US NIH: Responses to NANDS Request for Information: How to advance ME/CFS Research

The effect of exertion is unpleasant. It's not immediate. Here it starts next day but 48hours sees it peaking - the descent time varies.

Energy impact is complex as it is not a constant, even for routine things :
I think at certain life stages ( puberty / menopause / if a child simply growing) the body's preprogrammed processes precedence can knock things out significantly as they consume a lot of energy and you can't avoid them.

Emotional impact is the hardest to predict/ manage/ gauge.

I thought the Myhill hypothesis on PEM made sense. Having depleted ATP/ ADP and limited recycling of AMP via whatever mechanism ( more energy intensive) to manufacture ATP from scratch takes time.

Having limited availability of cofactors doesn't help. Being at wrong core body temperature doesn't help.

I would agree re signalling probably being the issue, but does signalling alone account for the heterogeneity?

 

One thing I do not understand about the Myhill approach is why blood cells should show anything if the problem is due to using up ATP during activity. Blood cells do not work hard when we are running or doing mental arithmetic.

ATP depletion makes sense as an explanation of why if I carry a heavy bag with my right arm after a certain time I cannot carry it any more with the right arm so use the left. Then after a while I can do it with the right again. The loss of power affects the bit that has been used.

I don't see why that should show up in blood cells that don't do any carrying, so to speak.

If the problem was a general body depletion of something the we could measure the depletion just by sampling plasma - like blood sugar.

 

Exactly.

That's why it's so easy to do too much.

And why it's inutterably silly for anyone to think that we need to be convinced to do more. Likely we're already doing too much, because in order to not do too much, we have to stop before we feel bad (er, feel colossally bad, worse than the usual-terrible, bad). And nobody likes to do that. (Also it's hard to predict, becuase the rules change frequently.)

 

This is kind of rambling, so I don't know how helpful it is, but thought I'd add my two cents.

Maybe it partly depends on how sick the patient is? When I was very sick, any exertion was unpleasant and the post-exertion symptoms were even worse.

Now that I'm more moderate, if I have rested for a few days then some exertion is often not a problem in the moment. If the exertion lasts long enough (5 minutes? 10 minutes?) then I might get some symptoms during exertion but often I don't.

It's the post-exertion symptoms are the real problem for me. And it's very hard to tell how much exertion will lead to PEM. I have a rough idea but it's very hard to pace because there are a million other variables - how well did I sleep the night before, is it too warm (I do better in the cold), and so on.

Once I'm already in the PEM stage then any exertion feels terrible (out of breath, higher heart rate, feeling nausea and dizziness, sensory overload).

It is really hard to track when a more serious "crash" will happen vs. just some PEM that is unpleasant. I imagine I could rest more and have fewer symptoms but the trade-off would not be worth it (I'm already champing at the bit at all the time I have to rest in order to stay functional).

On top of the symptoms I get due to exertion (most of which are post-exertion), I also get symptoms when I stand still (eg, standing line, taking a shower standing, and so on). And even sitting upright (in a straight backed chair with feet on floor) can cause symptoms.

This inability to stay in an upright position without moving, as measured by the tilt table test or the NASA lean test, is what I previously thought was called Orthostatic Intolerance (OI) - with various subsets such as POTS, NMH, maybe more.

I think that you disagree with the usefulness of the term OI but, sadly, I don't have a better phrase to use for this particular set of symptoms.

 

I wanted to say thank you, @Michiel Tack , for summarizing the comments.

And there are some good suggestions there.

 

he can testify to this effect (basically he can say anything needed to say in our case) in front of us congress.

nih has confirmed this in email.