Schlömer et al. (2025)
- Authors: Ella Schlömer, Elisa Stein, Claudia Kedor, Rebekka Rust, Anna Brock, Kirsten Wittke, Carmen Scheibenbogen, Laura Kim.
- Institutes: Institute of Medical Immunology, Charité-Universitätsmedizin Berlin; Experimental and Research Center (ECRC), Charité-Universitätsmedizin Berlin.
- Publisher: Frontiers in Neuroscience
- Link: DOI
Summary
This research provides objective evidence that pyridostigmine, a drug that helps nerve communication, can offer immediate, short-term improvement in both muscle weakness and orthostatic intolerance for ME/CFS patients. The findings suggest that a disruption in acetylcholine signaling may be a component of the disease, contributing to symptoms like muscle fatiguability and heart rate dysregulation. While this was a small, preliminary study, it provides a strong scientific basis for pursuing larger clinical trials to determine if pyridostigmine could become an effective treatment for these debilitating symptoms.
What was researched?
This study investigated the immediate effect of a single, low dose of pyridostigmine on muscle strength and orthostatic tolerance in patients with post-infectious ME/CFS. Researchers measured changes in hand grip strength (HGS) and heart rate during a standing test after administering the drug.
Why was it researched?
ME/CFS is characterized by muscle weakness and fatiguability, and many patients also suffer from orthostatic intolerance like POTS. Pyridostigmine 💊, a drug known to increase the availability of the neurotransmitter acetylcholine, has previously been shown to improve cardiac output in ME/CFS and is sometimes used off-label. This study aimed to objectively measure if it could also provide a rapid benefit for muscular and orthostatic symptoms.
How was it researched?
This was a within-subject study involving 20 patients with post-infectious ME/CFS. On a baseline visit, their HGS was measured ten times and then repeated after one hour to assess strength recovery. On a second visit, the same procedure was followed, but patients received a single 30 mg dose of pyridostigmine after the first set of measurements. Orthostatic function was also assessed with a passive standing test with and without the drug, and patients were tested for myasthenia gravis autoantibodies to rule out that condition.
What has been found?
Without the drug, patients’ maximum hand grip strength significantly decreased by a median of 32% when re-tested after an hour, showing poor strength recovery. In contrast, one hour after taking pyridostigmine, their maximum hand grip strength significantly improved by a median of 2.6 kg. Pyridostigmine also improved orthostatic function, significantly reducing the increase in heart rate upon standing from a median of 17 bpm to 13 bpm. None of the patients tested positive for myasthenia gravis autoantibodies.
Discussion
The authors suggest that pyridostigmine’s positive effect on muscle strength could be due to increased acetylcholine availability at the neuromuscular junction, improving the signaling from nerves to muscles. The improvement in orthostatic function is likely due to the drug’s known ability to enhance parasympathetic (the “rest and digest”) nervous system activity. The study’s main limitations were its small sample size and its non-controlled, non-randomized design.
Conclusion & Future Work
The study concludes that a single dose of pyridostigmine can rapidly and significantly improve both muscle strength and orthostatic function in ME/CFS patients. The authors state these promising findings warrant further investigation in larger, controlled clinical trials to properly assess the drug’s potential as a treatment for key symptoms of ME/CFS.