I randomly came across an article on McArdle disease (a genetic disorder that mainly affects skeletal muscles), and found the description of exertion intolerance both interesting and relatable. Does anyone here know if there has been any scientific attempts to compare the exertion intolerance in McArdle disease to the one experienced by pwME? Similarities, differences, maybe some clues as to what might be going on in pwME's bodies? McArdles sjukdom https://www.socialstyrelsen.se/kuns...en/sallsynta-halsotillstand/mcardles-sjukdom/
Thanks for bringing this to our attention @mango. I think it is a condition that people with ME/CFS symptoms should consider. It sounds as though the condition is under-diagnosed. There seem to be issues with histology that mean that the condition could be missed: There is a wide variety of presentations, including fatigue: I expect that some people with this disease have had a functional disease label applied to them e.g. I recalled Rowe's use of a pressure cuff on an arm to induce PEM when I read the following: This too, the typically elevated creatine kinase, was interesting. I recall the UK ME/CFS biobank study (I think) that found elevated levels of creatine kinase in (severe?) ME/CFS. Creatine kinase is elevated in people who are inactive of course, so it is a bit confounded.
I have found rhabdomyolysis interesting in the context of ME/CFS before, given the symptoms of muscle pain and stiffness. I can get a series of muscle cramps. Is that common in ME/CFS? I have noticed I periodically get dark-coloured urine, not dark yellow, definitely more red-brown, that does not correlate with hydration levels. It occurs with generalised muscle pain and lower back pain. I'm pretty convinced that it is a symptom correlated with activity. It was interesting to read about the idea of metabolic encephalopathy resulting from rhabdomyolysis. It's a general term: Symptoms of metabolic encephalopathy are Could ME/CFS, or at least some version of ME/CFS, be a condition that results in a low threshold for rhabdomyolysis and associated temporary mild metabolic encephalopathy? edit - Perhaps this is the link between the commonality of symptoms we see between ME/CFS and traumatic brain injury?
"causes pain, cramps and muscle weakness during intense muscle work" That rules out PEM, which I think is defined as symptoms post-exertion, not during. A 24 hr delay seems common, which really rules out the 'during' part. I expect there are plenty of different causes for pain, cramps, and weakness that are unrelated to ME.
McArdle's disease has a characteristic "second wind phenomenon" where progressive fatigue and muscle weakness appears during the first 15 minutes of exercise but then disappear. The person can then continue exercising. This is because the glycolytic energy production is impaired. In ME/CFS the impairment appears to be more in the aerobic energy production (mitochondrial respiration in this graph) https://pubmed.ncbi.nlm.nih.gov/30363996/ I am curious about the possibility of PEM in other diseases. It would be interesting to ask doctors who deal with rare diseases if they know of other diseases with a PEM-like phenomenon.
I think it would also be interesting to ask alternative practitioners, particularly of the ancient practices, whether they were familiar with the phenomenon. Since they didn't have blood tests and RNA scans, they would have focused on patient's descriptions of symptoms, and "consistently, 24 hrs after I do something strenuous, I abruptly feel weak and can't think clearly" seems like a fairly clear symptom, and something worth recording.
These are different things. I think many people with ME/CFS can at times experience symptoms during muscle work, but also experience the constellation of symptoms at a later time that is PEM.
I agree, Hutan. I certainly experience increasing pain and weakness in muscles during activity which I would define as fatiguability, or exertion intolerance. I also experience PEM later if the activity was beyond my current limit. It's not either/or, we can have both.
Yep both definitely happen for me. Both physical and cognitive. As well as getting physically drained mostly linked to orthostatic issues standing for say 10 minutes will do it or sitting for a meal out. I experience cognitive issues during activity eg if I’m socialising with family or on a phone call with friends eg word finding, losing thread or if I’m online visual triggers like large bold text or large images causing brain freeze. not just waking up the following day after feeling normal during an activity with worse functioning.
Another hard yes. For me, exercise intolerance pains are specific to the limbs used, and feel more like muscular-skeletal damage, while PEM pain is an all-over neuropathic fizzing, accompanied by that poisoned feeling. Very different, but both feel core to this illness.
Can we definitely rule out rhabdomyolysis as part of the delayed response that is PEM? It seems to fit, for me, with the dark urine and kidney ache and all. I wonder if testing for metabolites has actually been done enough when people really do have the full-on PEM experience with pain and extreme exhaustion, rather than just after a short exercise challenge, often immediately after? Has there been careful tracking of changes in creatinine phosphokinase (CPK) before and during PEM? If it was rhabdomyolysis, would we expect to see more people with ME/CFS heading into hospital with life-threatening organ damage? and a lot more muscle wasting? It's a question I'd like to poke into sometime. Maybe people here have thoughts?
https://www.atsjournals.org/doi/full/10.1513/AnnalsATS.201701-014FR A review of exercise testing in metabolic myopathies.
That interesting review covers McArdle disease and mitochondrial myopathies On mitochondrial myopathies: I note the last point about higher than normal respiratory exchange rates in exercise tests in people with mitochondrial myopathies. We've seen the RERs of people with ME/CFS reported as normal in many CPET studies (that is, around 1.1). However, I think we've seen at least one member who has reported their RER being higher than that. Perhaps a high RER is a useful diagnostic clue for mitochondrial myopathies.
