2020 – Page 16 – American ME and CFS Society

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

Abstract:

Metabolic profiling studies have recently indicated dysfunctional mitochondria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This includes an impaired function of pyruvate dehydrogenase complex (PDC), possibly driven by serum factor(s), which leads to inadequate adenosine triphosphate generation and excessive lactate accumulation. A reminiscent energy blockade is likely to occur in primary biliary cholangitis (PBC), caused by anti-PDC autoantibodies, as recently proposed. PBC is associated with fatigue and post-exertional malaise, also signifying ME/CFS. We herein have investigated whether ME/CFS patients have autoreactive antibodies that could interfere with mitochondrial function.

We found that only 1 of 161 examined ME/CFS patients was positive for anti-PDC, while all PBC patients (15/15) presented significant IgM, IgG, and IgA anti-PDC reactivity, as previously shown. None of fibromyalgia patients (0/14), multiple sclerosis patients (0/29), and healthy blood donors (0/44) controls showed reactivities. Anti-mitochondrial autoantibodies (inner and outer membrane) were negative in ME/CFS cohort. Anti-cardiolipin antibody levels in patients did not differ significantly from healthy blood donors.

In conclusion, the impaired mitochondrial/metabolic dysfunction, observed in ME/CFS, cannot be explained by presence of circulating autoantibodies against the tested mitochondrial epitopes.

Source: Nilsson I, Palmer J, Apostolou E, Gottfries CG, Rizwan M, Dahle C, Rosén A. Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Not Due to Anti-mitochondrial Antibodies. Front Med (Lausanne). 2020 Mar 31;7:108. doi: 10.3389/fmed.2020.00108. eCollection 2020. https://www.frontiersin.org/articles/10.3389/fmed.2020.00108/full (Full text)

Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by medically unexplained debilitating fatigue with suggested altered immunological state. Our study aimed to explore peripheral blood mononuclear cells (PBMCs) for microRNAs (miRNAs) expression in ME/CFS subjects under an exercise challenge. The findings highlight the immune response and inflammation links to differential miRNA expression in ME/CFS.

The present study is particularly important in being the first to uncover the differences that exist in miRNA expression patterns in males and females with ME/CFS in response to exercise. This provides new evidence for the understanding of differential miRNA expression patterns and post-exertional malaise in ME/CFS.

We also report miRNA expression pattern differences associating with the nutritional status in individuals with ME/CFS, highlighting the effect of subjects’ metabolic state on molecular changes to be considered in clinical research within the NINDS/CDC ME/CFS Common Data Elements.

The identification of gender-based miRNAs importantly provides new insights into gender-specific ME/CFS susceptibility and demands exploration of sex-suited ME/CFS therapeutics.

Source: Cheema AK, Sarria L, Bekheit M, Collado F, Almenar-Pérez E, Martín-Martínez E, Alegre J, Castro-Marrero J, Fletcher MA, Klimas NG, Oltra E, Nathanson L. Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS. J Cell Mol Med. 2020 Apr 14. doi: 10.1111/jcmm.15260. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32291908

Acupuncture for Chronic Fatigue Syndrome: An Overview of Systematic Reviews

Abstract:

OBJECTIVE: To evaluate the quality of the existing studies and summarize evidence of important outcomes of meta-analyses/systematic reviews (MAs/SRs) of CFS.

METHODS: Potentially eligible studies were searched in the following electronic databases from inception to 1 September, 2019: Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), Web of Science, Embase, PubMed and Cochrane Library. Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence. The methodological quality of the literature was evaluated by A Measure Tool to Assess Systematic Reviews-2 (AMSTAR-2) and the quality of the report was assessed by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The intra-class correlation coefficient was used to assess the consistency of the reviewers, with an overall intraclass correlation coefficient score of 0.967.

RESULTS: Ten MAs/SRs were included. The overall conclusions were that acupuncture had good safety and efficacy in the treatment of CFS, but some of these results were contradictory. The GRADE indicated that out of the 17 outcomes, high-quality evidence was provided in 0 (0%), moderate in 3 (17.65%), low in 10 (58.82%), and very low in 4 (23.53%). The results of AMSTAR-2 showed that the methodological quality of all included studies was critically low. The PRISMA statement revealed that 8 articles (80%) were in line with 20 of the 27-item checklist, and 2 articles (20%) matched with 10-19 of the 27 items.

CONCLUSION: We found that acupuncture on treating CFS has the advantage for efficacy and safety, but the quality of SRs/MAs of acupuncture for CFS need to be improved.

Source: Yin ZH, Wang LJ, Cheng Y, Chen J, Hong XJ, Zhao L, Liang FR. Acupuncture for Chronic Fatigue Syndrome: An Overview of Systematic Reviews. Chin J Integr Med. 2020 Apr 1. doi: 10.1007/s11655-020-3195-3. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32279152

Post-exertional Malaise in People With Chronic Cancer-Related Fatigue

Abstract:

CONTEXT: Cancer-related fatigue (CRF) is a distressing and persistent sense of tiredness or exhaustion that interferes with usual functioning. Chronic CRF continues for months after curative cancer treatment is complete. Post-exertional malaise (PEM) is a worsening of symptoms after physical or mental activity, with limited investigations in people with chronic CRF.

OBJECTIVES: The purpose of this study was to identify and describe self-reported incidences of PEM in people with chronic CRF.

METHODS: Participants (n = 18) were eligible if they scored ≤34 on the Functional Assessment of Chronic Illness Therapy-Fatigue scale and had a cancer-related onset of fatigue. Participants completed a brief questionnaire to assess PEM during a six-month time frame (the DePaul Symptom Questionnaire-PEM). In addition, a maximal exercise test was used to investigate self-reported symptom exacerbation (via an open-ended questionnaire) after strenuous physical exertion.

RESULTS: On the DePaul Symptom Questionnaire-PEM, three participants met previously defined scoring criteria, which included experiencing moderate to very severe symptoms at least half of the time, worsening of fatigue after minimal effort, plus a recovery duration of >24 hours. Content analysis of responses to open-ended questionnaires identified five people who experienced a delayed recovery and symptoms of PEM after maximal exercise.

CONCLUSION: A subset of people with chronic CRF (up to 33% in this sample) may experience PEM. Exercise specialists and health care professionals working with people with chronic CRF must be aware that PEM may be an issue. Symptom exacerbation after exercise should be monitored, and exercise should be tailored and adapted to limit the potential for harm.

Source: Twomey R, Yeung ST, Wrightson JG, Millet GY, Culos-Reed SN. Post-exertional Malaise in People With Chronic Cancer-Related Fatigue. J Pain Symptom Manage. 2020 Feb 24. pii: S0885-3924(20)30098-1. doi: 10.1016/j.jpainsymman.2020.02.012. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32105793

Connectivity differences between Gulf War Illness (GWI) phenotypes during a test of attention

Abstract:

One quarter of veterans returning from the 1990–1991 Persian Gulf War have developed Gulf War Illness (GWI) with chronic pain, fatigue, cognitive and gastrointestinal dysfunction. Exertion leads to characteristic, delayed onset exacerbations that are not relieved by sleep. We have modeled exertional exhaustion by comparing magnetic resonance images from before and after submaximal exercise.

One third of the 27 GWI participants had brain stem atrophy and developed postural tachycardia after exercise (START: Stress Test Activated Reversible Tachycardia). The remainder activated basal ganglia and anterior insulae during a cognitive task (STOPP: Stress Test Originated Phantom Perception). Here, the role of attention in cognitive dysfunction was assessed by seed region correlations during a simple 0-back stimulus matching task (“see a letter, push a button”) performed before exercise. Analysis was analogous to resting state, but different from psychophysiological interactions (PPI).

The patterns of correlations between nodes in task and default networks were significantly different for START (n = 9), STOPP (n = 18) and control (n = 8) subjects. Edges shared by the 3 groups may represent co-activation caused by the 0-back task. Controls had a task network of right dorsolateral and left ventrolateral prefrontal cortex, dorsal anterior cingulate cortex, posterior insulae and frontal eye fields (dorsal attention network). START had a large task module centered on the dorsal anterior cingulate cortex with direct links to basal ganglia, anterior insulae, and right dorsolateral prefrontal cortex nodes, and through dorsal attention network (intraparietal sulci and frontal eye fields) nodes to a default module. STOPP had 2 task submodules of basal ganglia–anterior insulae, and dorsolateral prefrontal executive control regions. Dorsal attention and posterior insulae nodes were embedded in the default module and were distant from the task networks.

These three unique connectivity patterns during an attention task support the concept of Gulf War Disease with recognizable, objective patterns of cognitive dysfunction.

Source: Clarke T, Jamieson JD, Malone P, Rayhan RU, Washington S, VanMeter JW, et al. (2019) Connectivity differences between Gulf War Illness (GWI) phenotypes during a test of attention. PLoS ONE 14(12): e0226481. https://doi.org/10.1371/journal.pone.0226481 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226481 (Full text)

Please Help David Tuller, Our Champion!

David Tuller’s fundraiser is now live! Tuller has been tireless in his battle against the GET/CBT ideological onslaught! He has much more work to do and he needs our support.

Tuller has written more than seventy-five posts on Vincent Racaniello’s Virology Blog, spanning seven years. His articles comprise a full history of how the PACE trial was used to mislead health care providers into thinking ME/CFS could be cured with “a walk and a talk.” Tuller has taken on some of the authors of the PACE study and, despite threats from them, has continued to challenge their findings.

This year, Tuller will be looking at intersections between the pandemic and ME, such as concerns about whether some COVID-19 patients will develop an ME-like disease. He will be keeping an eye out for new bad research (think: CBT and GET) and keeping an eye on goings-on at the CDC, the NIH and elsewhere.

Last year, Tuller successfully raised money through Crowdrise in order to continue investigating and blogging about the PACE trial. The funds went to the School of Public Health at the University of California, Berkeley, which created a position for Tuller to continue his investigative work. Now, a year later, the funds have run out, and Tuller has to depend on the generosity of our community to continue his work.

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The effect of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function

Abstract:

Myalgic encephalomyelitis/ Chronic fatigue syndrome (ME/CFS) has been associated with abnormalities in mitochondrial function. In this study we have analysed previous bioenergetics data in peripheral blood mononuclear cells (PBMCs) using new techniques in order to further elucidate differences between ME/CFS and healthy control cohorts. We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs.

Both ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort. This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction. Equations devised by another research group have enabled us to calculate ATP-linked respiration rates and glycolytic parameters. Parameters of glycolytic function were calculated by taking into account respiratory acidification.

This revealed severely affected ME/CFS patients to have higher rates of respiratory acidification and showed the importance of accounting for respiratory acidification when calculating parameters of glycolytic function. Analysis of previously published glycolysis data, after taking into account respiratory acidification, showed severely affected patients have reduced glycolysis compared to moderately affected patients and healthy controls. Rates of ATP-linked respiration were also calculated and shown to be lower in both ME/CFS cohorts.

This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotype.

Source: Tomas C, Elson JL, Strassheim V, Newton JL, Walker M. The effect of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function. PLoS One. 2020 Apr 10;15(4):e0231136. doi: 10.1371/journal.pone.0231136. eCollection 2020. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231136 (Full study)

Emotional Awareness Correlated With Number of Awakenings From Polysomnography in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-A Pilot Study

Abstract:

INTRODUCTION: Unrefreshing sleep is one of the diagnostic criteria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which could be explained by sleep disorders, for example obstructive sleep apnea, reported in our previous study with polysomnography. Our previous findings also indicate difficulties in emotional regulation when measuring alexithymia by TAS-20 (Toronto Alexithymia Scale) and level of emotional awareness by LEAS (Level of Emotional Awareness Scale) in ME/CFS patients. However, the reasons for this are unknown. The purpose of this study was to investigate correlations between data from subjective emotional regulation and polysomnography.

METHODS: Twenty-three ME/CFS patients (5 men and 18 women) of mean age 43, and 30 matched healthy controls (9 males and 21 women) of mean age 45, filled in TAS-20, LEAS, and Hospital Depression and Anxiety Scale (HADS). A polysomnography was performed on patients but not on healthy controls. Thus, values of normal population were used for sleep evaluation in ME/CFS patients.

RESULT: There were significant differences between patients and controls in several aspects of emotional regulation, for example LEAS-self and LEAS-total. Seventy percent of the patients had increased numbers of awakenings (shifts from any sleep stage to awake), 22% had obstructive sleep apneas, and 27% had periodic limb movements. Correlation analysis showed that number of awakenings significantly correlated with LEAS-self and LEAS-total, p < 0.01, respectively. There were no other significant correlations.

CONCLUSION: This pilot study demonstrated significant correlations between reduced emotional awareness and number of awakenings in polysomnography. Future studies with larger cohorts need to be conducted.

Source: Bileviciute-Ljungar I, Friberg D. Emotional Awareness Correlated With Number of Awakenings From Polysomnography in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-A Pilot Study. Front Psychiatry. 2020 Mar 26;11:222. doi: 10.3389/fpsyt.2020.00222. eCollection 2020. https://www.ncbi.nlm.nih.gov/pubmed/32273857

The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE)

Abstract:

We have developed a Europe-wide approach to investigating the economic impact of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), facilitating acquisition of information on the economic burden of ME/CFS, and international comparisons of economic costs between countries. The economic burden of ME/CFS in Europe appears large, with productivity losses most significant, giving scope for substantial savings through effective prevention and treatment.

However, economic studies of ME/CFS, including cost-of-illness analyses and economic evaluations of interventions, are problematic due to different, arbitrary case definitions, and unwillingness of doctors to diagnose it. We therefore lack accurate incidence and prevalence data, with no obvious way to estimate costs incurred by undiagnosed patients. Other problems include, as for other conditions, difficulties estimating direct and indirect costs incurred by healthcare systems, patients and families, and heterogeneous healthcare systems and patterns of economic development across countries.

We have made recommendations, including use of the Fukuda (CDC-1994) case definition and Canadian Consensus Criteria (CCC), a pan-European common symptom checklist, and implementation of prevalence-based cost-of-illness studies in different countries using an agreed data list. We recommend using purchasing power parities (PPP) to facilitate international comparisons, and EuroQol-5D as a generic measure of health status and multi-attribute utility instrument to inform future economic evaluations in ME/CFS.

Source: Pheby DFH, Araja D, Berkis U, Brenna E, Cullinan J, de Korwin JD, Gitto L, Hughes DA, Hunter RM, Trepel D, Wang-Steverding X. The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE). Healthcare (Basel). 2020 Apr 7;8(2). pii: E88. doi: 10.3390/healthcare8020088. https://www.ncbi.nlm.nih.gov/pubmed/32272608

HERV-K and HERV-W transcriptional activity in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases.

METHODS: Here the expression of Endogenous retroviruses K and W (HERV-K and HERV-W) was determined in blood from moderately and severely affected ME/CFS patients through real time PCR.

RESULTS: HERV-K was overexpressed only in moderately affected individuals but HERV-W showed no difference.

CONCLUSIONS: This is the first report about HERV-K differential expression in moderate ME/CFS. Although the relationship between HERVs and ME/CFS has yet to be proven, the observation of this phenomenon deserves further attention.

Source: Rodrigues LS, da Silva Nali LH, Leal COD, Sabino EC, Lacerda EM, Kingdon CC, Nacul L, Romano CM. HERV-K and HERV-W transcriptional activity in myalgic encephalomyelitis/chronic fatigue syndrome. Auto Immun Highlights. 2019 Nov 15;10(1):12. doi: 10.1186/s13317-019-0122-8. eCollection 2019 Dec. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065355/ (Full text)