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I think it's extremely unlikely that ME is a classical muscle disease, however even if it is predominantly a central or peripheral neurological phenomenon (I believe it is,...), mitochondrial and endothelial dysfunction are probably unavoidable in the muscle tissue for anyone more severe than...

I definitely agree with you that there is no evidence—apart from a slight increase in CRP in the DecodeME dataset—for ‘classical inflammation’ in ME/CFS as it is currently defined. I think there might be evidence for micoglial activation (to use your preferred term) with as of yet unclear...

Sure. Understanding more about the spark might help in understanding the mechanisms, though.

I am not sure what makes you think that. You could have 10 different pathogenic/inflammatory triggers causing the same downstream causal pathway patholgy in people prone for ME/CFS, but finding 'the missing link' via just one of these triggers (and if it's by accident) might illuminate the whole...

I think I understand what you are saying, but that seems quite arbitrary? I understand that's part of the current diagnostic criteria of course, but that might be a mistake. It’s a bit like an electrical short circuit and a house fire: of course the short circuit isn’t the fire itself, but the...

Infection always (?) leads to classical inflammation. Is that right, @Jonathan Edwards? And if not, it's only because the immune system doesn't detect it?

I don't think we know that, my own case is actually quite exemplary of that. When I say I had increased CRP during mild/moderate ME - that's my retrospective assessment. I was sick but it was years before a formal diagnosis. It's impossible to know what might be prodromal or early/mild disease...

That’s just how the phrase is currently used by, I would say, the majority (?) of researchers in the field. It might not be the most useful or correct term, but it is the one being used. You can seek treatments for Malaria without renaming it or believing a HEPA Filter will solve the issue. I...

Peripheral “classical” inflammation = swelling, heat, infiltration of neutrophils, increased CRP, etc. Neuroinflammation (microglial inflammation) = microglia and astrocytes producing cytokines, reactive oxygen species, and signaling cascades, but without the classic peripheral signs. (I...

A 'surplus' in mitophagy taking out mildly damaged mitochondria can over time lead to decreased numbers of mitochondria. Moreover, mildly damaged mitochondria are still producing energy which is why in classical mitochondrial disease treament isn't as 'straightforward' as improving mitophagy...

I completely agree. Which is why I find it questionable to say that 'no structural changes' have been observed in ME/CFS patients. Something that's being pushed on here quite a bit. Mirostructural brain changes have been observed in ME/CFS using advanced MRI techniques, findings are still...

That's just a matter of definition, I guess. My hunch is that we can't know for certain whether mental health issues predispose to or are MS yet. Even if we would understand the whole process of every individual's MS mechanistically (we are not even close) you would have to draw a line at some...

People don’t just get Alzheimer’s, Parkinson’s, or MS overnight. These diseases begin silently, often decades before diagnosis. ME/CFS doesn’t appear out of nowhere, either. That there is an increased likelihood of coming down with ME/CFS or LC after an infection if you had prior mental health...

I haven't seen it, but that's huge if true. It wouldn't be very surprising, it seems very unlikely you can get to a state like severe ME without 'inflammation' - past or present - despite what some people on here think.

Oh definitely, I am not arguing with that at all. I am just saying the surface level analysis, while obviously incomplete, is not wrong. That this adminstration doesn't take their own analysis very seriously and/or takes the wrong actions to ameliorate the situation is very obvious. They just...

RFK and his lot are obviously morons. That said, all but one of these bullet points are probably true. I don't think most Europeans appreciate how bad nutrition really is for the average child in the US, for example. Food deserts are a real issue. The accumulation of environmental chemicals...

That's the kind of research we need much more of for ME/CFS. Neuroimaging work (in a broad sense) is a very sensible investment, I believe.

I can't read the full abstract, let alone the full paper, but I wonder how many neuroimaging studies with relatively similar results it will take for this to be taken more seriously and maybe more importantly for larger patient samples to be used. Elevated lactate levels have been observed in...

That's an interesting choice, as Wilde used Lady Bracknell to mock the ignorance of the Victorian upper class. "Ignorance is like a delicate exotic fruit; touch it and the bloom is gone", is an original quote.

How would it be apparent clinically if it was an 'oxygen issue?' It isn't apparent in MM, so why would it necessarily be in ME/CFS? (I am not saying ME is MM.) I have been part of a small group of patients who had a metabolon which found hypoxanthine increased in all patients (not exactly...