Myalgic Encephalomyelitis is clear to see in the blood

[Oliver3]

I agree a spinal tap is not sufficient.
The vast majority have a myriad of problems not just limited to thr brain.
I.e vascular issues, , muscle issues, immune deficiencies, hormonal issues not directly related to the brain ir in feedback loops, collagen issues, leaky gut issues. You really can't say this disease is exclusive to the brain

 

[Wishful]

You really can't say this disease is exclusive to the brain

No, but many (most? all?) of the symptoms could be due to brain cells not doing their job properly. Heart failure doesn't kill you; it's the failure of the brain due to lack of blood flow that ends your life. Lack of blood flow, or low oxygen, would be a biomarker for that, but that's far easier to detect than the failure of possibly just a few brain cells whose dysfunction causes serious symptoms elsewhere in the body.

I was going to say "effects" rather than "symptoms", but so far they haven't found any clear markers of physical effects in the body. Some PWME can't get out of bed, but there's no apparent physical cause (muscle metabolism or whatever), but that doesn't rule out a malfunction in the control circuitry in the brain. We don't have the technology to readily identify that sort of malfunction, and it probably wouldn't show up in spinal fluid. One transistor failing in a CPU can crash your computer, but measuring the supply voltage or current isn't going to reveal that (one transistor out of billions, switching at GHz frequency). The marker is there, it's just buried in too much noise to be practical to dig out.

So yes, there might be some physical measurements of collagen, muscles, capillaries, etc, that are due to ME, but it's buried in too much noise and too far removed from the core dysfunction to be useful.

That's why I favour the black box approach: vary some inputs and hopefully find something that causes a reliable response in ME symptoms. If someone had studied my body when I had a reliable way (cuminaldehyde) to switch my PEM off, that might have revealed something. Dynamic abnormalities are much easier to identify than static ones, especially when they are weak abnormalities in a lot of noise, and what's "normal" varies a lot between individuals.

 

[Oliver3]

No, but many (most? all?) of the symptoms could be due to brain cells not doing their job properly. Heart failure doesn't kill you; it's the failure of the brain due to lack of blood flow that ends your life. Lack of blood flow, or low oxygen, would be a biomarker for that, but that's far easier to detect than the failure of possibly just a few brain cells whose dysfunction causes serious symptoms elsewhere in the body.

I was going to say "effects" rather than "symptoms", but so far they haven't found any clear markers of physical effects in the body. Some PWME can't get out of bed, but there's no apparent physical cause (muscle metabolism or whatever), but that doesn't rule out a malfunction in the control circuitry in the brain. We don't have the technology to readily identify that sort of malfunction, and it probably wouldn't show up in spinal fluid. One transistor failing in a CPU can crash your computer, but measuring the supply voltage or current isn't going to reveal that (one transistor out of billions, switching at GHz frequency). The marker is there, it's just buried in too much noise to be practical to dig out.

So yes, there might be some physical measurements of collagen, muscles, capillaries, etc, that are due to ME, but it's buried in too much noise and too far removed from the core dysfunction to be useful.

That's why I favour the black box approach: vary some inputs and hopefully find something that causes a reliable response in ME symptoms. If someone had studied my body when I had a reliable way (cuminaldehyde) to switch my PEM off, that might have revealed something. Dynamic abnormalities are much easier to identify than static ones, especially when they are weak abnormalities in a lot of noise, and what's "normal" varies a lot between individuals.

They're literally looking at muscle metabolism at the moment.
We are built different.
Referring to our bodies as simple machines doesn't cut it as we're massively complex. Is there just one computer in the human body. I doubt that very much. It's a system that's talks to itself all around the body.
Fir example, we don't understand the gut microbiology, the immune system,
Dynamic abnormalities? I don't think it's that simple in m.e.
The core dysfunction is eds anyway but that's going to show up differently in everyone

 

[cfs since 1998]

No, but many (most? all?) of the symptoms could be due to brain cells not doing their job properly. Heart failure doesn't kill you; it's the failure of the brain due to lack of blood flow that ends your life. Lack of blood flow, or low oxygen, would be a biomarker for that, but that's far easier to detect than the failure of possibly just a few brain cells whose dysfunction causes serious symptoms elsewhere in the body.

Multiple groups have described endothelial dysfunction, neurovascular dysregulation, impaired peripheral oxygen extraction, etc. These things happen in the body not the brain. The only way your conclusion can be supported is by cherry-picking and ignoring the evidence that exists.

 

[Wishful]

The only way your conclusion can be supported is by cherry-picking and ignoring the evidence that exists.

No, as Oliver3 pointed out, we're a mass of interconnected systems. One malfunction in one subsystem can affect others, which affect others, for who knows how many levels.

As for multiple groups describing those various abnormalities, I haven't seen any really definitive evidence, at least nothing along the lines of "90% of PWME have capillaries that are 30% narrower than expected for their bodies". Studies with small cohorts and results that just barely exceed a probability threshold aren't convincing me. There's a lot of pressure to publish positive findings. I think it's a matter of perspective: if you are desperately wanting some sign of progress, you consider scant evidence that supports your beliefs as strong, while a skeptic considers it weak. Even if you gathered a panel of world experts to judge the evidence, they'd probably argue for a long time about it and maybe reach a we're not sure" conclusion.

I'm fairly sure than none of those studies provides strong evidence of those small abnormalities being the cause of a symptom rather than an effect of some malfunction elsewhere in the body (or brain), possibly far removed from the root cause.

Claiming that the weak evidence that supports something you want to believe (that ME is related to muscle or endothelial or mitochondrial dysfunction) is valid is cherry-picking too.

 

[Oliver3]

The vascular system is an integral part of m.e. tho.
The open medicine foundation are finding muscle abnormalities.
I watched Ron's lecture from last year and Chris Armstrongs recent chat. Their ideas seem to be converging on the energy switch in m.e. metabolic dysfunction. Combined with muscle dysfunction abd a shut down in nitric oxide production.
The findings are coming up frequently.
There is more than how the brain is acting for sure.
Mitochondrial dysfunction is an important part of many diseases, but this constellation of symptoms that keep cropping up suggest a phenotypical reaction to stressor of any kind.
Of course this will present slightly differently on ameveey patient.
If memory serves me correctly, they're going to elucidate on the reasons that shut down occurs.
He mentioned anti purigenic therapies, also mentioned by tmron Davies, to restore healing cycles in the organism. There are cardiologists researching anti purigenic therapies for high blood pressure and cerebral vasoconstriction.
Hypotfusion in the brain is another biomarker that keeps occurring.
When you start adding all these things up. The constellation as I said is a number of phenotypical responses to stressors of infection, mental stress, ecogenic stress in general.
I don't think you can say these are weak connections. They keep appearing

 

[Oliver3]

No, as Oliver3 pointed out, we're a mass of interconnected systems. One malfunction in one subsystem can affect others, which affect others, for who knows how many levels.

As for multiple groups describing those various abnormalities, I haven't seen any really definitive evidence, at least nothing along the lines of "90% of PWME have capillaries that are 30% narrower than expected for their bodies". Studies with small cohorts and results that just barely exceed a probability threshold aren't convincing me. There's a lot of pressure to publish positive findings. I think it's a matter of perspective: if you are desperately wanting some sign of progress, you consider scant evidence that supports your beliefs as strong, while a skeptic considers it weak. Even if you gathered a panel of world experts to judge the evidence, they'd probably argue for a long time about it and maybe reach a we're not sure" conclusion.

I'm fairly sure than none of those studies provides strong evidence of those small abnormalities being the cause of a symptom rather than an effect of some malfunction elsewhere in the body (or brain), possibly far removed from the root cause.

Claiming that the weak evidence that supports something you want to believe (that ME is related to muscle or endothelial or mitochondrial dysfunction) is valid is cherry-picking too.

I understand your desire to want to focus on the brain because ut fits your symptoms. Fair enough. But the evidence for certainty are even more scant regarding issues of the brain.
I keep saying it. This is a connective tissue disease with everything else being downstream of that weakness.
There are numerous studies coming out in recent years saying thirty to fifty percent of m.e. and long covid sufferers are hypermobile.
Or meet citeria for the beighton scale.
the problem with that is the Beighton score us such a numb measurement. They haven't found the genes for heds and score to see how bendy you are justcisnt accurate enough a way to diagnose or realise the extent of eds in somones body.
I hope I'm wrong but it's just too common a finding

 

[Wishful]

I don't think you can say these are weak connections. They keep appearing

Actually, I can. Themes that are popular, for whatever reason, will spur a lot of "me too" studies based on looking for anything that even slightly supports the belief. It's not that hard to rig a study to show desired results. I haven't seen anything that convinces me that ME's core dysfunction is whole-body mitochondrial dysfunction or connective tissue problems. I don't have any apparent connective tissue problems, so it'll be hard to convince me that's the cause of my ME. Connective tissue problems don't fit the rapid switching of ME states either.

I can accept that ME could cause connective tissue problems downstream, or that comorbid connective tissue problems could worsen ME. I think ti's unlikely to be part of the core dysfunction, or even a critical part of the feedback loop that seems to be involved. It's just too slow to fit the rapid switching.

 

[Oliver3]

Sorry but that's just not the experience of so many m.e. sufferers. Your also making creative leaps to call the evidence weak

Like I said, what research are you referring to to say tgis is a brain disorder in origin.
As I've pointed out, akaheimers is now thought to originate from the kidneys first.

Ron Davies originally thought this was a diseqse of the kidneys coincidentally.
You're very unusual ( and I'm not saying this to other you, uts just an odd but relevant expression of the disease, in that you only get pem through mental / emotional exertion( for most if us, it's any kind of exertion .
It's so obviously phenotypical that ignoring that fact seems obtuse.
I can post the many studies saying all-round 50 percent of m.e. and long civid suffers are classically hypermobile? Or just Google glthem.
How many others have atypical connective tissue problems like Jen brea..I don't see how it's possible to call ut weak evidence