PEM has become a mandatory symptom in many CFS guidelines, so I would expect that there is plenty of data of monitored patients during the malaise/fatigue interval because this is when the disease's mechanism of action is amplified and certain biomarkers should stick out and be clearer. Maybe I'm not using the correct search terms, but I can't find anything. Fortunately, @Forbin referenced this study in another post (10.1016/j.jpain.2009.06.003), which is a gene expression monitoring, but it's not primarily what I'm looking for. I'm looking for typical metabolic profiles, blood biomarkers, and neurotransmitters over the course of the malaise. Maybe you have found something like this. I would appreciate any comments.
Workwell foundation researchers have done some biomedical studies during and after CPET used to trigger PEM. This might be a good place to look: https://workwellfoundation.org/resources/#pubsfull
Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787670/
I agree that reliable before/during/after testing should provide a better chance of finding what changes. If I was doing the testing, I'd want EEG, CSF samples, and any other brain scanning that was available. If only blood and urine are available (cheap & convenient to sample), there might be some neurological markers that could be found, but maybe not. There might be neurochemical markers that don't cross out of the BBB, or which are too short-lived to travel into the body, but which are unpleasantly potent in the brain.
Methylated neurotransmitters and precursors could be monitored via blood+urine. BH-4/BH-2 and other pterins can only be monitored in CSF and would provide better insight into activation and buffer of neurotransmitter metabolism. @Trish @strategist This is exactly what I was hoping for. Thanks!
Does anyone know whether long-covid PEM is consistent? Many PWME can reliably trigger PEM and have it show up a consistent x hrs after the exertion and have it last a consistent x hrs after it shows up. If so, then maybe we can get long-covid researchers, with their better funding, to do the before/after testing and figure out what changes occur. If someone knows who to pass that suggestion along to, please do so.
From what I'm seeing it appears as diverse and wild as with ME. Some have it more predictable and can avoid if they can, although the unpredictability of everyday life still makes it a challenge, while others can't make heads or tails of it. It seems to make a huge difference simply knowing about it, to know there is a pattern at all. I've seen so many comments of people saying they were going mad until they learned about pacing and at least could make some sense of it. Not knowing about PEM is frankly cruel and unusual punishment. For sure there would be significant value using patients who can reliably trigger PEM without causing a significant relapse or crash, but it would be a sub-set, not necessarily representative of the whole.
I agree, in retrospect the most important things I could have been told about in the early days of my ME were in order of importance: PEM orthostatic intolerance the risk of food intolerances sensory hypersensitivities. I have included sensory hypersensitivities because, though in extreme they are self evident, for me at milder levels they contribute towards triggering PEM, that is it takes less physical exertion in noisy environment to trigger PEM than in a quiet environment. However, being left to discover these things by chance alone, it delayed my understanding the daily and weekly variation in my ME by many years. I was between fifteen and twenty years post onset before understanding the impact and the interactions of all four. It is particularly important to note that humans generally are relatively poor at spotting causal relationships when cause and the effect are separated by a period of time.
The triggering and recovery of PEM would have different subsets, but the point is to discover the mechanism of PEM: whatever it is that changes as the result of triggering. That is likely to be the same for most PWME and maybe long-covid. Even if the reliable, consistent PEM subset was small, I'd view them as the subset which is particularly valuable as research subjects for before/after testing.
PEM was first used in the CDC guidelines for diagnosing CFS. Now when the CDC was asked to investigate an outbreak of an unknown disease in Incline Village at Lake Tahoe it would reasonable to assume that the symptoms experienced by the patients would have been investigated but you would be wrong. Because it started among teenagers it was thought to be EBV so they called in a specialist on chronic EBV, Stephen Strauss. When it turned out that people were getting sick who did not have EBV he did not bother changing the guidelines, he just removed the need for a positive test for EBV. Meanwhile, ME experts said that this was another outbreak of ME but the CDC did not want to know. In a nod to their insistence that ME was a disease with an abnormal response to exercise, they included PEM as one of a range of secondary symptoms along with headache and sore throat but the emphasis was now on fatigue with no association with exertion. It was never discussed in the US for many years and I never realised it was included into the Fukuda definition until I was able to read about it on the internet. About 2000 in the UK, at the same set of meetings that led to the PACE trial, Dr Derek Pheby asked for urgent research to be done to see exactly what symptoms people with ME were experiencing but he was refused a grant. When the patients were finally heard again, the relationship with exercise became central once more but we were stuck with the term PEM which has no real definition, at least the psychologists keep getting it wrong, and I suspect that people outside the ME world use it to mean post exertional fatigue.
I don't under stand this: https://twitter.com/user/status/1802588845525090339 PEM’ is best conceptualized in 3 dimensions 1. PEM - malaise / fatigue 2. PESE ( symptom exacerbation ) - Here I've seen a range of symptoms depending on domains affected - e.g Dizziness, temperature regulation, hair pulling, RLS, sleep difficulties. 3. PENE (Neuroimmune exhaustion) - repeated infections, neurological signs ( hemiplegic migraines ) etc All 3 should be evaluated in the management as when the broad domains improve - e.g cognition, ANS regulation, sleep ; one must look at when PEM/ PESE etc occurs The treatment must target complete day cover i.e ideally at least till 5 pm in the initial 8 weeks ( gets better over time) This is important as - if ‘wired fatigue’ creeps in late - sleep is affected and treatments will lose effect over time.
I really don't like the term "neuroimmune exhaustion". Hemiplegic migraine is rare (prevalence about 0.01%) and I've never seen any evidence of a link to ME. Hair pulling and RLS? And what treatment is he talking about?
He has a website Its an example. The entire constellation of neuroimmune symptoms aren't going to be mentioned See diagram ( Grach, 2023) It can be any of these domains. Flu like symptoms, fever etc One doesn't choose which immune symptoms are PEM and which aren't. Same with neurological - I've had patient with hemiplegic migraine during PEM- ceased after treatment. This was a marker https://twitter.com/user/status/1802659352748409204
