Tag: acetylcholinesterase

Pyridostigmine improves hand grip strength in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

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 1 h. 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 1 h. In contrast, 1 h 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.

Source: Schlömer Ella , Stein Elisa , Kedor Claudia , Rust Rebekka , Brock Anna , Wittke Kirsten , Scheibenbogen Carmen , Kim Laura. Pyridostigmine improves hand grip strength in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Frontiers in Neuroscience, Volume 19 – 2025. DOI: 10.3389/fnins.2025.1637838 ISSN: 1662-453X https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1637838/full (Full text)

Acetylcholinesterase inhibitor exposures as an initiating factor in the development of Gulf War Illness, a chronic neuroimmune disorder in deployed veterans

Abstract:

Gulf War Illness (GWI) is a chronic multi-symptom disorder, characterized by symptoms such as fatigue, pain, cognitive and memory impairment, respiratory, skin and gastrointestinal problems, that is experienced by approximately one-third of 1991 Gulf War veterans. Over the nearly three decades since the end of the war, investigators have worked to elucidate the initiating factors and underlying causes of GWI. A significant portion of this research has indicated a strong correlation between GWI and exposure to a number of different acetycholinesterase inhibitors (AChEIs) in theater, such as sarin and cyclosarin nerve agents, chlorpyrifos and dichlorvos pesticides, and the anti-nerve agent prophylactic pyridostigmine bromide.

Through studying these exposures and their relationship to the symptoms presented by ill veterans, it has become increasingly apparent that GWI is the likely result of an underlying neuroimmune disorder. While evidence indicates that AChEIs are a key exposure in the development of GWI, particularly organophosphate AChEIs, the mechanism(s) by which these chemicals instigate illness appears to be related to “off-target”, non-cholinergic effects. In this review, we will discuss the role of AChEI exposure in the development and persistence of GWI; in particular, how these chemicals, combined with other exposures, have led to a chronic neuroimmune disorder.

This article is part of the special issue entitled ‘Acetylcholinesterase Inhibitors: From Bench to Bedside to Battlefield’.

Source: Michalovicz LT, Kelly KA, Sullivan K, O’Callaghan JP. Acetylcholinesterase inhibitor exposures as an initiating factor in the development of Gulf War Illness, a chronic neuroimmune disorder in deployed veterans. Neuropharmacology. 2020;171:108073. doi:10.1016/j.neuropharm.2020.108073 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398580/ (Full article)