Should we initiate development of a new, short questionnaire to identify PEM (to aid diagnosis)?

[ME/CFS Science Blog]

The Common Data Elements previous description of PEM was quite useful as it highlighted the key components.

Post-exertional malaise is an abnormal response to minimal amounts of physical or cognitive exertion that is characterized by

i. Exacerbation of some or all of an individual study participant's ME/CFS symptoms. Symptoms exacerbated can include physical fatigue, cognitive fatigue, problems thinking (e.g. slowed information processing speed, memory, concentration), unrefreshing sleep, muscle pain, joint pain, headaches, weakness/instability, light-headedness, flu-like symptoms, sore throat, nausea, and other symptoms. Study participants can experience new or non-typical symptoms as well as exacerbation of their more typical symptoms.
ii. Loss of stamina and/or functional capacity
iii. An onset that can be immediate or delayed after the exertional stimulus by hours, days, or even longer
iv. A prolonged, unpredictable recovery period that may last days, weeks, or even months.
v. Severity and duration of symptoms that is often out-ofproportion to the type, intensity, frequency, and/or duration of the exertion. For some study participants, even basic activities of daily living like toileting, bathing, dressing, communicating, and reading can trigger PEM.

Source: https://www.commondataelements.ninds.nih.gov/Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

 

[Simon M]

The Common Data Elements previous description of PEM was quite useful as it highlighted the key components.


Source: https://www.commondataelements.ninds.nih.gov/Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Yes, a decent de Unfortunately, the NIH group still endorsed the DPSQ as the way to assess PEM, even though it was clearly describing something for a different. S4ME made a sufficient the NIH arguing in vain that should start developing a better tool.

 

[Jonathan Edwards]

So it would be valuable to have something that is better than the questions that are used today such as: do you have PEM, do you get tired after exertion, etc.

Maybe, but how to you establish that it is 'better'? And is using questionnaires justified? It might introduce all sorts of biases. And the bit you quote from me was not referring to research!!

 

[Jonathan Edwards]

Think it would be valuable to have questions that differentiate the characteristic PEM that ME/CFS patients experience from similar conditions such as chronic fatigue, depression, chronic pain that do not involve PEM as we know it.

Yes but how exactly do you circumscribe this 'typical PEM'? Is there a condition of chronic fatigue? If defining these other conditions is just by 'not involving PEM' we still have no gold standard.

My main point is that i can see, like you, that there might well be better questions, but that eliciting information in a medical history doesn't work by standardising questions because people are so variable in how they will understand and interpret questions.

 

[Jonathan Edwards]

As I see it we would have to make a list of PEM statements that reflect how we as patients understand the concept and are useful to detect ME/CFS. We would then need to test these in ME/CFS patients and various controls to check the sensitivity and specificity.

But when you say 'we as patients' you are chiefly talking of a very select group of intelligent self-critical people who can survive on a forum like this where a lot of the threads are highly analytical. The majority of people might find your concepts unintelligible. And how do you test for sensitivity and specificity if you are defining ME/CFS patients and controls by the questionnaire you are testing?

 

[Jonathan Edwards]

And as soon as there is an official questionnaire out there everybody will take it as the gospel and ask leading questions of patients who will discuss it on social media and you end up with a huge cohort of people who have PEM because they heard about it.

This is a real problem. We have seen what happens with hEDS, POTS and MCAS. On the radio today there was a short piece on a recent study proving 'brain fog' was due to CSF being pumped through your brain by day instead of night and of course everybody suffers from it, for goodness sake. Everything gets taken up by the twitterati.

Ralph Waldo Emerson lurks, as ever.

 

[Yann04]

Maybe, but how to you establish that it is 'better'?

Isn’t it like making a new diagnostic criteria. Like when the CCC was made to succeed the fukuda its not that there is objective evidence that it is better, but a will to measure/define a concept in a different way that currently exists. From chronic fatigue based CFS to chronic fatigue + PEM based ME/CFS.

So here PEM is being defined differently by the questionnaires than to how many of us envision. And the idea is to create one that captures PEM as envisioned.

Ie. not long lasting fatigue after exertion, but long lasting functional impairment and symptom burden after exertion.

Whether questionnaires like this should be used at all is another question. But there is much demand for them within research. And I’d rather they be studying a more stringent definition of PEM than something that doesn’t seem to be as good as it should be at differentiating ME/CFS.

 

[Jonathan Edwards]

Isn’t it like making a new diagnostic criteria.

Yes, but we don't know that CCC criteria are better for anything in particular. We like to think so but we have evidence as far as I know.

If it is a matter of trying to describe a different conception then researchers should be free to do that as often as they feel justified by their use of scientific method.

I am not sure I see PEM as about symptom burden or functional impairment. To me it is something to do with a delayed reaction that involves feeling unwell rather than tired, and persists. So it still looks as if we haven't actually got an agreement about what we want researchers to ask about.

 

[Sasha]

And as soon as there is an official questionnaire out there everybody will take it as the gospel and ask leading questions of patients who will discuss it on social media and you end up with a huge cohort of people who have PEM because they heard about it.

Don't we currently have a huge cohort of PwME not getting diagnosed because GPs haven't heard about PEM? And not able to have a stab at diagnosing themselves with ME/CFS and seeking help for it because they haven't heard of it either?

 

[Verity]

I strongly agree with Jonathan here. I think those of my doctors who don’t know much about ME would not be able to wade through all the biases introduced by using a questionnaire in order to properly diagnose it, and my doctors who already know what it is don’t need a questionnaire. It would only complicate things, especially once patients find the questionnaire online.

What we actually need is for physicians to be reasonably familiar with an illness that is not any more rare or complicated to learn about than many of the illnesses they’re already required to recognize. Advocating to introduce it through med school curricula, grand rounds, and continuing ed would be a better use of our time.

 

[Utsikt]

It might be that for research, using the DecodeME approach to identifying patients might be sufficient for recruitment, and that using FUNCAP + objective measurements (steps, body position, etc.) is sufficient for outcomes.

It’s not perfect, but we’d have a hard time justifying why anything else is better.

The only improvement might be to have good doctors doing the selection, but those are very rare so it might not be feasible yet.

 

[Jonathan Edwards]

Don't we currently have a huge cohort of PwME not getting diagnosed because GPs haven't heard about PEM?

No, we have a huge cohort undiagosed because GPs don't believe in the diagnosis of ME/CFS. PEM is a nicety. When I became aware that ME/CFS was a real disease it had othing to do with defining PEM. It was the whole picture that convinced me.

 

[Kiristar]

I can see it's potentially a good idea, but I wonder if it is the most urgent question we need to tackle right now if other team are developing alternatives to the DePaul one.

It would be more interesting if patients could be meaningfully segmented using it I feel.

I guess one of the pitfalls though is that, at least for me as a PwME of 30 years, is that my PEM has evolved and transformed over that time. Now in late stage illness it's totally different from what it was like in the beginning.

So we're trying to capture something that is of itself not a consistent phenomenon longitudinally even within one individual.

For example
-My time lag after trigger has massively shortened: it originally took about 5 days of 20km hikes to trigger it. Now it's maybe a hour or two going off major pem events.
- When v mild my symptoms were malaise - "weekend tonsillitis" I used to call it
- Now after 30 years and becoming
severe, I don't get any of those early tonsil or lymph gland symptoms but do get a shed load of different ones, like extreme burning joint pain, palpitations.

Elapsed time since assumed infection or trigger as well as severity feels like an invisible significant consideration.

 

[Medfeb]

Not sure, the link you shared isn't explicit about this. I thought the Common Data Elements was mainly about selecting tools to recommend for use in research, rather than developing new ones.

Perhaps someone on the forum knows more?

NIH's Common Data Elements has not been a tool development effort. Its focus has been on reaching consensus on what data needs to be collected in research to improve the standardization and quality of data collection and analysis. The latest effort in 2023 focused on a narrow set of elements intended to capture the key feature of the disease such as PEM.

This page, linked above, also mentions a current effort focused on PEM, disease severity, and cognitive assessment and states the primary objective is to submit newly defined or updated ME/CFS CDEs for these three domains to NIH. PEM and if I remember, cognitive assessment was part of the 2023 effort so this sounds like a refinement. Disease severity was not part of that but is sorely needed.

The page doesn't mention who's involved.

 

[jnmaciuch]

I don’t think the primary benefit of a questionnaire like this would be for the purposes of diagnosis, but rather for systematically capturing more prescient information about the phenomenon of PEM. I‘m not sure if there’s even a need to make sure that it’s a specific phenomenon to ME/CFS only. PEM may well not be unique to ME/CFS, but it would still be useful to have a better way of detecting it in other populations.

The validation part is more checking off a box than anything to convince people to use the tool—the gold standard here is just the assessment of “expert clinicians.” Any way you go about it, there’s going to be bias. But none of that means a tool like this wouldn’t be useful.

Even just being able to identify participants who report similar clusters of PEM symptoms from electronic health records would be an extremely useful starting point for research questions. If the tool can help systematically discriminate between people who just have immediate post-exercise fatigue and those who have full blown flu-like symptoms for 48 hours, all the better.

 

[Jonathan Edwards]

Even just being able to identify participants who report similar clusters of PEM symptoms from electronic health records would be an extremely useful starting point for research questions.

I agree that using details of symptoms to categorise could be useful but pulling stuff from electronic records is not a questionnaire. And health records should not be expected to carry answers to questionnaires rather than a physician's considered assessment of whether a symptom is present or not.

PEM also suffers from the problem that it entails a causal inference - that a particular exertion caused the six weeks of being bedbound for instance. And we know that in the field of ME/CFS people are making inappropriate causal inferences all the time, often because of memes fed by physicians, historic folklore or social media. The focus on 2 day CPET has arisen because of the misconception that it 'measures PEM'.

My first degree was, officially, in Art and Architecture, with a module on the history of connoisseurship and attribution. I learnt that art historians are much more rigorous about evidence than medics. They have to be because being wrong can cost $100M. In the nineteenth century, following Morelli, it became clear that good evidence often depended on trivial signs that had nothing to do with the quality of the artist or their contribution to fine art. The same is true of medicine. The most reliable signs are often trivial tricks that just happen to reflect a unique physiological path. Morelli noted that the way fingernails are painted often gives away the artist's name. Intriguingly, John Moll realised that lifting of fingernails is the most specific sign for seronegative spondarthritis. (And there are a host of other nail signs: splinter haemorrages under the nail for endocarditis, nailfold capillary widening for scleroderma, clubbing for lung disease ....)

It is a mistake to think that a sign must reflect the 'essence' of something. I don't think we have any idea what is likely to be the best way to document whatever it is that makes some people have PEM in ME/CFS.

 

[Trish]

And as soon as there is an official questionnaire out there everybody will take it as the gospel and ask leading questions of patients who will discuss it on social media and you end up with a huge cohort of people who have PEM because they heard about it.

This is a real problem. We have seen what happens with hEDS, POTS and MCAS. On the radio today there was a short piece on a recent study proving 'brain fog' was due to CSF being pumped through your brain by day instead of night and of course everybody suffers from it, for goodness sake. Everything gets taken up by the twitterati.

Ralph Waldo Emerson lurks, as ever.

The trouble is there are already inadequate questionnaires like the current Jason one that claim to be assessing PEM and are not. You are probably right that a questionnaire is not the best approach for diagnosis as part of individual clinical care, but questionnaires are regularly used in ME/CFS clinics. That being the case, we need ones that actually find out what they purport to find out, so people are diagnosed more accurately and given care and advice appropriate to their condition.

And research includes awful psych studies where they throw a pile of questionnaires at people recruited through social media and see what mud sticks, use of inadequate questionnaires helps to perpetuate false conclusions about pwME,

Researchers need to check whether the people wanting to take part in studies have been accurately diagosed. Isn't it useful to have a quick tool like a questionnaire that checks whether someone actually gets PEM, given lots of doctors are wrongly diagnosing tired people with ME/CFS? For example, DecodeME used a few questions to check for PEM to help in narrowing the sample down to those meeting diagnostic criteria.

 

[Evergreen]

I understand the desire to clarify what PEM is and is not, and I would very much like to see more studies comparing ME/CFS with other illnesses, but I'm with @Jonathan Edwards and @Verity on this one.

The golden rule is that you start by asking the patient to describe what their problems are in their own words. As soon as you start trying to standardise words you run into serious trouble because there is a huge range of ways people talk and a huge range of what they might understand by what you say.

Agree wholeheartedly.

When people are answering questions in a medical context they are hugely biased by what they think they are supposed to say or what will get taken most notice of.

If you have a questionnaire for PEM then half the patients will already have seen it on the net and will give all the right answers.

I agree. I remember seeing Jason talking a lot about a "dead, heavy feeling after starting to exercise" being the key part of PEM and thinking "Huh?" Until then, I had only seen this mentioned occasionally by a person with ME/CFS here and there. Sure enough, a few years later 100% of people in Jason studies started endorsing it. Apart from anything, I would have expected a lower percentage purely because many if not most people with ME/CFS do not start to exercise because they have learned what happens when they finish.

A problem with PEM is that there is no complete agreement on what constitutes it and what doesn't quite make it.

Agree wholeheartedly.

On S4ME a conviction has emerged that the delayed onset is key but...is it? That would mean we have to argue that what patients experience after a maximal exercise test is not PEM because their symptoms start immediately. We'd have to argue that I'm not currently on day 9 of a PEM episode because my symptoms started when I struggled to open a container 9 days ago, rather than starting a day later. What if delayed onset is simply a sign that you've got a bit of reserve?

As far as I know, we've only got snippets of information about what might make post-exertion phenomena in ME/CFS different from other diseases. The 2018 Jason study @Simon M linked to above gives some valuable info on what might e.g. duration of PEM over 24 hours. Kim et al's study on Sjögren′s noted that people with Sjögren′s didn't have post-exertional symptoms lasting longer than 24 hours, and that they reacted differently to physical exertion, but they didn't compare Sjögren′s and ME/CFS head to head.

In terms of possible PEM mechanism, we have even less info - a smattering of experimental studies that seem to have petered out (or maybe I just haven't found them?) For example, Jones et al. 2011 demonstrated that unlike people with primary biliary cirrhosis and mitochondrial disorders who also have reduced aerobic capacity during exercise, people with CFS were not able to compensate for that reduced aerobic capacity using increased proton flux. But we don't know whether patients went on to have what S4ME members might classify as a PEM episode triggered by participating in the study. Meeus et al. 2010 showed that in response to exercise, the pain thresholds of people with chronic low back pain increased, but the opposite happened for people with CFS - their pain thresholds decreased. But again, we don't know what happened in the days that followed.

I think a thread on studies comparing response to exercise or exertion in ME/CFS and other diseases would be worthwhile.

No, we have a huge cohort undiagosed because GPs don't believe in the diagnosis of ME/CFS. PEM is a nicety. When I became aware that ME/CFS was a real disease it had othing to do with defining PEM. It was the whole picture that convinced me.

Yeah, I don't think this would help undiagnosed people get diagnosed.

On 12 May 2021 a Consultant in Infectious Diseases was interviewed about long covid and asked whether it's the same as ME.

Pat Kenny: Paddy, a number of people are wondering if this [long covid] is the same as ME or chronic fatigue, you know, a post-viral syndrome of some kind, um, whether they can all be bracketed together?

Dr Paddy Mallon: It's a really good question...in my experience, 20 years of infectious diseases, we've seen a lot of ME cases, we see a lot of post-infectious fatigue, this is something completely different. And I think that as the research develops...it will be classified as a separate entity, because the characteristics here...This concept of overdoing it for a day and then paying for it for a week is something that we don’t really see in a lot of the other chronic fatigue conditions. But it’s a real characteristic of this, especially in people like Rachel who have these tachycardias and these chest pains. So these are, there’s a definite difference in what’s going on here.”

So this doctor who has 20 years of experience with ME/PVF describes PEM as what makes long covid different from ME. You can listen to it here. The bit quoted above is at around 18 mins.

That was broadcast on ME Awareness Day.

I don't think a questionnaire on PEM in ME/CFS would change his mind about his 20 years of prior clinical experience.

I think our time would be better spent thinking up how to design studies that would give us the information we need.