Utility of Serial Repetitive Nerve Stimulation in Differentiating Pharmacological From Immunological Exacerbation of Myasthenia Gravis: A Case Report

Myasthenia gravis (MG) can be exacerbated by certain medications. However, the contribution of many suspected medications remains uncertain, often based on case reports and confounded by variable drug responses and the fluctuating nature of MG. Objective drug evaluations are needed to establish causation. This report examines cibenzoline, an antiarrhythmic suspected of exacerbating MG, and proposes a method for assessing the causal role of medications in MG exacerbations through daily repetitive nerve stimulation (RNS) correlated with drug levels. We present a case of a 78-year-old man with stable ocular MG, treated with prednisolone and cibenzoline, who developed a myasthenic crisis requiring intubation. The patient's worsening chronic kidney disease raised concerns about potentially increased cibenzoline levels and their role in the crisis. Serial co-evaluation of RNS studies and cibenzoline blood levels over three consecutive days demonstrated a strong correlation between cibenzoline levels and the severity of neuromuscular junction fatigue. Rapid clinical and electrophysiological recovery within a day following withdrawal, and subtle improvement after the drop in blood cibenzoline level, suggested a primary pharmacological mechanism rather than an immunological one, as immunological improvement usually requires at least several days. This case highlights the importance of serial electrophysiological assessments combined with drug-level monitoring to evaluate the causality in suspected medication-induced MG exacerbations. Given the increasing number of elderly patients with MG or chronic kidney disease and the potential for undiagnosed MG, the risk of iatrogenic adverse events could increase. The proposed methodology, which utilizes serial RNS with blood concentration monitoring of the suspected drug, can facilitate an accurate evaluation of the causal relationship in pharmacological versus immunological exacerbations of MG.