Post-exertional malaise in daily life and experimental exercise models in patients with [ME/CFS], 2023, Vøllestad and Mengshoel

[duncan]

I understand why they are used but the problem with standardised doses of exertion in research of pwME is that different levels of exertion will have different effects, depending on how seriously, or not, each participant is affected and their normal activity level. Particular towards the mild end, there is potential for huge variation in activity in individuals.

If PEM is to be researched, and it should be, then lets research PEM, then we can understand what 'pre-PEM' looks like. We don't need a partial job done - stopping before PEM could potentially lead to some unhelpful assumptions being made and precious research funding being wasted.

The process of measuring what ends up being up PEM when we go beyond our limits certainly could start before the patient participants experience symptoms, but without evidence that the process ends up being PEM then claiming the process is PEM could well be misleading.

I agree with everything you've said here @Andy .

I was in an ME/CFS study once a few years back that in part tried to assess PEM through two CPETs and fMRIs. I was in a hospital for the testing four days, if I recall correctly. Blood work drawn every few hours for those four days and nights. Hooked up to heart monitors to tests for POTS every few hours. Lumbar puncture. Etc.

I remember thinking a couple things worrisome:. Just getting to the hospital thrust me into PEM, so my hospital baseline was PEM, but they didn't know that. Moreover, we talk about exertion, and that of course is correct, but another way of looking at it is "triggers", like in channelopathies, and not everyone's trigger is the same, or threshold either. So, studying how a stationary bike exercise impacts patients or elicits PEM might be futile if the exertion or trigger is more cognitive. That's even more of an issue if you're in PEM before the testing begins.

This study pooled participants results. The disease manifests so independent of groups dynamics, that pooling of results could be completely misleading.

Also, these guys supposedly knew their stuff about ME/CFS, but geez, they didn't follow up on some results I think as a patient should have piqued their interest. They just followed testing protocol. I appreciate protocol, but when you're in no man's land, leeway isn't always a bad thing. I had some results that may have been tied into PEM that they appeared to think unimportant or irrelevant.

Point being: If you're going to try to capture PEM, you better know what you're looking for, and you better be willing to listen to the very folk you are studying since they are most likely the only PEM experts in the room.

 

[bobbler]

I agree with everything you've said here @Andy .

I was in an ME/CFS study once a few years back that in part tried to assess PEM through two CPETs and fMRIs. I was in a hospital for the testing four days, if I recall correctly. Blood work drawn every few hours for those four days and nights. Hooked up to heart monitors to tests for POTS every few hours. Lumbar puncture. Etc.

I remember thinking a couple things worrisome:. Just getting to the hospital thrust me into PEM, so my hospital baseline was PEM, but they didn't know that. Moreover, we talk about exertion, and that of course is correct, but another way of looking at it is "triggers", like in channelopathies, and not everyone's trigger is the same, or threshold either. So, studying how a stationary bike exercise impacts patients or elicits PEM might be futile if the exertion or trigger is more cognitive. That's even more of an issue if you're in PEM before the testing begins.

This study pooled participants results. The disease manifests so independent of groups dynamics, that pooling of results could be completely misleading.

Also, these guys supposedly knew their stuff about ME/CFS, but geez, they didn't follow up on some results I think as a patient should have piqued their interest. They just followed testing protocol. I appreciate protocol, but when you're in no man's land, leeway isn't always a bad thing. I had some results that may have been tied into PEM that they appeared to think unimportant or irrelevant.

Point being: If you're going to try to capture PEM, you better know what you're looking for, and you better be willing to listen to the very folk you are studying since they are most likely the only PEM experts in the room.

100% agree on the issue with 'pooling' of participants' results, I don't think that can be justified as an approach given the lack of controllability of all these key factors and how these things show in the individual

One thing to maybe bear in mind is that if CPET is about 'initiating maximum exertion' (exercise-based only) and they are only then measuring 'what happens and when' following this [being used as a 'dose'], then perhaps the issue with the getting there is merely about all the additional doses either producing different timings (did something PEM-causing 2 days before) or different 'additional types' (overload of having had motion sickness, sensory, cognitive and all related to getting there and lack of sleep from alarm clocks)

There would be an even bigger issue if it were a 2-day CPET where the results were being reported as if they were replication attempts of the Workwell study and thought the 'maximum ability' meant something. Because they could well have people who are in PEM on the first as well as the second and they don't know enough about either the timing/cycle of PEM for that individual (or collective individuals) or a log of their other exertions.

I partly suspect where studies say those with ME/CFS are 'lower than healthy controls' on the first CPET that is failing to include the explanation that the exertion started for those with ME with the beginning of the journey and not the CPET. Which perhaps makes the dip seen on the second even more remarkable, but it would be interesting to one day be able to back-fill given all the presumptions about our 'fitness' etc.

These testing regimes sound like they are filled with other things going on that could trigger what for me might be the more 'immediate' sensory or cognitive fatigue as well as orthostatic etc too.

 

[Mij]

Please could you describe how "PVFS with delayed symptoms" was different to "ME/PEM"?

My experience with PVFS delayed symptoms appeared the next day after small amounts of exercise. I had leg muscle exhaustion (nothing else) they felt like hot wet towels, one time it lasted 6 months. I was unable to stand or walk very far in my apartment. My cognitive function was normal, I never had OI or felt as though I had a lack of blood flow going to my brain. I finally stopped doing even small amounts of walking/exercising altogether.

I also had a similar experience from contracting Covid last year, but the delayed leg exhaustion only lasted 3 weeks and then I was over it. It never came back after I rested and took a few months to recover. I was able to return to my usual walking routine.

The ME/delayedPEM is a whole other pathology that everyone here knows very well. I can't stand upright, I shake and feel hot, I feel dehydrated, very little muscle power in both arms and legs, swaying when I walk, chest pressure that is so scary that one time I wanted to go the ER, tight band feeling around my forehead, cognitive impairment, unable to process or hold on to information, slurring et Takes around 3 days or more to recover depending on how much I over do. Very distinctive symptoms that reoccur every time I go over my energy limit for the past 23 years.

So how do you then suggest we study it?

Continue to research and advance CBF imaging before, during and after a small amount of exercise for 2 days in a row. Perhaps we only need a one day challenge because we can see the changes develop in real time. The wearable ear device that Workwell is involved with is fascinating.

Why continue CPET when we already know that our aerobic capacity is broken? Not sure it distinguishes pwME from other illnesses either.

 

[Mij]

I was in an ME/CFS study once a few years back that in part tried to assess PEM through two CPETs and fMRIs. I was in a hospital for the testing four days, if I recall correctly. Blood work drawn every few hours for those four days and nights. Hooked up to heart monitors to tests for POTS every few hours. Lumbar puncture. Etc.

What a nightmare you had go through