Muscle abnormalities worsen after post-exertional malaise in long COVID, 2023/4, Wüst, van Vugt, Appelman et al

More recently in LC, we have biopsies also taken at rest. Myopathy as a cause of fatigue in long-term post-COVID-19 symptoms: Evidence of skeletal muscle histopathology (2022, European Journal of Neurology). They also used biceps rather than the usual vastus lateralis —

All biopsies displayed some types of change. None of the biopsies showed necrotic fibers, but degenerative changes were common. In six, we found atrophic fibers seen as small fibers with fragmented fibrils, and excess of basal lamina material. Immunohistochemistry showed three with type 2 atrophy, one with predominantly type 1, and two with mixed type atrophy.
Click to expand...

Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles (2023, Acta Neuropathologica Communications) —

Routine histopathological examination revealed a selective atrophy of type-2b muscle fibers of differing extent in 72% (n = 8/11) of individuals with PCS and – by definition of our inclusion criteria – in none (n = 0/8) of the HDC cohort and in all (n = 8/8) of the 2BA cohort.
Click to expand...

While patients with PCS did not show overt signs of myositis, increased numbers of CD169+ macrophages were evident. The capillary-to-fiber ratio was decreased and ultrastructural analysis revealed a capillary basement membrane enlargement.
Click to expand...

No specific mention of necrosis (+ or -) that I could see.
 
Lidia Thompson said:
I was wondering, has any muscle necrosis been seen in pwME in a post mortem/autopsy? I would have thought that would have been fairly easy to spot ... or am I missing something?
Click to expand...

If necrosis is significant it should show up easily on standard MRI. Muscle biopsy is an invasive procedure and suffers badly from sampling variation. Before doing more biopsies I think we should have a basic study of muscle by MRI after similar activity. There are other techniques using radioisotope scans that should show necrosis easily too.
 
Kalliope said:
What a disappointing article with a lot of mess. Another expert from the article is professor emeritus Omdal who has researched into fatigue, but emphasised many times that his work does not include ME. I don't think he understands that PEM is a different symptom than fatigue.
Click to expand...

I noticed that the group had used the term PEM when what had been found could have been referred to as exercise intolerance which is found in many muscle pathologies. It may be that PEM is based on exercise intolerance in some people but discussions on here show it goes well beyond. So, were the Dutch patients showing symptomatically PEM or an exercise intolerance type profile?
 
I'm answering from a very basic understanding and probably going off-topic for the thread. Any potential benefit would depend on whether cognitive dysfunction / brain fog in ME is fully or partly explained by ACh dysfunction in the brain itself. AChE inhibitors seem to show positive effects in neurodegenerative diseases, but I think for ME we have more evidence for extracranial causes such as reduced cerebral blood flow on sitting and standing, and not really any suggestion at all of long-term neurodegeneration. There could be significant adverse effects and I don't think messing with brain neurotransmitters would be wise unless there was solid evidence that we were reversing the right mechanisms.
 
Jonathan Edwards said:
If necrosis is significant it should show up easily on standard MRI. Muscle biopsy is an invasive procedure and suffers badly from sampling variation. Before doing more biopsies I think we should have a basic study of muscle by MRI after similar activity. There are other techniques using radioisotope scans that should show necrosis easily too.
Click to expand...

And if it is significant there should be corroborative biochemical evidence of this - a very quick skim of the paper shows that they tested for CK & there was no elevation. Perhaps it might have been useful to test for other potential markers (off the top of my head: lactate dehydrogenase, various aminotransferases, aldolase...)?

The -stigmines are used in conditions where there is evidence either of the loss of cholinergic neurons (as in Alzheimer's) or conditions that feature the development of antibodies to & autoimmune destruction of nAChRs like myasthenia gravis or similar neuromuscular junction diseases; there's no evidence of anything like this in ME. Not to mention that anticholinesterase drugs can have some quite nasty side effects.
 
Last edited:
SNT Gatchaman said:
They might have missed the CK rise by testing on days 1 and 8. See my previous post a long way upthread.
Click to expand...
Thanks, I missed that post - your point about the timings is well made, although I think if there were an atypically high exercise-induced CK elevation in ME patients I expect there would've been a number of case reports already and we would know about it by now.

Nonetheless, a very interesting study. Will be fascinating to see if they follow this up.

(Edit to add a little background for others: CK testing is usually considered very sensitive - in rhabdo where there is widespread breakdown of muscle tissue you can get levels 100s or even 1000s of times higher than normal range. Obviously any necrosis - or indeed anything that damages myocyte membranes or alters their permeability - is going to result in its release. I'm fairly sure CK elevations would've been noticed by those caring for ME patients over the years.)
 
Other considerations, though I don't know if any of these are realistic possibilities: is something unusual limiting the CK rise in blood or its detection? Eg if it wasn't transported into the blood in a rapid surge as in "normal" rhabdomyolysis, or it gets there but something were sponging the CK in plasma, so that measurement was spuriously low. Alternatively, the underlying pathology with major metabolic shifts might mean that muscle cells are not as CK-rich as we expect.
 
SNT Gatchaman said:
Other considerations, though I don't know if any of these are realistic possibilities: is something unusual limiting the CK rise in blood or its detection? Eg if it wasn't transported into the blood in a rapid surge as in "normal" rhabdomyolysis, or it gets there but something were sponging the CK in plasma, so that measurement was spuriously low. Alternatively, the underlying pathology with major metabolic shifts might mean that muscle cells are not as CK-rich as we expect.
Click to expand...
Indeed, which is why I mentioned that I would've liked to see testing for a wider set of markers. Both aldolase & LDH are more widely expressed, having central roles in glycolysis, & obviously they have far lower sensitivity & specificity for muscle injury but nonetheless might well have been worth testing for. If I remember correctly, there are certain unusual myopathies where CK can be unexpectedly normal but the less specific markers are elevated, but I can't remember which ones or the mechanism by which this occurs. If I have a good day soon I might search the literature...
 
https://podcasts.apple.com/gb/podcast/episode-73-dr-rob-wüst-post-exertional-malaise-p-e-m/id1574768076?i=1000651198002

Episode 73: Dr Rob Wüst - Post-exertional Malaise (P.E.M)TLC Sessions - Living with Long Covid
    • Medicine




Dr Rob Wüst, Assistant Professor in the Faculty of Movement and Behaviour Sciences, is an expert cardiac and skeletal muscle metabolism and mitochondrial function. He and the team at Vrije Universiteit, Amsterdam, published the “PEM study” in Nature Communications, which investigated the muscular changes in Long Covid patients who experience post-exertional malaise (PEM), or “the worsening of fatigue- and pain-related symptoms after acute mental or physical exercise”.

In this week’s episode Wüst talks us through the key findings of their study, including the muscular changes, mitochondrial dysfunction and microclots that were present in the Long Covid patients compared to their control group. He discusses the effects of bedrest on the human body and how exercise is usually beneficial for overall health, but highlights what was revealed through blood tests and muscle biopsies in their study – that Long Covid patients have limited exercise capacity with lower mitochondrial function and our rehabilitation needs to be handled with this unique understanding.



Living with Long Covid? How was your week?


Website - https://www.tlcsessions.net/

Twitter - @SessionsTlc https://twitter.com/sessionstlc

Insta - @tlcsessions https://www.instagram.com/tlcsessions

https://twitter.com/user/status/1775228815389663569
Click to expand...
 
Last edited:
I made a post a while back on the News from the Netherlands thread that was not the most complementary to Wüst.

So of course he then produces what may be one of the most important studies, and accompanying research programs, in the game. Exactly the sort of thing I have been arguing for years should be done, especially properly assessing the alleged deconditioning that is supposed to be happening and is so critical to the psycho-behavioural model. :rolleyes:

So, thank to Wüst and his team for persisting and delivering some serious results, with the promise of much more to come. I hope they maintain their interest.

That said, I don't exactly withdraw what I said at the time. I think he was a bit naive, had not yet come to fully appreciate how bad the situation really was, and was on a learning curve of his own, and I do wonder if he would make the same comments now.
 
You must log in or register to reply here.
Back
Top Bottom