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ORIGINAL RESEARCH article

Front. Neurosci.

Sec. Autonomic Neuroscience

Volume 19 - 2025 | doi: 10.3389/fnins.2025.1637838

This article is part of the Research TopicExploring Chronic Fatigue: Neural Correlates, Mechanisms, and Therapeutic StrategiesView all 12 articles

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

Provisionally accepted
  • 1Institute for Medical Immunology, Charité University Medicine Berlin, Berlin, Germany
  • 2Charite - Universitatsmedizin Berlin Institut fur Medizinische Immunologie, Berlin, Germany
  • 3Experimental and Research Center (ECRC), Charité-Universitätsmedizin Berlin, Berlin, Germany

The final, formatted version of the article will be published soon.

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystemic disease characterized by exertional intolerance and fatigue which is often accompanied by muscle weakness and fatiguability. A study showed efficacy of the acetylcholinesterase inhibitor pyridostigmine 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 electric dynamometer 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 rate from lying to standing was median 17 beats per minute without pyridostigmine (IQR: 13 beats per minute – 23 beats per minute) and 13 beats per minute (IQR: 9 beats per minute – 20 beats per minute) (p = 0.017) with pyridostigmine. None of the patients tested positive for myasthenia gravis specific 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.

Keywords: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, post-COVID syndrome, Hand grip strength, Orthostatic Intolerance, Myasthenia Gravis, COVID-19, Pyridostigmine

Received: 29 May 2025; Accepted: 20 Aug 2025.

Copyright: © 2025 Schlömer, Stein, Kedor, Rust, Brock, Wittke, Scheibenbogen and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ella Schlömer, Institute for Medical Immunology, Charité University Medicine Berlin, Berlin, Germany

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