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Allow me to add chronic inflammation from stress to the pathogenesis. Overtraining, in particular, has been one of the more common causes MECFS. Training without letting your body recover sufficiently will lead to chronic inflammation, which in turn can lead to overtraining syndrome which is...

Ha, this was exactly what I was saying a while ago when they came up with the study showing vascular damage in long-COVID: whatever was causing vascular damage could be also causing neuro-inflammation. People, including those in academia, are too quick to extrapolate correlation to causation. Of...

This is what I've been think about too. I've heard that microglia has multiple states, not just on and off. Perhaps there is a state that it gets activated but not chew up neurons. Just my guess.

That would be impossible to know for something as complicated as MECFS. I was speaking only in theory. Personally, I'm not trying to model the entire MECFS. I'm just looking at the response to exertion. There are some universal observations, like being able to walk much farther if you...

Engineers and physicists (I happened to pretend to be one) would disagree with you. You DON'T have to work out the underlying mechanism to model the workings of a system if you have complete set of inputs and outputs. Inputs and outputs define function, in other words. To (sorta) paraphrase...

Not sure if the analogy stands. Monje study was specifically about brain fog of long-COVID, not long-COVID or MECFS in general. She gave COV-SARS-2 virus, which is suspected input for the long-COVID brain fog, not some random thing that can cause brain fog. Not sure about this one either...

Nobody should! I'm not a biomedical scientist. Could well be a case of seeing what I want to see, but most of the reports of microglial activation have been from fields unrelated to MECFS. I wouldn't call it a bandwagon unless they somehow colluded or glial theory is in vogue.

What purpose of reclassifying PEM would serve? Unless you think that different PEMs are different phenomena caused by different factors, it doesn't. Then you have to search for multiple different causes for, not only different types of PEMS, but also different worsening of symptoms. 3-4 hours of...

Microglial activation has been linked to concussion fatigue, age related fatigue, etc. It has also been implicated to brain fog in chemotherapy, GWI, etc. Are those proven? I have no idea. But it keeps popping up in fatigue/cognitive impairment just about everywhere I look. I think some do...

One Idea I had was to knock out all glial cells and see the MECFS patient recover. That would conclusively prove if they are directly involved in the chain of MECFS pathology. Glial cells are supposed to regenerate to full in 7 days as I understand, but I wouldn't know of ethics of such...

I'll have to disagree. You don't have to know what is under the hood to build a model to study or predict. This is routinely done in systems engineering. I can model a transfer function just based on the input and output to reasonably predict how the system will behave. And that is the point...

I don't know brain physiology well enough to comment, but here is a Statnews article and the actual paper. She is actually a chemo fog researcher, not MECFS or long-COVID. In ‘chemo brain,’ researchers see clues to unravel long Covid's brain fog (statnews.com) Mild respiratory SARS-CoV-2...

I used to be one (without mentally triggered PEM). Then I recently did a serious mental exertion trying to solve a problem (with a language design and transfer function modeling) for 3 days, something I hadn't been able to do while I was sick. The effect was nearly identical to biking 40 miles...

This is not surprising given the publish-or-perish culture of academia, medical/bio science community in particular. Theo Baker did an expose on this: Opinion | The Story of the Student Journalist and the Stanford President - The New York Times (nytimes.com)

Yeah, that "initial phase" will have to lead to a common mechanism, something like physical, mental -> inflammation -> PEM, for example. But physical->muscle change->PEM does not leave much room for a common pathway. I think it is best to leave it as muscle change after exercise without any...

No it doesn't, but we need to. The study presents muscular changes and putatively link it to PEM. It's possible that the observed physiological change is real, and I 'll have to assume it is till it fails to replicate, but it's hard to imagine PEM having separate mechanisms for physical and...

And what does this study say about PEM from mental exertion? The short answer is: it doesn't. Since PEM from mental exertion is the same, and nobody said they are different afaik, you have to wonder how a mental exertion could bring about muscle damage or amyloid deposit. I'll have to see a...

Yeah, no idea if microglia is the ground zero or not. But the microglial activation, perhaps as the result of the hypersensitivity somewhere else, could explain most, if not all, of the symptoms. Mental exertion triggering PEM seems to point to somewhere in the brain though.

(This is a long thread and I'm catching up whenever I have time:)) Michelle Monje of Stanford recently showed that the microglial activation in hippocampus area is the cause of the brain fog in long-COVID using the mouse model developed by Akiko Iwasaki. Would that count as some evidence? Also...

That's the thing: we don't know, and we are imagining something that we don't know without any proof. It's like saying there may or may not be God, and we should leave the possibility that there is. That's not how science is supposed to work. The "subtype" hypothesis should propose ways to test...