Preprint: Broken Connections: The Evidence for Neuroglial Failure in ME/CFS

[Wishful]

https://osf.io/ef3n4

I just came across this, and I think it's the best explanation for the root cause of ME to come along. It seems to explain all the symptoms we experience, and why the various other hypotheses (viral infections, CCI, microbiome problems, etc) apply via their effects on neuroglia.

It's a fairly long paper, so I've only managed to read part of it before my brain gave up, but I highly recommend checking it out.

Disclaimer: I admit I'm enthusiastic about it because it fits what I'd been thinking for a while now. What got me thinking along these lines was reading that astrocytes typically connect to 10,000 neurones, and some connect to 2 million or more. That's such a big difference from the drawings of astrocytes which show a few 'tendrils' (actually called 'processes'). Further investigation showed that astrocytes are really important for brain function, and are strongly influenced by the rest of the body (close link to microbiome). It might be hard to find an ME symptom that can't be explained by astroglial activity.

Unfortunately, no simple treatment offered by the paper. Still, it might be a good start to unravelling the mystery of ME.

 

[Rufous McKinney]

I just came across this, and I think it's the best explanation for the root cause of ME to come along.

well, page 7-9 seem brilliant.

That sentence, wow. I guess they are just citing: somebody else's sentence-

"ME/CFS is
described as the most vicious disease in the hell of diseases..."


(I" ve had a strong feeling that the Germans are going to solve ME).....

I hope to wade thru the 98 pages......

 

[ljimbo423]

I just came across this, and I think it's the best explanation for the root cause of ME to come along. It seems to explain all the symptoms we experience, and why the various other hypotheses (viral infections, CCI, microbiome problems, etc) apply via their effects on neuroglia.

Great find Wishful, thanks!

I agree with this view. I no longer think that dysbiosis and/or leaky gut are the root cause of most ME/CFS. I now think it is neuroinflammation, as this paper suggests. Without the neuroinflammation, I don't think dysbiosis and/or leaky gut, would be an issue.

I'm going to dig into the paper more tomorrow.

I downloaded the PDF, below. I found it's alot easier for me to read, maybe for others too.

 

[Rufous McKinney]

thanks for the PDF, much better...

 

[andyguitar]

Without the neuroinflammation, I don't think dysbiosis and/or leaky gut, would be an issue.

So what is your gut feeling about the source of the neuroinflammation @ljimbo423 ?

 

[ljimbo423]

So what is your gut feeling about the source of the neuroinflammation @ljimbo423 ?

My best guess rate now, and it's just a guess at this point, would be stress from viral infections, bacterial infections, car accidents, chemotherapy. Almost anything that can cause significant stress.

 

[Rufous McKinney]

First hit when I ask the question:

LPS causes neuroinflammation:

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2871685/

 

[Rufous McKinney]

about the hardest thing to Prevent In One's Life are: significant stressors....

I mean, sometimes we can chose this or that but, other times we know the bumper sticker: Stuff Happens

 

[ljimbo423]

First hit when I ask the question:

LPS causes neuroinflammation:

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2871685/

Thanks Rufous. Well, it looks like a leaky gut is back in play! But stress can, and often does cause or contribute to a leaky gut.

 

[Rufous McKinney]

neuroinflammation

Something about all this might be very PHYSICAL. By that, I'm thinking about the spine and it is connected to our brainstem.

So my spinal problems go all the way back to: the early days....of life....

 

[Rufous McKinney]

. Well, it looks like a leaky gut is back in play!

I was laughing: GUT WINS, yet again! (funny how the gut so often wins)

Lets for now stick to:

A virus is needed in genetically predisposed bodies....

We meet the viruses, very early on.....

the viruses interfere with collagen and connective tissue...the enzymes they secret for some reason...it weakens our tissue which weakened the gut barrier....And brain barrier....Both are weekend by the virus and Off We Go....

hello LPS and now we have cycles of neuroinflammation.

ADD: something about the ATP which is clearly required to defend the gut and blood brain barrier- so both energy and construction materials are affected by: the virus.

 

[Consul]

Great article trying to connect the dots. The author appears to have me/cfs himself since 2016 if i read it correctly.

Also he appears to be interrested in thiamine:

[...]Interestingly, a patient driven initiative has recently suggested an investigation of high dose thiamine
as a possible therapeutic agent for ME/CFS after collecting case reports from patients who had tried
the medication.351,352 It has been suggested by the initiator of this pilot study that high dose thiamine
may act in similar ways as acetazolamide, a known diuretic that may decrease intracranial pressure.
As of now, it is unknow if and how this therapy holds up in a controlled study and which subset of
ME/CFS patients may be responders.

 

[ljimbo423]

Also he appears to be interrested in thiamine:

A fairly low dose of thiamine, about 100 mg a day, stopped my moderate to severe insomnia. I now get about 8 hours of sleep out of 8.5-9. Without the thiamine, I would only get 3-4 hours of sleep, 3-5 days a week!

Ironically, it's very stimulating during the day, that's why I haven't tried higher doses to see if it could better help with my other symptoms.

My bet is that neuroinflammation was causing my insomnia and somehow, the thiamine tweaked it, relieving my insomnia. Although I do think there is at least one study that found benfotiamine (a form of b-1) effects microglia.

 

[ljimbo423]

From the paper-

For a devastating disease with obvious evidence of chronic inflammation this is remarkable:

the defects in ME/CFS seem to remain benign in nature rather than destructive or cytopathic (which is not to say that secondary dysfunctions and even tissue damage may not occur in ME/CFS, yet this seems to happen to a surprisingly limited extent when measured against the severity and depth of
the pathology involved).

As a matter of fact, if tomorrow a cure for ME/CFS was found, I would expect the vast majority of ME/CFS patients to rise out of their misery like phoenix from the ashes.

 

[ljimbo423]

Another quote from the paper-

*Physiologic pathways basically means normal pathways. I looked it up.

Possibly, ME/CFS is playing on physiologic pathways that are normally only activated for short periods of time and under unusual circumstances (like fighting a disease or other threats) - and that for some reason have become "hijacked" at the onset of ME/CFS and from then on have remained perpetually activated.

Edit- I wonder if the "hijacking" they refer to could be caused by "primed" or "sensitized" microglia" in the brain, like ME/CFS researcher Jarred Younger thinks.

 

[Consul]

Edit- I wonder if the "hijacking" they refer to [...]

Metabolic trap maybe

 

[ljimbo423]

Metabolic trap maybe

Possibly. I think it would need to cause neuroinflammation, for that to be true.

 

[Wishful]

This statement: "As a matter of fact, if tomorrow a cure for ME/CFS was found, I would expect the vast majority of ME/CFS patients to rise out of their misery like phoenix from the ashes." caught my eye too, because the temporary remissions convinced me that it was possible to simply snap out of the ME state.

So what is your gut feeling about the source of the neuroinflammation @ljimbo423 ?

My feeling is that immune activation of any sort can initially trigger ME, which then gets locked into a positive feedback loop. One hypothesis is that glial cells become extra sensitive to cytokines or other chemicals, so they trigger even on normal levels of these chemicals, which causes them to release more chemicals which activates other immune cells to release more. Researchers haven't found abnormally high levels of these chemicals in our blood, but if the glial sensitivity is high, it doesn't require abnormal levels to trigger them. The brain doesn't need to show high levels of inflammation to affect glial function and thus neural function. Think of it as a smouldering fire rather than an open blaze. I wonder if any of the neuroinflammation studies have been done on PWME during peak PEM.

A leaky gut would be a source of extra inflammatory signals, which would worsen ME, but isn't likely to be the cause of ME for all victims. I think that fixing a leaky gut might reduce some people's ME, and could possibly switch a few people out of ME, but I don't think that it would cure ME in most PWME who do have a leaky gut.

As for spinal problems, I think they'd qualify as an extra inflammatory signal. It's damaged or stressed tissue, so immune cells would activate and release cytokines.

For those focused on mast cell issues, I did notice some mention about mast cells and astrocytes 'working hand in hand' or some such thing. I assume that means that mast cell activation would activate the astrocytes too, and maybe abnormal astrocyte function would make the mast cells misbehave as well.

 

[Martin aka paused||M.E.]

Another quote from the paper-

*Physiologic pathways basically means normal pathways. I looked it up.



Edit- I wonder if the "hijacking" they refer to could be caused by "primed" or "sensitized" microglia" in the brain, like ME/CFS researcher Jarred Younger thinks.

I talked to him on the phone two weeks ago and asked the same question and he said „for example“

 

[ljimbo423]

I talked to him on the phone two weeks ago and asked the same question and he said „for example“

You talked to Jarred Younger? What did he mean by "for example"?