Consequences of sarcolemma fatigue on maximal muscle strength production in patients with ME/CFS, 2023, Retornaz et al.

Highlights

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  Does force failure result from sarcolemma fatigue in Myalgic Encephalomyelitis patients?
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  Two groups of Myalgic Encephalomyelitis patients with or not M wave alterations were compared.
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  Maximal handgrip strength and M wave in forearm muscle were simultaneously measured.
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  Post-exercise changes in Maximal handgrip strength and M wave were positively correlated.
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  The post exercise sarcolemma fatigue measured could be the cause of muscle failure in these patients.

Abstract
Background
Myalgic encephalomyelitis is an invalidating chronic disease often associated with exercise-induced alterations of muscle membrane excitability (M wave). No simultaneous measurements of maximal isometric force production and sarcolemma fatigue in the same muscle group have been previously reported. We hypothesized that M wave alterations could be partly responsible for the reduced muscle force present in this invalidating disease.
Methods
This retrospective study compared two groups of patients who presented (n = 30) or not (n = 28) alterations of M waves evoked by direct muscle stimulation during and after a cycling exercise bout. The maximal handgrip strength was measured before and after exercise, concomitantly with electromyogram recordings from flexor digitorum longus muscle. The patients also answered a questionnaire to identify eventual exacerbation of their clinical symptoms following the exercise test.
Findings
The M wave amplitude significantly decreased in muscles and the M wave duration significantly increased in the group of patients with M wave alterations after exercise. Resting values of handgrip were significantly lower in patients with exercise-induced M-wave alterations than in patients without M-wave abnormalities. In patients with exercise-induced M-wave alterations, handgrip significantly decreased after exercise and the changes in handgrip and M wave were positively correlated. The frequency of post-exertion malaise, increased fatigue, myalgia, headache and cognitive dysfunction was significantly higher in patients with M-wave alterations and variations in handgrip after exercise.
Interpretation
These data suggest that post-exercise sarcolemma fatigue often measured in patients with myalgic encephalomyelitis could be the cause of muscle failure.

https://www.clinbiomech.com/article/S0268-0033(23)00186-9/fulltext

 

"This retrospective study was conducted in 58 patients of both sexes, with ME/CFS on the basis of the international consensus criteria (ICC 2011)"

 

Another study finding some differences between patients with shorter/longer disease duration. I don't really understand what sarcolemma fatigue is, but it doesn't read as if these differences are simply the result of adaptation.

 

The sarcolemma is the muscle cell's plasma membrane. While cell membrane covers the entire components of a cell, plasma membrane covers only the cell's organelles. Some main differences between the two are the fact that the plasma membrane encloses the organelles, whereas the cell membrane encloses the entire cell.

 

The bigger picture of how the brain controls muscle contraction. The nerve cell's axons connect to a structure called the neuromuscular junction, which transmits the signals to the sarcolemma, which is excitable and can propagate it across the cell.

 

Any comment @Jonathan Edwards?

Am I the only one who thinks this is really interesting? It seems that this might be a useful diagnostic test that also helps get us closer to understand the problem. It also aligns with the old description of PEM as postexertional muscle weakness.

Why I think this is important: the sarcolemma is where the problem is in certain other neuromuscular disorders, like muscle dystrophies. It's also just downstream of neuromuscular junctions which are affected by myasthenia gravis. It also raises the question of whether this problem in skeletal muscles is related to the neurovascular dysregulation that is believed to exist by Systrom et al (as far as I understand, this would be primarily dependent on smooth muscles functioning properly).

 

How do they account for the difference? I couldn't make it out.

Also, I miss @Snow Leopard's comments on studies like these (no pressure intended Snow Leopard)

 

I'm not sure they do, they just report it. It's possible they don't yet have an explanation.

 

Too foggy to write fresh comments on this study, but note comments on previous studies on m-wave 'alterations'

https://www.s4me.info/threads/long-...ctive-colgem-study-2022-retornaz-et-al.29661/

https://link.springer.com/article/10.1007/s00421-017-3788-5
https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1097-4598(199709)20:9<1197::AID-MUS20>3.0.CO;2-P
https://pubmed.ncbi.nlm.nih.gov/10204784/

 

From https://link.springer.com/article/10.1007/s00421-017-3788-5:

But that isn't the opinion of Sharma 1995a who wrote:

Other studies at the time, utilising supramaximal twitch interpolation to measure 'central activation failure' eg central fatigue, found clear evidence of that in ALS patients, as well as patients with mitochondrial diseases and peripheral neuropathies. Restated, the same finding of central fatigue in ME/CFS patients was found in mitochondrial myopathies, muscular dystrophies and peripheral neuropathies.

Anyway, the dispute between Jammes and Sharma may be clarified by comments by Rodriguez-Falces & Place:

The above points out one of the key problems of the supramaximal twitch interpolation approach - it relies on a short stimulus rather than a sustained stimulus and thus only really tests whether there is neuromuscular blockage through other means, rather than a transient decline in impaired sarcolemmal membrane excitability or a decline in force output over time due to metabolic availability (supramaximal twitch interpolation relies on maximal motor unit recruitment and measures primarily use of anaerobic glycolysis, compared to maximal aerobic metabolism that occurs at stimulus levels that does not recruit all available motor units.

They also state that the M-wave has strong limitations as a measure of sarcolemmal excitability:

The Jammes et al. manuscript is not clear on the specific methodology of measuring the M-wave amplitude.

 

Thanks Snow Leopard. Your perspective is highly valued. But please don't push through the fog

 

Too late

 

I did wonder whether that might be the case, but I can't read numbers and statistics very well (dyscalculia).

I suppose it's one of those things that has to be noted if you find it, because if it's also found in larger follow-up studies it could be something—but equally it may not be anything at all. Could even be some kind of measurement artefact, given what Snow Leopard has said.

 

I found this study interesting and wrote about it in my recent news article (Substack)

Here is what I wrote:


Research into Muscle Dysfunction
Consequences of Sarcolemma Fatigue on Maximal Muscle Strength Production in Patients with ME/CFS was published Aug 3, 2023 and discusses muscle fatigability issues in patients who have ME. This study used 58 participants who fulfilled the International Consensus Criteria (ICC). It discussed possible causes for the muscle fatigability issue including:

“Muscle failure called “peripheral fatigue” may result from a failure of different metabolic processes such as the imbalance between oxygen demand and supply, the reduced excitation–contraction coupling, and the impaired muscle membrane excitability due to the altered flux of potassium through the sarcolemma… may have also a central origin resulting from a reduced central motor command to muscles…”

This research points to how this muscle issue could be used as a biomarker:

See article here: https://colleensteckelmeiccinfo.substack.com/p/news-2023-august-05

“In conclusion, this study suggest that post-exercise sarcolemma fatigue often measured in ME/CFS patients could be the cause of muscle failure and MHGS [Maximal handgrip strength] measurement constitutes a good index of global muscle performance and fatigability in ME/CFS patients. This simple and unexpansive method could represent a potential screening tool.”

If I understood this correctly, there were two different patterns within this patient group. They compared 30 patients with and 28 without electromyography (EMG) abnormalities. EMG is a technique for evaluating and recording the electrical activity produced by skeletal muscles.

This difference between the two groups may be a result of issues with placement of the electrodes. The paper states this as a limitation: “we cannot give absolute normal or abnormal values of M wave configuration due to the variability of skin electrodes position and skin conductivity between patients.”

FYI - Sarcolemma is the plasma membrane of the muscle cell.

Note: The original description of ME included “muscle fatigability”. And the IC Primer states that patients have a “pathological low threshold of physical and mental fatigability in response to exertion.”

This lack of stamina in the muscles has also been suggested as a biomarker in the 2021 Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS paper. “Repeat HGS [hand grip strength] assessment is a sensitive diagnostic test to assess muscular fatigue and fatigability and an objective measure to assess disease severity in ME/CFS.”

This is a promising area of research which I think could be moved into the clinical area if doctors were aware to look. I do a grip strength test as part of my yearly physical (my doctor offers more in depth screening than most practices). I can see (and feel) the decline in muscle function as I repeat the hand grip test during the physical.