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A neuro-inflammatory model can explain the onset, symptoms and flare-ups of ME/CFS, 2019, Mackay

Discussion in 'BioMedical ME/CFS News' started by RoseE, Dec 19, 2019.

  1. RoseE

    RoseE Senior Member (Voting Rights)

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    This research article in the Journal of The Royal New Zealand College of General Practitioners has just been brought to my attention...
    http://www.publish.csiro.au/HC/fulltext/HC19041

    A neuro-inflammatory model can explain the onset, symptoms and flare-ups of myalgic encephalomyelitis/chronic fatigue syndrome
    Angus Mackay 1
    + Author Affiliations
    Journal of Primary Health Care 11(4) 300-307 https://doi.org/10.1071/HC19041
    Published: 29 November 2019
     
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  2. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Although there is not a lot novel in this account it seems a fair and plausible model, described in a clear and sensible way.
     
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  3. Ravn

    Ravn Senior Member (Voting Rights)

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    This sounds similar to a previous paper by the same author discussed here (I haven't read the new one yet so don't know if it adds anything new to the old one):
    https://www.s4me.info/threads/a-com...ry-paradigm-for-me-cfs-2018-mackay-tate.7187/
     
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  4. strategist

    strategist Senior Member (Voting Rights)

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    I agree that I'm sensitive to everything, but different kinds of stressors do not appear to have equal importance. Exertion stands out much more than others. Gut problems related to apparent reactivity to various foods also seem fairly important. I find that I tolerate emotional stress less but it doesn't seem to trigger the relapses that overexertion does.

    It does feel like there is a subtle kind of inflammation involved in the illness. And dysregulation of lots of things in an unpredictable and ever shifting way.

    I agree that the triggers leave a signal that appears to be additive and cumulative, meaning multiple things at once will sum their effects, and that the signal stays around for a while (a few days, maybe longer?). That seems consistent with some central stress register playing a role.
     
    Last edited: Dec 20, 2019
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  5. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    The hypothesis seems rather vague and most researchers who have invoked some kind of dysfunction of the hypothalamus as a model have generally failed to explain why their hypothesis is not consistent with the range of results from neuroendocrine studies.
     
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  6. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I agree it is vague. If the hypothalamus is targeted then I think it would have to be in a rather specific way - rather as for narcolepsy. That may not fit very well with a generic neuroinflammation model. On the other hand neuroinflammatory changes seen in other conditions may be secondary to specific changes - as in Parkinson's for instance.
     
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  7. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    Yes, the problem is that there is no specific dysfunction of the HPA axis and we've known this for many years. The studies of basal CRH, ACTH, Cortisol etc, along with CRH, ACTH and AVP challenges have all been inconsistent. Notably, in a prospective studies of EBV infection, those who were later diagnosed with CFS (Oxford) did not have any difference in cortisol either at onset of infection, nor 6 months after infection.
     
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  8. ladycatlover

    ladycatlover Moderator Staff Member

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    But the Oxford CFS "criteria" were very loose - they'd pick up many people who were depressed and/or "tired all the time" for any reason, once they got the CFS label they were on a hiding to nothing getting more tests to see what was really going on. Unless they had stellar GPs. So anything using Oxford is a waste of time really.
     
  9. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    But the argument around low basal cortisol by certain unnamed authors is often claimed to be associated with non-specific fatigue and various psychosocial conditions (PTSD, early childhood trauma etc) the fact that they didn't find any sign of this in an Oxford sample is revealing.
     
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  10. lansbergen

    lansbergen Senior Member (Voting Rights)

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    Recently I catched someting from a visitor. Seemed a cold and many cold bugs are going around here but no influenza virus yet.

    It started like a cold but then the immunesystem went after the mysterious chronic infection causing a nasty flare. As always no real fever.

    I am still not fully recovered.

    Luckly the normal pattern occured. So the ME is a little better then before it started.
     
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  11. dannybex

    dannybex Senior Member (Voting Rights)

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    THAT is the $64,000,000 dollar question. Why is it that if we happen to actually start to get a reaction to some bug going around, we never get a "real" fever, like one does with a functioning immune system, but instead, we barely manage a half-baked semi-fever, or struggle with chills, etc., in an attempt to raise one's body temperature even a degree or two or three?

    I mean, even in the many definitions of ME/CFS, one of the key descriptions is 'fever-like" or 'low grade' feverishness. Not a normal fever.

    Compare that to 'normals', where they get (and complain) about their fever going high for days, maybe even a week or so, but it helps burn off the bug(s) so they can then go back to work, to life, etc.

    Sigh...
     
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  12. Milo

    Milo Senior Member (Voting Rights)

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    Oh i did. I got the flu in 2019, i had a good 5 days of fevers (40C) and sweats followed by rigors and chills . I also had fevers following a surgery, it lasted a few days ( though for this one no infection was found)
     
    Last edited: Feb 8, 2021
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  13. dannybex

    dannybex Senior Member (Voting Rights)

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    I think that's extremely rare. Curious, did you feel better after the flu? I've had a few fevers, but they typically last 2, maybe 3 days at best, and maybe one has reached 102-103F.
     
  14. Milo

    Milo Senior Member (Voting Rights)

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    That time i got the flu, if we had been in the pandemic, i would have told you I might have had Coronavirus was so sick. One of those days, breathing was terribly painful, and i got near to checking in to emergency because it was getting difficult and i didn’t know which way it would go.

    And no i did not feel better after the flu, it took me a few weeks to return back to baseline, my ‘normal’ baseline.

    i would not say ‘it’s incredibly rare’- in my view our immune systems are not terribly abnormal at first glance, we have neutrophils and lymphocytes and they work when needed. Our body responds to a viral or a bacterial infections, it is able to mount an immune response (otherwise we’d be dead, especially in the case of a more aggressive infection).
     
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  15. dannybex

    dannybex Senior Member (Voting Rights)

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    Thanks @Milo. It would be interesting to do a poll on the topic some day. So sorry it was so rough for you.
     
  16. boolybooly

    boolybooly Senior Member (Voting Rights)

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    Off the top of my head, which is the only part still above water these days, what I like about this hypothesis is the focus on the activity of the innate immune system. I dont think inflammatory disruption of the midbrain (hypothalamus and limbic system) explains everything that I experience and I would not consider it a full explanation but it is part of the constellation of ME symptoms and the glial response idea may be part of a bigger story relating to innate immune system hyperactivity.

    However what I dont like is the nebulosity of this particular hypothesis and question the author's suggestion that glial activity causing ME could be induced by "emotional trauma" with no other factor or that this results in a condition which could be intrinsically self perpetuating due to the same. This is confused and smacks of BPS handwaving.

    I observe that my condition, diagnosed as ME CFIDS, disturbs my cognition and causes emotional lability and this is exacerbated by fatigue and PEM as well as stress etc due to the preexisting affect on my CNS but this should not be confused with the idea that stress or PEM causes the problem in the first place.

    Stress is known to cause immune suppression and PEM is observed to somehow exacerbate inflammatory responses in ME by some mechanism we dont understand.

    There is a subtle but important difference in the causal logic of suggesting these exacerbate symptoms for a patient with an inflamed CNS compared to suggesting these cause the inflammation which they exacerbate, which seems to be the error in thinking evident in this paper, which fails to explain onset. If stress and exercise cause ME then it follows everyone would have it. Clearly something else is happening in ME.

    After 34 years attempting to understand my condition I would characterise my own symptoms as inflammation following cyclical viral activity which for some reason my adaptive immune system cannot quash (post EBV).

    I believe this means my innate immune system has to act as a backstop and is overstimulated resulting in the inflammatory symptoms which constitute my ME.

    While I am not sure that other people with ME have exactly the same kind of condition I have, I think a lot of the shared symptoms of ME diagnosis credibly result from the innate immune system running amuck, for one reason or another, including glial cells.

    But the persistence in my own case unquestionably involves ongoing virus replication, by multiple +ve PCR tests over the years, so I do not believe my condition is due to a cognitively induced dysfunction of the hypothalamus which has become self-perpetuating or any kind of neurological sensitisation or memory effect but is an ongoing flawed immune response to active pathogens setting me up with an overactive innate immune system whcih in turn sets me up for PEM and the deleterious affects of stress.

    For this reason I consider any hypothesis which suggests cognitively induced inflammatory responses ex nihilo explain ME is not viable and ideas about intrinsic self perpetuation without reference to pathogens and immune system activity fail to describe the nature of my condition.
     
    Last edited: Feb 14, 2021
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  17. Snowdrop

    Snowdrop Senior Member (Voting Rights)

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    I'm not disagreeing with this but I find it to be a very vague statement. I know nothing about any of this but it occurs to me to wonder are we talking about an acute stress of say fleeing a gunman in a building?

    If the person experiencing that does not return to normal as expected after the threat is over does that necessitate a psychological explanation or is there the possibility that something physical was not quite working properly and when all ones friends and colleagues go back to normal one's system once overwhelmed gets stuck through no psychological effect at all?

    If this is the case I would think that anyone observing the person might identify what they see (the physical broken response) as psychological symptoms.

    I don't expect you to have the answers here @boolybooly just throwing some thoughts out as regards this idea.
     
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  18. Mij

    Mij Senior Member (Voting Rights)

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    Viral infection can be described as a stressor.
     
  19. Snowdrop

    Snowdrop Senior Member (Voting Rights)

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    That's my point really. Like the word fatigue 'stress' is a word that does a lot of heavy lifting. It is very generic and non-specific.
     
  20. boolybooly

    boolybooly Senior Member (Voting Rights)

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    There is no doubt it needs study and experimentation for ME.

    Wondering what kinds of mistakes psychologists can make to foul up the treatment of ME even more goes beyond useful speculation IMHO. The point would be not to make mistakes, in particular not jumping to conclusions about causal relationships between stress and ME.

    What we know about stress and immune activity makes it seem logically possible that stress could reveal immune dysfunction by suppressing the immune system long enough for a pathogen to gain the upper hand. I think its common knowledge that stress can exacerbate existing conditions. People usually bounce back, only end of life scenarios where fragile people are pushed over the edge.

    With ME there is also no bouncing back for some reason we dont understand but it is rarely killing people directly, just shortening life expectancy by decades. PWME need to be treated with the same kindness we should show to the very elderly, because such kindness, which people of good conscience practice instinctively, is a way of reducing stress.

    Regarding stress, FYI, as I understand it from my zoology degree and teacher training (lecture ahead!), at least two well known hormones mediate stress on the immune system. Broadly speaking cortisol handles state changes like waking up etc and adrenalin responds to cognitively anticipated demand for energy when planning activity.

    They both suppress the immune system because they shunt metabolic energy away from immunity, growth and digestion into muscles and nerves to fuel activity, that is their purpose. We evolved this diurnal circadian system to allocate different physiological activity to different times of the day because it helps us use 100% of available energy at times of challenge or healing.

    Getting up in the morning is sufficient stress to affect the immune system, cortisol levels typically rise in the morning as a natural function of the circadian rhythm suppressing use of metabolic energy for healing, shunting it into activity.

    Healthy people typically dont notice this kind of stress and take it for granted and even feel good for it, but this may be why some PWME find it much harder to get up in the morning than those without ME and have to go very gently. Which is not trivial, it is a difficult reality easily mistaken for laziness. Dr Paul Cheney is on record as saying PWME typically have low cortisol and behave as you would expect for this situation, they cannot focus mentally or remember stuff or handle complexity. I dont know if everyone with ME finds this but it matches my experience and I have read many accounts from other people saying likewise aka brain fog.

    PWME often cannot take stress which other people take in their stride or even enjoy. Another example is "friendly" social interaction. This is IMHO typically a significant stressor due to factors which we can understand from a perspective of social behaviour and its evolution. Social behaviour is evolutionarily important for reproduction, so we evolved to put energy into it and this activates pleasant "stress" hormone release (adrenalin) which causes happy excitement and yet in so doing shunts energy away from the immune system and digestion. This may be why social interaction tends to be unusually taxing for PWME and PWME run the risk of coming across as sociopathic which would be a mistaken interpretation of our plight.

    I do not think ME is stress induced but I think stress makes it worse because I know my own ME is due to an immune dysfunction with real pathogens vying to take advantage of it all the time.

    I think a lot of "experts" really do not understand the way the illness affects us and project all kinds of monsters from their own id onto us because this condition lays us lower than most human beings would ever want to go, particularly in regard to the social dimension because of the way this affects communication and mutual comprehension.

    It is their fear and ignorance of themselves which manifests as such idiocy as we see in BPS and LP and AR despite their conceited hypocrisy regarding their own self awareness. i.e. they claim to be super self aware ubermensch and they are not, but then people often teach what they most need to learn, myself included ;)
     
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