A Thought Experiment on Muscles

Thanks, I hadn’t seen that. I had a feeling I had seen a survey results of a similar question before, but I couldn’t say where.

But just to recap the results For those who have PEM after both physical and cognitive exertion:
Fundamentally different: 9 (13%)
Fundamentally the same: 17 (25%)
Some aspects feel fundamentally the same, others don’t: 42 (62%)

which is a nuanced result. We could say that 87% (corrected from the original 75%) of people say that at least some aspects are fundamentally the same.

I don’t think we should overinterpret such a small sample, but it might suggest there are separate mechanisms for muscle and cognitive-triggered PEM, and also a common mechanism.

 

Really helpful post, @Snow Leopard , thank you. I'm on tippy-toes trying to understand, so I hope you might be able to help clarify a couple of things.

I'm looking at what you have said here:

and what Amann 2012 said here https://pmc.ncbi.nlm.nih.gov/articles/PMC3351566

and trying to understand what it is that Walitt et al. did not understand that led to their story of:

Why did Walitt et al. resort to hypothalamic function to explain reduced motor drive if altered afferent feedback could have explained it? Is it that they saw there was no peripheral fatigue but hadn't reckoned with the excitory compensation mechanism, so they should not have concluded that there was no peripheral fatigue? If so, how should they have measured peripheral fatigue? Or is it central fatigue that they got wrong? Because this sounds like what they termed effort preference:

Can you point me to a more recent summary than Amann 2012?

My questions might make no sense, so just explain whatever does make sense!

 

Thanks for the helpful posts. I like the idea of focusing on afferent nerves.

 

Thanks so much for your explanation of all this. I’m somewhat familiar with some of the research on metabolic sensing, but it’s quite out of my depth. This was very helpful, and I’m very encouraged that it seems to line up with that I’m hypothesizing on the cellular metabolic level.

I’ll have to go back to the literature to understand more about some of the aspects you mentioned.

And side note, I have the same experience as you re: physical and cognitive PEM.

 

Might be a stupid question, but do we know if EMS can cause PEM through muscle contractions? Or does PEM come more frequently through more "systemic" exertion?
Say you could use EMS to contract your quads as strongly as they would contract when lifting 50 kg on a leg extension machine. One group gets this EMS, the other lifts 50 kg on the leg extension machine.

Would we expect PEM and in same strength in both groups?

In the leg extension machine, I'd expect the cardiovascular system to be more involved?

On the other hand, I guess it's similar to the hand grip tests, just that the brain is not actively telling the muscle to contract.

Just something that crossed my mind and might well be irrelevant.

 

That's an interesting thought. If you don't get as bad of PEM from externally activating muscles, maybe that's evidence that it has more to do with something on the pathway from the brain to the muscle.

I just worry that there is so much variance in how PEM presents itself (different delays, different amounts, variance from it being subjective, different presentations even within the same people on different days, etc) that you'd need a huge sample size to detect a significant difference. And I can't think of how this would be blinded.

Maybe something to come back to if/when we have an objective marker of PEM.

Edit: Though it might be worth checking in a few people in case the effect is actually really obvious.

 

I believe I’ve maybe heard of people that have gotten PEM from a physio moving their legs. But that might be because they were very severe and couldn’t tolerate the situation in the first place.

 

FYI - Stanford has a Biolog Omnilog instrument that measures mitochondrial function and in my limited understanding you can try various compounds to see how they affect the function of the mitochondria. I believe it is available to use if any researcher wants to come and run experiments on it.

The manufacturer has a new instrument that has superseded it called Odin but I think it uses the same mitoplates for analysis.
https://www.biolog.com/products/metabolic-characterization-microplates/mitoplate-phenotype/

 

Thanks for the info! I’ll definitely look into whether it would be of any use for testing my hypothesis.

 

That’s a great point. I know a couple pediatric healthcare workers, especially those working in infectious disease, who share your thoughts and concerns here.

They’ve affirmed that you’re basically 100% reliant on parents to notice a difference, and we already know plenty of horror stories of parents dismissing painful musculoskeletal disorders as “growing pains.”

Even as an adult, I don’t think many of my family members could accurately describe the characteristics of my illness (without defaulting to how I’ve already described it, if they’ve been listening).

Puberty also happens to correspond with when children might become articulate enough and good enough at comparing their own experiences over time that they can start reporting for themselves. I suspect it’s massively underdiagnosed in younger children.

 

I think the data are reasonably convincing though, having looked at graphs from at least two sources. Diagnostic ascertainment issues may well be relevant but ME/CFS is not trivial and the paediatric units would by now have picked this up I think. And as much as anything ME/CFS will present at school and I suspect every head teacher can tell you the ME/CFS age incidence profile. I wondered about EBV but it really doesn't fit - late acquired EBV is almost certainly very dependent on kissing, as the old name implies. The infectors who had early EBV have very low infectivity otherwise.

The profiles in boys and girls rising in adolescence are also different.

Interestingly, there is an analogous situation for seronegative spondarthropathy. It manifests in the student age group because of chlamydia infection but we also have good reason to think that it manifests as knee oligoarthritis in adolescents because of growth events (not puberty). In this case it is a change in structure of ligament insertions that occurs at points where growth is about to cease. Ankylosing spondylitis of the spine in most cases has an onset around the time of achieving maximum height.

 

Not sure it’s relevant, but I was reminded of a peculiar aspect of my ME/CFS experience yesterday because I overdid physical activity for the first time in a few months.

Essentially, I walked 20 meters to put away some plates before I walked an additional 10 meters in total in addition to using the bathroom. I normally don’t do those activities back to back but I forgot my own rules.

While sitting on a chair in the bathroom I started experiencing widespread muscular pain in the entire body (especially upper) and a substantial weakening of the muscles. I don’t think it was PoT/OI related because that usually comes with other symptoms as well.

The pain and weakness lasted all night.

 

Exactly, was just wondering whether passive vs active exertion could make a difference and if so, if it could give us hints to pathophysiology of PEM.

As for blinding, indeed quite difficult but maybe not entirely needed? Maybe a dose response trial could work as well - using more and more current or more and more weight and see if there's a difference. Idk I'm no expert in trial design.

Then again, was just something that crossed my mind.

 

We have reason to believe that PEM can result from an accumulation of exertion. So I think it would be extremely difficult to design a trial that is able to isolate the effect of external activation of the muscles. It would be an interesting thing to test, though.

 

1) Yes
2) Yes

For me it felt more like the PEM came from sensory overexertion of having someone touch me than my legs being gently moved.

(And just generally, for what it’s worth, when i was extremely severe it felt like literally anything could cause pem, even moving my toes too much)

 

Have you ever experienced temporary paralysation? Not «I can’t move because it causes PEM» but «I literally can’t move»?

I have on three occasions. Two were during extreme PEM and the last one just came out of nowhere many weeks into a crash. I slowly regained movement over many hours.

It felt like I wasn’t able to get my limbs to move even though I could feel them.

 

Yes have experienced decently often.

When in PEM it feels like I have to exert far more mental exertion to get my body to do things. Like my brain is not communicating with my body as well or my body is not accepting the signals unless they are very strong. And well sometimes I just cannot get to that level of mental energy required. To push through. So my limb(s) are essentially paralysed.

It's like a more extreme version of that feeling of feeling like you have weights weighing down on your entire body that seems common among less severe people w ME as well

 

Exactly! Great explanation.

 

Yep. Mostly the same pattern: wake up unable to move my arms and legs, which passed after 45 – 60 minutes. It left me with really heavy-feeling muscles, but I was more or less okay once my limbs had come back online.

It happened enough times that for my whole working life I set the alarm for three quarters of an hour before I needed to be out of bed, just in case. It wasn't weakness or fatigue, it was that my limb muscles (the others were unaffected) wouldn't contract at all.

I don't think it's common in ME/CFS, though, and I've never heard anyone describe that particular morning pattern.