Research Digest 26/03/21

Welcome to the 66th 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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Are circulating fibroblast growth factor 21 and N-terminal prohormone of brain natriuretic peptide promising novel biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome?

Authors: Domingo JC, Cordobilla B, Ferrer R, Giralt M, Alegre-Martin J, Castro-Marrero J (Vall d’Hebron Institut de Recerca, Spain)
Publication: Antioxidants & Redox Signaling
Oxidative stress and inflammation are thought to be common mediators in the pathobiology of ME/CFS. Protein fibroblast growth factor 21 (FGF21) and protein N-terminal prohormone of brain natriuretic peptide (NT-proBNP) have recently been shown to be robust respective markers of oxidative stress and inflammation in other diseases. This study aimed to investigate the roles of FGF21 and NT-proBNP in ME/CFS.
21 ME/CFS patients (meeting the Fukuda criteria) and 20 matched healthy controls completed a series of self-reported questionnaires relating to their current health status. Patients also provided a blood sample on which a series of biochemical tests were performed to measure oxidative stress markers, circulating cytokines, and circulating FGF21 and NT-proBNP.
The authors confirmed the findings of others that, compared to healthy controls, ME/CFS patients indeed experience an altered state of oxidative stress and low-grade systemic inflammation. Further to this, they show that ME/CFS patients have higher levels of circulating FGF21 and NT-proBNP. The observed increase in NT-proBNP in ME/CFS patients had a significant positive correlation with the markers of inflammation (cytokines). No correlations were found for FGF21.
The authors conclude that more research is needed in order to explore the utility of FGF21 and NT-proBNP as promising novel and reliable diagnostic biomarkers for ME/CFS.

Chronic fatigue syndrome: Abnormally fast muscle fiber conduction in the membranes of motor units at a low static force load
Authors: Klaver-Krol EG, Hermens HJ, Vermeulen RC, Klaver MM, Luyten H, Henriquez NR, Zwarts MJ (Academic Center for Epileptology Kempenhaeghe, Netherlands)
Publication: Clinical Neurophysiology
Previous studies have shown that muscle fiber conduction velocity (CV) is increased in the non-painful muscles of patients with fibromyalgia (FM). Given the overlapping of symptoms between FM and ME/CFS patients (particularly muscle fatigue and pain), this study aimed to determine whether ME/CFS patients also show CV abnormalities.
22 female FM patients (ACR criteria but not the Fukuda criteria), 25 female ME/CFS patients (Fukuda criteria), and 21 female healthy control participants were recruited for this study. All patients underwent surface electromyography (sEMG) of the biceps muscle when increasing levels of force (0%, 5%, 10%, and 20% of maximum voluntary contraction) were applied to the testing arm. The mean CV and motor unit potential (MUP) velocities were measured.

The study found that as a moderate level force was applied, the CV of ME/CFS patients was seen to increase to an abnormally high level. In contrast, the same levels of force resulted in a slight increase in CV in controls and no increase at all in FM patients (Fig 1).
The authors conclude that their findings highlight the abnormal behaviour of the muscle membranes in response to an applied load in female ME/CFS patients.
Figure 1 | Muscle fiber conduction velocity (CV) measurements in response to an increasing force load – unloaded 0%, and loaded by 5%, 10% and 20% of the maximum voluntary contraction force (MVC). Dash-dot line = CFS subjects, dashed line = FM subjects and solid line = Controls.
Myalgic encephalomyelitis/chronic fatigue syndrome: The human herpesviruses are back!
Authors: Ariza MA (Ohio State University, USA)
Publication: Biomolecules
This paper reviewed evidence of the involvement of human herpesviruses (HHVs) in ME/CFS. While in the past these viruses have been hypothesised to play a role in ME/CFS, the author acknowledged that inconsistent results due to small sample sizes, heterogenous patient cohorts, inadequate study controls and inconsistent methodologies have led this hypothesis to be discarded. However, more advanced techniques have suggested that some HHVs, particularly Epstein-Barr virus (EBV) and HHV-6, could contribute to ME/CFS for a subgroup of patients.
The author reviewed evidence suggesting that abortive lytic replication (expression of lytic genes but without production of infective viral cells) occurs in EBV, and outlined the impact of EBV on the immune system in ME/CFS. The author proposed a hypothesis model by which proteins released during abortive lytic replication of EBV could trigger ME/CFS in a subgroup of patients, resulting in the immune disruption observed in ME/CFS.
The author concludes that further studies are needed using advanced serological approaches to study the role of abortive lytic replication of EBV and the reactivation of HHVs in ME/CFS.
Experiences of living with severe chronic fatigue syndrome/myalgic encephalomyelitis

Authors: Strassheim V, Newton JL, Collins T (Northumbria University, UK)
Publication: Healthcare
People with severe ME/CFS are often excluded from research, as their limitations prevent them from engaging in research and healthcare. This qualitative study aimed to explore experiences of people living with severe ME/CFS, the factors which may put someone at risk of developing severe ME/CFS, as well as ways for research and healthcare sectors to better engage with individuals living with severe ME/CFS.
Five people with medical or self-reported ME/CFS who were wheelchair, house- or bedbound were interviewed using a semi-structured format. Each interview lasted 1-2 hours and all interviews were conducted by the same researcher.
Thematic analysis identified three themes: lived experience, challenges to everyday life and management. While the lived experience of each participant varied significantly and they became ill at different stages of life, they all reported a pre-existing vulnerability to becoming ill. The challenges to everyday life were divided into those intrinsic to the individual (to do with their own physical, mental and emotional capacity) and those extrinsic to the individual (factors outside the individual). While participants engaged in a range of strategies to manage their condition, these were impacted by their own capacity and the services and resources accessible to them.
All the participants had deteriorated over time with needs exceeding the available resources, limiting the opportunity for improvement. All had experienced poor or limited interactions with health professionals, and many relied heavily on the internet for management strategies.
The authors noted that healthcare systems are not tailored to meet the needs of people with severe ME/CFS, and instead leave patients trying to adjust to the system. They recommend that home visits, telephone consultations and even inpatient rehabilitation in specialist services be more widely adopted to better meet the needs of these patients.

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