Is PEM triggered by physical exertion the same as worsening triggered by sensory stimuli, cognitive exertion or emotions? What are the implications?

I think this is an important discussion, thank you for opening this thread @Trish. I think one has to approach this topic with more ingenuity than we have seen.

I think one might also have to ask: What are the cognitive deficits pwME report or at least what is this "cognitive PEM" some pwME/CFS report and how does it tie in with the above question or is it irrelevant to the above question, respectively can this question be answered without having to open that can of worms?

One easy thing to note is that for those people with OI, that OI cannot be part of this puzzle. That is to say the phenomena can at most be the same as engaging in physical activity in a reclined position (like doing a 2 day CPET in your bed whilst lying down and having the bicycle turned around glued to the ceiling).

 

My first thought relates directly back to the thread title: There is an argument that says emotional stress and sensory stimuli result in forms of exertion, e.g., heart rate, breathing etc. Concentration and focus are forms of exertion, too. If anything, there may be a consistency between what many would think of as disparate processes or bodily properties not typically considered physical which nevertheless can result in PEM.

 

I think the crucial part which has been alluded to is that they are forms of exertion that we don't understand very well, that is to say they are not really tied to any excessive use of energy in the sense of physics. That is to say, "thinking hard about something" doesn't require more much energy than just lying around. In which case all the ATP, mitochondrial, metabolic theories, aerobic threshold etc don't seem particulary sensible in these scenarios.

 

I've learned over the years to mitigate or often avoid PEM from overdoing things "physically" , that is walking, lifting etc, so I may be off in this, but it seems to me that those produce PEM in 48 hours or so. But emotional stress or heavy and prolonged concentration will total me within 12 hours, if not sooner.

I wish I could be clearer on the walking, lifting stuff, but I've become religious about observing my thresholds. Which is worse? They're all bad, but the relative immediacy of the emotional/cognitive penalties seem to weigh more heavily on me.

 

For me they are completely different phenomena. Cognitive exertion produces brain fog, which can be debilitating, but not PEM (except when combined with physical exertion). Sensory issues are painful & overwhelming stimuli that I have difficulty processing but have nothing to do with PEM. Emotional stress is not a factor. The only link to PEM seems to be physical exertion and the effect is both delayed and not 100% reliable. Could speculate about potential mechanisms although we have so little data it would just be pure speculation.

I suspect that many pwME haven't deliberately tried to test these things separately although I do seem to be in a small minority with not having cognitive effort trigger PEM?; I'd be interested to know how widely this is shared. Astonishing that after all this time we don't have hard answers to these questions from well-conducted research.

 

I my experience it is. In thay any long term worsening of baseline by them is pratctically the same. However immediately after the trigger, the symptoms flaring might be anlittle different depending on it.

 

Perhaps, even if ME/CFS is very much tied into energy issues, PEM is triggered by something other than exceeding or insulting energy thresholds, e.g. heart rate or blood flow or vascular impairments of a sort.

 

I wonder if we wouldn’t have found a “cheat” medication that vastly increases your PEM threshold in that case. For example if it was heart rate, beta blockers.

 

I don't get specific symptoms of cognitive dysfunction / brain fog. Even when crashed out my brain is active. Similarly I don't think I induce PEM from cognitive effort.

I definitely do have pathological fatigue, sleep disruption/failure, physical activity induced PEM, orthostatic intolerance, severe headache, sensory hypersensitivity, major gut disturbance etc. PEM causes more OI.

I do think energy generation will be at the heart of fatigue and PEM. Possibly OI too. One of my current mental models suggests —

Substance X is the something-in-the-blood.
Increased activity (eg muscle, neuron) increases resource demand.
As fuel resource is imported to meet demand, so substance X might also be imported into the cell (eg via membrane transporters)
Substance X in the cell impairs mitochondria +/- lipid membranes (external and internal)
OxPhos ATP generation is impaired with ETC uncoupling, producing more ROS, leading to fatigue and PEM symptoms, with a delay for ROS effects -> PEM
Over time intracellular substance x is cleared, with partial restoration of mito function, leading to resolution of PEM, reduction (partial?) of fatigue.

This is the sort of thing I'm wondering about given that the nanoneedle impedance findings are presumed to have been replicated (per Fatima Labood's comments back in I think June).

(Speculatively, perhaps substance X might be some form of early amyloid oligomer as recently reported on.)

I'll have a think about other possibilities, esp how different stimuli might take effect, but simplistically it might just be too much sensation = too much neuron activity as above.

 

This is the second time I've seen ibuprofen brought up recently, so on the off chance it's relevant, ibuprofen is basically the only med that reduces pain for me: headache, stomachache, sunburn, etc. Aspirin and acetaminophen do next to nothing. No effect on ME/CFS symptoms that I've noticed though.

 

Are we sure this is not sleepiness. Sleepiness with car vibration is surely something lots of people are familiar with. Both I and my wife fall asleep in a vibrating car but not in a train. The sleepiness is irresistible but nothing to do with tiredness. And of course some people feel sick with vibration and lots of people feel sick I a boat. I suspect these are vestibular effects, not to do with muscle.