What could it mean biologically that both physical and cognitive exertion can cause PEM?

alex3619 said:
This does not fit with the spontaneous temporary remission many of us have experienced though.
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Yep. For it to work as a model, your brain would have to be able to clear most of whatever it was during a single night.

That's why I find it easier to conceptualise as a signalling problem, perhaps akin to what happens when you get one of those 24/48-hour viruses. It passes and you wake up feeling back to normal. You know it's gone as soon your brain's fully awake.

That's happened to me twice in ME/CFS. The first one was so abrupt I found myself struggling to control my legs when I first got of bed—I hadn't had muscles that responded that eagerly for years.
 
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Kitty said:
It was only after my former manager described it to me that I was able to recognise it properly myself.
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I self monitor playing video games a lot, in order to identify when its necessary to rest. I tend to become erratic, lose focus, lose ability to set and achieve goals. In effect, in the games I play, its less about getting things done than running around and not doing anything. I also lose the capacity to respond to challenges. I can still talk though, but my cognitive focus is different.

If I do not rest it just gets worse. If I rest I can come back to my game in a few hours, or sometimes as little as twenty minutes. I also find it better to switch between different games with different cognitive demands. I am also finding something similar with using the 30s rule to do resistance training or regular chores. I rotate body areas and types of exercise.

I did not do this kind of self reflection when I was working, all those years ago. However as a student I would structure my time for half an hour or an hour studying, and the same for resting or a different activity. I got more done that way.
 
Utsikt said:
Some googling told me that FFI results in an accumulation of misfolded cellular prion proteins (PrPc).
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Maybe relevant new study:

S4ME thread: Amyloid-forming potential of Betacoronavirus including SARS-CoV-2, 2025, Haddad et al (Heliyon)
The findings of this study imply the high potential of some Betacorona viruses, including the Wild type of SARS-CoV-2 and some variants, such as Gamma and Delta, to develop prion-like sequence which can act as a regulator for viral infections.

[...]

In conclusion, the Q\N propensity scores might indicate the amyloid-forming potential or priogenicity of any short viral amino acid sequence and it can act as a regulator for viral infections and pathogenicity.

It is proven that priogenicity can cause prion protein aggregation where the human body cannot get rid of. The findings of this study imply the high potential of Betacorona viruses to develop prions. One of the most important negative impact of prions is on the nervous system where any accumulation of prion protein in the astrocyte may lead to an acceleration in neurodegenerative diseases like Creutzfeldt-Jakob disease (CJD) and Scarpie or even other manifestations like renal failure and heart attack. It is highly recommended that the developers and manufacturers of mRNA to exclude any coding sequences with high Q/N propensity scores that can be determined by any of the two adopted algorithms in this study the pRANK and PAPA.
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Would either require prions stick around after acute infection, or the infection persists. Also apparently only some variants.
 
I’m amazed at how many studies you find, remember and understand, @forestglip

I don’t have the head to search for things now, but I wonder if eg the MS-field has found anything related to EBV if the nervous system can be attacked by prions? I know MS is caused by autoimmunity, but maybe there are more processes involved?
 
Today, I'm suffering from what I've been calling post-high crash. I found nicotine patch still lying around on my desk and wanted to find out if it's still effective after months of 100F heat during the summer while I was away. I slapped on the whole patch (7mg), went way too high and crashed this morning. I spent 4 hours in bed already after spending 0-2 hours/day for weeks. 7mg was apparently too much -- I don't remember having the same problem with 3.5mg. This post-high crash sometimes happens spontaneously. I get high for no reason and pay the price the next day with familiar depletion and ache that goes with PEM.

Sasha said:
Does it indicate anything about the mechanism of ME/CFS that both physical and cognitive exertion can cause PEM?

Is it worth trying to clearly identify other possible triggers of PEM to help point at mechanism?
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I would certainly think so. A theory should be able to explain different triggers of PEM with the same underlying mechanism, the same way it should explain different triggers of ME/CFS with a single mechanism.

For what it's worth, I think different exertions produce the same thing which in turn triggers PEM. Whether it's physical, mental or emotional, they all produce inflammation. And that low grade inflammation could be triggering PEM sickness in people hypersensitive to it. People talk about unfamiliar activities triggering PEM even if it is not as intense. So, even a localized peripheral inflammation could be triggering PEM.
 
bobbler said:
Which makes me think of the term 'intensity' and I think it is @poetinsf (?) who has tended to use and underline this term and its relevance for the physical PEM side?
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Yeah, that might have been me. I use the term "intensity" to denote speed/weight, and "duration" for distance/time. It seems to me that the "damage" goes up exponentially as the intensity increases linearly. So, increasing your walking speed by 5% is equivalent to walking twice as far. I got the idea from watching Olympic skaters whose lap time drops about 5% whenever the distance is doubled. I tried different walking speed and that was pretty much what I got: I had to cut the distance by half whenever I increase my walking speed by about 5%. The problem, of course, was that I couldn't manage my daily activities precisely. So only way for me to be safe was to limit my walk speed to 90 steps/min.

[edit: grammatical]
 
Sasha said:
I've always wondered how come both physical and cognitive exertion can cause PEM. I'd have thought that moving around would have used very different biological mechanisms and energy expenditures than thinking, on the whole.
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As previously discussed, in many patients, the symptoms are not the same, depending on the triggering activity.

Four out of five people report differences:
https://www.s4me.info/threads/poll-physical-vs-cognitive-pem-same-or-different.16948/

Cognitive activity does not cause any additional fatigubility in my muscles for example, but it does exacerbate headache, brainfog etc for days.

In some patients it affects sleep which can mediate an increase in other symptoms.

Assuming that all triggers leads to the same symptoms is a fundamentally flawed assumption that has greatly held back research and led to substantial stigma against ME/CFS patients.

bobbler said:
can tell the difference between cognitive/sensory PEM and PEM that has been mostly physical for that reason - and the latter gave me both physical and cognitive/sensory symptoms where the cognitive/sensory just cognitive/sensory - although these days if I have my feet on the floor for too long when sitting that changes that.
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That is largely my experience too. Any muscular symptoms associated with cognitive exertion are actually due to how I held my body during that exertion, use of my eyes leading to eye pain etc.
 
Snow Leopard said:
Any muscular symptoms associated with cognitive exertion are actually due to how I held my body during that exertion
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I find the same with emotional exertion. Whether the emotions are positive, negative or mixed, there's a big change in how I hold myself. It uses a lot more capacity than, say, the bland neutral of sitting back listening to a factual podcast.

Laughing's probably worst of all. I laugh easily and a lot, and it's bloody knackering.
 
Maybe the different responses to different types of exertion is something we should try to highlight in a future fact sheet? Idk if there are any studies on it, but it should certainly be included in the next PEM-studies, and probably all exercise studies.

I also believe that there might be differences between year 1 and eg year 5, depending on what caused your ME/CFS in the first place.
 
I find a hot bath or shower a mixed bag.

It is kind of exhausting. OTOH, it does a nice job of relaxing and soothing aching tired muscles, and generally relaxing me.

Do often lie down and have a nap or quiet period afterwards. Not exactly energising, but in some way therapeutic.
 
Sasha said:
Problems with hot baths might be due to an exacerbation of orthostatic intolerance.
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When I was at my worst showers were difficult because of having to stand long enough and, as Trish points out, all the associated activity, however hot baths were impossible presumably related to the autonomic disruption. A bath would trigger an immediate worsening of symptoms whereas a shower if the right temperature would just add to the activity levels likely to trigger PEM.

Interestingly now I am a little better with orthostatic intolerance being less restrictive and better able to regulate my body temperature, I chose to have a bath rather than a shower because it involves less physical exertion.
 
I'm not sure if cognitive exertion causes PEM. Working for hours on something, especially to meet a deadline, often does cause PEM, but it could be the long periods of being upright and the tension in the body.

Re what a common mechanism could be if both cognitive exertion and physical exertion can cause PEM.

I have wondered it could be something to do with blood flow. I haven't thought too much beyond that, so what I write probably won't hang together.


Physical activity causes increased blood flow. Maybe cognitive activity does too, specifically in the brain. Could there be some ME/CFS specific effect of shear stress when the blood has to move with greater pressure? Could that somehow result in leakier blood vessels, with plasma leaking out into the tissues. Maybe it's easier for immune cells to get into the tissues too.

Could that explain headaches after cognitive activity?

Utsikt said:
And what about PEM from taking a bath? It doesn’t require more movement, but the stimuli seems to really mess with every single system.
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Heat stress might also cause increased blood flow.



Systrom's work I think suggested reduced oxygen extraction by tissues. Could it be that there is increased demand for oxygen in the tissues being used, but the blood isn't supplying enough? And there are downstream issues from that.

Might that help to explain orthostatic intolerance?
 
Hutan said:
Could it be that there is increased demand for oxygen in the tissues being used, but the blood isn't supplying enough? And there are downstream issues from that.
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This is partly where my current thinking is, but the decreased oxygen demand is due to both poor vasodilation and poor mitochondrial function.

ETA should be both demand and supply. The mitochondria has less demand, the blood vessels supply less. It might be these two are connected, one might be an adaptation to the other.
 
Hutan said:
I'm not sure of cognitive exertion causes PEM. Working for hours on something, especially to meet a deadline, often does cause PEM, but it could be the long periods of being upright and the tension in the body.
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I don't have OI, but I work mostly from bed to keep my heart rate low. I get PEM from cognitive exertion surprisingly quickly, but only if I'm working on something unfamiliar where I have to think quite hard. Routine tasks are not a problem.

I also monitor my heart rate and I get PEM even if it stays around my resting heart rate.
 
Hutan said:
I'm not sure of cognitive exertion causes PEM. Working for hours on something, especially to meet a deadline, often does cause PEM, but it could be the long periods of being upright and the tension in the body.
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Then why is it near universal in severe people that are completely horizontal that cognitive exertion causes PEM.
 
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