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

[Kitty]

I agree questionnaires are a pain, and for people who are very sick they are impossible. I am envisaging something very short, the shorter the better.
Maybe as simple as:

Choose the option that best reflects your experience:
If I significantly increase my current usual activity or exercise:
1. I feel no different or better in the following hours and days
2. I feel tired and/or sore for hours or a day or two
3. I become much sicker and less able to function for hours, days or longer.

To get back to the thread, I think this is for the diagnosing physician*, not the patient. The questions should be explored in whatever way is most appropriate and understandable for the individual, not necessarily all on the same occasion. Probing one of them might be enough to fill a consultation in some cases, specially if the person's responses seem inconsistent because they're not yet clear in their own mind.

This is the sort of thing I mean when I say diagnosis is a process. These are big questions about the character and time course of symptoms that may never have occurred to a newly ill person before. They might benefit from time to reflect on them away from the pressure of the consulting room.


* Obviously it has to be a physician, because diagnosis of a severely disabling, often lifelong illness cannot be left to people without medical training.

 

[Jonathan Edwards]

It's not only defined by the time course (though that's clear enough once you've spotted it), it's defined by symptoms that are different to the underlying ones. They aren't present unless you exert beyond a threshold or are subjected to some kind of external stress.

But nobody has defined what symptoms are underlying and what are extra, so I find it hard to see how you can define PEM that way. If it is just the type of symptoms then we can forget the PE part and just ask about the extra symptoms.

 

[Evergreen]

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?

No, they were right, because they wanted their participants to fulfill Canadian +/-IOM/NAM criteria which require PEM, and they could not get the numbers they needed assessed by physicians, so questionnaires were the only way. The two PEM questions were consistent with the Canadian criteria. You could quibble that the IOM criteria don't specifically require PEM to last 24 hours or more, but there are enough mentions of "prolonged" that this is reasonable, and there is at least some supportive evidence that duration of longer than 24 hours may be more specific for ME/CFS. They were right to try to get the participants to fulfill some criteria, so that they might be studying a similar population to other studies using the same criteria. So the two questions they asked were completely justified.

What we don't know is whether those who reported having been diagnosed with ME/CFS by a physician, but did not fulfill the PEM criteria in DecodeME, would have been genetically different from those who reported a diagnosis and did fulfill the PEM criteria.

I agree with Jonathan:

I think the GWAS context is very atypical. The hope is that by adding a questionnaire you get close enough to a biologically meaningful category of subjects to get a statistically significant result on signals you know are going to be causal with big numbers. For nearly all other research the situation is worse. DecodeME showed that its entry criteria for ME/CFS picked out a distinct biological pattern but whether our current concepts of what that pattern is are anywhere near appropriate is still very much up in the air. The PEM question may have refined the category or diluted it - we don't know. A different questionnaire that we think more closely reflects our concepts of PEM might do better or less well - who knows?

The problem for me is the assumptions underlying much of the discussion:

• we know what "true PEM" is
• people with other conditions do not have "true PEM"
• if we just get the questions right, it will pick out us and only us
• with the right questions, there would be less under- and overdiagnosis in ME/CFS
• the consequences of our questionnaire would be good, whereas other questionnaires cause harm

I can't get on board with any of those assumptions.

If this thread had asked: "If a study were done to explore post-exertional phenomena in ME/CFS compared to other fatiguing illnesses, what questions would you ask participants?" then I would have said "Finally!" and looked forward to a discussion on exploratory questions so that we would get good data about triggers, duration, onset, the lot. To do a good study we would have to not be tied to what the results might be. All assumptions have to be thrown out. We have to be open to everything.

When we have enough good quality data to actually know what the situation is, then in theory an alternative set of questions might be put together for the very unusual DecodeME situation, and clinicians might be educated about which open-ended questions might be more likely to elicit pertinent info, and to prick their ears a little more if certain things were said in responses to their open-ended questions.

I think we need to be much less territorial about PEM in order to find out the approximate boundaries of our territory and whether we're an island or a landlocked country with a lot of neighbours and blurry borders, plus, in either scenario, the endless possibilities of minorities, dual citizens etc.

What I really want to see are more experimental studies that compare post-exertion responses in ME/CFS and other diseases. A few teams were getting somewhere around 2010/2011 and then nobody took up the baton - a shame, as so many patients were doing GET in the decade that followed that we might well have had actual experimental evidence of lack of benefit or harm from it.

 

[Jonathan Edwards]

Symptoms are different again in a crash. Vivid hallucinations, back spasms with involuntary arching like tetanus, extreme thirst that drives me to drink 8 to 10 litres a day, etc. It's a long way removed from normal PEM, I've only had it three times in 50 years of illness—it also seems to be pretty uncommon, so probably a sidetrack.

But none of that is recognised by anybody else as far as I know. To me a crash is just a long lasting major set back. To others it is a sudden worsening rathan a long-lasting one.

So we don't seem to have much agreement.

 

[Jonathan Edwards]

I think the price of that may be missing PEM.

But the price of asking leading questions is that we get a community of people who think they all have the same disease because some doctors have told them this story that they have a special disease characterised by PEM, when in fact they have a variety of disease and the commonest one has a common feature that loosely correlates with PEm but isn't PEM.

I am sensing that exactly this sort of problem is likely to be going on, at least to some degree.

I would suggest that rather than trying to find a better definition of PEM we look at it differently and try and find a better description of what seems to be common to what we think of as the ME/CFS syndrome, whether or not it should be called PEM.

What seems to me crystal clear now is that the concept of PEM people have includes a range of aspects of symptoms - character, time course, etc. that do not necessarily go together, which makes the single PEM concept pretty shaky.

If nobody can agree what PEM is, how can anybody be diagnosed with ME/CFS?

That's easy. Human brains are good at picking out consistent patterns without knowing quite how they do it. Some people can reliably tell a caspian gull from a herring gull at a glance but the textbooks spend pages trying to explain how to learn how to do that. In the end one day you suddenly realise your brain picks up a "GISS" for caspian and you forget trying to work out how.

Identifying ME/CFS isn't that hard. The idea of PEM may be a useful guide but it may always be problematic.

We get these things wrong routinely. For decades rheumatology trainees were taught the RA is symmetrical and psoriatic arthritis is asymmetrical. Most trainees are probably still taught this. But Debbie Simmonds did a nice study showing that there is no difference, it is just that RA tends to affect more joints and so look more symmetrical. When it affects few joints it is as asymmetrical as psoriatic.

 

[Mij]

I definitely had delayed PEM for the first time after the first exercising I did 8 years after onset. No one talked about it back in the 90s so I thought it was just me and that it would eventually resolve on it's own.

The echoing voice of my ME specialist playing in my mind when he distinctively told me to 'do nothing' when I start feeling better and yet I continued to exercise until I realized 2 years later that this was a very abnormal bizarre response to exercise and not going away.

 

[Kitty]

But nobody has defined what symptoms are underlying and what are extra, so I find it hard to see how you can define PEM that way. If it is just the type of symptoms then we can forget the PE part and just ask about the extra symptoms.

People with ME/CFS have. PEM's a feeling of acute illness, often with 'flu-type symptoms, as opposed to the chronic symptoms.

"Very unwell and unable to do anything" is a different (much worse) experience to "Not particularly unwell but unable to do much".

I think of PEM as symptoms and underlying ME/CFS as features. One is an illness, the other is more like a set of impairments.

But none of that is recognised by anybody else as far as I know.

Agree, that's why I said it was a sidetrack. I was explaining that "crash" is my term for something very different to ongoing symptoms and PEM. I discussed that in the early 2000s with three or four people who experienced a similar pattern, but don't think it's useful here.

 

[rvallee]

Even several years after I got sick, I wouldn't have been able to make it clear that I had PEM because I hadn't noticed it. I'd just got used to feeling rubbish for ages after extra activity but hadn't thought about it as a 'thing'. I never mentioned it to my GP because I'd forgotten what 'normal' was. It was only when my dad pointed out to me that I was worse the day after an activity than on the same day that I became aware of it. If I'd been asked some clear questions by my GP about PEM, though, I think that would also have made the penny drop.

Pretty much. Looking back at my interactions with GPs all those years, there is zero chance they could have possibly asked the right questions, and I didn't tell them the needed information, mainly because I was so cognitively impaired that I couldn't even make sense. It needed a structured process and there just isn't anything like that.

Not that a questionnaire fixes this, but there is simply zero chance for GPs to work this out the normal way they do, it's just not going to happen. The decision-making process has to be taken out of their hands entirely, they will never manage it. Humans are not built for stuff like this, our judgment is not anywhere near as good for problems as hard as this.

We see the same problems with other diseases that are hard to diagnose, many of which are far easier to validate than ME/CFS, yet are still so hard that it's pretty much impossible without a validated test involved. Most neurological diseases take several years to diagnose on average, and in the end it's almost always an objective test that does it. The human judgment process involved during that time is pretty much useless, it involves things that can't be seen or reasoned.

This is why a questionnaire seems somewhat reasonable, by taking individual judgment out of the equation in matching clinical criteria, but that still involves way too much judgment, and is probably why it ultimately doesn't really work out. Human judgment has to be entirely bypassed here, it will never manage this, it's far too weak for it.

Honestly, patients presented with the right information are far more likely to work this out than 99.9% of clinicians. All of which feeds into the physician defence mechanism of "read about it on the Internet", but it's literally the only way this can work out. It's like those complex visual puzzles where you can look and look and look and see nothing but once you know what to look for it's obvious. It can't ever become obvious to GPs, only to the patients.

So most likely an intermediate solution must involve patients proactively working out the criteria so that GPs can then ask questions they would never think of on their own. This is all simply something that is beyond human abilities to work out.

 

[Jonathan Edwards]

People with ME/CFS have. PEM's a feeling of acute illness, often with 'flu-type symptoms, as opposed to the chronic symptoms.

But that is not the consensus here. Some are focusing on how long it lasts
It would be a plausible definition but is it what is most characteristic of ME/CFS?

I am cautious about that because of my own experience. When I had post-EBV fatigue for six months I had what you describe - feeling ill after exertion, flu-like. But I never had a setback that lasted days. The setback was gone by the next day. I don't think I had ME/CFS - in other words I don't think I had the illness most members seem to have.

 

[rvallee]

Now, hang on. PEM is such a subtle thing that you can have ME/CFS for several years without knowing you have it? It has to be suggested to you? That seems to mean that asking about PEM is not a reliable way to identify ME/CFS. Which wouldn't surprise me.

It's something that is almost impossible to work out without knowing to look for it, but once you know to look for it it becomes very obvious, yes. This is annoying but it is the reality we have to live with, and it's very far from being unique at that.

It still doesn't make PEM subtle, in fact it's as blunt as a car to the face. It's noticing the relations that is difficult, and this is normal because it doesn't have a linear relationship between cause and effect. Those are always the most difficult problems to work out, humans can only think linearly and about simple relationships.

Not many diabetics will notice a direct relationship with sugar intake either, and will likely not bring it up to their GPs either. This doesn't make diabetes any subtle when things veer way off safety limits.

 

[Jonathan Edwards]

It's something that is almost impossible to work out without knowing to look for it,

That seems to me strange since for me, with post-EBV fatigue it was barn door obvious and I remember telling my parents about it. It was the thing that got at me most, with all my friends doing sport.

 

[Kitty]

I am cautious about that because of my own experience. When I had post-EBV fatigue for six months I had what you describe - feeling ill after exertion, flu-like. But I never had a setback that lasted days. The setback was gone by the next day.

That's not uncommon for me either. I think it's a severity thing.

Quite a lot of the people who post in detail on S4ME are more severely affected—they couldn't go to the pub and listen to music, for instance, and they get worse PEM than moderately affected people from doing far less activity.

I feel just as you describe the day after I've been out. It's largely gone by the same evening, and is what I think of as "acceptable" PEM: the price of doing something I enjoy. I do it when I know it won't result in significant or long-lasting ill-effects, but that doesn't apply all the time. If my capacity's already overstretched (often due to things I can't control) it would result in a longer lasting dose of PEM.

 

[Mij]

People with ME/CFS have. PEM's a feeling of acute illness, often with 'flu-type symptoms, as opposed to the chronic symptoms.

I'm of the subset that feels 'viral-like-flu-like' 80% of the time for the last 20+ years. I feel like this without exerting myself so I don't use the term PEM to describe it. Sometimes when I feel flu-like I go for walk, my legs are sore/stiff, but after the walk I feel better, but sometimes I feel worse the next day. Who knows?

 

[rvallee]

So, this makes it even more difficult to believe we can usefully get to grips with a PEM deinfition. If you have it all the time it cannot be identified as PE M since it isn't post anything but all the time.

Living is exertion, it cannot be avoided. This is what trips most physicians. Even you tripped on it here. Normal activities of daily living are enough exertion to be a problem here. Plus most of the time that layer of malaise is itself the result of past exertion, which is hard to pin down because most of the time it's completely disproportionate.

If you can trip on it so easily after all this time, it can be asserted with certainty that it can't ever be expected that GPs can manage it. It's too bizarre, too remote from the normal experience of being human.

 

[Sasha]

But the price of asking leading questions is that we get a community of people who think they all have the same disease because some doctors have told them this story that they have a special disease characterised by PEM, when in fact they have a variety of disease and the commonest one has a common feature that loosely correlates with PEm but isn't PEM.

I am sensing that exactly this sort of problem is likely to be going on, at least to some degree.

I would suggest that rather than trying to find a better definition of PEM we look at it differently and try and find a better description of what seems to be common to what we think of as the ME/CFS syndrome, whether or not it should be called PEM.

What seems to me crystal clear now is that the concept of PEM people have includes a range of aspects of symptoms - character, time course, etc. that do not necessarily go together, which makes the single PEM concept pretty shaky.

In our 'What is ME/CFS?' factsheet, we ended up with:

The key feature of ME/CFS is that the illness gets worse after physical or mental activity. People with ME/CFS have limited energy and doing too much makes their symptoms more severe. The worsening can begin hours or days later and take a long time to recover from. Rest or sleep gives little relief. This is called post- exertional malaise.​

In our PEM factsheet, we ended up with:

People with ME/CFS experience episodes when they are much more ill and cannot do as much as usual following amounts of physical or mental exertion or sensory stimuli that they could easily tolerate before the illness. This is called post-exertional malaise, or PEM. PEM is the hallmark of ME/CFS and important for diagnosis.​

​

The main features of an episode of PEM are:​

• A person feels more ill. Their usual symptoms get much worse, and new symptoms may appear.
• They are much less able to function. They need to rest more, or even to lie still in silence and darkness, until it passes.
• The onset of PEM is typically delayed for hours or up to several days after it is triggered.
• The length and severity of an episode of PEM are out of proportion to the amount of exertion or stimulus that triggered it. An episode can last hours, but more often lasts days, weeks or longer.

In your factsheet for health professionals, we've got (from the thread on the members' forum):

Since 2003, post-exertional malaise has been taken as the unifying characteristic of ME/CFS. Following physical or mental exertion, which can be trivial in normal terms, patients experience a worsening of, and increase in range of, symptoms, together with loss of function. Post-exertional malaise is unlike normal fatigue following activity.​

Unless I'm reading these wrongly (and I'm reading in haste, with brainfog), we've consistently presented PEM as the essential characteristic of ME/CFS, and as having certain features. But your post above suggests that you think we might have got this wrong. If we have, we should face that and change it but am I understanding you correctly? As @Trish says, I thought we'd all agreed on this.

 

[Trish]

I think we are in danger of a few individuals' experience being taken as the basis for throwing out the usefulness of PEM as a key feature of ME/CFS on the shaky grounds that not everyone's experience is exactly the same.

That's why I think it would be useful for this discussion to try to step aside from describing our specifics of which symptoms get worse, and whether PEM is worse in severe ME/CFS, and focus on whether it's possible, and in some circumstances useful, to have a straightforward questionnaire to help identify whether someone has PEM.

 

[rvallee]

Someone should tell that to a lot of the doctors I've seen in the last nine years.

Yeah I really had to do a double take on that because wow do physicians ask a lot of leading questions, it's just that with us they are exactly the wrong kind.

But, really, when have you stopped beating your wife, senator?!

 

[Kitty]

That seems to me strange since for me, with post-EBV fatigue it was barn door obvious and I remember telling my parents about it.

But you were recovering from being ill.

What if you'd never been ill? You struggled with stuff the way other people don't, but you battled on because you had no option—if you didn't go out and earn a wage you could neither eat nor keep the roof over your head.

Over time you started cutting out more and more activities, but many of them were small routine things, so you didn't notice. Yes, you used to enjoy hiking and you don't do it any more, but these days work's so busy that you don't have the energy. You're living in a persistent cognitive fog that allows no overview (or even memory) of much of what's happened, but you're unaware of it. Knowing that would require a level of mental clarity you can't even remember having.

People don't always know they're ill. Their function can be severely impaired but they have no idea because humans are so good at adapting. They're not going to get feedback from friends if they're too impaired to socialise and talk things through, and anyway, it's not long before they reach the stage where some friends and colleagues have never seen them any other way. So they don't know either.

 

[rvallee]

But the price of asking leading questions is that we get a community of people who think they all have the same disease because some doctors have told them this story that they have a special disease characterised by PEM, when in fact they have a variety of disease and the commonest one has a common feature that loosely correlates with PEm but isn't PEM.

Which is about the same situation as trying to diagnose diabetes without a validated test. It works out there because there are tests. But very few diabetics will go to see a GP explaining how their sugar intake is clearly causing them trouble, whereas the only way a GP could know this would by... asking leading questions.

Asking such a leading question would lead some to figure out the relationship. It's almost impossible without it. And that's usually the point of having experts: they're people who know which questions to ask, questions that most people will not think of.

But even we can't figure out which questions to ask. It's impossible to expect someone to figure it out on their own. So we are still back with the necessity of having objective measures that remove human judgment entirely out of the equation, because human judgment cannot do any of this reliably.

So that should kind of settle the need for a questionnaire: does it solve this problem? And clearly it does not. It's really objective test or bust, because we face as much conflict out of the nature of the illness as we do with the fact that human judgment is totally unfit for this purpose.

 

[Evergreen]

I agree questionnaires are a pain, and for people who are very sick they are impossible. I am envisaging something very short, the shorter the better.
Maybe as simple as:

Choose the option that best reflects your experience:
If I significantly increase my current usual activity or exercise:
1. I feel no different or better in the following hours and days
2. I feel tired and/or sore for hours or a day or two
3. I become much sicker and less able to function for hours, days or longer.

End of questionnaire.

Option 2 indicates PEF and/or DOMS
Option 3 indicates PEM.

The reason I don't think a questionnaire like this would help doctors diagnose ME/CFS is because the ones who don't diagnose it don't (not) do so because they don't know about PEM. They're not struggling to distinguish between PEM and DOMs or normal fatigue after exertion. They don't diagnose it because they don't believe in it. If a person were to choose option 3 they would just dismiss that as severe deconditioning due to activity avoidance or as catastrophizing. The doctors who do believe patients, and who recognise that what the patients are describing is different from a normal response to increased activity, already diagnose it. It doesn't move us forward.

And DOMs can continue for a lot longer than a day or two. When I was healthy, I had plenty of episodes of DOMs that lasted one week and a few that lasted two weeks. For example, when you go back to training after the summer break (about 4-6 weeks off). You can feel quite unwell too, when it's severe enough. But crucially, you can push through it to do a normal level of activity, even if you can't exercise, and even if you're not at your sharpest mentally. And it ends. And then you can do the thing that caused the DOMs without triggering DOMs on top of your usual activity.