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Stanford Community Symposium 2018: Jarred Younger

Discussion in 'ME/CFS research news' started by Sasha, Sep 29, 2018.

  1. Sasha

    Sasha Senior Member (Voting Rights)

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    This thread has been split from the main Stanford Community Symposium thread.

    Is it just me or was the Jarred Younger stuff really exciting?

    Does that strike you as the sort of thing that should be getting replicated as a priority, @Jonathan Edwards? (Not sure if you're watching but he was presenting results of a study showing that PWME's brains are on average 1 degree F higher than those of healthy controls, and that the hot areas are also high in lactate and that it's in regions that you would expect to make us feel like crap (IIRC, the insula, the thalamus, and somewhere else I've forgotten, but I have an excuse because it's some memory bit of the brain...)
     
    Last edited by a moderator: Oct 6, 2018
  2. NelliePledge

    NelliePledge Moderator Staff Member

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    I thought it was well pitched by Younger for non scientists and when the video goes up will be sharing it in local group and on my social media.
     
  3. Trish

    Trish Moderator Staff Member

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    I thought Jarred Younger was exciting too. He has used several different ways of indicating which areas of the brain are overactive and overheated, and related them to symptoms of the 'sickness response' and the areas match those found by someone else with a completely different method. And more studies will be done to replicate, but more are needed - it was a very small study. He's a very good speaker.
     
  4. Kalliope

    Kalliope Senior Member (Voting Rights)

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  5. Rain

    Rain Senior Member (Voting Rights)

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    I have to watch this another day, but am really enjoying your reports!

    The Younger scans pictured with mostly green/yellow brains - is it MRI, PET scan, or a combination?
     
  6. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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  7. JaimeS

    JaimeS Senior Member (Voting Rights)

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  8. Milo

    Milo Senior Member (Voting Rights)

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    How about catastrophizing... does it show on the images too?
     
  9. JaimeS

    JaimeS Senior Member (Voting Rights)

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  10. Milo

    Milo Senior Member (Voting Rights)

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    Indeed i was being sarcastic! I have a difficult time coping with the concept of catastrophizing as it applies to pain psychology research. They seem to be using that terminology for unexplained pain as opposed to cancer pain.
     
    Last edited: Oct 6, 2018
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  11. JaimeS

    JaimeS Senior Member (Voting Rights)

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    A classic case of projection on my part, Milo... the first time I read 'sickness behavior' I bristled! :cautious:
     
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  12. Sasha

    Sasha Senior Member (Voting Rights)

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    OK, so Jarred Younger's talk on the video is at 5:27:45:



    Wondering what your thoughts are, if you've had a chance to watch this, @Jonathan Edwards? I thought this was very exciting but as a non-biologist, I know nothing...
     
  13. Sasha

    Sasha Senior Member (Voting Rights)

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    Something interesting on Cort's blog about Younger's work which I don't remember Younger mentioning (but that could just be my poor memory):

    Because he was also able to apply his new technology to traumatic brain injury (TBI) and rheumatoid arthritis patients, we now know another startling fact: the neuroinflammation in ME/CFS, at least thus far, appears to be distinct. Neuroinflammation was restricted to certain areas of the brain in TBI and wasn’t present at all in rheumatoid arthritis (RA) – a shocking finding given the high levels of fatigue in RA. The data strongly suggests that fatigue is produced in different ways in different diseases – from the central nervous system inflammation in ME/CFS to something happening in the periphery or the body in RA.

    Younger quickly applied for an NIH grant to expand the neuroinflammation study, bring in more disease groups, see what an exercise stressor will do to the brains of ME/CFS patients and other evaluations. He’s already got an answer. The NIH wants to redo the grant application and add something to the study (a PET scan group). Yes, the NIH is actually asking Younger to ask for more money…

    It’s hard to believe Younger won’t get that grant award, and when he does, it will constitute a massive return on investment for the SMCI and the ME/CFS community. The SMCI put in about $50K and the ME/CFS community will get out something like $3,000,000.​

    https://www.healthrising.org/blog/2...ne-the-smcis-2016-ramsay-award-winners-score/
     
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  14. Simon M

    Simon M Senior Member (Voting Rights)

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    My notes on the presentation from Dr Jarred Younger (@5h 27’):

    A new, simpler way to measure neuroinflammation

    Younger presented findings from his study in which he used brain scans to reveal levels of metabolites and changes in temperature across the brain. He proposed that these measures are proxies for neuroinflammation, potentially a cause of ME/CFS. There were clear differences between patients and controls, with patients showing inflammation and increases in temperature in areas that could produce symptoms of fatigue and malaise. If validated and replicated, the new method would give a non-invasive approach that could prove valuable both in research and routine clinical diagnosis.

    ——

    Younger's primary hypothesis is that ME/CFS is driven by neuroinflammation. The brain's main immune cells are called microglia. An infection in the body, such as influenza, leads to activation of microglia in the brain. The microglia produce proinflammatory cytokines, affecting nearby neurones, which leads to a “sickness response”. The sickness response, which includes fatigue, pain and the inability to concentrate, is designed to make us rest up so that the body can focus its resources on fighting off the infection.

    Younger thinks that something goes wrong in ME/CFS so that following an initial infection, instead of microglia returning to their normal, "on patrol", state, they end up in a primed, hyperactive state. And in the primed state, minor triggers, perhaps exertion, lead microglia to produce cytokines all over again, making us feel sick. He says the specific ME/CFS symptoms are down to where in the brain microglia are concentrated, which can vary between patients.

    2AC21F4B-3E67-4752-AE42-50E8B419ACF0.jpeg Microglia. Top left: normal, patrolling microglia with extended arms; bottom right: activated “neuroinflammatory“ state. Top right: primed, hyperactive state.​

    Up until now, the only way to detect neuroinflammation (at least without autopsy) has been the PET method which involves injecting a radioactive tracer that lights up activated microglia on MRI scans. That was the method used by the Japanese PET MRI study a few years back; it is hideously expensive and unsafe to do repeatedly.

    Younger used magnetic resonance spectroscopy (MRS), which is a good technique for identifying specific metabolites. Using some fancy physics, MRS can also reveal changes in brain temperature. Younger focused on the metabolite lactate which, as with exercise, indicates intense activity (or not enough oxygen to meet demand). He argued that this is a mark of neuroinflammation. He also identified an increase in temperature as another sign of neuroinflammation: such elevated temperatures “should only happen if you have a neuroinflammatory response, because you can’t think hard enough to heat up your brain.”

    The results showed that both lactate and temperature increases differed markedly between patients and controls, with more lactate and higher temperatures in patients. Red areas are 1°F (0.6°C) higher than green areas.

    BAE3C6B5-1D1C-4C37-B913-D26E4A07CE4A.jpeg Specific areas of ME/CFS patients brains (left) show higher levels of lactate, in red, than for healthy controls (right).​

    Importantly, neuroinflammation occurred in areas of the brain, such as the amygdala and the insula, whose activation Younger said would account for ME/CFS symptoms.

    Critically, said Younger, the increases in lactate and increases in temperature generally map together, giving him confidence that both were indeed measuring neuroinflammation.

    5FE488FE-E267-4CEA-A7CF-99C468AEA92A.jpeg Higher temperatures were recorded in ME/CFS patients’ brains than for controls​

    Younger noted that there was also a good match between the areas of neuroinflammation indicated by higher temperatures and high levels of lactate in his new study and the areas indicated by the original Japanese neuroinflammation study. This match is another reason for confidence in the method.

    Overall, it makes for a strong story. However, as Younger himself pointed out, these are preliminary data (on 15 patients and 15 controls) that are yet to be published, replicated or validated.

    Validation against the PET "gold standard" of neuroinflammation is critical. So what's needed is a study showing that, within individual patients, the areas of increased lactate and increased temperature map to microglial activation identified by the radioactive tracer. Younger said his group now have funds for this kind of work in fibromyalgia, but not ME/CFS.

    However, Cort Johnson has just reported that Younger applied to the NIH for a grant for a bigger version of his current study, and the NIH asked him to add a PET study using radioactive tracer to validate the findings.

    If everything works out, this new approach could prove to be very important, and not just in ME/CFS. No wonder that other researchers at the Stanford workshop were so interested in Younger’s work.

    Note that Michael VanElzakker has pointed out that neuroinflammation is likely to be common in a number of diseases (though the patterns might well be different) — so neuroinflammation itself probably wouldn't be diagnostic.

    ——

    Any chance of an opinion on this new work from @Jonathan Edwards? Also @Woolie?
     
  15. Binkie4

    Binkie4 Senior Member (Voting Rights)

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    Thanks @Simon M, and for the clarity of your writing which makes a big difference for a non scientist.
     
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  16. dreampop

    dreampop Senior Member (Voting Rights)

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    Is this true? This review on brain temperature says "brain temperature itself largely depends on the summed effects of the following principle variables: brain metabolism, CBF and volume, and blood temperature". And this study from 2010 says

     
    Last edited: Oct 17, 2018
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  17. mariovitali

    mariovitali Senior Member (Voting Rights)

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