Preprint Guardian angels off duty? ME/CFS is Sustained by an Impaired Stress Response in the Central Nervous System, 2024, Renz-Polster

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Guardian angels off duty? ME/CFS is Sustained by an Impaired Stress Response in the Central Nervous System

Herbert Renz-Polster

Abstract
ME/CFS researchers agree that ME/CFS is a multisystem disease with a multitude of pathobiological features including endothelial dysfunction, immune dysfunction, autonomous dysfunction, reactivation of endogenous viruses, mitochondrial dysfunction and neuroinflammation. They disagree, however, upon the tie that binds all these findings together and thus the process which may ultimately drive and sustain the disease. Is this a central process – i.e. a dysfunction within the central nervous system (CNS)? Or is it a process outside the CNS - which then secondarily may involve all body systems, including the CNS?

Here I review the evidence that the pathobiological core of ME/CFS lies in a dysfunctional stress response in the CNS which impairs the physiologic adaptaion to exertion. As a consequence, tissues all over the body stay unprotected against the noxious effects of exercise and get hit unbuffered by the inflammatory and oxidative load that exertion brings along. Many body tissues and functional cellular units (including vulnerable parts of the immune system) thus sustain damage and dysfunction from exertion.

This hypothesis can fully explain the hallmark of ME/CFS: the time-delayed disease deterioration induced by physical, cognitive, mental, orthostatic, emotional or sensory stress. It can also fully explain all pathobiological changes observed in ME/CFS.

PDF (Not peer reviewed)
 
Has anyone ever proposed in a paper that the body’s stress response is completely normal for whatever is going on elsewhere in the body? It seems a lot rarer than the other way around.

I sometimes wonder why there is this preference to perhaps put the cart before the horse…
 
Herbert Renz-Polster is a pediatrician and researcher at the Mannheim Institute of Public Health at the University of Heidelberg. His parenting books, lectures, and media appearances have won him a wide following and made him one of the most respected voices in childhood development and education. He has four children and lives near Ravensburg with his wife.
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He is not really an ME specialist, English is dodgy but I cannot write in German myself so some credit is deserved but its no excuse for wild thinking.

I think there are references to some valid observations in the paper but it creates the impression he cannot see the wood for the trees.

Why does he jump at the CNS as causal? This is unjustified. The CNS is not the only tissue capable of organising a systemic response and the endocrine system can and does govern the CNS and the immune system can effect both, therefore the CNS is as likely to be downstream of the real causes as causal itself. The title implies he thinks the CNS is involved in self perpetuating ME/CFS. I really dont like the presumption involved in that suggestion.

Pointing at the CNS as causal because it is badly affected in ME/CFS, ignoring the host of other systems involved, without clear evidence of cause, is irresponsible given the history of the medical debate. Worse than irresponsible, it is biased and fails to appreciate the systemic breadth of the physiological dysfunction involved in ME/CFS affecting many tissues, organs and systems, including but by no means limited to the nervous system and if treatment was based on such assumptions it could be very harmful, even kill people, like the BPS psychologists regularly do. Attributing cause to the CNS for no good reason is far too close to conceiving of it as psychogenic for no good reason, amenable to CBT and LP, for my liking. I hope he is not responsible for the clinical care of children with ME/CFS as I view this as crypto-BPS and potentially harmful.

There is also a massive class error involved in confounding all CNS disturbing conditions like TBI and EDS with ME/CFS. ME causes CNS dysfunction but not all CNS dysfunction is caused by ME, even if it looks symptomatically similar, of course it does, if the CNS is disturbed by different causes you get similar symptoms because the symptoms relate to the functionality of the CNS which isn't working properly. Symptoms are a product of the tissue not the cause of damage to it.

The real question is why the body is not responding to physical stress, in a systemic fashion in ME/CFS.

hotblack said:
Has anyone ever proposed in a paper that the body’s stress response is completely normal for whatever is going on elsewhere in the body? It seems a lot rarer than the other way around.

I sometimes wonder why there is this preference to perhaps put the cart before the horse…
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IMHO when a response is so systemic and coordinated it looks like an evolutionarily adaptive response gone haywire, as that can explain the complex signalling in multiple systems all coordinated and leading synergistically to the same behavioural outcome and physiological strategy.

In ME/CFS the entire body has been given an order, do not exert yourself... why? The possibility of making such a coordinated response has probably evolved to divert physiological energy away from cognition and exertion towards other functions.

There are two options at that level of function which are growth and immunological response and you could consider hibernation if we were a hibernating species but we are not. That does not mean genes involved in hibernation could not be adaptively involved in comparable processes.

Given the frequency with which ME/CFS onset is associated with immunological challenge, it looks like the immunological purpose is by far the most likely candidate for explaining this response. The question is why is the system diverting energy to the immune system chronically active in ME/CFS.

That is as much as I can do today.
 
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Yes, so did Garner...

https://www.healthrising.org/blog/2022/06/23/neuroglial-hypothesis-chronic-fatigue-syndrome/
How often did I say to my wife: “This is in my head!” This deeply felt notion of “something wrong in my head” made me curious about how the pathology of the central nervous system may be connected to all the things I knew about ME/CFS – including the symptoms and the many findings reported in the literature (like mitochondrial dysfunction, endothelial dysfunction, etc.)
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This is his bias.

He considers it feels like it is in his head because nerves are how one feels things, you cannot feel anything except with a nerve and ME makes your nerves act weirdly, this does not mean that having weird nerves causes ME.

All one can sense of ME is the way the nervous system is deranged by something else which causes it to become hypersensitive which in turn disturbs the balance of the nervous system, cognition, emotion, ANS, everything. ME stress and hypersensitivity can make people hypersuggestible IMHO. You can believe anything when you have ME, especially if you are desperate to make sense of it, this theory is clutching at straws.

His onset was 2016. That is eight years. It has taken me the best part of 38 years to compensate for the derangement.

Just keep going.

I am not a fan of this theory, hard empirical evidence is what we need. Belief and delusion, which is what this is, has always been the biggest obstacle to science. Nullius in verba... Prove it!!!
 
I think the best general guiding hypothesis we currently have, and the most likely to yield fruitful results, is that the known major systems in the body are probably functioning normally, but are being presented with a major physio-pathological load from an as yet unrecognised source, that is some combination of outside their sustainable operating parameters and invokes them to actively restrict (or send warning signals against) activity of all kinds.

But it is just a hypothesis.

I can see how that might be interpreted as a stress response, or impaired stress response, though it is technically neither.
 
Sean said:
I think the best general guiding hypothesis we currently have, and the most likely to yield fruitful results, is that the known major systems in the body are probably functioning normally, but are being presented with a major physio-pathological load from an as yet unrecognised source, that is some combination of outside their sustainable operating parameters and invokes them to actively restrict (or send warning signals against) activity of all kinds.

But it is just a hypothesis.

I can see how that might be interpreted as a stress response, or impaired stress response, though it is technically neither.
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It's yet another one of those situations where replacing stress with exertion, the body doing anything above just being alive, actually makes sense. Which is still not an explanation, so this is mostly tautological.

But with the creep of psychology into medicine, the word stress has multiple meanings that can be applied or morphed without revealing that its interpretation is different from what the patients mean or hear. Just like when psychosomatic ideologues pretend that they acknowledge that our symptoms are 'real', when by real what we mean is as we experience and report them, not the distorted version they invented to make them models seem relevant, what they actually mean by 'real'. Same word, different meaning.

But definitely any model involving dysregulation still makes far more sense here in the context of it actually being proper regulation of an upstream problem, a tree that bends in the wind even though the wind is not visible to the naked eye. The problem remains unknown in any such models, making them pretty much useless.
 
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