A Thought Experiment on Muscles

P.S. When I showed a short video of my funny gait to a psychiatrist, he named it 'motor fatigue'.

 

Consultant called mine pseudo-parkinsonism. Whatever that means!

 

N=1

I had weight trained in my youth and mainly worked in physically demanding jobs before being flattened with ME/CFS in my late 20s, so I was particularly aware of loss of strength in the early years of being ill.

There are two separate observation that were perhaps gross enough to be relevant - 1. Grip strength, this fell away rapidly at time of effort and was associated with what I'd interpret as ligament/joint pain within the hand and not as generalised weakness. 2. Weakness in the large muscle masses - biceps etc, post effort 12 hours plus, which was associated with measurable edema. The latter has become less pronounced as my ability to produce effort has reduced over time, the former however remains a notably disabling feature. Both are independent of PEM and, of a longer term and more tenuous observation of the main muscle masses fluctuating between becoming 'spongey' associated with muscle specific weakness and a more normal state accompanied by reasonable level of strenght in those muscles.

 

@CRG you’ve reminded me of one of my experiences. In the first 2 years of post-covid-ME/CFS I really struggled to use my muscles.

I used to describe it as the same experience that you have when you walk with someone that has a higher pace than you, and you have to constantly put in extra effort to keep up. I experienced that with everything, even moving my hand to grab the glass on the table by the sofa.

After I stopped exercising it partially went away. Now that I’m bedbound, it mostly occurs when I have PEM and often almost as a warning sign if I do anything physical for too long (like washing myself with a cloth). But I do not notice it when doing minor tasks (relative to my capabilities) when not in PEM.

 

I often find it interesting hearing how similar some of the descriptions of impacts are (qualitatively if not quantitatively) for people doing things like running or swimming are, to how I would describe impacts from say holding my arms up to trim my hair or trying to walk up a few stairs or even having someone talk loudly and quickly to me for a few minutes. That if nothing else tells me about commonality of whatever is underlying this. Which seems positive.

While the reservoir/tank theory is appealing, this description really doesn’t fit for me. In that it works one way, cumulative activity can be a problem. But not the other, sometimes cumulative activity doesn’t cause a problem and sometimes I can be hit out of the blue by an activity I have been managing fine.

I am severe and the answer is yes sometimes this is the case but no not always. I can be well rested and feeling ok, do an activity but get PEM and be very surprised.

 

I’ve never argued that there’s no knock on effect. Quite the opposite. Please see previous messages.

the reason for looking at NAD/NADH ratios is they provide a clear explanation of many of the experiences outlined in this thread—that PEM follows a distinct sense of “running out” of energy and having to push forward.

there’s some kind of signaling that must be triggered by that “running out.” I’ve already theorized what that might be.

why can’t we “just focus on the signaling”? Because it seems like nobody is experiencing PEM after only negligible activity except for very severe folks, in which case ‘negligible’ activity would not be negligible and still fits with the redox theory.

so any theory on signaling alone would need to account for why some but not all activity is a trigger. I have yet to see a convincing

 

Thanks for sharing your experience and thoughts! I suspect that the dynamics end up looking different for more severe folks.

in the instance where you’re hit out of the blue, is there still a lack of stimulation or otherwise taxing experience in the days before? I’m sure it might be quite hard to gauge.

for example, I am imagining a situation where someone was talking loudly and it happened for several days. Even if it didn’t trigger PEM, it was taxing. The overall energy ‘budget’ got used up slowly. So on the third day, an activity that normally you’d be able to handle ends up being the straw that breaks the camel’s back.

I can only speak from my experiences being mild/moderate—if I was in a vicious PEM spiral where pushing myself through PEM kept triggering more long term PEM, then my overall thresholds dropped quite a bit.

Activities that I managed well previously suddenly triggered PEM, but only because the threshold for “overdoing it” had been lowered overall due to my energy deficit state.

Do you see parallels with your experience?

 

That's not really true, though.

I've never been severely ill, but PEM can be triggered by both environmental stimuli (mostly noise) and eating certain foods. Neither demand much of skeletal muscle, yet they're still triggers.

 

I’ve experienced that as well! To clarify, I don’t think exertion is limited to the muscle. My NAD/NADH ratio theory definitely would not be limited to the muscle. It’s just a common but not exclusive starting point.

I’ve definitely had it from cognitive exertion or, like you, in response to things that I didn’t digest well which would make my stomach work very hard.

my point is just that I’ve never experienced PEM and not been able to point to some exertion as the cause.

Taking a stimulant reduces the time lapse for PEM for me, which makes it really clear what the trigger was. But even before the stimulant, I could pretty much always draw a connection when I was diligently keeping track in my journal.

added: for someone who is more severe, they will likely have a much harder time identifying everything that is meaningfully using up their energy and keeping track of it. I have the luxury of ignoring a lot of small “costs” unless I’m already in pretty bad deficit

 

Are you more accustomed to using your arm muscles that way than you are using your leg muscles the way that causes PEM? For me, it seemed that it was unaccustomed muscle usage that triggered PEM.

 

This is why I don’t think it’s a problem for the redox theory that the brain is metabolically active all the time with small fluctuations. In fact, it would explain why most of us report near-constant brain fog that just varies in intensity.

what matters is the “tipping point” that leads to some stronger signal, and that tipping point would be highly variable depending on baseline capacity and prior energy expenditures, as well as other factors which affect energy availability and usage.

That tipping point could easily be reached by a ‘small’ amount of exertion in certain cases, like processing sensory stimulation.

I agree with Jonathan that the brain is quite a different metabolic and immune environment than the muscle. But there will inevitably be overlap, which helps narrow down the search for that elusive ‘signal.’ It would have to be something that can be triggered by the same metabolic shift in both skeletal and muscle tissue (and other organs that people have linked to PEM).

Furthermore, it needs to be something that can travel in the body at high enough local concentrations.

 

This was really great information, thanks for sharing! It’s really encouraging to see others share experiences that are very close to mine and that fit the pattern I’ve sorted out for myself.

One person’s experience wouldn’t be the basis of a theory, but a strong consensus is great supporting evidence.

 

That's very interesting. I've only got to page 2 in this thread but this has triggered a thought I've had before. I've always said my illnesses started suddenly after an infection because that was when I went from being able to lead a normal life to suddenly feeling very unwell and being very incapacitated, but looking back I don't think I had been very well for about 4 or 5 years before I became unwell with ME/CFS. I was unusually tired, kept picking up infections, and I had some unexplained joint problems which prevented me playing sports. However, for about a year before the joint problems, when I was still playing team sports, I noticed that I seemed to get unusually stiff/sore muscles after intense exercise, to the point that I found it difficult walking normally and particularly difficult walking up and down stairs for much longer than my peers. It felt to me as though I might either be getting an unusually high build up of lactic acid, or that it was clearing unusually slowly. Of course, that might be completely irrelevant to my subsequent illness but it might not.

Since I've had severe ME/CFS I've never really complained of muscle pain as such (unlike when my CRP went through the roof and I had screaming muscle pain). To me, it feels like something builds up after exertion which has a toxic effect on my muscles and brain.

Sorry this is written in haste before reading other comments.

 

I’m not sure there’s much more I can add. Yes and no. Sometimes it’s the case, sometimes not. Therefore to me there is no clear cause and effect as you seem to experience. I used to spend a lot of time tracking and trying to understand this and gave up because there was nothing 100%.

Maybe there is a reservoir somewhere as you describe, but that feels downstream of any cause to me. Perhaps this gives rise to the inconsistency?

 

@jnmaciuch I have not been able to follow the entire thread so you might have described this already. But do you have any thoughts on why your hypothesis happens?

Why and how would someone that were previously healthy go into the state that you describe?

And why and how would someone get out of it seemingly on their own, but not most?

 

@Jonathan Edwards mentioned that mental exertion uses little extra energy, so it probably doesn't fit with thinking triggering PEM through simple energy demand.

In a nutshell: normal walking burns over 200 calories an hour. Thinking uses maybe 10 calries an hour.

Some figures from this BBC article illustrate the point:

Total brain energy demand = about 20% of total body energy use, say 500 calories a day (20 calories an hour)
If we were asleep all day, we'd use about half that. And most of the rest "is concerned with the largely automatic process of controlling your muscles and processing sensory input".
So maybe 80 calories a day for thinking tops. That would be 5 calories an hour overy 16 hours
For comparison, walking at normal speed uses over 200 calories an hour.

I'd previoiusly liked the idea that simple energy demand - mental or physical - triggers PEM. But I hadn't done the maths.

 

And perhaps equally important doing something less cognitively demanding doesn't require more energy (in the sense of ATP) than doing something less cognitively demanding, so from that point of view listening to a podcast shouldn't require more energy than playing chess, doing theoretical physics or doing something else which requires more thinking (at least if you're not engaging in other physical activities on the side). So from an ATP perspective not crashing whilst just existing can't explain crashing from "thinking harder".

 

Yes, this is one of the puzzles, but it must also be a clue about what is going on, and particularly what isn't going on. It is frustrating that so many people seem to overlook this when speculating about possible mechanisms.

Interestingly, Daniel Kahneman made this mistake in his book Thinking Fast and Slow, in which he claimed that blood sugar was significantly affected by high intensity mental exercises. I was aware of the mistake because of a conversation I'd had with a physician about the puzzle of how PEM can be triggered by mental exertion [when it doesn't significantly affect glucose uptake]. When I wrote to DK to point out the mistake he replied to say the claim was based on a questionable study and that he wouldn't make that claim again, but it made me wonder how widespread the misunderstanding is.

Another puzzle is why cognitive function can be so badly affected by PEM. People can be very physically weak/exhausted and unwell with other conditions without their cognitive function being affect in the same way, or to the same degree, that it is with ME/CFS.

[Edit in brackets above]

 

Maybe there are some clues in MS?

I keep coming back to my uncle with severe MS, he’s the only one that understands PEM. And he seemingly has many of the same cognitive difficulties that I experience in PEM.

Edit: I’m not sure I can claim he has delayed symptom worsening. But he understood it immediately.

 

I don't really know too much about MS but I watched the documentary about Selma Blair, an actress who has MS. And there was a scene where she was sitting in front of the camera for the documentary, talking about something and as she was talking, her speech started to become more and more slurred, then she sounded like someone with some kind of facial paralysis, her speech became unintelligible and eventually she just stopped talking and looked at the camera hopelessly. It was explained that this was due to too much sensory stimulus.

This is not PEM, but I found this kind of overload really interesting.