Post-Exertional Malaise - a discussion including defining and measuring PEM

Yes, I am. Also the differences that group found between severely and moderately ill patients with both having mitochondrial impairments but only the severe having glycolytic impairments.

Then there's Systrom's studies showing an impairment in O2 extraction peripherally

Yes, this lack of energy capacity is there all the time but I don't think we can dismiss the role of energy production impairment in ME based solely on this fact. We don't know the whole story yet but the fact that its abnormal on the second day is telling us something about people's ability to produce energy.

 

You've read it in more detail that I have. Was it the mt impairments that caused the o2 uptake probs, vice versa, bidirectional or unrelated parallel phenomena?

 

I view PEM in part as TCA cycle rewiring and mito changes. I've had tests done a few days after recovering from PEM that can't be explained w/o it being attributed to a viral infection.

 

We seem to be discussing PEM at two levels here which can get a bit confusing so I'm trying to disentangle them here, for my own clarification as much as anything

One side of the discussion is trying to describe what PEM feels like, what sets it off, how it progresses over time, etc

The other side of the discussion is trying to explain what we think is happening at the molecular or cellular level. So that's the various hypotheses, like whether PEM is caused by lack of ATP or by translocation of microbes from the gut into the blood stream, or by viral reactivation, etc

Few of us have the expertise needed to properly judge claims at this level. However, what we all can do is help tie the two levels together by asking any researcher making claims that their hypothesis "could explain some symptoms" explain exactly how their proposed explanatory mechanism would fit our observed experience, all of it, not just a little bit here or there.

This requires careful attention to language, a notoriously slippery and ambiguous beast and one not everybody is good at wrangling, least of all with brain fog. So yes, we can and should express ourselves as clearly and precisely as possible. But we also need to listen just as carefully to avoid talking past each other by too wide a margin. For example, I suspect what I call 'flu-like malaise' is the same thing others call 'fatigue' and others yet call 'feeling poisoned'. Probably all three terms are being used as shorthand to cover a long list of symptoms. That's fine amongst ourselves but risks sending other people down the wrong track. We have to keep asking each other 'what exactly do you mean by...?' and not be offended by being asked to clarify

We also need to be careful, specific and honest in our observations and be prepared to question our own conclusions. For example, I used to think cognitive exertion gave me PEM but I'm no longer certain. I definitely have very rapid cognitive fatigability when my ability to think just grinds to a halt. But after an hour or two of rest I'm back to baseline and ready for a few more minutes of brain work and there doesn't seem to be any next-day PEM - unless I also overdid it physically. So now I don't know how to interpret the cognitive exertion question. It could be that there's no link between cognitive exertion and PEM for me after all. Or it could be that my rapid cognitive fatigability protects me from reaching my cognitive PEM threshold (whereas I'm easily able to push my body past my physical PEM threshold). So based on careful reconsideration of my own experience I'm now unable to make any firm statement about whether cognitive and physical induced PEM are the same thing or not, or if the former even exists.

Other people will have their own experiences and they may be different from mine. That's fine and to be expected. My point is really just that we need to be careful not to get carried away uncritically by our own stories, especially when we want them to guide research

All of which would be an excellent topic for a qualitative study but it would have to be done by somebody with enough experience of PEM to (gently) ask pertinent questions of informants to get the clearest possible description of PEM out of them

 

Yes, it could be that some have an immediate response, which might be different from a delayed one but that the delayed one then piles in. The type of regression to wors e/t symptoms will be different if the worst symptoms are different. There is also the problem of ME knowledgeable talking about similar or allegedly similar phenomena in other illnesses which they are less familiar with.

 

Would you say that there is also the question of when/whether "circuitry" disorders step in, where the system just responds inappropriately/excessively to relatively non noxious stimuli? Such disorders must have a physiological correlate, but this kind of stuff is very challenging, as is e.g. the physiology of depression.

(This is dodgy territory as it opens doors to the BPS, but central pain, phantom limb pain etc. are no longer deemed to be mental illness and mental illness itself is routinely addressed by bio modalities.
"Circuits wrong"/neurofunctional problems does not in itself imply resorting to the old rot of "false illness belief, clinging on to illness ID, secondary benefits, imputed denial of mental illness to avoid stigma, deconditioning falsely diagnosed as causal and bizarrely if amusingly implicitly labelled as "a mental illness" as the BPSers tie themselves in knots).

 

We don't all have access to doctors/specialist who will investigate and eliminate other complex illnesses. Some of us diagnosed with M.E could be dealing with something else entirely when describing PEM.

 

Yes.

To me, ME is PEM and revolves always around it. Pacing will help eventually get a better quality of life and fewer severe PEM episodes. It can take years though, for me it took just over 10 years of pacing to get to moderate level. So there was no fast improvement with pacing. Painfully slow.

PEM is what will increase severity or hold you at the same level if pacing isn't adequate enough.

So I think there are layers of PEM at work. Rolling PEM that could be severe through to subtle, then immediate PEM and then the delayed PEM. As long as you have ME the PEM will be there whether subtle or severe. As long as we are at a baseline below a healthy person without ME, PEM must still be there.

When I can get my thoughts together properly I would like to go back to when my ME began, 1995 and try to record how I was affected by PEM throughout all the stages I have been through.

I acknowledge that this is my own view and experience and others may experience it differently.

 

It would be fantastic for someone to study PEM caused by cognitive exertion in more detail. Enrol people who experience PEM from doing mental work while lying in bed, get them to do so in a clinical setting and see what you can observe. Even better, provoke PEM both physically and mentally in the same patients and look for the commonalities between the two. Maybe that would help zero in on what's going wrong by looking for some factor or outcome that is common to both.

 

I think we need both. Studies of real life situations over time, definitely, but also highly controlled lab studies of specific phenomena. It's still an open question whether PEM after physical, cognitive, sensory, orthostatic, emotional, etc triggers is all the same thing. For example, anecdotally there seem to be more reports of immediate onset after cognitive challenge and more reports of delayed onset after physical challenge. Which could, hypothetically, point to different underlying mechanisms.

As could this entirely hypothetical example: it's conceivable that the problems many pwME report with sensory overload have more in common with whatever causes sensory overload in autism than with PEM after orthostatic challenge which, in turn, could be primarily related to poor blood flow to the brain whereas PEM after physical exertion might be triggered by some immune response to bacterial translocation from the gut. Or to something else.

Alternatively they could all be starting points capable of converging on a single symptom-creating pathway down the track e.g. microglial activation. Or whatever.

I've no particular view on any of the mechanisms above, they are just examples to illustrate that we really need to try to isolate the different types of triggers and effects, that could lead to some valuable mechanistic insights.

And then we need to learn more about how all the factors play together in real life situations.

 

The Roadmap webinar series has a presentation by Gudrun Lange (starts at 16min) about the ins and outs of cognitive testing in ME including in provocation studies.

Towards the end, about 40min in, she talks about an MCAM sub study designed to validate different types of cognitive tests for use in ME/CFS, results are currently being written up, apparently suitable tests were identified and differences in cognitive performance between ME & HC were found on several tests

Hopefully this will encourage more researchers to include cognitive challenges and testing into their study protocols

https://www.youtube.com/watch?v=f6KJH1_QhIg

 

Now into my third session of Longish Covid, or maybe PASC, I have made a new observation.

When ill with Covid for about a week I felt as I do when having a viral infection. I lost appetite, felt nauseous, sweaty at times, unsteady, and so on. I also had a runny nose and a sore throat but not for very long.

Then after a week I felt that the virus had resolved. My Covid antigen test, which had been brightly positive as soon as the fluid reached the reagent line, was totally negative. I was free of the 'viral malaise'.

But I was not sure that all would go well, as it had not before. And as soon as I stared doing things I had to give up. Moreover, by two or three days into this even sitting resting in the mid morning after breakfast I had something in my head saying no, leave that for now because you won't make it.

So I was free of malaise when keeping quiet but there was a present feeling of not having the capacity to do stuff. When I did, nausea and exhaustion re-emerged, but without the sweatiness of fever.

Nevertheless, throughout these three phases of post-viral exhaustion and have not at any stage had a sense that I should not gradually return to normal. I have not had the sense of getting nowhere I had 6 months after EBV. That is another thing again.

I am tempted to think that these are all different phases of a hypothalamic response to an initial immune stimulus and that the regulatory feedback loops that are involved are pretty complex. I suspect that there is something about ME PEM that relates to a unique regulatory disturbance that emerges over a period ion months, even if it is set up right at the start.

 

Sorry to hear you're having to go through this again.

Whatever those loops are, a small proportion of pwME find that a further immune stimulus—a virus, say, or a Covid jab—ties them up in such knots that they stop working properly for a few days. It's great while it lasts.

 

I get the feeling it is almost as if you see a green light ahead and expect your lane of traffic to move, which it does a teeny bit, only to realise that it is a green filter for another lane and that you are back to waiting interminably for some ability to get going.

 

Just catching up with this thread and not at my best so can only get to page 6 - apologies i know i very behind in the discussion & things have likely moved on but just wanted to make these points now while i think of them

I gree. In addition, being driven in a car, even without the sensory processing, is still quite a 'work out' physically - the body has to be making small muscle contractions to keep the body in place when going around corners etc. I once travelled in a racing type car with bucket seats - it was a huge problem getting in & out because it was so low, but the side supports & the way the seat itself held my body in place instead ofmy core/trunk/leg muscles having to do it, when going around corners etc was wonderful & made a major difference to how much it took out of me.
Also the issue with travelling is the vibration, something i never noticed as a healthy person but it's actually a significant sensory input that has to be processed & adapted to. usually throw up on arrival because when the engine turns off the sensation of the movement & vibration continuing gets more intense causing a massive 'head rush' & making me extremely nauseated.

I cannot begin to imagine the horror of what it would be like to have to hold myslef upright on seat on a train being shaken about!

Actually i find the greatest mental exertion to be trying to multitask rather than think hard about 1 thing - so taking an exam while patting my head in a rythm for example while listening to music in a different rythmn for example. Cant spell rythmn.
But i think i know what you mean in principle. Certainly playing that with my neice is as demanding as a tough crossword. More in fact, because the crossword is done in total silence. The issue is that once 'PEM' hits (i talking about the 24-48hrs later malaise that also involves the experience i would describe as 'thinking through treacle' or 'the scrambling of all mental signals/processing), the ability to actually think & even understand the crossword clue, becomes impossible, no matter how hard i try, and the act of recognising the cards in order to play snap, becomes so ridiculously slow as to be comical - like it would take me about 90 seconds to recognise a card match, not 1 or 2.

This leads me to think we're on the same page.

this resonates very well, thats how it feels to me - like all the signals have been scrambled once i done more than my limit of activity

So here, where you describe brushing teeth

it seems (assuming by exertion you mean 'mental exertion, and by being on 'autopilot' you mean not having to think about/concentrate on something) its an accurate description of what happens to me once i am actually in PEM - this is what PEM does to me. Which is one of the reasons its different to PEF, which i experienced as a healthy person when recovering from surgery or from a standard viral/infectious recovery, but it never involved autopilot faliure.

But in PEM i lose ability to do all the mental/physical autopilot functions, its like my brain forgets how to do things, including communicate - speak/understand, plus physical things also - like how to walk in a straight line or move my legs/feet appropriately/naturally, resulting in weird gait & having to concentrate really hard on it Needing to use my hands to pull my trousers like sling to lift my legs out of the car because i cant make them move properly. Body just stops following the usual automatic instructions.

BUT the experience @Trish describes - taking a shower etc, where autopilot is fine but just cant complete the activity that the pilot is steering, due to 'energy' running out and symptoms getting to big to push through,(sorry Trish i paraphrasing your post I forgot to add it to multiquote & now cant find the post)...
That is also my experience but *BEFORE* PEM hits. So pre PEM autopilot works fine, but the plane runs out of gas and the radiator runs out of coolant very fast indeed brining the plane to a halt regardless of autopilot function. But once i go into PEM the sutopilot fails as well as there being little to no fuel in the tank. Degree of failure commensurate with degree of 'overdone it' that triggered the PEM.

To be clear... for me this is what makes delayed PEM different than immediate, or even delayed, PEF (delayed PEF being a thing i experienced when doing exercise i not used to when i was healthy - immediate post exercise endorphin rush & pleasant sense of tiredness, & then day or 2 after feel knackered and aching with DOMS).

When in PEM my autopilot fails, and things that took pretty pretty much no mental or physical exertion (at least to start with) before i'm in PEM, become a massive mental and physical exertion after it. Possibly to use your analogy they are activty pre PEM but exertion once in it? And things i'd have considered mere 'activity' pre developing ME have now become exertion since having it.

For example... Pre PEM I can walk up 2 steps into my house with little issue except I'm a bit slow, need rail for balance & it takes an amount of 'energy' that it wouldnt have as a healthy person so i need to pause to catch my breath before walking forward.
But once PEM hits (which, if i understand your distinction correctly, is post activity for me - as it can be caused by reading or too mush sensory input eg music, while lying down), once it hits, those same 2 steps feel like the last 6 feet to the summit of everest lol!

my muscles shake like i just run a marathon, i so weak i have to use whole body pulling with arms on rails to heave self up because leg strangth isnt enough alone. Plus that autopilot-controlled coordination has disappeared, so that i aim my foot in one place and step somewhere else - wider or narrower than approapriate, making me stumble, I have to concentrate incredibly hard but still struggle to move legs appropriately. & often simply cannot get up the spets at all, vomit with the effort of trying to go up them on my hands & knees,, , trying to be heaved up by carer.

In addition the cognitive autopilot has failed as well, & i cant explain what i need to my carer what to do or what help i need. Either i cant think of what i need, or i cant make the words go from thought to speech, or i say totally wrong words, or my speech is so unintelligible she cant tell what i saying, or i simply cant speak at all.

I have tried to ring for help while in that state but i cant undestand how to use my phone, & if i do it takes me 10 mins to work it out. 1st to grasp that i can ring someone, then that i need my phone, then that my phone is in my pocket (all that takes several minutes), then work out how to turn it on with several failed attempts, then how to find the contacts, then how to dial or what to press to ring them, who it is i need, & then eventually if i can work it all out & make the call.... i have all the difficulties with communication that i just described.

But when not in PEM i can go up the steps, get phone out, make a call without much issue or even without really thinking about it other than taking the steps slowly & using the rail. and then i can lie down & speak about something quite intellectually sophisticated.... but only for very limited reps of the steps & limited time on the phone before i will trigger PEM & become unable to do any of it. And of course there is the gradation between able & unable its not binary, but rather a decline and then a faster & faster decline, before the falling over the PEM cliff, but i trying not to complicate my description too much.

 

Yes, that is what I was wanting to convey.