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

[Kitty]

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.

I'm thinking more and more it should be a summary of information for the physician to elicit, not a questionnaire for the patient.

It's not a questionnaire for the physician either, because that would imply these are the only questions that matter or they're supposed to reach a diagnosis by calculating a score. It's a brief guide to help identify PEM.

 

[Jonathan Edwards]

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.

These things are not simple. I am not saying that we are entirely on the wrong track. I doubt that very much. But the point of a questionnaire would be to get a yes or no answer as to whether someone has "PEM". And the problem I see is that we have no clear consensus on what the boundaries of PEM, that would determine yes or no, are. And to go back to my Art History point, the best way to identify a specific process (like painted by Caravaggio) may have little or nothing to do with what we think of as its main characteristic (chiaroscuro).

 

[Jonathan Edwards]

to have a straightforward questionnaire to help identify whether someone has PEM.

But unless we know the boundaries of what we mean by PEM how do we do that?

 

[forestglip]

I wonder if instead of focusing on trying to create a questionnaire with optimal accuracy in separating healthy from ME/CFS, it might be better to think about making a questionnaire with virtually 100% specificity, at the cost of poor sensitivity. Meaning make a questionnaire where only people with very clear, obvious PEM test positive, but where some people who really do have PEM might not.

This would not be for clinical diagnosis, but just for research to make sure everyone in your case group really has PEM to give the best shot at getting significant findings.

Currently they try to make sure people have ME/CFS with criteria like CCC, but all the associated symptoms seem kind of arbitrary to me since we don't know how related they are to ME/CFS. If a person saying they have PEM isn't enough to be sure they have ME/CFS, then adding in things like sore lymph nodes and IBS is still sure to let in a lot of people who have unrelated conditions.

Instead, is it possible to come up with a questionnaire specifically about PEM where we can say with virtual certainty that the person actually has it if they answer a certain way?

Something like a very clear delay of at least 12 hours after exertion, and a delay that the patient has recognized as occurring at least 10 times in the past year. After the crash starts, the person feels much worse for at least 48 hours.

Edit: Corrected specificity to sensitivity and vice versa.

 

[Utsikt]

a questionnaire with virtually 100% sensitivity, at the cost of poor specificity. Meaning make a questionnaire where only people with very clear, obvious PEM test positive, but where some people who really do have PEM might not.

If the sensitivity is 100 %, it would identify all cases of PEM as PEM.

If the specificity is low, it would identify some cases on non-PEM as PEM.

So I think what you’re suggesting is a questionnaire with virtually 100 % specificity (no false positives) and lower sensitivity (some false negatives).

I’m not sure that would be possible without also utilising other diagnostic measures like excluding differential diagnoses.

 

[forestglip]

So I think what you’re suggesting is a questionnaire with virtually 100 % specificity (no false positives) and lower sensitivity (some false negatives).

Oh yes sorry mixed up my specificity and sensitivity. But yes, primarily focused on making sure there are as few false positives as possible.

I’m not sure that would be possible without also utilising other diagnostic measures like excluding differential diagnoses.

You mean excluding people who might have another condition that explains PEM? I don't really agree with that view. If they have PEM, they have PEM, whether the cause is unknown, as in most people with ME/CFS, or it's related to some other condition like a mitochondrial disorder.

The research is trying to figure out the biology behind PEM, and we don't have a good reason to believe the biology is substantially different for PEM depending on what disease it happens in.

But I suppose if one wants to specifically focus on PEM with no known cause, then exclusion criteria for various diseases could be used, which is basically also trying to exclude false positives, so same general idea as what I was saying, just even more strict.

 

[Utsikt]

The research is trying to figure out the biology behind PEM, and we don't have a good reason to believe the biology is substantially different for PEM depending on what disease it happens in.

We also don’t have a good reason to think that it’s not substantially different. We simply know far too little at this point.

 

[forestglip]

We also don’t have a good reason to think that it’s not substantially different. We simply know far too little at this point.

Sure, I think it'd also be valid to separate out people with well-characterized diseases.

 

[Utsikt]

Sure, I think it'd also be valid to separate out people with well-characterized diseases.

You’d have no way of knowing if you’ve actually drawn up the lines in a position that aligns with the underlying biology.

All of these things would be nice in theory, but I don’t see how we could make it a reality.

 

[forestglip]

You’d have no way of knowing if you’ve actually drawn up the lines in a position that aligns with the underlying biology.

I'm just suggesting that, even if imperfect, it makes more sense than the criteria being a mishmash of random symptoms that don't really even seem related. For example, one requirement for CCC:

6. At Least One Symptom from Two of the Following Categories:

a. Autonomic Manifestations: orthostatic intolerance–neurally mediated hypotenstion (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension; light-headedness; extreme pallor; nausea and irritable bowel syndrome; urinary frequency and bladder dysfunction; palpitations with or without cardiac arrhythmias; exertional dyspnea.

b. Neuroendocrine Manifestations: loss of thermostatic stability–subnormal body temperature and marked diurnal fluctuation, sweating episodes, recurrent feelings of feverishness and cold extremities; intolerance of extremes of heat and cold; marked weight change–anorexia or abnormal appetite; loss of adaptability and worsening of symptoms with stress.

c. Immune Manifestations: tender lymph nodes, recurrent sore throat, recurrent flu-like symptoms, general malaise, new sensitivities to food, medications and/or chemicals.

So you could fulfill this specific category (which to be fair is only one category of the criteria) if you have heart palpitations and weight change, and you could also fulfill it if you have nausea/IBS and tender lymph nodes. These seem like quite distinct symptom groupings to me, and I'm not sure how much it's adding in making sure that people who don't have PEM are not included.

All of these things would be nice in theory, but I don’t see how we could make it a reality.

Just as I suggested: Instead of trying to define some amorphous grouping of various symptoms from all over the body, the inclusion criteria for studies of PEM or ME/CFS would be something like:

Something like a very clear delay of at least 12 hours after exertion, and a delay that the patient has recognized as occurring at least 10 times in the past year. After the crash starts, the person feels much worse for at least 48 hours.

Something where anyone on this forum would say, yep that person definitely has PEM, not chronic fatigue, muscle weakness, depression, etc. And maybe also exclude people with diagnosed diseases that are known to have some kind PEM-like presentation to make it even more homogenous.

 

[Utsikt]

@forestglip we’re still running into the issue of justifying why this approach would be better for determining who should be included in studies or not, because we don’t know what we’re trying to optimise for, because we don’t know how the relevant parts of the underlying biology affects how the symptoms present.

 

[Kitty]

@forestglip we’re still running into the issue of justifying why this approach would be better for determining who should be included in studies or not

We're also not separating research studies and initial diagnosis by GPs. They're very different.

DecodeME seems to have shown that in-depth questionnaires can be useful, though I guess a genetics study is a very particular case. It has a way of showing whether or not a cohort has things in common, which isn't necessarily true in other study types.

I'm more concerned about initial diagnosis, as it's mostly done by non-specialists. They're either trained to recognise one model of ME/CFS but don't have the medical knowledge to spot signs of something else, or they're trained, experienced physicians who don't know much about ME/CFS.

We're relying for diagnosis on recognition of a pattern of worsening after exertion, but there's a lot of focus on how it presents. Maybe we should look at the pattern instead. It ought to be distinctive enough; it might exist in other diseases, but they often have pathology that would eventually differentiate them from ME/CFS. Apart from this pattern we call PEM, the other distinctive thing is a complete absence of detectable pathology. An unusual presentation of OI could potentially be a third leg.