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Biomedical research findings in ME/CFS that were replicated by multiple groups

Discussion in 'BioMedical ME/CFS Research' started by Michiel Tack, Jul 31, 2020.

  1. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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    I'm hoping to get an overview of biomedical abnormalities found in ME/CFS that were replicated by multiple groups. I realize that, due to the paucity of research, most of the findings are unimportant and non-specific with some inconsistencies in the findings but I still think it would be useful to have an overview.

    I was thinking of:

    Low Natural Killer Cell Cytotoxicity
    https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-019-1202-6

    increase heart rate at rest, lower at peak - chronotropic intolerance
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824690/
    https://www.frontiersin.org/articles/10.3389/fped.2019.00082/full

    Decrease in workload at the ventilatory threshold during 2-day CPET.
    https://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy2.14138
    https://pubmed.ncbi.nlm.nih.gov/24755065/
    https://content.iospress.com/articles/work/wor203170
    https://www.scirp.org/journal/paperinformation.aspx?paperid=98389
    https://pubmed.ncbi.nlm.nih.gov/28782878/
    https://academic.oup.com/ptj/article/93/11/1484/2735315
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1836-0

    Reduced VOpeak on singular CPET
    https://pubmed.ncbi.nlm.nih.gov/30557887/

    Reduced cerebral blood flow?
    https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1475-097X.2006.00649.x
    http://europepmc.org/article/med/1491843
    https://pubmed.ncbi.nlm.nih.gov/8542261/
    https://www.sciencedirect.com/science/article/abs/pii/S0022510X10005666

    Increase prevalence of POTS
    https://www.frontiersin.org/articles/10.3389/fped.2018.00349/full
    https://pubmed.ncbi.nlm.nih.gov/24206536/
    https://pubmed.ncbi.nlm.nih.gov/18805903/

    ...​

    Any other suggestions or things that I should look at? Does anyone know what the situation is with hypocortisolism and a attenuated morning response? Are the findings consistent?
     
    Last edited: Jul 31, 2020
  2. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    Very low ESR

    https://ashpublications.org/blood/article/132/Supplement 1/4874/262252/Erythrocyte-Deformability-As-a-Potential-Biomarker

    https://www.consultant360.com/content/chronic-fatigue-syndrome-update-diagnosis-primary-care

     
    Last edited: Jul 31, 2020
  3. John Mac

    John Mac Senior Member (Voting Rights)

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    These studies found a reduced Left Ventricle though mainly done by Miwa.

    2003
    Peckerman
    Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome
    https://pubmed.ncbi.nlm.nih.gov/12920435/

    2008
    Miwa
    Small Heart Syndrome in Patients withChronic Fatigue Syndrome
    https://onlinelibrary.wiley.com/doi/epdf/10.1002/clc.20227

    2009
    Miwa
    Cardiovascular Dysfunction with Low Cardiac Output
    Due to a Small Heart in Patients with Chronic Fatigue Syndrome
    https://www.jstage.jst.go.jp/article/internalmedicine/48/21/48_21_1849/_pdf

    2011
    Miwa
    Small Heart With Low Cardiac Output for Orthostatic Intolerance in Patients With Chronic Fatigue Syndrome
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652296/

    2012
    Julia Newton
    Impaired cardiac function in chronic fatigue syndrome measured using magnetic resonance cardiac tagging
    https://pubmed.ncbi.nlm.nih.gov/21793948/
    substantially reduced left ventricular mass (reduced by 23%), end-diastolic volume (30%), stroke volume (29%) and cardiac output (25%).

    2015
    Miwa
    Cardiac dysfunction and orthostatic intolerance in patients with myalgic encephalomyelitis and a small left ventricle
    https://pubmed.ncbi.nlm.nih.gov/24736946/

    2016
    Olimulder
    Chronic fatigue syndrome in women assessed with combined cardiac magnetic resonance imaging
    https://link.springer.com/article/10.1007/s12471-016-0885-8
    "In patients with CFS, CMR demonstrated lower LV dimensions and a mildly reduced LV function."



    ETA:
    1994
    Dworkin, Lawrie, Lerner
    Abnormal left ventricular myocardial dynamics in eleven patients with chronic fatigue syndrome.
    https://europepmc.org/article/med/7955743


    ETA:
    2016
    Newton
    Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study
    https://openheart.bmj.com/content/3/1/e000381

    ETA: There are also several studies by van Campen that mention cardiac problems.
     
    Last edited: Jul 31, 2020
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  4. Andy

    Andy Committee Member & Outreach

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    Haven't a number of groups independently flagged MAIT cells as being of potential interest? Which isn't to say that anything has been replicated, just that different groups have found readings that don't look 'normal'.
     
  5. cassava7

    cassava7 Senior Member (Voting Rights)

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    Neuroinflammation? Referring to VanElzakker's paper [1] (esp. Table 1) for studies that found significant differences between ME/CFS vs. control groups (not listing others).

    [1] VanElzakker MB, Brumfield SA and Lara Mejia PS (2019) Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods. Front. Neurol. 9:1033. https://doi.org/10.3389/fneur.2018.01033

    PET

    Nakatomi, Y., Mizuno, K., Ishii, A., Wada, Y., Tanaka, M., Tazawa, S., Onoe, K., Fukuda, S., Kawabe, J., Takahashi, K., Kataoka, Y., Shiomi, S., Yamaguti, K., Inaba, M., Kuratsune, H., & Watanabe, Y. (2014). Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 55(6), 945–950. https://doi.org/10.2967/jnumed.113.131045

    There might be older PET or SPECT studies.

    MRS -- all show increased ventricular lactate

    Mueller, C., Lin, J.C., Sheriff, S. et al. Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy. Brain Imaging and Behavior 14, 562–572 (2020). https://doi.org/10.1007/s11682-018-0029-4
    (Lactate levels correlated with levels of fatigue)

    Benjamin H. Natelson, Diana Vu, Jeremy D. Coplan, Xiangling Mao, Michelle Blate, Guoxin Kang, Eli Soto, Tolga Kapusuz & Dikoma C. Shungu (2017) Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia, Fatigue: Biomedicine, Health & Behavior, 5:1, 15-20, https://doi.org/10.1080/21641846.2017.1280114

    Shungu DC, Weiduschat N, Murrough JW, Mao X, Pillemer S, Dyke JP, et al. Increased ventricular lactate in chronic fatigue syndrome. III relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology NMR Biomed. (2012) 25:1073–87. https://doi.org/10.1002/nbm.2772

    Murrough JW, Mao X, Collins KA, Kelly C, Andrade G, Nestadt P, et al. Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder. NMR Biomed. (2010) 23:643–50. https://doi.org/10.1002/nbm.1512
    (Lactate levels correlated with levels of fatigue)

    --------

    The following ME/CFS research summaries and reviews may be helpful:

    General summaries and reviews

    Komaroff AL. Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome. JAMA. 2019;322(6):499–500. https://doi.org/10.1001/jama.2019.8312

    Cortes Rivera, M., Mastronardi, C., Silva-Aldana, C., Arcos-Burgos, M., & Lidbury, B. (2019). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Comprehensive Review. Diagnostics, 9(3), 91. https://doi.org/10.3390/diagnostics9030091

    ME Association's research summary with links to reports on some consistent findings, e.g. NK cells (May 2020): https://meassociation.org.uk/wp-content/uploads/MEA-M.E.-Research-Summary.pdf

    ME Action's research summary (June 2019): https://www.meaction.net/wp-content/uploads/2019/06/19_MEA_Revised_2019_Research_Summary_190610.pdf

    Wasn't a research review conducted for the IOM report too? Although now a bit old (2015), it could list some of the older but consistent studies.
    EDIT: the IOM report does contain a research review (Chapters 4 & 5, pp. 71-180), but it doesn't exclusively focus on objective findings of abnormalities in ME/CFS. Rather, it goes into great detail about the prevalence and the assessment of ME/CFS symptoms (and then they try to link them to evidence of biological abnormalities when possible).

    Specific systematic reviews

    Maksoud R, du Preez S, Eaton-Fitch N, Thapaliya K, Barnden L, et al. (2020) A systematic review of neurological impairments in myalgic encephalomyelitis/ chronic fatigue syndrome using neuroimaging techniques. PLOS ONE 15(4): e0232475. https://doi.org/10.1371/journal.pone.0232475

    Up to Aug 2019 only, so it doesn't include the recent results on cerebral blood flow from van den Campen et al. and the MRS study by Younger.
    Huth, T.K., Eaton-Fitch, N., Staines, D. et al. A systematic review of metabolomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID). J Transl Med 18, 198 (2020). https://doi.org/10.1186/s12967-020-02356-2
    Holden, S., Maksoud, R., Eaton-Fitch, N. et al. A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease. J Transl Med 18, 290 (2020). https://doi.org/10.1186/s12967-020-02452-3
     
    Last edited: Aug 2, 2020
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  6. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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