Post-exertional malaise in daily life and experimental exercise models in patients with [ME/CFS], 2023, Vøllestad and Mengshoel

Discussion in 'ME/CFS research' started by SNT Gatchaman, Dec 4, 2023.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

    Messages:
    4,586
    Location:
    Aotearoa New Zealand
    Post-exertional malaise in daily life and experimental exercise models in patients with myalgic encephalomyelitis/chronic fatigue syndrome
    Vøllestad, Nina K.; Mengshoel, Anne Marit

    Post-exertional malaise (PEM) is commonly recognized as a hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is often used as one of several criteria for diagnosing ME/CFS. In this perspective paper we want to reflect on how PEM is understood, assessed, and evaluated in scientific literature, and to identify topics to be addressed in future research.

    Studies show that patients use a wide variety of words and concepts to label their experience of PEM in everyday life, and they report physical or mental exertions as triggers of PEM. They also report that PEM may have an immediate or delayed onset and may last from a few days to several months. When standardized exercise tests are used to trigger PEM experimentally, the exacerbation of symptoms has a more immediate onset but still shows a wide variability in duration. There are indications of altered muscular metabolism and autonomic nervous responses if exercise is repeated on successive days in patients with ME/CFS. The decreased muscular capacity appears to be maintained over several days following such controlled exercise bouts. These responses may correspond to patients' experiences of increased exertion.

    Based on this background we argue that there is a need to look more closely into the processes occurring in the restitution period following exercise, as PEM reaches the peak in this phase.

    Link | PDF (Frontiers in Physiology)
     
    ahimsa, MEMarge, Michelle and 17 others like this.
  2. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

    Messages:
    4,586
    Location:
    Aotearoa New Zealand
    Submitted in July 2023. Does include eg Recovery from Exercise in Persons with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS (2023, Medicina) but not Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients (2023, International Journal of Molecular Sciences)

     
  3. Hoopoe

    Hoopoe Senior Member (Voting Rights)

    Messages:
    5,258
    I agree, this should be common sense because that's where the abnormalities are most apparent. It's a problem of recovery from exertion, not a problem of doing any activity in particular. The sleep disruption is part of the defective recovery. At least for me.

    Edit: also my initial orthostatic hypotension is aggravated during the recovery phase.
     
    Last edited: Dec 4, 2023
  4. Mij

    Mij Senior Member (Voting Rights)

    Messages:
    8,433
    Studying and measuring the differences(if any) between immediate and delayed PEM onset.

    I recover within the same day from immediate PEM without cognitive issues, but delayed PEM which includes all sorts of distressing symptoms normally takes 3 days or more depending on how much I went over my energy limit. There might be similarities and possible distinctive differences between the two because I have an established baseline.
     
    Simone, MEMarge, Kitty and 9 others like this.
  5. Hutan

    Hutan Moderator Staff Member

    Messages:
    27,216
    Location:
    Aotearoa New Zealand
    Perhaps it is just a difference in how PEM is defined, but I think this sentence indicates that there is still not a clear understanding of what PEM is.

    For me, PEM is not something I experienced after exercise when healthy, not even briefly. The experience that I term PEM is when the only thing I can do is lie in bed, feeling as though I have been crushed. Everything hurts, movement takes conscious thought and willpower.

    My experience is that there can be immediate onset of other symptoms after exercise, or not. But PEM is delayed.

    I don't think it is impossible to define PEM better based on self-reported symptoms. But, so far, it seems to have been very difficult. And so looking at things that are easily measured - heart rates, metabolites, protein expression... in the days following exercise seems like a productive way to proceed. One key thing is controlling exertion, so that you are sure the person has achieved a rested baseline before exerting.
     
  6. Andy

    Andy Committee Member

    Messages:
    22,077
    Location:
    Hampshire, UK
    Personally I hope very much that research moves on from "immediate PEM" and puts far more focus on the delayed response. It is simply the same response that someone healthy but sedentary might have if they exerted themselves to the same extent that patients do, relative to their available energy.

    The delayed part is crucial to look at. The process in the body that allows people to build fitness is obviously impaired/faulty in pwME, and I would imagine would explain our reduced energy levels.
     
  7. Hoopoe

    Hoopoe Senior Member (Voting Rights)

    Messages:
    5,258
    By the way, I'm currently in a long period of substantial improvement to point where I can do prolonged and moderately intense exercise and recover within a day or a few. When I exercise like that, the PEM hits as soon as the body begins to wind down from the "activated" state induced by exercise. And the PEM can coexist with the good feeling produced by the exercise. I feel both at the same time.

    My muscles feel much healthier nowdays. The PEM that remains feels more like a nervous system problem or some metabolic problem.
     
    Last edited: Dec 4, 2023
  8. bobbler

    bobbler Senior Member (Voting Rights)

    Messages:
    2,647
    it all seems to sound like it’s thinking scientifically/methodologically then, probably because of not listening to experienced patients I think it misses two pertinent issues:

    1. Arbitrary ‘amounts’ of exercise doesn’t equal the same amount of over-exertion in each individual (whilst I know it’s catch 22 of research would have to find out what indicators are of 'this', shall we call it threshold thing, to have this I think it’s a first step)

    2. as we are talking about exertion of all kinds and not exercise - again perhaps shows lack of experienced patient involvement in steering research - researchers need to know they must control or log exertion undertaken in the days before (as that PEM from two days ago will be hitting them but adding to accumulation),

    and be logging other types of exertion at time to cross-log with symptoms. Eg light or noise then immediately causing cognitive.
     
    Last edited: Dec 5, 2023
    alktipping, oldtimer, sebaaa and 9 others like this.
  9. Ravn

    Ravn Senior Member (Voting Rights)

    Messages:
    2,090
    Location:
    Aotearoa New Zealand
    Not all bad but not quite there either

    On the one hand the authors correctly observe that there are significant problems with the language used to identify PEM
    On the other hand they don't then apply this knowledge when assessing the validity of claims of PEM in other diseases. They simply take PEM reports in other diseases at face value, ignoring the fact that those reports could just as easily be the outcome of ambiguously worded questions. They even cite Hodges whose repeat CPET work actually showed pwME and pwMS recover differently. So while pwMS may well experience some superficially PEM-like symptoms that doesn't necessarily mean they experience ME-PEM.
    But I do agree that the delayed PEM peak - as opposed to onset - has been rather ignored to date. It would be worthwhile looking more closely into the entire trajectory of PEM, including the peak, taking samples at multiple time points not just the one or two typically done
     
  10. Midnattsol

    Midnattsol Moderator Staff Member

    Messages:
    3,628
    I also think we need to look at the entire trajectory, we don't know yet if it's something that is being triggered directly after exertion that then at some point passes a threshold and turns into PEM, or if what happens directly after exercise triggers something else down the road and that is again what is causes delayed PEM.
     
    Sean, Michelle, alktipping and 9 others like this.
  11. Peter Trewhitt

    Peter Trewhitt Senior Member (Voting Rights)

    Messages:
    3,717
    Have not looked at the paper yet, but for me it is vital that any measure of PEM distinguishes it from more ‘rapid fatiguability’.

    In many conditions patients get fatigued by activity more rapidly and more readily than they would have been pre-morbidly. This is also true in ME and I assume in any other condition displaying PEM if such exist, however increased fatiguability is essentially an exaggeration of a normal response, whereas PEM is a qualitatively different response.

    Any measure of PEM needs to focus on what distinguishes it from normal fatigue:
    • potential for delayed response
    • cross modality effects, such as cognitive exertion resulting in muscle symptoms
    • increase in disease specific symptoms, such as flue like symptoms in ME or swollen glands
    • emergence of new symptoms when in PEM not necessarily related to the triggering exertion
    • accumulation of total activity over a period of time, for example traveling the day before might increase the effect of subsequent exertion
    • accumulation of non specific activity or stimuli, for example bright light or noise, or the amount of time spent upright increases the effect of an exertion episode
    • paradoxical recovery in that the effects of PEM as well as having a delayed onset can go on increasing despite rest over hours or days
    • etc
    I believe that fatigue/symptoms starting during the exertion and showing immediate diminution on stopping the activity and/or rest are more likely to reflect increased fatiguability rather than PEM. For example taking my teenage goddaughter perfume shopping I had to leave the shop and sit down as the scents triggered headache and fatigue, but I recovered rapidly over fifteen minutes, this I would classify as increased fatiguability, but the whole shopping trip including travelling and going out for a meal resulting in a dramatic worsening of all my ME symptoms some twenty four hours later would be PEM.

    It is confusing as whatever triggered a more rapid fatigue response and any associated hypersensitivity issues can contribute to any subsequent PEM, and when in PEM any fatiguability effects become more rapid and any hypersensitivities are increased. So though PEM and increased fatiguability interact, I would argue they are qualitatively distinct.
     
  12. Mij

    Mij Senior Member (Voting Rights)

    Messages:
    8,433
    Does exertion also affect pwMS ability to effectively process or interpret information, word finding, process and absorb information, impaired blurry vision, do they slur et?

    My brain just shuts down, I can't stand upright, I slur and feel nauseas after talking too much.
     
    Joan Crawford, Sean, MEMarge and 8 others like this.
  13. Mij

    Mij Senior Member (Voting Rights)

    Messages:
    8,433
    Give pwME a cognitive challenge for half and hour and see how far they can walk a straight line after without staggering and speak coherently.
     
    Joan Crawford, Sean, obeat and 9 others like this.
  14. Kitty

    Kitty Senior Member (Voting Rights)

    Messages:
    5,657
    Location:
    UK
    Absolutely.

    Moderately ill people often can't predict accurately whether the PEM triggered by a familiar activity will fall into the minimal, pain-in-the-neck, or cancel-everything category. I don't even think this level of variability is understood by many researchers.
     
    Sean, MEMarge, obeat and 12 others like this.
  15. Peter Trewhitt

    Peter Trewhitt Senior Member (Voting Rights)

    Messages:
    3,717
    Understanding variability in ME is so important. This may just be because symptoms and PEM involve complex interactions of cumulative physical, cognitive and emotional exertion over an unknown time span, hypersensitivities, orthostatic intolerance, food intolerances or because variability is further reflecting something else.

    Only when I got my food intolerances identified and under control, became aware of orthostatic issues, recognise the contribution of sensory hypersensitivities and recognised that physical, cognitive and emotional activity cumulatively impact on PEM did I get anywhere near being able to predict what activity levels will trigger PEM, but even then there is more variability that I can not predict.
     
    Sean, MEMarge, obeat and 12 others like this.
  16. JemPD

    JemPD Senior Member (Voting Rights)

    Messages:
    4,048
    This pretty much perfectly reflects my opinion and experience thank you

    Particular emphasis on this
     
    Sean, Midnattsol, alktipping and 8 others like this.
  17. Hutan

    Hutan Moderator Staff Member

    Messages:
    27,216
    Location:
    Aotearoa New Zealand
    I've said it before, but I would really like to see a proteomic study with multiple CPETs (more than 2, maybe 5, one per day ) done in people with relatively mild ME/CFS (with very careful control of activity levels before and between the tests, and frequent testing of blood and reaction time. It would be risky, but I think there would be some people willing to do it. We need to understand how cumulative exertion affects function and gene expression.
     
    Sean, obeat, Midnattsol and 6 others like this.
  18. Trish

    Trish Moderator Staff Member

    Messages:
    52,757
    Location:
    UK
    I think more than 2 successive CPET's on successive days would be far too risky. Reading patients stories of how they collapsed suddenly from one day to the next into years long severe ME after a relatively short time of doing GET, which is less intensive than CPET, I think it would be unethical to do more than 2.
     
    Sean, Mij, Midnattsol and 7 others like this.
  19. Hutan

    Hutan Moderator Staff Member

    Messages:
    27,216
    Location:
    Aotearoa New Zealand
    I know we've had that discussion before. But many people with ME/CFS push themselves to do activities that are as exhausting and risky as a CPET in order to achieve something they think is worthwhile. Fluge and Mella found participants for the cyclophosphamide trial. I think a multiple CPET study could be ethical if the risks were explained very clearly, and if participants knew that they could stop doing the daily CPET at any point.

    Such a study could provide useful evidence to explain why GET is a bad idea - thereby helping to prevent much greater harm.
     
  20. Trish

    Trish Moderator Staff Member

    Messages:
    52,757
    Location:
    UK
    I think we already have evidence of why GET is a bad idea from the 2 day CPET tests and the average time it took participants to recover to pre CPET level which on this trial was 12 days.

    For example:
    Recovery from Exercise in Persons with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) 2023, Moore, Hanson et al
    "Using a Symptom Severity Scale (SSS) that includes nine common symptoms of ME/CFS... 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)."
    "Pharmacokinetic models showed an extremely prolonged decay of the PEM response (Chi2 > 22, p < 0.0001) to the 2-day CPET."
     
    Joan Crawford, Sean, MEMarge and 8 others like this.

Share This Page