Clinical Significance of Repetitive Compound Muscle Action Potentials in Patients with Myasthenia Gravis: A Predictor for Cholinergic Side Effects of Acetylcholinesterase Inhibitors

Abstract

Background and PurposeAcetylcholinesterase inhibitors (AChEIs) are widely used to treat myasthenia gravis (MG). Although AChEIs are usually tolerated well, some MG patients suffer from side effects. Furthermore, a small proportion of MG patients show cholinergic hypersensitivity and cannot tolerate AChEIs. Because repetitive compound muscle action potentials (R-CMAPs) are an electrophysiologic feature of cholinergic neuromuscular hyperactivity, we investigated the clinical characteristics of MG patients with R-CMAPs to identify their clinical usefulness in therapeutic decision-making.MethodsWe retrospectively reviewed the clinical records and electrodiagnostic findings of MG patients who underwent electrodiagnostic studies and diagnostic neostigmine testing (NT).ResultsAmong 71 MG patients, 9 could not tolerate oral pyridostigmine bromide (PB) and 17 experienced side effects of PB. R-CMAPs developed in 24 patients after NT. The highest daily dose of PB was lower in the patients with R-CMAPs (240 mg/day vs. 480 mg/day, p<0.001). The frequencies of PB intolerance and side effects were higher in the patients with R-CMAPs than in those without R-CMAPs [37.5% vs. 0% (p<0.001) and 45.8% vs. 12.8% (p=0.002), respectively]. The MG Foundation of America postintervention status did not differ significantly between MG patients with and without R-CMAPs, and the response to immunotherapy was also good in both groups.ConclusionsSide effects of and intolerance to AChEIs are more common in MG patients with R-CMAPs than in those without R-CMAPs. AChEIs should be used carefully in MG patients with R-CMAPs. The presence of R-CMAPs after NT may be a good indicator of the risks of PB side effects and intolerance.

Revisiting the compound muscle action potential (CMAP)

“…The presence of CMAP “after-discharges” when recording a single CMAP may offer clues in abnormalities of neuromuscular transmission ( Lee et al, 2016 , Yang et al, 2021 , . One uncommon situation is when a myasthenic patient becomes increasingly weak after taking excessive acetylcholinesterase inhibitors (“cholinergic crisis”).…”

Treatment of experimental autoimmune myasthenia gravis rats with FTY720 and its effect on Th1/Th2 cells

“…Clinical manifestation of MG is general skeletal muscle fatigue and blepharoptosis, both of which are aggravated following periods of activity and alleviated with rest, thus exhibiting relief in the morning and progression of symptoms in night (4). MG progression may affect neural tissues other than neuromuscular junction or may affect non-neural tissues, which may lead to epilepsy, pyramidal tract sign and memory deficit (5,6). The pathogenic mechanism of MG is complex and involves genetic, environmental, physical and chemical factors (7).…”