Recovery from Exercise in Persons with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) 2023, Moore, Hanson et al

Abstract:
Background and Objectives: Post-exertional malaise (PEM) is the hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but there has been little effort to quantitate the duration of PEM symptoms following a known exertional stressor. Using a Symptom Severity Scale (SSS) that includes nine common symptoms of ME/CFS, we sought to characterize the duration and severity of PEM symptoms following two cardiopulmonary exercise tests separated by 24 h (2-day CPET).

Materials and Methods: Eighty persons with ME/CFS and 64 controls (CTL) underwent a 2-day CPET. ME/CFS subjects met the Canadian Clinical Criteria for diagnosis of ME/CFS; controls were healthy but not participating in regular physical activity. All subjects who met maximal effort criteria on both CPETs were included. SSS scores were obtained at baseline, immediately prior to both CPETs, the day after the second CPET, and every two days after the CPET-1 for 10 days. Results: There was a highly significant difference in judged recovery time (ME/CFS = 12.7 ± 1.2 d; CTL = 2.1 ± 0.2 d, mean ± s.e.m., Chi2 = 90.1, p < 0.0001). The range of ME/CFS patient recovery was 1–64 days, while the range in CTL was 1–10 days; one subject with ME/CFS had not recovered after one year and was not included in the analysis. Less than 10% of subjects with ME/CFS took more than three weeks to recover. There was no difference in recovery time based on the level of pre-test symptoms prior to CPET-1 (F = 1.12, p = 0.33). Mean SSS scores at baseline were significantly higher than at pre-CPET-1 (5.70 ± 0.16 vs. 4.02 ± 0.18, p < 0.0001). Pharmacokinetic models showed an extremely prolonged decay of the PEM response (Chi2 > 22, p < 0.0001) to the 2-day CPET.

Conclusions: ME/CFS subjects took an average of about two weeks to recover from a 2-day CPET, whereas sedentary controls needed only two days. These data quantitate the prolonged recovery time in ME/CFS and improve the ability to obtain well-informed consent prior to doing exercise testing in persons with ME/CFS. Quantitative monitoring of PEM symptoms may provide a method to help manage PEM.

https://www.mdpi.com/1648-9144/59/3/571

 

Excellent job to Workwell and their partners. The graphs can be freely shared (Creative Commons license) and are an excellent demonstration of how exercise affects PwME, and the huge difference between us and healthy controls.

Modeling PEM as a "drug" is an interesting exercise but reveals little. It's another way of saying it takes PEM a long time to pass. The real question is why? What malfunctioning chemical processes can make it take a week or two to recover from brief but intense exercise? Why can PEM sometimes pass in hours, but in other cases, stretch into months or become a worsening of the illness? The cause of PEM is arguably the most important question in ME research.

 

I greatly disagree. It's a symptom of ME, and not absolutely part of ME. Curing PEM doesn't do anything for the rest of the ME symptoms (it didn't for me), so it's not that important of a goal. Figuring out (and successfully treating) the root cause of ME is the most important goal.

 

Given that PEM is characteristic of ME, figuring out the root cause of PEM is likely to figure out a large part of the story of the "root cause" of ME, and give clues of where to look for treatments.

 

Why not?

 

I guess the statistical analysis of times to recovery would be mathematically compromised by this "infinity" / not-a-number result. Mean time to recovery would also be infinity.

 

Wanted to know what the SSS contained (Symptom severity scale):
“To quantitate PEM, we chose the Specific Symptom Severity questionnaire (SSS) [9]. This questionnaire has nine domains, using a combination of 10-point Likert and visual analog scales for each domain. The nine domains are fatigue, brain fog, sore throat, tender lymph nodes, myalgia, arthralgia, headache, disturbed sleep and PEM.”

i.e. I’d be asked to rate (1-10) my:
Fatigue
Brain fog
Sore throat
Tender lymph nodes
Myalgia (muscle pain)
Arthralgia (joint pain)
Headache
Disturbed sleep
PEM

(Seems a bit redundant to include PEM itself but perhaps it helps us to understand what the person sees as experiencing PEM even if the symptoms listed aren’t covering it. They also included free text entry.)

 

The glaring omission is “weakness”, the core element of ME which is a mile away from fatigue and which never seems to be acknowledged.

 

Yes, it pretty much IS most of mine, since symptom levels are to a large extent determined by how much PEM hangover there is.

Symptoms never go away, but then again, nor does PEM. It's hard to decide whether to call it cause or effect, as simply being alive will result in PEM-triggering energy deficit.

 

Agree, and there are those of us who don't experience many symptoms but still get severe PEM when they go over their limit.

 

I think it's unsafe to assume that PEM is only found in one distinct syndrome that we call ME. We don't know enough about PEM in other illnesses to know that.

 

I see my case as "curing PEM didn't affect the other ME symptoms", so PEM isn't the root cause of those symptoms. Also, I think many of us suffer from those other symptoms even when we haven't done anything to trigger PEM, thus ME is not due to PEM. Before I got rid of my PEM, I did think that doing exhaustive studies of PWME before, during and after PEM would have been a good research path, but getting rid of my PEM and not losing the rest of the symptoms has changed my mind.

The core dysfunction of ME seems to affect a lot of systems. It seems logical to me that one of those effects might be to make ME's other symptoms generating mechanism more sensitive to stressors, such as cytokines, chemokines, blood changes, etc, that arise from exertion or emotional stress. If that link is a short-range chemical signal in a small portion of the brain, it would be very hard to backtrack from PEM measurements to the core dysfunction, so I don't think that's a good path to solving ME.

I think the best path to the core dysfunction is studying the brain, especially near the brainstem, in the highest detail that technology offers, looking for differences between PWME and controls without ME but with similar limited lifestyles.

 

If "weakness" means reduced physical strength, that's another symptom that not all of us have. My ME never reduced my physical strength or endurance; it just made me feel so lousy that I didn't want to make the effort ... but I could have if I really had to. However, I agree that for some people it might be an important feature of their PEM, or ME in general.

 

It certainly seems unsafe to assume that ME is only one distinct syndrome, or even that all of us have the same disease.

 

With a lifetime of being disabled especially when there was money for disabled support, I have talked about the response to exercise with people who had a lot of different diseases. None of them had anything like I get.

In particular, the way it is possible to think you are doing fine then 3 days after an unusual exertion you get floored. The nearest was a friend who had exercise induced asthma where it was the next day her asthma became worse but even then she did not get a new suite of symptoms just an exacerbation of her illness.

In particular, no one ever said that they got swollen lymph glands a few days after exertion. That is not in the public consciousness, never heard it referred to in a novel or conversation except among people with ME.

PEM is a very bad term because people think they know what it means but it doesn't often match what I get. Right from the start, even when I was fairly mild exercise was what triggered me being ill in the same way pollen makes my husband's hay fever start.

 

I worked in clinics where we saw pts with post-polio syndrome, MS, R/A et and not once has anyone ever described what I experience with PEM.

I think PEM syndrome is pretty distinctive and bizarre that we would have heard it described by others without M.E by now.

I'm still on the fence as to whether LC pts experience the same PEM as pwME considering the theory on micro-clots and low O2 levels. Perhaps similar pathways but distinctive differences in others. It will be interesting to see how it all evolves.

 

Absolutely, weakness. Maybe that's where the term Raggedy Anne Syndrome came from.

I feel, just limp in PEM. Also, sometimes in such pain during PEM I can hardly stand it.

 

I did a 2 day CPET. I felt horrible after day 1. Several symptoms were exacerbated: fatigue of course, weakness, I became quite uncoordinated, and muscle pain really increased. After day 2, I could hardly stand up, my OI kicked in right away, and I was cognitively very fatigued. It took me about 7 to 10 days to get back to my normal crappy level.

 

Such a test might be difficult to find, since PEM symptoms may be fairly far downstream of the core dysfunction of PEM, and vary greatly with the individuals. They might find a marker that works for 40% of PWME, and another that works for 25%, and another that works for 7%. Not having one or more of those markers wouldn't mean that you don't have PEM, but at least you'd have some people with reliable clinical evidence of PEM.