Warning Signals of Post-Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Retrospective Analysis of 197 Patients, 2021, Ghali

Abstract
Post-exertional malaise (PEM), the key feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is characterized by baseline symptom exacerbation after exposure to a stressor, and some patients can experience new or non-typical symptoms. We hypothesized that new or non-typical symptoms occurring long enough before onset of baseline symptom exacerbation could be warning signals predicting PEM.

Adult ME/CFS patients who attended the internal medicine department of Angers University Hospital (France) between October 2011 and December 2019 were included in a retrospective medical records review. Patients who experienced one or more new or non-typical symptoms before baseline symptom exacerbation were compared with the rest of the study population for PEM features, epidemiological characteristics, fatigue features, and comorbidities. New or non-typical symptoms preceded baseline symptom exacerbation in 27/197 (13.7%) patients, and the most frequent ones were mood disorders (37%). When compared to the rest of the study population, only PEM intensity was significantly lower in these patients (p = 0.004), even after adjustment for sex and age at disease onset (p = 0.007). New or non-typical symptoms preceding baseline symptom exacerbation in some ME/CFS patients could be warning signals for PEM. Their identification could help preventing PEM occurrences or reducing their intensity leading to improving disease prognosis.

https://www.mdpi.com/2077-0383/10/11/2517?type=check_update&version=1

full paper
https://www.mdpi.com/2077-0383/10/11/2517/htm

 

Differences between patients didn't seem to relate to new or atypical pre-onset symptoms, and those symptoms were varied:

PEM frequency did not differ between both groups of patients (p = 0.93) (Table 1). Patients both diagnosed with comorbid reactional depression and/or fibromyalgia and exhibiting prodromal new or non-typical symptoms were comparable to the rest of the study population in terms of medication intake (Supplementary Table S1).

In the group of patients who experienced new or non-typical symptoms before onset of baseline symptom exacerbation, the analysis of these symptoms showed that they were heterogeneous and varied between patients, however, they were almost constant for each patient. Table 2 shows the proportion of the different prodromal new or non-typical symptoms.​

The most common reported new/atypical pre-onset symptoms were mood disorders, nausea and paresthesia:

Mood disorders, including emotional lability, irritable mood, lack of motivation, and depressed mood, were the most frequent new or non-typical prodromal symptom experienced by 10 (37%) patients before onset of baseline symptom exacerbation. Nausea was also frequent and preceded baseline exacerbation in 8 (29.6%) patients. In six (22.2%) patients, the prodromal phase of PEM was characterized by the sudden appearance of paresthesia that generally lasted from many hours to many days. For each patient, the topography of paresthesia was the same but differed largely between patients: hemi-facial, perioral, one-sided, or diffuse. Paresthesia was not part of baseline symptoms and no patients reported paresthesia in PEM-free periods.

No association was found between the type of stressors and the nature of prodromal new or non-typical symptoms (Supplementary Table S2).
​

The rate of 13.7% patients reporting new/atypical pre-onset symptoms seems low. Ghali's patients are taught symptom-contigent pacing (the internal medicine department at the CHU Angers is the only one in France to offer such a therapeutic educational program) so there could be recall bias for those who manage to pace consistently and avoid PEM most of the time.

Further, it is noted that the "new or non-typical symptoms before [PEM] onset (...) were almost constant for each patient". This suggests that patients who experience those on an inconsistent basis (e.g. 30-50% of the time) may not have reported them.

It is interesting to see that mood disorders are the most prevalent (bolding mine):

Mood disorders were the most frequent prodromal new or non-typical symptoms. It is worth noting that none of the patients who experienced mood disorders had underlying psychiatric conditions, and that mood disorders regressed spontaneously throughout the PEM recovery period. One possible explanation for this finding might be that, in some ME/CFS patients, PEM and mood disorders share the same pathophysiological mechanisms. For instance, mitochondrial dysfunction including low ATP production, and increased oxidative stress and nitric oxide, was reported to be one of biological anomalies encountered in both PEM and mood disorders [22,23]. The exposure to a physical, cognitive, or emotional stressor could thus trigger both conditions, and mood disorders could precede baseline symptom exacerbation in some patients. Moreover, the concomitant improvement of both conditions could be evidence supporting this hypothesis.
​

Personally, irritable mood (getting very snappy) is an early symptom of orthostatic intolerance and/or cognitive overexertion that I get as I start wading into PEM territory. Depressed mood, however, appears when PEM sets on later.

 

I've been dealing with a vestibular neuritis virus for over a year and this negatively affects my mood. I've never experienced anything like it. A couple of years ago I posted a link (can't find it) that explains pacing to prevent "post exertional malaise' when dealing with vestibular neuritis. It was very similar to what is recommended for ME pacing/managing and preventing PEM.

 

I'm puzzled by the sample criteria:

"Adult ME/CFS patients who attended the internal medicine department of Angers University Hospital (France) between October 2011 and December 2019 were included in a retrospective medical records review."

Haven't got the mental energy to look at the paper, but does this mean that the people studied went to hospital with ME symptoms and had them noted in their records?

If so, how typical is this? I'm fairly sure that there is very little in my medical records about ME symptoms, and the only times I've been to hospital have been for other things.

 

Yes, Dr Ghali and his team interview new patients, asking about symptoms related to ME. Presumably they note changes in symptoms at follow-up consultations.

 

why is it classed as a mood disorder to be short tempered when your feeling awful .this seems to be the very natural response anyone should have to symptoms like pain and nausea .

 

So, only 13.7% of participants reported "new or non-typical" prodomal symptoms but they still had PEM just as often albeit milder.

I wonder what the study's results would have been had they not specifically asked about "new or non-typical" symptoms?

All the symptoms I get with PEM I also have at baseline, just milder, so I don't get any "new or non-typical" symptoms at all. However, some of my symptoms increase much earlier than others, notably the cardiac ones like resting heart rate and POT. At that stage PEM is already unavoidable (fits with the study finding of equal frequency of PEM) but if I reduce my activity level as soon as I notice, PEM will be milder and shorter (also fits the study finding of milder PEM).

What the study was really hoping to find (but failed to do) was a symptom signal that, if noticed and acted upon, could prevent PEM altogether. The holy grail.

For me this sort of symptom signal doesn't exist for physical exertion. By the time I notice anything at all it's way too late. But others here report that they do have early warning signs that allow them to avoid PEM.

I do have warning signals for cognitive and/or orthostatic exertion (I can't reliably separate the two). Basically it's just a sense of the brain slowing and tiring in the sense of running out of energy. If I rest there and then I can avoid PEM.

So maybe it's not a matter of looking for "new or non-typical" symptoms but of looking for early signs of fatiguability?

 

Personally, the only "warning" I've had that some experience might result in PEM the next day is the knowledge that some similar level of exertion has caused PEM in the past. I've never noticed any warning sign indicating that I might have crossed (or might be about to cross) some threshold that will result in PEM the next day.

 

Same, it's only from past experiences that I'm able to avoid PEM, and when it occurs there is no stopping it.

 

It especially doesn't help when sometimes PEM hits and you look back at the last few days and can't find a damn thing to explain it, zero warning. There are no reliable signals, although with experience it gets easier to spike the probability curve above random chance.

That's been expressed a lot by long haulers, how damn frustrating it can be to be super careful and crash anyway, how you can't effectively just rest and pace, it helps but it doesn't work reliably. That's despite knowing about it as early as possible.

 

I was always a fairly snappy individual. If anything that's improved since I got ME - you do learn some patience.

I think anyone who is tired, or tiring quickly, or starting to struggle to pay attention (even if they aren't quite aware of it yet) will be more inclined to be snappy.

In my case being snappy (or snappier) is a sign of fatiguability kicking in. Unfortunately, once cognitive fatiguability kicks in I'm already on my way to PEM and that's that.

I used to think I could avoid physical PEM, especially when I was still able to practise yoga. Long before weakness or the shakes I would start to lose fine coordination and muscle control, those minute tweaks that happen while you work in a pose but look like you're doing nothing.

However, I no longer believe this was the case, I may have avoided many of the symptoms of PEM but that doesn't mean that PEM didn't happen. I think it's entirely possible we can be accumulating issues that cause long term deterioration even if you manage to avoid triggering PEM. The symptoms of PEM being downstream.

Th snag with all this is ME is by it's very nature a fluctuating condition. In addition many of us are affected by such a wide range of other factors - temperature, light, noise, etc. It's a bit like trying to find a flat bit in the Irish Sea. There may be readily identifiable storms, high seas & tides but there will also always be waves, no matter what.

 

I'm permanently bad-tempered, so this warning signal is bugger all use to me.