PEM-like descriptions and accounts in non-ME illnesses

[forestglip]

PEM is not defined as «delayed worsening of any symptoms not explained by anything else», though?

I added the "not explained by anything else", but otherwise that basically seems like the NICE definition. They don't specify any specific symptoms in this definition.

What if you only get a delayed headache? Or only delayed light sensitivity? Is that PEM? What about other symptoms like vomiting? Seizure?

Why not? I think the most potentially useful way to separate PEM from pretty much anything else is that following a delay after exertion, symptoms get worse. The delay and the exertion components are the interesting parts, not the specific symptoms, in my opinion.

 

[poetinsf]

And I’m not sure what you mean by «for research purposes», can you clarify?

I meant for studying. If you want to test your hypothesis about PEM, only include those with often-delayed worsening as subjects. That may entail the risk of incomplete picture, but that's better than ending up with a wrong picture. At least till we have some idea what its mechanism is.

I think something that might make sense would be to exclude people that do not have «often delayed» PEM from research, i.e. that appears to have «mostly instant PEM» or «mostly instant symptom worsening». At least until we figure out the ones with delay.

That seems reasonable to me.

 

[jnmaciuch]

I think it's also interesting to compare to the symptom pattern for most common viral illnesses. I think the typical onset tends to be something like:
1) feel tired for no good reason for a day or two, write it off as bad sleep
2) wake up with a sore throat/fever/malaise/etc. and retroactively realize that the fatigue was the first sign of infection

Which presents an interesting story of some immunological cascade that has different presentations based on either some stepwise progression of signals, or based on increasing concentration of one particular signal (or both!).

I've been idly wondering if it is actually the same cascade in PEM vs. viral infection, it's just that pwME don't really register the 1st fatigue phase because that's already their baseline. So for pwME it can seem like "I do activity one day, I feel normal the next, and then I feel like I got hit by a truck on the third day"

[Edited to remove tangential point]

 

[Utsikt]

I added the "not explained by anything else", but otherwise that basically seems like the NICE definition. They don't specify any specific symptoms in this definition.

I’ve taken that to mean «symptoms within the context of what we have described ME/CFS as».

If you have fatigue, OI, brainfog, and/or all of the «usual» ME/CFS symptoms, but the only thing that happens 24 hrs after exertion is that you start vomiting, do you have PEM?

Why not? I think the most potentially useful way to separate PEM from pretty much anything else is that following a delay after exertion, symptoms get worse. The delay and the exertion components are the interesting parts, not the specific symptoms, in my opinion.

I agree that the delay after exertion is the interesting part - but if you don’t use an inclusion criteria of symptoms you definitely have to experience worsening of, you’ll end up including lots of things that probably are not related at all.

I doubt that whatever ME/CFS is, it’s the only thing that can lead to a delayed worsening of a symptom following exertion.

 

[forestglip]

I’ve taken that to mean «symptoms within the context of what we have described ME/CFS as».

Maybe. So in that case, delayed fatigue, brain fog, and unrefreshing sleep are the three things required for it to be PEM?

If you have fatigue, OI, brainfog, and/or all of the «usual» ME/CFS symptoms, but the only thing that happens 24 hrs after exertion is that you start vomiting, do you have PEM?

If someone had worsening fatigue, brainfog, and vomiting after 24 hours consistently, and the vomiting was considered related to PEM and not some total coincidence, then I don't see why it can't be related to PEM if it's on its own.

you’ll end up including lots of things that probably are not related at all.

We don't even know if ME/CFS is one thing. Maybe if it's just the symptoms listed on NICE, it's one process, and if it includes gut symptoms and feeling cold, it's something entirely different. If we don't know whether these different presentations are the same or different, how can we know whether any specific symptoms are "probably" something different?

My main concern is patients having a diagnosis and a community, and I don't think it's helpful to exclude people based on picking out specific symptoms when we already have the decent cutoff description using delay and exertion.

 

[Yann04]

Maybe. So in that case, delayed fatigue, brain fog, and unrefreshing sleep are the three things required for it to be PEM?

I wouldn’t like that definition. Definitely had “refreshing sleep” until I became very severe.

My sleep helped so much. I was just sleeping like 14 hours.

What about a definition that needs at-least 3 from a list of things like:
- fatigue
- brain fog
- unrefreshing sleep
- headaches and migraines
- stomach/bowel/ibs type symptoms

 

[Utsikt]

Maybe. So in that case, delayed fatigue, brain fog, and unrefreshing sleep are the three things required for it to be PEM?

I would think so? You have to have those symptoms, and they have to generally worsen when you get symptoms worsening following exertion.

If someone had worsening fatigue, brainfog, and vomiting after 24 hours consistently, and the vomiting was considered related to PEM and not some total coincidence, then I don't see why it can't be related to PEM if it's on its own.

I was thinking about if only vomiting occurred, and the other symptoms stayed the same. Sorry, should have been clear about that.

We don't even know if ME/CFS is one thing. Maybe if it's just the symptoms listed on NICE, it's one process, and if it includes gut symptoms and feeling cold, it's something entirely different. If we don't know whether these different presentations are the same or different, how can we know whether any specific symptoms are "probably" something different?

Because it doesn’t make any sense that the same process can lead to completely different symptoms worsening following exertion. Some variation around common themes - sure. Completely different in unrelated systems - I don’t understand how.

My main concern is patients having a diagnosis and a community, and I don't think it's helpful to exclude people based on picking out specific symptoms when we already have the decent cutoff description using delay and exertion.

My main concern would be avoiding misdiagnosis of potentially treatable/manageable conditions. I think of it a bit like hEDS vs EDS. The latter have a genetic signature, the former is just lumped together because some of the symptoms are the same as EDS and is probably not a very helpful concept.

And too much noise for research.

 

[Utsikt]

I wouldn’t like that definition. Definitely had “refreshing sleep” until I became very severe.

My sleep helped so much. I was just sleeping like 14 hours.

What about a definition that needs at-least 3 from a list of things like:
- fatigue
- brain fog
- unrefreshing sleep
- headaches and migraines
- stomach/bowel/ibs type symptoms

Yeah, good point. The CCC have some symptoms you have to have, and some from a list where you need X of Y.

 

[jnmaciuch]

Because it doesn’t make any sense that the same process can lead to completely different symptoms worsening following exertion. Some variation around common themes - sure. Completely different in unrelated systems - I don’t understand how.

I think it is absolutely possible to have one common underlying process with different sets of "modulating" factors on top of it that change disease presentation.

[Edited for conciseness]

 

[forestglip]

I was thinking about if only vomiting occurred, and the other symptoms stayed the same. Sorry, should have been clear about that.

No, I understood. I'm saying if we accept that vomiting is part of the pathophysiological PEM process if it occurs alongside fatigue, it seems logical to assume it could be related on its own as well.

Because it doesn’t make any sense that the same process can lead to completely different symptoms worsening following exertion. Some variation around common themes - sure. Completely different in unrelated systems - I don’t understand how.

I'm mainly considering a delay of a single symptom if it's already associated with PEM if combined with other symptoms, as above for vomiting or fatigue. For other symptoms, the question I have is if a delay of some completely unrelated symptom after exertion even happens in anyone consistently, and doesn't already have a name?

My main concern would be avoiding misdiagnosis of potentially treatable/manageable conditions. I think of it a bit like hEDS vs EDS. The latter have a genetic signature, the former is just lumped together because some of the symptoms are the same as EDS and is probably not a very helpful concept.

Who is missing out on treatment in this situation? I'm saying specifically if an explanation comes along for a delay of a specific symptom after exertion, like vomiting, it gets to graduate to a new label. If not, the people with only the vomiting symptom aren't missing out.

And too much noise for research.

Well research already often uses stricter criteria. Even if the NICE definition was amended to not require unrefreshing sleep, researchers could continue on using CCC.

 

[forestglip]

What about a definition that needs at-least 3 from a list of things like:

I just think its arbitrary to use 3 symptoms instead of 1. I think we should err on the side of being potentially over-inclusive, not over-exclusive, for the sake of patients who, without the established ME/CFS communities [edit: like this forum] and support systems, [edit: and without any other diagnosis], might be left to fend for themselves.

 

[Yann04]

I just think its arbitrary to use 3 symptoms instead of 1. I think we should err on the side of being potentially over-inclusive, not over-exclusive, for the sake of patients who, without the established ME/CFS communities [edit: like this forum] and support systems, [edit: and without any other diagnosis], might be left to fend for themselves.

But literally 50+ % of the population is likely to have delayed fatigue or muscle soreness after exertion.

I don’t see a world where that isn’t going to do the exact thing the “CFS” label did to the clinical construct

 

[richie]

Mea Culpa. I left out "typically" or "often".


Actually, no. I'm talking more about PEM definition applied to other condition rather than ME/CFS. Not requiring the delay will end up including energy deficit and others. And I'm not sure if requiring prolonged recovery time can differentiate ME/CFS PEM from PEM look-alikes of other conditions, including aging.

Stricter definition is necessary IMO if you are trying to investigate "PEMs" of other conditions are indeed worthy of looking into for ME/CFS PEM investigation.

I agree on prolonged recovery but delay is also noted in sarcoid post exertional worsening (but not always), so even delay is not a fool-proof identifier. I have heard "the next day....." from Pompe's disease sufferers and that is a definite metabolic disorder.
I still feel that definition before investigation is cart before horse, though definition for the purpose of investigation of a phenomenon which is more likely to be singular because of the strict defnition is rational, but it should imo remain a working definition for specific i.e research purposes until we know more.

 

[forestglip]

But literally 50+ % of the population is likely to have delayed fatigue or muscle soreness after exertion.

Is that the case? With muscle soreness, there's the DOMS diagnosis, right? But, people often suddenly get a lot more fatigued a day later? Maybe I'm working with an incorrect assumption that that is pretty rare.

 

[Yann04]

Is that the case? With muscle soreness, there's the DOMS diagnosis, right? But, people often suddenly get a lot more fatigued a day later? Maybe I'm working with an incorrect assumption that that is pretty rare.

I’m just working from how I experience things when I was healthy and my friends and family talk.

But it seems pretty common to have a big day where you’re pumped up with energy, do a lot of things, feel pretty good. And then the next day you try to do something and realise “oh damn I’m tired”, and have to take a chill day. So usually not delayed 24+ hours but like 1-12 hours.

 

[Utsikt]

No, I understood. I'm saying if we accept that vomiting is part of the pathophysiological PEM process if it occurs alongside fatigue, it seems logical to assume it could be related on its own as well.

Even it vomiting is the only symptom that happens? So you go from baseline fatigue, OI, etc., do an exertion, and then start throwing up a day later, but with no changes to your other symptoms? Is the vomiting then PEM?

I'm mainly considering a delay of a single symptom if it's already associated with PEM if combined with other symptoms, as above for vomiting or fatigue.

I don’t understand what you mean here, I might be too foggy atm.

For other symptoms, the question I have is if a delay of some completely unrelated symptom after exertion even happens in anyone consistently, and doesn't already have a name?

I don’t know if it happens to others or if it has a name. But it isn’t automatically PEM just because it hasn’t been defined as something else.

Who is missing out on treatment in this situation? I'm saying specifically if an explanation comes along for a delay of a specific symptom after exertion, like vomiting, it gets to graduate to a new label. If not, the people with only the vomiting symptom aren't missing out.

I don’t know if they are missing out on treatments. But what are they missing out on if not included in PEM? And why is even «not wanting people to miss out» an argument for expanding a diagnosis?

I’m reminded of this argument by JE:

The bottom line is that medical diagnoses are really much more about predicting the future than describing the situation now. They are there to tell people what will happen, including how likely treatments are to change what happens.

If we treat PEM as we would with a diagnosis, then it makes no sense to include things in PEM that we don’t have a reason to believe will behave like «regular» ME/CFS PEM.

 

[forestglip]

I’m just working from how I experience things when I was healthy and my friends and family talk.

But it seems pretty common to have a big day where you’re pumped up with energy, do a lot of things, feel pretty good. And then the next day you try to do something and realise “oh damn I’m tired”, and have to take a chill day. So usually not delayed 24+ hours but like 1-12 hours.

Hmm, yeah I suppose. I think my mental model of PEM is a delay plus it lasting strangely long (greater than 2 or 3 days) plus it being quite out of proportion to the exertion.

 

[Yann04]

Hmm, yeah I suppose. I think my mental model of PEM is a delay plus it lasting strangely long (greater than 2 or 3 days) plus it being quite out of proportion to the exertion.

Yeah the out of proportion thing is crucial.

I’m kinda against having strict rules on delay, personally I’ve experienced anything from immediate to months long delay (in the sense of pem adding up but i can still function for months ignoring it before I “crash”).

 

[forestglip]

Even it vomiting is the only symptom that happens? So you go from baseline fatigue, OI, etc., do an exertion, and then start throwing up a day later, but with no changes to your other symptoms? Is the vomiting then PEM?

Well, it wouldn't really fit the name of "malaise", so if only for that reason, it wouldn't seem to fit. But for the reasons I said, I think that is kind of arbitrary.

I don’t understand what you mean here, I might be too foggy atm.

Just saying that if fatigue+brain fog+vomiting is considered PEM, then vomiting is considered connected to the PEM process, right? It's part of the landscape of associated symptoms. So if there exist people who have even more "malaise-associated" symptoms as part of PEM, it seems probable that there are people with fewer symptoms, such as only vomiting.

But what are they missing out on if not included in PEM?

A forum like S4ME for one. Disability benefits. Support from family and friends because you have a real "scientific" symptom.

And why is even «not wanting people to miss out» an argument for expanding a diagnosis?

Because the diagnosis is arbitrary as it is, and is just describing a heterogenous collection of symptoms. Strict criteria exist for research. If one day, the research finds that those who fit CCC have one condition and those who only have delayed fatigue fit another, then they can be called different things.

I guess it's possible if clinical criteria got watered down, it could seep into research that just uses clinical criteria and add noise. But I'm not sure if any serious biological research is doing this.

 

[forestglip]

I’m kinda against having strict rules on delay, personally I’ve experienced anything from immediate to months long delay (in the sense of pem adding up but i can still function for months ignoring it before I “crash”).

Similar for me. Sometimes delayed, sometimes seems pretty immediate.