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Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome, 2024, Walitt et al

Discussion in 'ME/CFS research' started by pooriepoor91, Feb 21, 2024.

  1. pooriepoor91

    pooriepoor91 Established Member

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  2. Andy

    Andy Committee Member

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    Abstract

    Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.

    Open access, https://www.nature.com/articles/s41467-024-45107-3
     
    sebaaa, DokaGirl, Anna H and 19 others like this.
  3. Braganca

    Braganca Senior Member (Voting Rights)

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    https://www.eurekalert.org/news-releases/1034817
    To study fatigue, Dr. Nath and his team asked participants to make risk-based decisions about exerting physical effort. This allowed them to assess the cognitive aspects of fatigue, or how an individual decides how much effort to exert when given a choice. People with ME/CFS had difficulties with the effort choice task and with sustaining effort. The motor cortex, a brain region in charge of telling the body to move, also remained abnormally active during fatiguing tasks. There were no signs of muscle fatigue. This suggests that fatigue in ME/CFS could be caused by a dysfunction of brain regions that drive the motor cortex, such as the TPJ.

    “We may have identified a physiological focal point for fatigue in this population,” said Brian Walitt, M.D., M.P.H., associate research physician at NINDS and first author of the study. “Rather than physical exhaustion or a lack of motivation, fatigue may arise from a mismatch between what someone thinks they can achieve and what their bodies perform.”
     
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  4. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    Looks like these are the treatment recommendations/targets.

    “The finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigen. Immune dysfunction leads to neurochemical alterations that impact neuronal circuits, which may be another point of intervention. “

    Not particularly super-specific.


    Some links for checkpoint inhibitors

    https://amp.cancer.org/cancer/manag...munotherapy/immune-checkpoint-inhibitors.html

    https://www.cancer.gov/publications/dictionaries/cancer-terms/def/immune-checkpoint-inhibitor
     
    Last edited: Feb 21, 2024
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  5. Three Chord Monty

    Three Chord Monty Senior Member (Voting Rights)

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    DokaGirl, EzzieD, Ariel and 10 others like this.
  6. Andy

    Andy Committee Member

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    "To be considered an adjudicated case, participants were required to be unanimously considered to be a case of PI-ME/CFS by the protocol’s adjudication committee, meet at least one of three ME/CFS criteria (1994 Fukuda Criteria64, 2003 Canadian Consensus Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome65, or the Institute of Medicine Diagnostic Criteria66), have moderate to severe clinical symptom severity as determined by having a Multidimensional Fatigue Inventory (MFI) score of ≥13 on the general fatigue subscale or ≥10 on the reduced activity subscale, and functional impairment as determined by having a Short-Form 36 (SF-36) score of ≤70 on physical function subscale, or ≤50 on role physical subscale, or ≤75 on social function subscale."
     
    sebaaa, DokaGirl, EzzieD and 12 others like this.
  7. EndME

    EndME Senior Member (Voting Rights)

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    Quite a few findings to discuss, especially the negative results (for example no evidence of POTS or SFN). I found this part rather interesting:

    "Within four years of participation, four of the 17 PI-ME/CFS participants had a spontaneous full recovery. No other new medical diagnoses were reported by the PI-ME/CFS participants."

    The sample size of the study is very small, but maybe re-analysing the data with this in mind could be useful (even if this yields null results).
     
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  8. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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  9. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    That’s a real sh*t headline.
     
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  10. siobhanfirestone

    siobhanfirestone Established Member (Voting Rights)

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    Can anyone break down what the T cell findings are here, and how they came up with this claim "immune checkpoint inhibitors may be theraputic by promoting clearance of forgein antigen" - did they find foregin antigen or active t cells? or both, this makes little sense to me ngl
     
  11. Andy

    Andy Committee Member

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    NIH Press Release

    NIH study offers new clues into the causes of post-infectious ME/CFS

    In a detailed clinical study, researchers at the National Institutes of Health have found differences in the brains and immune systems of people with post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). They also found distinct differences between men and women with the disease. The findings were published in Nature Communications.

    “People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult,” said Walter Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “This in-depth study of a small group of people found a number of factors that likely contribute to their ME/CFS. Now researchers can test whether these findings apply to a larger patient group and move towards identifying treatments that target core drivers of the disease.”

    A team of multidisciplinary researchers discovered how feelings of fatigue are processed in the brains of people with ME/CFS. Results from functional magnetic resonance imaging (fMRI) brain scans showed that people with ME/CFS had lower activity in a brain region called the temporal-parietal junction (TPJ), which may cause fatigue by disrupting the way the brain decides how to exert effort.

    https://www.ninds.nih.gov/news-even...offers-new-clues-causes-post-infectious-mecfs
     
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  12. Andy

    Andy Committee Member

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  13. Trish

    Trish Moderator Staff Member

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    I skimmed most of the article.

    Allowing diagnosis by Fukuda criteria is unforgivable.

    I continue to be concerned that the researchers don't understand and don't even mention delayed PEM. That and the concentration on deconditioning when they should have used a sedentary healthy control group with an equal level of deconditioning seems a very poor basis for drawing any conclusions about ME/CFS.

    And they go on about effort preferences and seem to only vaguely explain the preference for less demanding tasks in the ME/CFS group when given free choice seems to me to be judgemental.

    Sadly I think the way this is written will add fuel to the BPS deconditioning/effort avoidance/fear of exercise ideas.
     
  14. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I thought the same.

    I think the T cell populations they flagged up were those with more innate function. Nothing in what they or others have found would suggest a need to clear foreign antigen. This looks to me like pretty low level immunological analysis-by-meme.
     
  15. Trish

    Trish Moderator Staff Member

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    Is this a fatigue/deconditioning study or an ME/CFS study?
     
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  16. siobhanfirestone

    siobhanfirestone Established Member (Voting Rights)

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    I honestly thought i was going mad. To keep it simple, as i read the data it seemed to be they were saying stuff like "population totals of certain cells like NK cells and T cells are no different" and that there are "indications of chronic activation" sort of type stuff, including the dodgy gene work they did. As far as i can tell here they didnt even test for say micro-RNA from viruses or anything, like there is no "foreign antigen" analysis even within this work?
    How has this passed review in NATURE when the conclusions seem so divorced from their own data? I might be missing a huge point here
    The only good of this is it shits on the pyscho babble we all have to deal with, but unless this becomes a part of doctor education it wont even change that.
     
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  17. siobhanfirestone

    siobhanfirestone Established Member (Voting Rights)

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    it made me very sad to see that they pushed participants to extreme exercise. i cant imagine how they suffered after
     
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  18. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I agree. The only hope maybe is that since this theory is a bit different from the old false beliefs one the BPS juggernaut cannot quite continue on the same tracks. But it is reminiscent of the Mark Edwards story about 'FND' that claims to use MRI data to explain mental processes.

    The comment from Wallitt is about as 'dualist' as you can get - something about patients perceptions not matching what their body can do. From personal experience my perceptions are entirely based on what 'my body' can do. I keep being caught out by 'my body' not being able to do stuff. So the explanation that actually fits is that patients have learnt to plan differently because their bodies don't do the stuff. The absence of abnormality in muscle doesn't mean the body can do stuff because 'the body' also includes the signalling the brain that is controlled by immune stimuli.

    Maybe at least they are one step nearer to a meaningful story. Unfortunately, my experience in immunology is that the vast majority of researchers never get to understand what a fully meaningful story would look like. You need ordinary sensible people for that.
     
  19. Trish

    Trish Moderator Staff Member

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    I didn't read it as extreme exercise. They did a single CPET, not the two day CPET often used to research ME/CFS. They don't seem to mention any follow up of whether patients had PEM after the CPET that I can see.
     
  20. siobhanfirestone

    siobhanfirestone Established Member (Voting Rights)

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    "During testing, all but one PI-ME/CFS participant reached the peak respiratory exchange ratio (RER) of ≥1.1 and there was no difference between the groups"
    is this not quite extreme cardio for a ME patient? genuine question i dont know
     

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