The Potential Causes Of Myasthenia And Fasciculations In The Severely Ill Me/Cfs-Patient: Role Of Disturbed Electrophysiology, 2025, Wirth et al.

Chandelier

Chandelier

Senior Member (Voting Rights)

Authors: Klaus Wirth, Jürgen M. Steinacker

Abstract

Severely ill ME/CFS patients are bedridden and suffer from hypersensitivities against light and noise, severe orthostatic intolerance reducing cerebral blood flow, and skeletal muscle symptoms including loss of force, fatigue, pain, fasciculations and cramps.

Since neurological investigations exclude neuronal causes for myasthenia, we assume a muscular pathomechanism.

In previous papers we considered insufficient activity of the Na+/K+-ATPase as the main cause of mitochondrial damage via high intracellular sodium which reverses the transport mode of the sodium-calcium-exchanger to import calcium causing calcium-overload.

Low Na+/K+-ATPase-activity also causes sarcolemmal depolarization leading to less effective action potential propagation and loss of force.

Depolarization brings membrane potential closer to the firing threshold causing hyperexcitability explaining fasciculations and cramps. These raise sodium influx during excitation to further increase the workload of Na+/K+-ATPase. Thereby, depolarization causes further depolarization.

Higher intracellular sodium favors calcium-overload and mitochondrial damage to lower energy supply of Na+/K+-ATPase and to increase reactive-oxygen species that further inhibit it.

Even at rest, muscle is in a state of depolarization. Depolarization and mitochondrial damage reinforce each other.

Thus, dysfunction of Na+/K+-ATPase as a single mechanism can explain the different skeletal muscle symptoms of the severely ill ME/CFS patient comprising loss of force, fatigue and fasciculations.
 
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Chandelier said:
Severely ill ME/CFS patients are bedridden and suffer from hypersensitivities against light and noise, severe orthostatic intolerance reducing cerebral blood flow, and skeletal muscle symptoms including loss of force, fatigue, pain, fasciculations and cramps.
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I think this sentence might need to be reworked. What is reducing what? I also think it might be wrong how it’s written now, I assume they mean that reduced CBF causes OI?
Chandelier said:
Thus, dysfunction of Na+/K+-ATPase as a single mechanism can explain the different skeletal muscle symptoms of the severely ill ME/CFS patient comprising loss of force, fatigue and fasciculations.
Click to expand...
How does this tie into PEM?
 
An earlier review if you’re not familiar with his work:

Easier language article:
www.healthrising.org

An Enigma No More? Is ME/CFS an Acquired Muscle Myopathy Disease? - Health Rising

Klaus Wirth shows how ME/CFS and long COVID may be acquired muscle diseases caused by poor blood flows and mitochondrial dysfunction
www.healthrising.org
 
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"Mitochondrial damage" is a very effective battle cry because it sounds scary, but it carries vague biological meaning at best and I am aware of no clear evidence of anything of the sort in people with ME/CFS that would invite the seemingly confident statement in the third abstract sentence that "damage" is at play. Muscle studies thus far, to my knowledge all bear the activity matching caveat because it is very hard to match even "sedentary controls" to people that are disabled. Healthy "sedentary" people will still score like a 5.8+ on funcap at worst, in my experience. And because of the difficulty in sampling muscle the sample sizes are usually small.

Certainly, even if not for this issue, mean levels of structural differences that we cannot yet attribute to a known pathological mechanism should not be used to make sweeping statements of "mitochondrial damage" that are going to send sick people down a rabbit hole of taking expensive supplements or mitochondrial poisons and so on. Morphological results cited as the evidence for this are not too convincing, whether the quantitative data or the cherry picked microscopy image examples (https://www.mdpi.com/1422-0067/25/3/1675#Results), with possible exceptions of maybe one or two of the cristae scores that have greater differences... but this is without getting to the possible issue of multiple comparisons (being the various tested parameters). This is all certainly not sufficient grounds to confidently state that people with ME/CFS have "damaged mitochondria".

The concept of ROS or salt/ion/calcium mediated cellular damage associated with mitochondrial function has some issues as a possible explanation for ME/CFS. If it was a widespread or genetic issue, or one otherwise present in brain as we are learning is probably involved in a disease process, we may expect to see some neuronal loss like in parkinsons disease. We do not see this in ME/CFS. If by some mechanism it is present only in muscle, an accumulation of "damage" may be plausible because the cells are generally long-lived but then where is the clear evidence of this occurring?

It is not entirely implausible in principle but the questions around tissue specificity need to be addressed, and the data couching the theory need to be much better.
 
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