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 —

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

No specific mention of necrosis (+ or -) that I could see.

 

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.

 

A question/poll by Rob Wüst for the patient community on Twitter/X:

"#Longcovid related #PEM question: do female patients experience PEM symptoms that align with the menstrual cycle?"

www.twitter.com/RobWust/status/1760039059227918709

Seems like something that would have probably been discussed before?

 

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?

 

Rivastigmine crosses the blood brain barrier unlike pyridostigmine. Could it be of any therapeutic benefit to us?

@Jonathan Edwards
@SNT Gatchaman

 

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.

 

agreed

 

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.

 

They might have missed the CK rise by testing on days 1 and 8. See my previous post a long way upthread.

 

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.

 

Yes, I have a faint memory of hearing that interfering with cholinergic signalling in brain produces really nasty effects but I forget which drug class.

 

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...

 

I have this open-access recent article which might have useful refs itself. Disease spectrum of myopathies with elevated aldolase and normal creatine kinase (2023, European Journal of Neurology)

 

See also Transcription Profile Analysis of Vastus Lateralis Muscle from Patients with Chronic Fatigue Syndrome (2009, International Journal of Immunopathology and Pharmacology)

 

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

 

Never assume .
There are a myriad of things that you would have thought would have been looked into

 

"#Longcovid related #PEM question: do female patients experience PEM symptoms that align with the menstrual cycle?"

In my case, in 2.5 years of long Covid: no.