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

[forestglip]

Hopefully the full paper describes a placebo control. Otherwise, it seems possible the hand grip strength change is placebo effect.

Yeah, no blinding.

Limitations of our study include the small sample size and the non-controlled design without randomization of the treatment order and the lack of a control group.

 

[Utsikt]

It’s a shame they go beyond the evidence and claim that PS improved the measurements. We have no way of knowing if it was actually caused by the PS.

 

[forestglip]

For reference, here is the main hand grip strength result:

As depicted in Figure 1A, HGS exhibited a linear decrease over the course of the ten measurements without PS but remained stable following PS administration. Further patients had a lower Fmax and Fmean HGS in the second session compared to the first without PS, while it increased after PS. In total, 16 of 20 patients had an improved HGS after 1 h. In four of 20 patients Fmax or Fmean did not increase following PS administration.

The light pink line is one hour after taking PS.

Figure 1. Hand grip strength (HGS) in patients with post-infectious ME/CFS (n = 20). Handgrip strength (HGS) was assessed in two separate sets, each consisting of ten consecutive measurements, with a 1 h rest period between sets. Mean and maximum HGS were calculated for each measurement set. The visit without pyridostigmine (PS) is shown in blue, while the visit with 30 mg of PS administered after the first measurement set is shown in pink. (A) Course of the single HGS values, left: without PS, right: with PS. (B) Maximum force (Fmax2) of the second HGS measurement set, with and without PS. (C) Mean force (Fmean2) of the second HGS measurement set, with and without PS. (D) Difference in maximum force (Fmax) between the first and second measurement set. Group comparisons were performed using the Wilcoxon matched paired-signed rank test with significance levels indicated as * p < 0.05, ** p < 0.01, *** p < 0.001.

 

[Formerhuman]

Am I right that if this effect is real, it is in favor of periferal mechanism of fatigability? It is strange to me that researchers in Charite didn't do for example crossover trial.

 

[Utsikt]

Am I right that if this effect is real, it is in favor of periferal mechanism of fatigability?

I think there’s a difference between muscles being unable to perform at close to max after exertion and the general feeling of fatigue.

This test focuses on the former.

It is strange to me that researchers in Charite didn't do for example crossover trial.

Yeah, it’s a shame they didn’t do any kind of placebo and blinding.

 

[EndME]

Am I right that if this effect is real, it is in favor of periferal mechanism of fatigability? It is strange to me that researchers in Charite didn't do for example crossover trial.

The only thing real here is likely the lack of a control or perhaps even worse (people participating because there's a chance they'd get the drug and being dissapointed when your in the non-drug group).

 

[ScoutB]

It's interesting that Pyridostigmine is being investigated as a treatment for ME/CFS while at the same time being investigated as a possible cause of gulf war syndrome (for example). Not implying anything about safety with this comment, biology is always counterintuitive, just very curious what this line of research ultimately says about the two diseases.

 

[ChronicallyOverIt]

It's interesting that Pyridostigmine is being investigated as a treatment for ME/CFS while at the same time being investigated as a possible cause of gulf war syndrome (for example). Not implying anything about safety with this comment, biology is always counterintuitive, just very curious what this line of research ultimately says about the two diseases.

Skimmed the paper, to me they make a ton of assumptions with little data. But also wouldn’t this be the people most exposed to AChEis were given PB? So the people most exposed to nerve agents used the most PB, it doesn’t mean that PB caused the illness?

 

[Dolphin]

It's interesting that Pyridostigmine is being investigated as a treatment for ME/CFS while at the same time being investigated as a possible cause of gulf war syndrome (for example). Not implying anything about safety with this comment, biology is always counterintuitive, just very curious what this line of research ultimately says about the two diseases.

I wondered that myself before: could the gulf war veterans have got a higher dosage/more intensive regimen would anyone know?

 

[forestglip]

I wondered that myself before: could the gulf war veterans have got a higher dosage/more intensive regimen would anyone know?

From some cursory research I did previously, it seemed like military got a relatively low dosage:

I'm curious what dose of PB the military personnel were taking and if it's significantly higher than the dose often prescribed for orthostatic intolerance.

Information from Veterans Affairs:

Supplied in the Gulf War as 21-tablet blister pack, with prescribed dosage as one 30-mg tablet every 8 hours. Veterans’ actual exposure is not known, because pills were self-administered and there are few examples in individual or unit health records from the Department of Defense.

Bateman Horne Center says this for dosages for orthostatic intolerance:

The doses usually range from 30-60 mg every 4-6 hours depending on tolerance and response. There is a 180 mg extended-release version.

Interestingly, potentially lower dosage for military than for OI patients.

 

[ScoutB]

ChronicallyOvert, my understanding is that PB was widely given prophylactically, but your concern still stands. There's also the problem that we have better data on who took PB pills than we do about who was exposed to a nerve agent. The researchers try to address this in table 2 by comparing OR of different exposures and by investigating the dose response, but ultimately I doubt anything definitive can be concluded from the kind of rough observational data we have about the gulf war exposures.

Dolphin, surprisingly, according to this PBS article the soldier's dose was quite low. I guess a theory might be that maybe under certain circumstances it's bad in conjunction with other exposures (like PB, many of the nerve agents and pesticides under investigation inhibit acetylcholinesterase) but tbh I haven't seen anyone state that definitively.