Pyridostigmine Improves Hand Grip Strength in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2025, Scheibenbogen et al

John Mac

John Mac

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Frontiers | Pyridostigmine Improves Hand Grip Strength in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystemicdisease characterized by exertional intolerance and fatigue which i...
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Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystemic disease characterized by exertional intolerance and fatigue which is often accompanied by muscleweakness and fatiguability. A study showed efficacy of the acetylcholinesterase inhibitorpyridostigmine on cardiac output in ME/CFS patients. Pyridostigmine is currently used off-label in ME/CFS and postural orthostatic tachycardia syndrome.

Methods: We evaluated the effect of pyridostigmine on hand grip strength in 20 patients with post-infectious ME/CFS. Hand grip strength testing was performed ten times using an electricdynamometer and was repeated after one hour. In a second test, 30 mg of pyridostigmine was given immediately after the first measurement. Orthostatic function was assessed using a passive standing test. Neurological examination and autoantibody testing were performed to rule out a diagnosis of myasthenia gravis.

Results: All patients had reduced maximum hand grip strength with a median of 16.45 kg (IQR:11.45 kg – 22.8 kg). Hand grip strength was diminished by a median of 4.65 kg after one hour. In contrast, one hour after pyridostigmine administration, patients showed an improvement in maximum hand grip strength with a median increase of 2.6 kg. The maximum hand grip strength after exertion was about 1.5 fold higher with then without pyridostigmine (p = 0.01). The increase in heart ratefrom lying to standing was median 17 beats per minute without pyridostigmine (IQR: 13 beats perminute – 23 beats per minute) and 13 beats per minute (IQR: 9 beats per minute – 20 beats perminute) (p = 0.017) with pyridostigmine. None of the patients tested positive for myasthenia gravisspecific autoantibodies.

Conclusion: Pyridostigmine exerts an immediate effect on muscle strength and orthostatic function. This may be attributed to increased acetylcholine availability at neuromuscular junctions, and its augmentation of parasympathetic tone.
 
While interesting, I'm not sure what the point of this is. If my hand grip strength improved and my increase in heart rate on standing became slightly less, would I be any better off?

I'm really only interested if these two improvements are accompanied by improved overall functional capacity, reduced symptoms and raised PEM threshold. AND if that is not outweighted by negative side effects of the drug.

I've only read the abstract. What if that increase in muscle strength and lowered heart rate encourages the pwME to be more active, and thereby crash more?
 
Yann04 said:
I can’t see it but my brain is foggy so I’ll trust you
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Hand grip:

Control: Hand grip strength was diminished by a median of 4.65 kg after one hour.

Pyridostigmine: In contrast, one hour after pyridostigmine administration, patients showed an improvement in maximum hand grip strength with a median increase of 2.6 kg.

Comparison between control and drug: The maximum hand grip strength after exertion was about 1.5 fold higher with then without pyridostigmine (p = 0.01).

Heart rate on standing:

Control: The increase in heart rate from lying to standing was median 17 beats per minute without pyridostigmine (IQR: 13 beats perminute – 23 beats per minute)

Pyridostigmine: and 13 beats per minute (IQR: 9 beats per minute – 20 beats perminute) (p = 0.017) with pyridostigmine.
 
Trish said:
Hand grip:

Control: Hand grip strength was diminished by a median of 4.65 kg after one hour.

Pyridostigmine: In contrast, one hour after pyridostigmine administration, patients showed an improvement in maximum hand grip strength with a median increase of 2.6 kg.

Comparison between control and drug: The maximum hand grip strength after exertion was about 1.5 fold higher with then without pyridostigmine (p = 0.01).

Heart rate on standing:

Control: The increase in heart rate from lying to standing was median 17 beats per minute without pyridostigmine (IQR: 13 beats perminute – 23 beats per minute)

Pyridostigmine: and 13 beats per minute (IQR: 9 beats per minute – 20 beats perminute) (p = 0.017) with pyridostigmine.
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Wow that’s so much clearer than the text, thanks.
 
Trish said:
While interesting, I'm not sure what the point of this is. If my hand grip strength improved and my increase in heart rate on standing became slightly less, would I be any better off?

I'm really only interested if these two improvements are accompanied by improved overall functional capacity, reduced symptoms and raised PEM threshold. AND if that is not outweighted by negative side effects of the drug.

I've only read the abstract. What if that increase in muscle strength and lowered heart rate encourages the pwME to be more active, and thereby crash more?
Click to expand...
I've been taking it for about 7 years now, at a typical dose for MG (3x higher than used for POTS). I had side effects initially, the dose needs to be incremented very gradually, but they're not noticeable now.

I'd agree it does encourage me to be more active, but it also appears to reduce the severity and duration of PEM for me, n=1.

Mild PEM for me is noticing that I can't get up the stairs without my legs burning and needing to recruit my arms. Or feeling a similar burn and lack of strength towards the end of brushing my teeth, for example. Activities that i'd complete without much problem when at baseline. I experience these episodes much less frequently when taking pyridostigmine. I also recover from PEM much more quickly, what would be 3x days of feeling terrible are rarely more than 1x day and sometimes less.
 
Hand grip strength was diminished by a median of 4.65 kg after one hour in placebo group, seems to be quite a massive value and doesn't seem to match what is seen elsewhere. If the results are that clear why do people even do CPETs? I wonder whether they checked for maximal exertion during the grip strength test somehow (for example using the tests we've seen in the intramural study).

Also notable: Not a single person in the study meets sems to meet criteria for POTS (the increase is below 30 BPM), so what's even the point of a treatment that adresses BPM?
 
It appears that the drug has anti-inflammatory property as well. So, if the drug is working for some patients, I'd guess it could be reducing the symptoms by reducing neuroinflammation. That would be apart from what the paper is saying about muscle functions.

"This elevated acetylcholine can then activate the cholinergic anti-inflammatory pathway, which plays a role in regulating the immune response."

The elevated acetylcholine level could also elevate dopamine level.
 
Do you mind saying how and by whom you got yours prescribed @Ryan31337 and the prior testing you had? I seem to remember you getting high levels of testing including by Dr Gall for ? Pots/ OI, and others I can't remember.
Reducing the severity of Pem and its duration is huge. Did this happen as you increased the dose of
pyridostigmine to quite a high level or was it a quick response to the drug?
I hope you are doing well overall.
 
Binkie4 said:
Do you mind saying how and by whom you got yours prescribed @Ryan31337 and the prior testing you had? I seem to remember you getting high levels of testing including by Dr Gall for ? Pots/ OI, and others I can't remember.
Reducing the severity of Pem and its duration is huge. Did this happen as you increased the dose of
pyridostigmine to quite a high level or was it a quick response to the drug?
I hope you are doing well overall.
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When I was under Dr Gall he wouldn't let me trial it, which was very frustrating. I didn't want to trial fludrocortisone as it's a steroid. The compromise was bisoprolol which do wrok on hr but no other benefits.
 
rapidboson said:
In my experience (since April) absolutely.
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Same. Mestinon 3x a day 60mg since December 2024. Quality of life improvements are substantial when your heart isn’t going ballistic during simple tasks such as cooking and showers (still have to use stool).

I still get PEM, I think it sets my threshold higher. I don’t want to make broad PEM improvement claims as there too many variables and variability month to month in my own disease state to draw conclusions on PEM tolerance.

Overall slow gains not immediate but life has been better since mestinon, it’s the one drug that has made noticeable improvements in POTS and quality of life. Stomach impact sucks at first but I’ve adapted now, also fiber in the mornings help.
 
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Kiristar said:
When I was under Dr Gall he wouldn't let me trial it, which was very frustrating. I didn't want to trial fludrocortisone as it's a steroid. The compromise was bisoprolol which do wrok on hr but no other benefits.
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I take bisoprolol. Cardiologist was pleased with last echo and said 'keep doing what you're doing'. So I will. The OI isn't as bad as its worst but sometimes, when I first get up, I feel very unwell. I spend little time very upright, most time reclining. It's odd - the body seems to know without conscious thought what it needs. I occasionally find myself almost flat and realise that it's what I needed because I feel better.
 
Binkie4 said:
I take bisoprolol. Cardiologist was pleased with last echo and said 'keep doing what you're doing'. So I will. The OI isn't as bad as its worst but sometimes, when I first get up, I feel very unwell. I spend little time very upright, most time reclining. It's odd - the body seems to know without conscious thought what it needs. I occasionally find myself almost flat and realise that it's what I needed because I feel better.
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I wasn’t so keen on beta blockers.

1. I have a low resting heart rate so it was not advised to lower it with beta blockers further.
2. At the time I had read about potential low cerebral blood flow in ME/CFS. My thought was that maybe my increased heart rate was trying to get more blood to my head, I didn’t want to slow it down just to improve POTS symptoms.

Again this is all anecdotal and loosely based on science. I went with Mestinon as it seems to lower POTS symptoms by not just slowing down heart rate. Mestinon research seems pretty vague on why it helps with POTS, lots of “improve vagal tone” and potentially help with vasoconstriction however.
 
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