Jarred Younger confirms neuroinflammation in brains of ME patients

[svetoslav80]

Cort does a really good job on promoting M.E. dropping these bombs. I wish at least half of them were true though.

 

[Milo]

Re: It’s hard to imagine that that grant application won’t get funded

Right. Now we’re jinxed. Thanks a lot.

Health care research funding happens at a rate of 10% of all applications in Canada. For all topics.

 

[Forbin]

It was a small study, "15 ME/CFS women and 15 age and sex matched healthy controls," but...

Usually the results of studies apply to groups, not individuals; some healthy controls typically will have findings that are similar to the MEC/CFS patients and vice-versa, but not here – the two groups were absolutely distinct.

If this hold's up, it will be a biomarker. That alone would probably qualify it as the most important discovery in ME/CFS... ever.

And that could change everything.

 

[Milo]

It was a small study, "15 ME/CFS women and 15 age and sex matched healthy controls," but...


If this hold's up, it will be a biomarker. That alone would probably qualify it as the most important discovery in ME/CFS... ever.

What matters though in a biomarker is, can it discriminate between patients with ME and other diseases that causes brain inflammation?

 

[Amw66]

It was a small study, "15 ME/CFS women and 15 age and sex matched healthy controls," but...


If this hold's up, it will be a biomarker. That alone would probably qualify it as the most important discovery in ME/CFS... ever.

And that could change everything.

Mmm. Selection criteria for the study @Londinium mentioned may be more critical than may initially appear.

 

[Inara]

This is so interesting. I'd like to be tested for this before and after having read some long texts, as that's when I feel the brain is burning. The only thing that helps is to not read, not write, not concentrate.
I don't usually get this particular symptom after physical exertion, but it can be part of severe crashes.

My headaches often behave like muscle soreness, and I called it "muscle soreness in the head" (more as a joke), only that talking, reading, conentraining is the "training".

I hope to see some papers. That would be great.

 

[Forbin]

What matters though in a biomarker is, can it discriminate between patients with ME and other diseases that causes brain inflammation?

Even if the test turns out just to be for non-specific brain inflammation, it would show that ME patients have such inflammation, which would still be a big deal in world where people claim that ME patients can exercise their way to health.

 

[andypants]

My headaches often behave like muscle soreness, and I called it "muscle soreness in the head" (more as a joke), only that talking, reading, conentraining is the "training".

That's a good description of post exertion headaches, Inara I agree, it feels like I strained my brain muscle after too much mental effort. Not to be confused with the crash headache attacks, which are more like someone put an ice pick through my eye and asked a giant to stand on my head.

 

[Sasha]

@Jonathan Edwards, is the fact that the Japanese work is in Japanese a barrier to the work getting taken up? Is there anything that patients could/should be doing to get it translated, such as contact the team and offer to pay for professional translation, or try to find a patient with the skillset to offer a translation to them (bearing in mind that they'll need not to just know Japanese but also enough about science?

Maybe one of our charities could pay for translation.

 

[Hoopoe]

I am sure that neuroinflammation is real. I don't need a test to know I have it. The inside of my head feels warm. Not just warm actually, but it's very hard to describe the full sensation. A term that might fit is low grade brain nausea, malaise and a little bit of headache thrown in too. The sense of balance is also a little abnormal. I would never fall due to it, but it feels like my perception of movement and balance is not 100% aligned with what's actually happening. I also don't tollerate car traveling well due to acceleration, stops, curves, and bumpy roads making these symptoms worse.

Interestingly other people say no when I ask them if my head feels warm. It may not be possible to feel the increased temperature on the skin.

Also interestingly, I am not sure I ever brought this up in front of a doctor because it's subtle, always present and thus has become normality, and hard to describe. Maybe this means that this kind of problem tends to go unreported, or it could mean that maybe other aspects of the illness are more important.

 

[Amw66]

If you have low basal temperature, as lots of PwME have, would a" normal" temperature represent inflammation?
Sorry if this is a stupid question.

 

[mariovitali]

I am sure that neuroinflammation is real. I don't need a test to know I have it. The inside of my head feels warm. Not just warm actually, but it's very hard to describe the full sensation. A term that might fit is low grade brain nausea, malaise and a little bit of headache thrown in too. The sense of balance is also a little abnormal. I would never fall due to it, but it feels like my perception of movement and balance is not 100% aligned with what's actually happening. I also don't tollerate car traveling well due to acceleration, stops, curves, and bumpy roads making these symptoms worse.

Interestingly other people say no when I ask them if my head feels warm. It may not be possible to feel the increased temperature on the skin.

Also interestingly, I am not sure I ever brought this up in front of a doctor because it's subtle, always present and thus has become normality, and hard to describe. Maybe this means that this kind of problem tends to go unreported, or it could mean that maybe other aspects of the illness are more important.

Just to add here : I hypothesise that any active inflammations are being affected negatively by ME as well.

 

[Mattie]

I also don't tollerate car traveling well due to acceleration, stops, curves, and bumpy roads making these symptoms worse.

exactly the same here

 

[Jenny TipsforME]

muscle soreness in the head"

I get what you mean by this phrase.

My brain doesn’t feel on good form this morning but I wonder if there’s some connection between Younger’s finding and the NRXN1 variants OMF are finding to be much higher in ME?



I’m not well enough to read it this morning but I have this paper bookmarked Wang, X., Christian, K. M., Song, H., & Ming, G. (2018). Synaptic dysfunction in complex psychiatric disorders: from genetics to mechanisms. Genome Medicine, 10, 9. http://doi.org/10.1186/s13073-018-0518-5 :

For example, adhesion molecules, such as neurexin (NRXN) at the presynaptic site and its ligand, neuroligin (NLGN), at the postsynaptic site, are central organizing proteins for synapse formation and maintenance. Mutations of NRXN, NLGN, and SHANK, which encodes the stabilizer scaffolding protein SHANK at the postsynaptic site, are risk factors for both ASD and SCZ. Immune system components, such as microglia and complement factor C4, also regulate synapse numbers, and mutations in these pathways are linked to both ASD and SCZ. Here, we focus on recent genetic and mechanistic studies that provide novel insights into synaptic dysfunction in complex psychiatric disorders.

 

[adambeyoncelowe]

Worth noting that a team at Oxford are also looking at lactate levels (https://www.s4me.info/threads/oxfor...ing-into-energy-status-mrs-in-cfs.2661/page-2) using similar MRS techniques I believe... though when I spoke to them as a potential candidate (turned down unfortunately) they were still looking at selection criteria, and I did worry they might end up not excluding those with MDD which might skew the results given reported changes in brain lactate in those suffering a depressive episode.

They never followed up with me either. I wondered at the time if they were filtering out more defined ME patients, but I'm not a conspiracy theorist, so...

 

[Binkie4]

exactly the same here

Car travel has become impossible.
Was ill ( unable to sit up without severe dizziness) for 2 weeks after my last car journey and had to fly home.

 

[Jenny TipsforME]

@Binkie4 car journeys trigger really bad PEM for me too (I assume as a sensory overload type of thing), but was a plane better? Train journeys make me very nauseous/vertigo so I thought it was traveling in general.

 

[Londinium]

They never followed up with me either. I wondered at the time if they were filtering out more defined ME patients, but I'm not a conspiracy theorist, so...

There was quite a long delay in follow-up as they'd filled the quota but then apparently got extra funding to do more scans, which is when I was contacted. FWIW, I wasn't turned down due to any kind of ME/CFS selection criteria - the scanner they're using is much stronger than a normal MRI and so they excluded anyone who'd had *any* surgery, ever - so the fact I had a small op when I was 18 months old was enough to exclude me. Apparently the magnet is so strong they also excluded anybody with a tattoo as any metal in the ink would heat up and cause a burn!

 

[Londinium]

What matters though in a biomarker is, can it discriminate between patients with ME and other diseases that causes brain inflammation?

Mmm. Selection criteria for the study @Londinium mentioned may be more critical than may initially appear.

FWIW, I would be cautious about thinking this will lead to a specific biomarker. As Milo notes, a biomarker would need to discriminate between this and other diseases - and I believe there is some evidence that some depressive disorders noticeably impact lactate levels in the brain. Indeed, the study I referenced was planning to use bipolar disorder as an extra control group for that very reason (though when I spoke to them a few months back I got the impression that was still to be confirmed).

So, if this replicates, you might end up at least being able to demonstrate something is going on (i.e. it's not malingering) but it might be tough to distinguish between a number of other conditions that have traditionally* been seen as psychiatric in nature.


*though I am interested in the increasingly popular hypothesis that some psychiatric conditions have an immunological basis - I've been meaning to add this book to my reading list...

 

[Jenny TipsforME]

So, if this replicates, you might end up at least being able to demonstrate something is going on (i.e. it's not malingering) but it might be tough to distinguish between a number of other conditions that have traditionally* been seen as psychiatric in nature.

This could be useful for evidencing Disability. Laziness or perfectionism or any of the other contradictory and unhelpful stereotypes about ME wouldn’t look like general inflammation on a brain scan. And people with mental health issues are able to claim disability benefits.

I wonder if initial biomarkers might be a combination of say three or four tests? Eg this might possibly differentiate us from healthies as a first step, another might show muscle/metabolism problems which differentiate from purely psychiatric conditions and another which differentiates it from a similar condition which isn’t otherwise ruled out eg autoimmune conditions?

We don’t necessarily need just one test for ME which has no false positives/negatives.