in Appl Spectrosc. 2018 May; 72(5):715-724 [Epub 2018 Feb 13]

Research abstract:

Unexplained abnormal fatigue is characterized by chronic fatigue persisting for at least six months and not sufficiently explained by any recognized medical condition.

In this pilot study, twelve individuals with abnormal fatigue remaining unexplained after thorough screening were investigated using a near-infrared (NIR) spectroscopy handgrip test.

Four of them were found to have an abnormal oxygen extraction pattern similar to participants with documented mitochondrial myopathy. In three of the four individuals, diverse mitochondrial abnormalities were documented by spectrophotometric, immunocytological, fluorescent, and morphological analyses performed in skeletal muscle and in cultured skin fibroblasts.

Three of the four participants with decreased muscular oxygen extraction were each shown to harbor a different homoplasmic pathogenic mitochondrial DNA point mutation (m.961T > C, m.1555A > G, m.14484T > C). In the fourth participant, the presence of multiple large mitochondrial DNA deletions was suspected in muscle tissue.

In contrast, none of the eight abnormally fatigued participants with normal NIR spectroscopy results harbored either a pathogenic mitochondrial DNA point mutation or large deletions ( P < 0.001).

This pilot study shows that NIR spectroscopy may serve as a noninvasive screening tool to delineate a subgroup (of participants) with mitochondrial dysfunction among the large group of individuals with unexplained abnormal fatigue.

Read full article

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