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

[Kitty]

While I agree ideally doctors are knowledgeable enough to be able to elicit the key features of a patient's illness through careful questioning and listening, and make an accurate diagnosis on that basis, that's rarely in my experience what happens.

That's not unique to ME/CFS, though. Delayed diagnosis and initial misdiagnosis are probably more common in new onset chronic conditions than getting it right first time, but that's not necessarily indicative of bias, poor knowledge or failing to ask the right questions. Diagnosis is a process that can take time, and a doctor's opinion might change as the picture clarifies.

One of the issues with the ME/CFS clinics is that they seem to force diagnosis into a simple decision-making tree, or make it a one-time event. It probably shouldn't be either of those things.

After looking through the thread, I wonder if we should be arguing against the use of questionnaires in diagnosis (research is a bit different), and instead promoting the use of our PEM information sheet to inform the physician's approach to diagnosis. That leaves them free to tailor it to the individual patient.

 

[Evergreen]

Descriptions of PEM occurring after a maximal exercise test tend from what I recall, to report PEM symptoms continuing to worsen to a peak that happens hours or days after the exertion. If it had reached its peak immediately, how would the pwME who do 2 day CPET be able to do the test on the second day.

I don't understand this bit. Why do the symptoms have to peak immediately? Immediate onset just means symptoms start immediately, not that they peak immediately. I'm sure plenty of pwME doing the 2nd day of a 2 day CPET feel all kinds of rotten.

In the NIH study, Stussman et al. 2024 reported:

A wide variation was seen in timing of peak PEM with occurrences at every timepoint measured after CPET.

In addition, several ME/CFS volunteers reported having more than one PEM peak during the time course

If you look at fig 4 in the Stussman study, most pwME's PEM ratings start climbing right away.

I think you might be addressing Jonathan here so I'll leave that unless you tell me otherwise!

If you are rejecting the idea of a PEM questionnaire, what do you think should be done about existing questionnaires like the Jason one, and the ones currently being produced by UK BACME therapists and the MEA intended to be used in UK ME/CFS clinics run largely by physios and OTs?

 

[Simon M]

It's good to have so much debate about the idea of a PEM questionnaire. I just wish my health allowed my health to get involved, but I want to make one comment now (more in the next few days if I can manage it).

I think it would help if we brought in data to support or challenge some of the assumptions being made here. I hope to be able to do that (and I know 'jam tomorrow' is the ultimate unconvincing line), but here is one example at random:

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.

@Evergreen
-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.

That question is pretty old and heavily predates this 2018 paper, which I have to hand. These are results for agreeing with the symptom:
"Dead, heavy feeling after starting to exercise"
ME/CFS = 78%
MS = 51%
So not 100%. Maybe those differences are real? Though I agree it's a weird question.

I'm also not sure half the people on the net will have seen the questions already. As @Jonathan Edwards points out, we are unrepresentative of pwme, and I doubt many on social media spend any time discussing such details. Certainly not those without a diagnosis, who may not know what they have, and one of the main proposed uses of the questionnaire is for them.

 

[Trish]

I don't understand this bit. Why do the symptoms have to peak immediately? Immediate onset just means symptoms start immediately, not that they peak immediately. I'm sure plenty of pwME doing the 2nd day of a 2 day CPET feel all kinds of rotten.

I don't have any more answers to this than you do.

I am only able to go on my own experience and what I have observed and heard about from others, as well as what is written in the official descriptions of PEM.

What I'm trying to separate is:

1. the immediate exacerbation of symptoms during and after any exertion that if someone is able to pace effectively ease off and enable them to do about the same amount of exertion the next day - not PEM, and I think wrongly confused with PEM by the Jason questionnaire, and by Stussman and others.

2. the same immediate effects as usual, but followed by days or longer of being much sicker - PEM

In my case, I often can't tell until the next day whether the usual increased pain, OI, exhaustion, nausea that all my activity exacerbates is going to be in retrospect the first stages of PEM that will kick in the next day with added and worse symptoms, or whether I'll be much the same as usual the next day. Because those additional symptoms I don't usually have kick in the next day, not immediately after the activity, I take that as PEM not starting until the next day.

As for the Stussman paper, I'm afraid I don't take anything in it seriously. The process of eliciting data was so flawed and based on leading questions asking about all effects of any exertion, not just PEM, as well as the group phone calls which are totally inappropriate for pwME, excluding anyone with severe or very severe ME/CFS. I therefore reject all their conclusions which seemed to simply elicit common symptoms of ME/CFS, not specific features of PEM.

 

[Evergreen]

@Evergreen
-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.

That question is pretty old and heavily predates this 2018 paper, which I have to hand. These are results for agreeing with the symptom:
"Dead, heavy feeling after starting to exercise"
ME/CFS = 78%
MS = 51%
So not 100%. Maybe those differences are real? Though I agree it's a weird question.

Absolutely fair to question that. I did look in my Jason folder for the study where I think I saw that, but there are a ton of studies and I'm wrecked, so I didn't find it. I could be remembering wrong - it might not have been a Jason study and it might not have been 100%. But that's my memory.

 

[Jonathan Edwards]

Isn't it useful to have a quick tool like a questionnaire that checks whether someone actually gets PEM,

No. No more than it is useful to have a quick check whether somebody has emigrated by finding flights to Norway that were never actually taken. The solution to bad methodoogy is not to be slightly less bad. It is to ignore it. That is what I did for RA and it worked out very well. There is nothing worse than giving credibility to something that is just slightly less bad.

I see no immediate need for any questionnaires.
For most studies, involving maybe 100-200 people at most, it is imperative that a physician or nurse specialist who has enough experience of ME/CFS to make a reliable diagnosis gets to do the recruiting. Otherwise you are just wasting time. For studies like GWAS the practicalities are more tricky but DecodeME probably did as well as it could have.

My point is just that requiring a delay would not be consistent with expert opinion over the years.

The trouble with that is that, as John Kirwan showed in a nice paper on what rheumatologists say they do and what they actually do is that 'experts' come up with recipes for how they think they decide which aren't actually how the decide in practice.

 

[Jonathan Edwards]

I'm also not sure half the people on the net will have seen the questions already. As @Jonathan Edwards points out, we are unrepresentative of pwme, and I doubt many on social media spend any time discussing such details.

My real concern is that people who don't have ME/CFS will see these things on the net and convince themselves they have them. Judging by my experience with other diseases like RA and lupus there are usually more people who think they have a chronic disease than actually have it.

 

[Evergreen]

What I'm trying to separate is:

1. the immediate exacerbation of symptoms during and after any exertion that if someone is able to pace effectively ease off and enable them to do about the same amount of exertion the next day - not PEM, and I think wrongly confused with PEM by the Jason questionnaire, and by Stussman and others.

2. the same immediate effects as usual, but followed by days or longer of being much sicker - PEM

You see, I look at those two and see the difference being one of duration, not of timing of onset. #1 is short-lived and #2 is prolonged. The few studies we have do seem to suggest that duration differentiates ME/CFS from other diseases.

But I think we have to be realistic that #1 has been included in many of the descriptions of PEM to date (see post 41 above). So clinicians and patient organisations have been telling people that that is PEM.

The trouble with that is that, as John Kirwan showed in a nice paper on what rheumatologists say they do and what they actually do is that 'experts' come up with recipes for how they think they decide which aren't actually how the decide in practice.

That sounds true. I'm with you on this, I don't think a questionnaire is a good idea. My comment to Trish was just about the fact that I also don't think delayed onset is necessarily the key feature of PEM.

I don't think this is a problem that gets solved with rearranging words. I think if people want a definition of PEM that is as sensitive and specific to ME/CFS as possible, we need studies rather than either patient consensus or clinician consensus. And we have to be open to finding that PEM, defined in words, is not as specific to ME/CFS as we thought, or that it's pointless to argue over this stuff until we understand what's actually happening in pwME's bodies post-exertion.

 

[duncan]

Judging by my experience with other diseases like RA and lupus there are usually more people who think they have a chronic disease than actually have it.

That made me chuckle. Judging by my experience with other diseases like Lyme or Babesia or ME/CFS there are usually less doctors who think those patients have a chronic disease than actually have it.

 

[jnmaciuch]

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

Many practices do use questionnaires as part of clinical care, and that data is stored alongside clinician notes, lab results, and everything else available in the EHR. They have their uses, [edit: they don’t replace assessments they supplement them in more standardized format]. It’s part of a project proposal that I’m working on right now.

 

[rvallee]

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.

This is a great example of what we're up against. We can't fix that with questionnaires, that's for sure. And it's coming up again and again with Long Covid, the same hubris being repeated over and over again. People who claim themselves to be experts, even saying something they would have laughed at not long before ("we've seen a lot of ME over the years") to establish credibility, then to go on and literally not just prove their incompetence, but in the absolute worst way possible: getting the most basic, defining, parts of the illness wrong and insisting on it. It's the confidently incorrect part of it that is so astounding. People love to mock AIs for their confident sloppiness, but human slop is always so much worse than AI slop.

We can't fix that with questionnaires. We can't fix that by changing textbooks either, because this is the sort of "expert" who may be called to write it or teach it to students. We can't fix that with criteria, that's been tried.

So what can we fix? Nothing but a test based on pathology. I really can't see any other way, we've tried all the other ways and the problem isn't with the ways or the substance but with who we are dealing with. It's mainly a matter of politics, in a context in which we are the only stakeholders but have zero influence on anything.

We have to work with what is feasible, with what will work, on the baseline that this is the level of ineptitude we have to work with. We can't even write the "ME/CFS for dummies" version because we can't dummy it enough to not be misunderstood or misapplied.

 

[NelliePledge]

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.

I have only skimmed this thread but I agree that the good elements that already exist should be considered before putting people’s cognitive energy into something that may be very hard to pin down.

 

[Jonathan Edwards]

Judging by my experience with other diseases like Lyme or Babesia or ME/CFS there are usually less doctors who think those patients have a chronic disease than actually have it.

And that as well. For ME/CFS I suspect we have shedloads of both.

 

[Trish]

My comment to Trish was just about the fact that I also don't think delayed onset is necessarily the key feature of PEM.

You see, I look at those two and see the difference being one of duration, not of timing of onset. #1 is short-lived and #2 is prolonged. The few studies we have do seem to suggest that duration differentiates ME/CFS from other diseases.

But I think we have to be realistic that #1 has been included in many of the descriptions of PEM to date (see post 41 above). So clinicians and patient organisations have been telling people that that is PEM.

I agree with you that duration and severity of episodes of PEM is what distinguishes ME/CFS from other conditions, though I also think the fact that many pwME report a delay between what they identify as the trigger and the onset of these severe and prologued episodes is potentially a useful feature giving clues to possible biology.

I don't agree that we have to go along with lumping all symptoms after any exertion with crashes as if they were all called PEM just because some others think so.

We don't yet know biologically whether they are the same or part of the same phenomenon or not, but by lumping together all effects of exertion and calling them PEM I think this carries two risks for patients:

1. it risks misleading patients and their clinicians into diagnosing anyone who has any after exertion symptoms such as PEF or DOMS as having ME/CFS instead of investigating their symptoms further,

2. that it may hamper pwME learning to identify what triggers crashes and what they can do without crashing. If we are told to avoid any exertion that triggers PEM, and we think all symptoms after exertion are PEM, we can end up afraid of moving at all.

Edit to add. I meant to say earlier, @Evergreen that I'm sorry you are in a 9 days so far PEM episode, and of course I believe that is PEM, whether there was a delay in onset or not. I would never question the reality of any pwME's experience.

 

[ME/CFS Science Blog]

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

More in line with how the patient community reports and understands PEM, which seems quite different from the exertion intolerance that it is often confused with.

And is using questionnaires justified?

I think in many studies, researchers need to screen or select patients using questionnaires as DecodeME had to. Luckily we had smart researchers and good patient involvement in that study so they worked out something reasonable, but this won't always be the case.

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.

The goal would be to translate our ideas and understanding about PEM into simple questions that can easily be understood by new patients with no background knowledge.

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.

Questionnaires are used all the time to assess fatigue, physical functioning, depression, etc. Pretty much all ME/CFS research studies use questionnaires to assess symptoms and case definitions. For PEM they either ask 'do you have post-exertional malaise' which is unclear or they use the DSQ-PEM which includes a lot of questions about post-exertion fatigue. Think we can do better than that.

Sure, standardized questions can be misunderstood and will be imperfect but don't think the problem is as hopeless as you suggest.

And how do you test for sensitivity and specificity if you are defining ME/CFS patients and controls by the questionnaire you are testing?

By using current ME/CFS criteria and PEM definitions. We're not aiming to optimize sensitivity or specificity. We just want to avoid including questions that are supported by say only 30% of ME/CFS patients. That's too few for core questions about PEM. Similarly we don't want to focus on questions that are supported by 90% of patients with depression without ME/CFS.

Take the example of delayed onset that Evergreen mentioned. We could check how common this is in the ME/CFS community and controls. Say that only 60% of ME/CFS patients reports this but almost none of the controls. Then it would not be sufficient to make it a requirement but still a useful question to ask.

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.

One option might be to include fake or reverse questions (where a positive answer is irrelevant or indicates a participant doesn't have PEM).

 

[Evergreen]

I don't agree that we have to go along with lumping all symptoms after any exertion with crashes as if they were all called PEM just because some others think so.

We don't yet know biologically whether they are the same or part of the same phenomenon or not, but by lumping together all effects of exertion and calling them PEM I think this carries two risks for patients:

1. it risks misleading patients and their clinicians into diagnosing anyone who has any after exertion symptoms such as PEF or DOMS as having ME/CFS instead of investigating their symptoms further,

2. that it may hamper pwME learning to identify what triggers crashes and what they can do without crashing. If we are told to avoid any exertion that triggers PEM, and we think all symptoms after exertion are PEM, we can end up afraid of moving at all.

I didn't say we have to lump all post-exertional symptoms together. What I'm saying is that if people are going to advocate separating some things out, then there should be some evidence behind those separations, not just "We think." Do a study about it. Find out what separates ME/CFS from other diseases.

The title of the thread specifies a questionnaire to aid diagnosis. We don't know what distinguishes post-exertion responses in ME/CFS from those in other diseases. We have ideas, and possibilities from a handful of studies, but they're not rigorous enough at all to draw firm conclusions from. But I'm not convinced that defining PEM differently, even if done based on solid evidence that certain features are more specific for ME/CFS, would solve either the under- or overdiagnosis of ME/CFS (if the latter is occurring). I'd be surprised if people presenting to their doctor with PEF only or DOMS only are being told they have ME/CFS. If they think they have PEM because of a definition they saw online, or think they have ME/CFS because they think they have PEM because of a definition they saw online, I think [shrug]. Such is communication.

I think there has been a lot of poor quality and oversimplified information conveyed during and since the pandemic that may well have misled some people into doing less than they could. But a questionnaire for doctors will not help that.

I meant to say earlier, @Evergreen that I'm sorry you are in a 9 days so far PEM episode, and of course I believe that is PEM, whether there was a delay in onset or not. I would never question the reality of any pwME's experience.

Thanks @Trish. Don't worry, I know you well enough to know you wouldn't do that.

 

[Trish]

I've said more than enough in this discussion for now, and will try to step away to give others a chance to catch up.

I'll leave those who are against the idea with 3 questions:

What do you think pwME should do about the already existing and about-to-be-published problematic questionnaires by Jason and Tyson?

What do you think pwME should do if they attend a specialist clinic and are asked to fill in questionnaires, including a flawed one purporting to identify PEM, before they get access to any support?

Was DecodeME (and other studies) wrong to ask participants to fill in a questionnaire that included questions intended to check for PEM, and to only include samples from those who answered yes to the PEM questions in the study?

 

[Jonathan Edwards]

Pretty much all ME/CFS research studies use questionnaires to assess symptoms and case definitions.

Yes, but as I have already said in various posts, that is no reason to follow suit. Research into ME/CFS is largely too poor to be useful. We need to up the game. If people are minded to go on doing poor studies we are unlikely to persuade them to stop.

What people with ME/CFS see as a central concept of PEM may be heavily dependent on suggestion picked up from various media. We follow fashion without knowing it. This is just what Morelli showed is not the way to discriminate!!

 

[Peter T]

My feeling is that it would be useful to have a PEM questionnaire, but we should stress that of themselves each is not diagnostic of PEM as seen in ME/CFS, as any firm conclusion requires an appropriate professional making a judgement on the overall pattern of symptom change following exertion.

For me no individual symptom is diagnostic of PEM, though certain things like delayed onset do make a conclusion that PEM is occurring is more likely or rather easier to make. The key feature of PEM is that it is not simply an exaggerated or more readily triggered fatigue response that occurs in a wide range range of conditions, rather it is an abnormal fatigue response, that may be unique to ME/CFS and ME/CFS type Long Covid, though this requires further scientific evaluation.

Below is a list of symptoms that make it more likely that PEM is taking place, but their occurrence alone does not necessitate that we are observing PEM, nor does their absence necessitate that what is being observed is not PEM:

• feeling ill, in addition to any fatigue/exhaustion
• swollen or sore lymph nodes
• an exaggeration of existing symptoms
• exaggeration of sensory hypersensitivities
• the appearance of new or reappearance of previously experienced symptoms
• the appearance of symptoms in different modalities to the triggering exertion, eg cognitive exertion triggering physical symptoms
• delayed onset of the response
• rest alone not necessarily resulting in immediate recovery onset
• symptoms may continue to worsen or evolve over time despite rest
• symptoms may not return to the pre onset levels
• etc

A major problem with this approach is that currently there are few or no appropriate professionals, and that ideally all patients would be aware as soon as possible post onset of the possibility of PEM and have the tools to be able to distinguish it from increased fatiguability or post exertion symptom exacerbation. Certainly understanding of the concept of PEM would be top of my list of things that everyone diagnosed with ME/CFS should have explained.

[continued to edit to clarify after posting, and further clarification is probably still required]

 

[Hoopoe]

It would be good to have a short questionnaire that can be used by doctors and patients to get a sense of whether someone has PEM.

In my opinion, if non-delayed reactions to exertion are allowed to count as possible indicators of PEM, the questionnaire would be too unreliable. By focusing on the specific, unusual features of PEM, it becomes more reliable.

A PEM questionnaire also needs to treat experiencing PEM and avoiding activities that might trigger PEM as the same otherwise it could give a false negative in cases where the patient has learned to live with PEM.

I also think that in milder cases PEM is more likely to present in the cumulative form.