PEM may be triggered by cognitive exertion alone. Thus if a patient does not have physical exertion PEM, they may still get an ME/CFS diagnosis

[Hip]

Modern ME/CFS diagnostic criteria require post-exertional malaise (PEM) as a mandatory symptom for an ME/CFS diagnosis. PEM of course is the well-known temporary period of worsened ME/CFS symptoms that usually hit in the next day or two after engaging in exertion (but may also appear on the same day, or even immediately after exertion).

Thus on ME/CFS forums we often see it said that "if you do not have PEM, you do not have ME/CFS".

But we should be mindful that PEM may be triggered either by physical exertion, and/or by cognitive, mental or emotional exertion.

This means that if a patient has all the usual ME/CFS symptoms, but they do not get PEM after physical exertion, they may still qualify for an ME/CFS diagnosis, provided they experience PEM after cognitive, mental or emotional exertion.

So for example, if someone finds that cognitive activity such as reading for some time, performing arithmetic, doing their home accounts, engaging in lengthy conversation, etc, later triggers a period of worsened ME/CFS symptoms (such as worsened brain fog, worsened fatigue, malaise, worsened sound sensitivity, or any other worsened ME/CFS symptoms), then I believe that would count as PEM.

Likewise, if someone finds that being involved in stressful or emotional activity triggers a period of worsened ME/CFS symptoms, that also counts as PEM.

When seasoned ME/CFS patients chat with brand new patients who are wondering whether they may have ME/CFS, these new patients are often asked if they have PEM. And if they reply that they do not get PEM after physical exertion, then they may be told that the possibility of having ME/CFS is in doubt.

However, it's important to check not just whether new patients have physical exertion-triggered PEM, but also whether they might have cognitive, mental or emotional exertion-triggered PEM. Because either counts as having PEM.

If you do not experience physical exertion-induced PEM, but do get cognitive, mental or emotional exertion-induced PEM, you still have PEM.

The Canadian consensus criteria (see page 4) make this clear:

Post-Exertional Malaise and/or Fatigue: Physical or mental exertion often causes debilitating malaise and/or fatigue, generalized pain, deterioration of cognitive functions, and worsening of other symptoms that may occur immediately after activity or be delayed.

And the IOM criteria also make this clear:

Post-exertional malaise (PEM) — worsening of symptoms after physical, mental, or emotional exertion that would not have caused a problem before the illness.

Fatigue, Rapid Fatigability and PEM in ME/CFS Diagnostic Criteria

It may be worth reviewing these three cardinal ME/CFS symptoms, so that we understand them. In some ME/CFS diagnostic criteria, such as the Canadian consensus criteria, all three must be present for an ME/CFS diagnosis. Other diagnostic criteria are less strict.

All these three symptoms also come in two forms: the physical form and the mental form.


Fatigue

Physical fatigue involves feeling physically drained or weak. Physical fatigue is characterised by difficulties in performing physical activities, due to lack of muscular strength or lack of physical energy.

Mental fatigue or mental exhaustion involves feeling mentally weary, frayed or drowsy. Mental fatigue is characterized by difficulties concentrating and performing cognitive tasks (such as reading, arithmetic, filling in forms, talking to people, etc).


Rapid Fatigability

Rapid physical fatigability (poor physical stamina) is a muscular fatigability that quickly appears during physical exertion, such that the longer the exertion goes on, the weaker the muscles feel. This muscle weakening can occur fast, within a minute of starting a physical exertion.

Rapid mental fatigability (poor mental stamina) is a fatigability of mind that quickly appears when performing mental or cognitive tasks (tasks which quickly exhaust you mentally might include reading, arithmetic, filling in forms, talking to people, etc).


PEM

Physical exertion-induced PEM is where physical exertion or physical exercise triggers a temporary period of worsened ME/CFS symptoms (and during this period, flu-like symptoms or pain may also appear).

Mental exertion-induced PEM is where cognitive or emotional exertion, or sometimes just sensory overload (light and sound), triggers a temporary period of worsened ME/CFS symptoms (and during this period, flu-like symptoms or pain may also appear).



IOM Criteria Requirements

The IOM criteria require ongoing fatigue to be present for an ME/CFS diagnosis, but do not distinguish between physical fatigue and mental fatigue, so presumably either (or both) are acceptable. The IOM criteria require PEM to be present, but do not distinguish between physical exertion-induced PEM and mental exertion-induced PEM, so presumably either (or both) are acceptable.


Canadian Consensus Criteria Requirements

The CCC criteria require ongoing physical fatigue as well as ongoing mental fatigue to be both present for an ME/CFS diagnosis. The CCC also requires the presence of both rapid physical fatigability as well as rapid mental fatigability. But the CCC will accept either physical exertion-induced PEM or mental exertion-induced PEM as satisfying PEM criterion.


International Consensus Criteria Requirements

The ICC criteria do not require either ongoing physical fatigue or ongoing mental fatigue to be present for an ME/CFS diagnosis. The ICC requires rapid fatigability to be present, but will accept either rapid physical fatigability or rapid mental fatigability. The ICC requires PEM to be present, but will accept either physical exertion-induced PEM or mental exertion-induced PEM.

So the ICC are not as strict as the CCC when it comes to fatigue, fatigability and PEM requirements.

 

[heapsreal]

Wouldn't it be good if they added biomarkers to help confirm cfsme like the 2 day treadmill test, nk function test, chronic dysregulated immune markers or any other test commonly found in the cfs research over the last 30yrs.
Not that everyone can get these things tested but if they could, it would help the diagnoses. Also not used as the soul or isolated test for cfsme.

 

[Wishful]

Wouldn't it be good if they added biomarkers

I get the impression that those biomarkers aren't yet proven to be reliable. They're based on selected subjects. They might find the marker in 88% of those carefully-selected subjects, but what is the rate in subjects selected at random? A wrongly-chosen set of criteria could be harmful for those outliers who have the disease but don't quite fit the overly strict criteria.

 

[Hip]

Wouldn't it be good if they added biomarkers to help confirm cfsme

Yes, we already have a number of imperfect biomarkers, which might not be good enough to use on their own, but used in conjunction with other biomarkers, might give us an insight.

For example, we could employ the buspirone challenge test for ME/CFS, and observe the results for both PEM positive and PEM negative patients. This test's sensitivity and specificity are 87% (although it has only been validated on a small number of patients).

We might also do viral testing, since studies have shown ME/CFS patients usually have persistently high antibody titres to certain enteroviruses and herpesviruses (when appropriately sensitive tests are employed), whereas healthy controls mostly do not.

Even ME/CFS patients whose illness was triggered by a vaccine, not a viral infection, usually have these high viral antibody titres.

Reduced natural killer cell activity is usually found in ME/CFS, so that is another biomarker test, albeit imperfect. And TGF-beta is usually elevated in ME/CFS. And there are various other imperfect biomarker tests that could be used.


If you used all these biomarkers together, and then gave the patient a score depending on how many biomarkers they tested positive for, that might provide a good indication of who really has ME/CFS.

 

[hapl808]

For example, we could employ the buspirone challenge test for ME/CFS, and observe the results for both PEM positive and PEM negative patients. This test's sensitivity and specificity are 87% (although it has only been validated on a small number of patients).

We might also do viral testing, since studies have shown ME/CFS patients usually have persistently high antibody titres to certain enteroviruses and herpesviruses (when appropriately sensitive tests are employed), whereas healthy controls mostly do not.

Even ME/CFS patients whose illness was triggered by a vaccine, not a viral infection, usually have these high viral antibody titres.

Reduced natural killer cell activity is usually found in ME/CFS, so that is another biomarker test, albeit imperfect. And TGF-beta is usually elevated in ME/CFS. And there are various other imperfect biomarker tests that could be used.

So many promising things. Combined with simple ML models, we already likely have 90% and higher accuracy biomarkers.

Instead of spending significant money on urgently validating this and putting together more accurate EHRs, we spend millions on symptom surveys and absolute nonsense. Even the ones that prove something, no one believes because they have no biomarkers.

Tragic.

 

[Mary]

For example, we could employ the buspirone challenge test for ME/CFS, and observe the results for both PEM positive and PEM negative patients. This test's sensitivity and specificity are 87% (although it has only been validated on a small number of patients).

I'd never heard of this test before and clicked on the link, and was very surprised to see a study from 1996 with Michael Sharpe (!) of the PACE trial, which showed definite abnormalities in persons with ME/CFS given the buspirone challenge test.

What happened to Mr. Sharpe? Apparently at one time he was actually a scientist, hard as that may be to believe --

 

[junkcrap50]

Yes. This is true and important to highlight. This is how my CFS began. My major symptom (nearly only symptom) was cognitive difficulties and cognitive PEM. I could run, lift weights, exercise, etc. but just couldn't think, read, remember things, had brain fog, or perform in college. My cognitive PEM felt like my brain was fried and burnt out. Like, how one's brain felt after a studying for and taking final exams, but it felt like that all the time. I still had sleep disruption, fatigue, and gut difficulties but those seemed normal from just burn out feeling. I spent the first 6 years thinking it was head injury related.