TGI Friday! Our weekly round-up of recently published research abstracts | 31 March 2017

March 31, 2017

From Pain Physician (open access). March/April 2017.

This study is funded by the MEA Ramsay Research Fund. We commented on it HERE.

The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis⁄Chronic Fatigue Syndrome and Healthy People

Jessica Van Oosterwijck, PhD1,2,3, Uros Marusic, PhD4, Inge De Wandele, PhD3, Lorna Paul, PhD5, Mira Meeus, PhD1,3,6, Greta Moorkens, MD, PhD7,
Luc Lambrecht, MD, PhD8, Lieven Danneels, PhD3, and Jo Nijs, PhD1,2,9
1. Pain in Motion international research group,;
2. Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium; 3
3. Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium;
4. Science and Research Centre, Institute for Kinesiology Research, University of Primorska, Koper, Slovenia;
5. Nursing and Health Care, School of Medicine, University of Glasgow, Glasgow, United Kingdom;
6. Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium;
7. Department of Internal Medicine, University Hospital Antwerp (UZA), Antwerp, Belgium;
8. Private practice for Internal Medicine, Ghent, Belgium;
9. Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium
Address Correspondence: Jo Nijs, PhD, MSc Universiteit Brussel, Building F-Kine, Laarbeeklaan 103, BE- 1090 Brussels, Belgium Email:



Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are unable to activate brain-orchestrated endogenous analgesia (or descending inhibition) in response to exercise. This physiological impairment is currently regarded as one factor explaining post- exertional malaise in these patients. Autonomic dysfunction is also a feature of ME/CFS.


This study aims to examine the role of the autonomic nervous system in exercise- induced analgesia in healthy people and those with ME/CFS, by studying the recovery of autonomic parameters following aerobic exercise and the relation to changes in self-reported pain intensity.

A controlled experimental study.


The study was conducted at the Human Physiology lab of the Vrije Universiteit Brussel.


Twenty women with ME/CFS- and 20 healthy, sedentary controls performed a submaximal bicycle exercise test known as the Aerobic Power Index with continuous cardiorespiratory monitoring. Before and after the exercise, measures of autonomic function (i.e., heart rate variability, blood pressure, and respiration rate) were performed continuously for 10 minutes and self-reported pain levels were registered. The relation between autonomous parameters and self-reported pain parameters was examined using correlation analysis.


Some relationships of moderate strength between autonomic and pain measures were found. The change (post-exercise minus pre-exercise score) in pain severity was correlated (r = .580, P = .007) with the change in diastolic blood pressure in the healthy group. In the ME/CFS group, positive correlations between the changes in pain severity and low frequency (r = .552, P = .014), and between the changes in bodily pain and diastolic blood pressure (r = .472, P = .036), were seen. In addition, in ME/CHFS the change in headache severity was inversely correlated (r = -.480, P = .038) with the change in high frequency heart rate variability.


Based on the cross-sectional design of the study, no firm conclusions can be drawn on the causality of the relations.


Reduced parasympathetic reactivation during recovery from exercise is associated with the dysfunctional exercise-induced analgesia in ME/CFS. Poor recovery of diastolic blood pressure in response to exercise, with blood pressure remaining elevated, is associated with reductions of pain following exercise in ME/CFS, suggesting a role for the arterial baroreceptors in explaining dysfunctional exercise-induced analgesia in ME/CFS patients.

From BMC Medical Genetics (open access), 16 March 2017.

Clinically proven mtDNA mutations are not common in those with chronic fatigue syndrome

Elizna M. Schoeman (1, ^), Francois H. Van Der Westhuizen (2, ^), Elardus Erasmus(1, 3), Etresia van Dyk(1), Charlotte V. Y. Knowles(2), Shereen Al-Ali (4,5), Wan-Fai Ng (4, 6), Robert W. Taylor(3), Julia L. Newton(4,6) and Joanna L. Elson(1,3)
1. Centre for Human Metabolomics, North-West University
2. Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University
3. Institute of Genetic Medicine, Newcastle University
4. Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University
5. Department of Biology, College of Science, University of Basrah
6. Newcastle Hospitals NHS Foundation Trust
7. ^ contributed equally to the study



Chronic Fatigue Syndrome (CFS) is a prevalent debilitating condition that affects approximately 250,000 people in the UK. There is growing interest in the role of mitochondrial function and mitochondrial DNA (mtDNA) variation in CFS. It is now known that fatigue is common and often severe in patients with mitochondrial disease irrespective of their age, gender or mtDNA genotype. More recently, it has been suggested that some CFS patients harbour clinically proven mtDNA mutations.


MtDNA sequencing of 93 CFS patients from the United Kingdom (UK) and South Africa (RSA) was performed using an Ion Torrent Personal Genome Machine. The sequence data was examined for any evidence of clinically proven mutations, currently; more than 200 clinically proven mtDNA mutations point mutations have been identified.


We report the complete mtDNA sequence of 93 CFS patients from the UK and RSA, without finding evidence of clinically proven mtDNA mutations. This finding demonstrates that clinically proven mtDNA mutations are not a common element in the aetiology of disease in CFS patients. That is patients having a clinically proven mtDNA mutation and subsequently being misdiagnosed with CFS are likely to be rare.


The work supports the assertion that CFS should not be considered to fall within the spectrum of mtDNA disease. However, the current study cannot exclude a role for nuclear genes with a mitochondrial function, nor a role of mtDNA population variants in susceptibility to disease. This study highlights the need for more to be done to understand the pathophysiology of CFS.

From Fatigue: Biomedicine, Health & Behavior, 13 March 2017.

SEID, ME and CFS: Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria

Lily Chu(a), Jane L. Norris(a), Ian J. Valencia(b) and Jose G. Montoya(a)
a) Stanford ME/CFS Initiative, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA, USA;

b) Formerly of Stanford ME/CFS Initiative, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA, USA



Myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) remains undiagnosed in up to 91% of patients. Recently, the United States-based Institute of Medicine (IOM) developed new diagnostic criteria, naming it systemic exertion intolerance disease (SEID).


We examined how subjects fit SEID criteria and existing ME/CFS case definitions early in their illness.


A total of 131 subjects fitting 1994 Fukuda CFS criteria at the time of study recruitment completed a survey of symptoms they experienced during their first 6 months of illness.

Symptoms were drawn from SEID and existing criteria (1994 Fukuda, 2003 Canadian Consensus Criteria (CCC), and 2011 Myalgic Encephalomyelitis-International Consensus Criteria (ME-ICC)).

We calculated and compared the number/percentage of subjects fitting single or combinations of case definitions and the number/ percentage of subjects with SEID experiencing orthostatic intolerance (OI) and/or cognitive impairment.


At 6 months of illness, SEID criteria identified 72% of all subjects, similar to when Fukuda criteria (79%) or the CCC (71%) were used, whereas the ME-ICC selected for a significantly lower percentage (61%, p < .001).When severity/frequency thresholds were added to the Fukuda criteria, CCC and ME-ICC, the percentage of these subjects also fitting SEID criteria increased to 93%, 97%, and 95%.Eighty-seven percent of SEID subjects endorsed cognitive impairment and 92%, OI; 79% experienced both symptoms.CONCLUSIONSSEID criteria categorize a similar percentage of subjects as Fukuda criteria early in the course of ME/CFS and contain the majority of subjects identified using other criteria while requiring fewer symptoms.The advantage of SEID may be in its ease of use.

From the Journal of Translational Medicine, 16 March 2017.

Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study

Brett A. Lidbury (1,2), Badia Kita(3), Donald P. Lewis(4), Susan Hayward(5), Helen Ludlow(6), Mark P. Hedger(5) and David M. de Kretser(5,7)
1. Pattern Recognition and Pathology, Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University
2. The National Centre for Epidemiology and Public Health, The Research School of Population Health, ANU
3. Paranta Biosciences Limited
4. CFS Discovery, Donvale Medical Specialist Centre
5. The Hudson Medical Research Institute, Monash University
6. Centre for Proteins and Peptides, School of Life Sciences, Oxford Brookes University
7. Department of Anatomy and Developmental Biology, Monash University



Investigations of activin family proteins as serum biomarkers for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). CFS/ME is a disease with complex, wide-ranging symptoms, featuring persistent fatigue of 6 months or longer, particularly post exertion. No definitive biomarkers are available.


A cross-sectional, observational study of CFS/ME patients fulfilling the 2003 Canadian Consensus Criteria, in parallel with healthy non-fatigued controls, was conducted. Comparisons with a previously defined activin reference population were also performed. For the total study cohort the age range was 18–65 years with a female: male participant ratio of greater than 3:1. All participants were assessed via a primary care community clinic. Blood samples were collected for pathology testing after physical examination and orthostatic intolerance assessment. Cytokines, activin A, activin B and follistatin were also measured in sera from these samples. All data were compared between the CFS/ME and control cohorts, with the activins and follistatin also compared with previously defined reference intervals.


Serum activin B levels for CFS/ME participants were significantly elevated when compared to the study controls, as well as the established reference interval. Serum activin A and follistatin were within their normal ranges. All routine and special pathology markers were within the normal laboratory reference intervals for the total study cohort, with no significant differences detected between CFS/ME and control groups. Also, no significant differences were detected for IL-2, IL-4, IL-6, IL-10, IL-17A, TNF or IFN-gamma.


Elevated activin B levels together with normal activin A levels identified patients with the diagnostic symptoms of CFS/ME, thus providing a novel serum based test. The activins have multiple physiological roles and capture the diverse array of symptoms experienced by CFS/ME patients.

From the Journal of the Neurological Sciences, published online 22 February 2017.

Multimodal and simultaneous assessments of brain and spinal fluid abnormalities in chronic fatigue syndrome and the effects of psychiatric comorbidity.

Natelson BH, Mao X, Stegner AJ, Lange G, Vu D, Blate M, Kang G, Soto E, Kapusuz T, Shungu DC.


• Patients have higher brain ventricular lactate, more abnormal spinal fluids, lower brain GSH, and reduced cerebral blood flow than controls

• Psychiatric comorbidity does not influence any of these potential biological markers of CFS

• 50% of the patients had more than one of these abnormalities

• The subgroup of patients with brain abnormalities may have an underlying encephalopathy producing their illness


The purpose of this study was to investigate whether CFS patients without comorbid psychiatric diagnoses differ from CFS patients with comorbid psychiatric diagnoses and healthy control subjects in neuropsychological performance, the proportion with elevated spinal fluid protein or white cell counts, cerebral blood flow (CBF), brain ventricular lactate and cortical glutathione (GSH).

The results of the study did not show any differences in any of the outcome measures between CFS patients with and without psychiatric comorbidity, thus indicating that psychiatric status may not be an exacerbating factor
in CFS.

Importantly, significant differences were found between the pooled samples of CFS compared to controls. These included lower GSH and CBF and higher ventricular lactate and rates of spinal fluid abnormalities in CFS patients compared to healthy controls.

Thirteen of 26 patients had abnormal values on two or more of these 4 brain-related variables. These findings, which replicate the results of several of our prior studies, support the presence of a number of neurobiological and spinal fluid abnormalities in CFS. These results will lead to further investigation into objective biomarkers of the disorder to advance the understanding of CFS.

1 thought on “TGI Friday! Our weekly round-up of recently published research abstracts | 31 March 2017”

  1. Re: Clinically proven mtDNA mutations are not common in those with chronic fatigue syndrome.

    “However, the current study cannot exclude a role for nuclear genes with a mitochondrial function, nor a role of mtDNA population variants in susceptibility to disease.”

    This paper is important for ME research and ME Sufferers.

    It is not uncommon for sufferers of mtDNA disease, particularly those who develop symptoms in teenage/adult years (have a look on any mitochondrial disease sufferers support website) to report being diagnosed with ME/CFS (or for that matter a psychiatric conditions) before receiving a diagnosis of mtDNA disease. mtDNA disease is still very rare, although adult presentations of the illness are now being recognised far more than they used to be. So, of course, within the body of people suffering from ME/CFS, persons suffering from mtDNA disease would be uncommon while perhaps over-represented.

    No news there really. Although it is nice to think that a group of sufferers who suffer a very similar, often identical, spectrum of symptoms to ME/CFS sufferers can now expect even the NHS to diagnose their condition and offer them appropriate treatment for their condition or at least advice on what to buy! Note the ‘mitochondrial cocktail’ of dietary supplements often recommended and reported by sufferers to help, (such as; certain minerals, mega Vit B2 doses, other B Vitamins, Ubiquinol (reduced CoQ10), to name a few) are not prescribable on the NHS despite their relative cheapness.

    mtDNA is inherited almost exclusively from your mother. Occasionally a few mitochondria from your father may sneak in on fertilization of the ovum but, even then, these paternal mitochondria will make up around 5% or less of the total mitochondria in the fertilised cell that will become the whole person. Of the dozens of mitochondria in a fertilised cell, not all will be the same, and subsequent cell divisions can result in unequal distributions throughout tissues and systems of the different mtDNA ‘breeds’. This can lead to quite different symptom presentations and phenotypes in people carrying the same identified proven mtDNA mutations.

    For ME sufferers this highlights many things! Firstly, if you have a mother, maternal grandmother, siblings, maternal aunts/uncles, maternal aunt cousins or you are also the mother of a co-ME-sufferer, it is not unreasonable to ask to be screened for mtDNA disease.

    Secondly, the similarities between ME sufferers and mtDNA disease sufferers are strong enough to support the idea of exploring every other possible cause of mitochondrial dysfunction including; chronic and historical (particularly mitochondrial) toxin exposure, pan-vitamin/mineral/pseudovitamin/co-factor status, nuclear (chromosomal) mitochondrial function genes, mitochondrial biogenesis factors and pathways to name a few. As this paper also acknowledges, there may even be mitochondrial ‘breeds’ that leave certain individuals more susceptible to ME and more susceptible to certain symptoms of the condition compared to others.

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