Welcome to the 47th Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles.

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A new paper from Prof Paul Fisher’s research team at La Trobe University identifying a promising diagnostic biomarker has drawn huge interest from the scientific community.

Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome’ published in the International Journal for Molecular Sciences on February 8, has become the most downloaded paper in its area for the first quarter of 2020, with more than 1650 unique views. The study identified three different tests with the potential to be developed as blood-based biomarkers for ME/CFS. Promisingly, the three tests in combination “provided a cell-based biomarker with sensitivity and specificity approaching 100% in our sample”.


Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy


Authors: Mueller, C., Lin, J.C., Sheriff, S., Maudsley, A.A., Younger, J.W.
Link:  https://www.ncbi.nlm.nih.gov/pubmed/30617782

This study used magnetic resonance spectroscopy (MRS) in an attempt to assess possible neuroinflammation in ME/CFS. The study examined brain metabolites commonly associated with inflammation, and brain temperature, which can be seen as a proxy measure for inflammation. While MRS has been used to study the brain in ME/CFS before, this was the first study to use it to examine the whole brain.

The participants included 15 female ME/CFS patients (diagnosed according to the Fukuda criteria, and the revised Canadian Consensus Criteria) and 15 matched controls. 

There were significant differences in metabolite ratios between the groups in several areas of the brain. In several of these areas of the brain, there were also significant positive correlations between the metabolite and self-reported fatigue in the patient group. ME/CFS patients also had a higher brain temperature than matched controls, and this was independent of total body temperature and regional blood flow.

These differences in metabolites and temperature were evident across large regions of the brain, suggesting that ME/CFS involves pathophysiological processes affecting the whole brain rather than discrete regions, and supports the notion that chronic, low-level neuroinflammation is present in ME/CFS.

The authors acknowledge that the small sample size was a limitation of this study and advise that the results should be interpreted with caution until confirmed with a larger sample


Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome.

Author: Jammes,Y., Adjriou, N., Kipson, N., Criado, C., Charpin, C., Rebaudet, S., Stavris, C., Guieu, R., Fenouillet, E., Retornaz, F.
Link: https://www.ncbi.nlm.nih.gov/pubmed/32306967

The authors of this study note that ME/CFS patients exhibit altered muscle membrane excitability during exercise as well as increased oxidative stress. The aim of this study was to test their hypothesis that oxidative stress could be causing muscle dysfunction in ME/CFS.
 
The study sample included a total of 72 patients (diagnosed according to both the Canadian Consensus Criteria and Institute of Medicine criteria). Participants underwent a maximal exercise challenge, and M-waves were measured during exercise and at rest. Oxidative stress plasma markers and plasma potassium concentration were also measured.

The authors found that there were two subgroups of patients: one subgroup (39 patients) which had M-wave alterations during and after exercise, as well as increased resting values of oxidative stress plasma markers and decreased exercise-induced potassium outflow. The second subgroup (the remaining 33 ME/CFS patients) had no M-wave alterations and lower baseline oxidative stress markers. The authors note that, in contrast to the first subgroup, which had no comorbidities, half the subjects in the second subgroup had comorbidities which could contribute to physical fatigue. 
 
In support of their hypothesis, high oxidative stress markers were associated with alterations in M-waves during both exercise and rest, but not in all ME/CFS patients. The authors conclude that levels of an oxidative stress marker could be used to differentiate these two patient groups and recommend further research to understand the presence or absence of muscle fatigue in ME/CFS patients.


Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Not Due to Anti-mitochondrial Antibodies


Author: Nilsson, I., Palmer, J., Apostolou, E., Gottfries, C.G., Rizwan, M., Dahle, C., Rosén, A.
Link: https://www.frontiersin.org/articles/10.3389/fmed.2020.00108/full

Dysfunctional mitochondria in ME/CFS has been strongly suggested in recent metabolic profiling studies. One possible mechanism involves impaired function of the pyruvate dehydrogenase complex (PDC), which leads to inadequate adenosine triphosphate (ATP) generation and excessive lactate accumulation (potentially explaining PEM).

This energy blockade is similar to what is thought to be occurring in primary biliary cholangitis (PBC). In PBC, energy production is thought to be inhibited by anti-PDC autoantibodies. Therefore, this study aimed to investigate the presence of autoreactive antibodies in ME/CFS patients, which may interfere with mitochondrial function. Plasma samples were analysed from patients diagnosed with ME/CFS (125), fibromyalgia (14), ME/CFS & fibromyalgia (36), PBC (15), multiple sclerosis (29) as well as healthy blood donor controls (61). All ME/CFS patients in this study were diagnosed acccording to the Canadian Consensus Criteria. 

Only 1 ME/CFS patient out of the 161 studied was positive for the PDC autoantibodies, compared with the 15 PBC patients who all tested positive. None of the fibromyalgia, multiple sclerosis or healthy controls were positive for the PDC autoantibodies. In addition, 29 ME/CFS were randomly chosen from the sample and tested for the presence of anti-mitochondrial antibodies. All were negative. Finally, there was no significant difference found in anti-cardiolipin antibody (IgG, IgM, IgA) levels in the plasma of ME/CFS or FM patients compared with the healthy controls.

Due to these findings, the authors conclude that mitochondrial dysfunction seen in ME/CFS is not due to the same mechanism thought to be found in PBC, nor due to anti-mitochondrial autoantibodies.


Confined: Facing life in confinement after COVID-19

In light of current COVID-19 self-isolation requirements and travel restrictions, this week’s SBS Insight episode interviewed people who have had experience with long-term confinement prior to the COVID-19 pandemic.

In the show 45-year-old Ricky Buchanan described her experience of being homebound and bedridden for almost 20 years with severe ME/CFS. She explained how COVID-19 has provided many opportunities - such as access to telehealth and live concerts – things that have not been previously available to her.


Ricky’s 3-minute segment can be viewed here: https://www.sbs.com.au/news/insight/tvepisode/confined

The full episode can be viewed here: https://www.sbs.com.au/ondemand/video/1730810435973