Pyridostigmine improves hand grip strength in patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Schlömer, Ella, Stein, Elisa, Kedor, Claudia et al. · Frontiers in neuroscience · 2025 · DOI
Quick Summary
This small study tested whether a medication called pyridostigmine could help ME/CFS patients recover hand grip strength after exertion. Twenty patients with ME/CFS showed significant muscle weakness and fatigue. When given pyridostigmine, their hand strength improved by about 2.6 kg after one hour, compared to a loss of 4.65 kg without the medication. The medication also appeared to help with blood pressure responses when standing up.
Why It Matters
ME/CFS patients commonly experience disabling muscle weakness and exertional intolerance with limited treatment options. This study provides mechanistic evidence that acetylcholinesterase inhibition may rapidly improve neuromuscular function and orthostatic regulation, offering a potential therapeutic target for symptoms that significantly impact daily functioning. These findings support further investigation of pyridostigmine as a therapeutic option for ME/CFS.
Observed Findings
All 20 patients demonstrated reduced baseline hand grip strength (median 16.45 kg).
Without pyridostigmine, hand grip strength declined by a median of 4.65 kg after one hour of exertion.
With pyridostigmine, patients showed a median improvement of 2.6 kg in maximum grip strength (approximately 1.5-fold higher than without medication, p=0.01).
Orthostatic heart rate increase decreased from median 17 bpm without pyridostigmine to 13 bpm with the medication (p=0.017).
No patients tested positive for myasthenia gravis-specific autoantibodies.
Inferred Conclusions
Pyridostigmine produces an immediate effect on muscle strength and orthostatic function in ME/CFS patients, likely through increased acetylcholine availability at neuromuscular junctions.
The medication's improvement of grip strength recovery post-exertion suggests potential benefit for exertional intolerance.
Pyridostigmine's enhancement of parasympathetic tone may contribute to improved autonomic regulation in ME/CFS.
Remaining Questions
Does the acute benefit of a single pyridostigmine dose persist or improve with repeated dosing over weeks or months?
Do improvements in grip strength translate to functional gains in activities of daily living and overall quality of life?
What This Study Does Not Prove
This study does not prove that pyridostigmine is an effective long-term treatment—it only demonstrates acute effects in a single dose. The small sample size (n=20), lack of randomization and placebo control, and absence of follow-up data limit generalizability. The study cannot establish whether benefits persist with repeated dosing or translate to meaningful improvements in patients' daily activities and quality of life.