Tag: 2021

Radiation exposure and mitochondrial insufficiency in chronic fatigue and immune dysfunction syndrome

Abstract:

Chronic fatigue and Immune Dysfunction Syndrome (CFIDS) is a heterogeneous disease that may be promoted by various environmental stressors, including viral infection, toxin uptake, and ionizing radiation exposure. Previous studies have identified mitochondrial dysfunction in CFIDS patients, including modulation of mitochondrial respiratory chain activity, deletions in the mitochondrial genome, and upregulation of reactive oxygen species (ROS). This paper focuses on radiation effects and hypothesizes that CFIDS is primarily caused by stressor-induced mitochondrial metabolic insufficiency, which results in decreased energy production and anabolic metabolites required for normal cellular metabolism. Furthermore, tissues neighbouring or distant from directly perturbed tissues compensate for this dysfunction, which causes symptoms associated with CFIDS.

This hypothesis is justified by reviewing the links between radiation exposure and CFIDS, cancer, immune dysfunction, and induction of oxidative stress. Moreover, the relevance of mitochondria in cellular responses to radiation and metabolism are discussed and putative mitochondrial biomarkers for CFIDS are introduced. Implications for diagnosis are then described, including a potential urine assay and PCR test for mitochondrial genome mutations. Finally, future research needs are offered with an emphasis on where rapid progress may be made to assist the afflicted.

Source: Rusin A, Li M, Cocchetto A, Seymour C, Mothersill C. Radiation exposure and mitochondrial insufficiency in chronic fatigue and immune dysfunction syndrome. Med Hypotheses. 2021 Jul 27;154:110647. doi: 10.1016/j.mehy.2021.110647. Epub ahead of print. PMID: 34358921. https://pubmed.ncbi.nlm.nih.gov/34358921/

Diffusion tensor imaging reveals neuronal microstructural changes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) patients suffer from a variety of physical and neurological complaints indicating the central nervous system plays a role in ME/CFS pathophysiology. Diffusion tensor imaging (DTI) has been used to study microstructural changes in neurodegenerative diseases. In this study, we evaluated DTI parameters to investigate microstructural abnormalities in ME/CFS patients.

We estimated DTI parameters in 25 ME/CFS patients who met Fukuda criteria (ME/CFSFukuda ), 18 ME/CFS patients who met International Consent Criteria (ICC) (ME/CFSICC ) only, and 26 healthy control subjects (HC). In addition to voxel-based DTI-parameter group comparisons, we performed voxel-based DTI-parameter interaction-with-group regressions with clinical and autonomic measures to test for abnormal regressions.

Group comparisons between ME/CFSICC and HC detected significant clusters (a) with decreased axial diffusivity (p=0.001) and mean diffusivity (p=0.01) in the descending cortico-cerebellar tract in the midbrain and pons, and (b) with increased transverse diffusivity in the medulla. The mode of anisotropy was significantly decreased (p=0.001) in a cluster in the superior longitudinal fasciculus region. Voxel-based group comparisons between ME/CFSFukuda and HC did not detect significant clusters. For ME/CFSICC and HC, DTI parameter interaction-with-group regressions were abnormal for the clinical measures of information processing score, SF36 physical, sleep disturbance score, and respiration rate in both grey and white matter regions.

Our study demonstrated that DTI parameters are sensitive to microstructural changes in ME/CFSICC and could potentially act as an imaging biomarker of abnormal pathophysiology in ME/CFS. The study also shows that strict case definitions are essential in investigation of the pathophysiology of ME/CFS.

Source: Thapaliya K, Marshall-Gradisnik S, Staines D, Barnden L. Diffusion tensor imaging reveals neuronal microstructural changes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Eur J Neurosci. 2021 Aug 6. doi: 10.1111/ejn.15413. Epub ahead of print. PMID: 34355438. https://pubmed.ncbi.nlm.nih.gov/34355438/

A common language for Gulf War Illness (GWI) research studies: GWI common data elements

Abstract

Aims: The Gulf War Illness programs (GWI) of the United States Department of Veteran Affairs and the Department of Defense Congressionally Directed Medical Research Program collaborated with experts to develop Common Data Elements (CDEs) to standardize and systematically collect, analyze, and share data across the (GWI) research community.

Main methods: A collective working group of GWI advocates, Veterans, clinicians, and researchers convened to provide consensus on instruments, case report forms, and guidelines for GWI research. A similar initiative, supported by the National Institute of Neurologic Disorders and Stroke (NINDS) was completed for a comparative illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and provided the foundation for this undertaking. The GWI working group divided into two sub-groups (symptoms and systems assessment). Both groups reviewed the applicability of instruments and forms recommended by the NINDS ME/CFS CDE to GWI research within specific domains and selected assessments of deployment exposures. The GWI CDE recommendations were finalized in March 2018 after soliciting public comments.

Key findings: GWI CDE recommendations are organized in 12 domains that include instruments, case report forms, and guidelines. Recommendations were categorized as core (essential), supplemental-highly recommended (essential for specified conditions, study types, or designs), supplemental (commonly collected, but not required), and exploratory (reasonable to use, but require further validation). Recommendations will continually be updated as GWI research progresses.

Significance: The GWI CDEs reflect the consensus recommendations of GWI research community stakeholders and will allow studies to standardize data collection, enhance data quality, and facilitate data sharing

Source: Cohen DE, Sullivan KA, McNeil RB, Klimas NG; Gulf War Illness Common Data Elements Working Group; Symptoms Assessment Working Group, McNeil R, Ashford W, Bested A, Bunker J, Cheema A, Cohen D, Cook D, Cournoyer J, Craddock T, Golier J, Hardie A, Helmer D, Lindheimer JB, Lloyd PJ, Kerr K, Krengel M, Nadkarni S, Nugent S, Paris B, Reinhard M, Rumm P, Schneiderman A, Sims KJ, Steele L, Turner M; Systems Assessment Working Group, Sullivan K, Abdullah L, Abreu M, Abu-Donia M, Aenlle K, Arocho J, Balbin E, Baraniuk J, Block K, Block M, DeBeer B, Engdahl B, Filipov N, Fletcher MA, Kalasinsky V, Kokkotou E, Lidie K, Little D, Loging W, Morris M, Nathanson L, Nichols MD, Pasinetti G, Shungu D, Waziry P, VanLeeuwen J, Younger J; GWI CDE Administrative Team, Klimas N. A common language for Gulf War Illness (GWI) research studies: GWI common data elements. Life Sci. 2021 Aug 2:119818. doi: 10.1016/j.lfs.2021.119818. Epub ahead of print. PMID: 34352259. https://pubmed.ncbi.nlm.nih.gov/34352259/

The Importance of Listening in Treating Invisible Illness and Long-Haul COVID-19

Abstract:

Primary and specialty care clinicians strive to base diagnoses and treatment on specific, measurable abnormalities. Yet those with invisible, controversial illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often have symptoms not explained by standard laboratory values. For instance, one of the cardinal features of ME/CFS is postexertional malaise, the exacerbation of symptoms-fatigue, pain, cognitive dysfunction-following exertion, which contradicts studies showing the health benefits of exercise. In these cases, overly physicalist approaches to caring for patients are not likely to be helpful, and a clinician’s willingness to listen to a patient’s experience of illness becomes essential.

Source: Wall D. The Importance of Listening in Treating Invisible Illness and Long-Haul COVID-19. AMA J Ethics. 2021 Jul 1;23(7):E590-595. doi: 10.1001/amajethics.2021.590. PMID: 34351274. https://pubmed.ncbi.nlm.nih.gov/34351274/

Questioning Biomedicine’s Privileging of Disease and Measurability

Abstract:

Within biomedicine, the diagnosis of disease is often privileged over a patient’s experience of illness. Yet up to 30% of primary care visits might be attributable to persistent illness without a diagnosed disease, including functional somatic syndromes like fibromyalgia and chronic fatigue syndrome. When clinicians are unable to diagnose disease or correlate symptoms with measurable changes in biomarkers, patients experiencing such an illness are at increased risk for suspicion, misplaced questioning, or having their motives misinterpreted through damaging social and cultural narratives about gender, race, ethnicity, socioeconomic status, or disability. Adhering strictly to a biomedical model of thinking about disease and diagnosis can prevent clinicians from empathically engaging with patients and helping them navigate their illness experiences.

Source: Kroll C. Questioning Biomedicine’s Privileging of Disease and Measurability. AMA J Ethics. 2021 Jul 1;23(7):E537-541. doi: 10.1001/amajethics.2021.537. PMID: 34351263. https://pubmed.ncbi.nlm.nih.gov/34351263/

A Womanist Approach to Caring for Patients With Empirically Unverifiable Symptoms

Abstract:

Some illnesses and diseases are not apparent to onlookers. Conditions like chronic fatigue syndrome, fibromyalgia, multiple sclerosis, postconcussive syndrome, endometriosis, and many psychiatric illnesses, for example, have symptoms that are not easily or at all measurable. Both clinicians and health care systems, however, tend to focus exclusively on measurability, which can result in evidentiary overreliance and undervaluation of experience narratives and can have clinically, ethically, and socially important consequences for patients with these conditions.

Source: Gatison AM. A Womanist Approach to Caring for Patients With Empirically Unverifiable Symptoms. AMA J Ethics. 2021 Jul 1;23(7):E519-523. doi: 10.1001/amajethics.2021.519. PMID: 34351260. https://pubmed.ncbi.nlm.nih.gov/34351260/

Human herpesvirus 6 infection and risk of Chronic fatigue syndrome: a systematic review and meta-analysis

Abstract:

Introduction: Chronic fatigue syndrome (CFS) is a neurological disease that is accompanied by excessive fatigue or tiredness. There are several reports confirming the association between human herpesvirus 6 (HHV-6) infection and CFS illness. This systematic review and meta-analysis was performed to integrate the information of published studies with regard to this association until May 2021.

Methods: The literature search was based on keywords including “chronic fatigue syndrome and HHV 6,” “chronic fatigue syndrome and HHV-6,” “chronic fatigue syndrome and HHV6,” “chronic fatigue syndrome and Herpes virus 6,” and “chronic fatigue syndrome and Herpesvirus6” in MEDLINE (PubMed), Web of Science, and EMBASE.

Results: The literature search identified 17 studies to be included in the systematic review and 11 studies in meta-analysis. The symmetry funnel plot and Egger’s test (p value = 0.2) identified no publication bias among studies. Moreover, the low level of I2 revealed homogeneity across studies.

Discussion: In conclusion, the association between the HHV-6 infection and CFS incidence was substantiated. However, the results of this study also suggest that further comprehensive studies are needed to solidify the association between HHV-6 and CFS. Future studies should consider additional factors that may have affected the significance of such a correlation.

Source: Sayed-Hamidreza Mozhgani, Farid Rajabi, Mohsen Qurbani, Yousef Erfani, Somayeh Yaslianifard, Azam Moosavi, Kiomars Pourrostami, Ali Baradaran Bagheri, Alireza Soleimani, Farida Behzadian, Mahshid Safavi, Farhad Rezaei. Human herpesvirus 6 infection and risk of Chronic fatigue syndrome: a systematic review and meta-analysis. Intervirology (IF1.763), Pub Date : 2021-06-23, DOI: 10.1159/000517930 https://www.karger.com/Article/Abstract/517930 (Full text as PDF file)

Exclusive: Four members of NICE’s guideline committee on ME/CFS stand down

Four members of the NICE guideline development committee for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) left the group just weeks before the final guideline was due to be published, The BMJ has learnt.

The departures suggest divisions within the committee over the guideline’s final content, which is an update on 2007 guidance on diagnosing and managing ME/CFS. Three have resigned, and one has been removed by NICE.

The draft guidance, published in November 2020,1 included significant changes to the 2007 recommendations2 and raised questions about how the evidence could have shifted so substantially.

In 2007 NICE recommended interventions such as cognitive behavioural therapy and graded exercise therapy for people with mild or moderate ME/CFS, whereas the draft update cites a “lack of evidence for the effectiveness of these interventions.” …

Source: BMJ 2021;374:n1937

Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors?

Abstract:

SARS-CoV-2 survivors may report persistent symptoms that resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We explored (a) ME/CFS-like symptom prevalence and (b) whether axonal, inflammatory, and/or lung changes may contribute to ME/CFS-like symptoms in SARS-CoV-2 survivors through clinical, neuropsychiatric, neuropsychological, lung function assessment, and serum neurofilament light chain, an axonal damage biomarker. ME/CFS-like features were found in 27% of our sample. ME/CFS-like group showed worse sleep quality, fatigue, pain, depressive symptoms, subjective cognitive complaints, Borg baseline dyspnea of the 6-min walking test vs. those without ME/CFS-like symptoms. These preliminary findings raise concern on a possible future ME/CFS-like pandemic in SARS-CoV-2 survivors.

Source: Mantovani E, Mariotto S, Gabbiani D, Dorelli G, Bozzetti S, Federico A, Zanzoni S, Girelli D, Crisafulli E, Ferrari S, Tamburin S. Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors? J Neurovirol. 2021 Aug 2:1–7. doi: 10.1007/s13365-021-01002-x. Epub ahead of print. PMID: 34341960; PMCID: PMC8328351. https://pubmed.ncbi.nlm.nih.gov/34341960/

The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a meta-analysis of public DNA methylation and gene expression data

Abstract:

People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report a high frequency of viral infections and flu-like symptoms during their disease course. Since this reporting is in line with different immunological abnormalities and altered gene expression profiles observed in the disease, we aimed to explore whether the expression of the human angiotensin-converting enzyme-2 (ACE2), the major cell entry receptor for SARS-CoV-2, is also altered in this neglected clinical population. In particular, a low expression of ACE2 is usually indicative of a high risk of developing COVID-19.

We then performed a meta-analysis of public data on CpG DNA methylation and gene expression of this enzyme and its homologous ACE protein in peripheral blood mononuclear cells and related subsets. We found that patients with ME/CFS have decreased methylation levels of four CpG probes in the ACE locus (cg09920557, cg19802564, cg21094739, and cg10468385) and of another probe in the promoter region of the ACE2 gene (cg08559914). We also found a decreased expression of ACE2 but not of ACE in patients with ME/CFS when compared to healthy controls.

Accordingly, in newly collected data, we found evidence for a higher proportion of samples with an ACE2 expression below the limit of detection in patients with ME/CFS than in healthy controls. Altogether, patients with ME/CFS could be at a higher COVID-19 risk when infected by SARS-CoV-2. To further support this conclusion, similar research should be conducted for other human cell entry receptors and other cell types, namely, those mainly targeted by the virus.

Source: Malato J, Sotzny F, Bauer S, Freitag H, Fonseca A, Grabowska AD, Graça L, Cordeiro C, Nacul L, Lacerda EM, Castro-Marrero J, Scheibenbogen C, Westermeier F, Sepúlveda N. The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a meta-analysis of public DNA methylation and gene expression data. Heliyon. 2021 Jul 29;7(8):e07665. doi: 10.1016/j.heliyon.2021.e07665. Epub ahead of print. PMID: 34341773; PMCID: PMC8320404. https://pubmed.ncbi.nlm.nih.gov/34341773/