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

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)

 

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)

 

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.

 

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.

 

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.

 

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.

 

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.

 

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

 

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.

 

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.

 

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.

 

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.

 

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.

 

This pretty much perfectly reflects my opinion and experience thank you

Particular emphasis on this