Pyridostygmine, A Potential Therapy for Dysphagia Secondary to Ineffective Esophageal Motility

Abstract

Purpose: Clinical Presentation: A 47-year-old white woman with GERD initially presented 7 years ago for possible anti-reflux surgery evaluation due to heartburn and severe dysphagia of solids and liquids. She was previously treated with multiple antireflux regimens and endoscopic dilations without improvement. Esophageal impedance manometry testing confirmed the diagnosis of severe ineffective esophageal motility (IEM). Over the next 4 years, acid control therapy was continually altered and a prolonged trial of bethanechol yielded little improvement. Repeat testing continued to reveal severe IEM, normal number of reflux episodes and esophageal acid exposure, and negative symptom association. She was then started on Mestinon 30 mg BID based on recent studies showing increased esophageal contraction amplitudes. Within the next 3 months the patient's dysphagia drastically improved as evidenced by a 15 lb weight gain. Although repeat esophageal impedance manometry continued to show severe IEM, distal contraction amplitudes improved and the patient's dose of Mestinon was increased to 60 mg BID. Most recently the patient still struggled with heartburn but her dysphagia has disappeared, and her biggest health concern currently is obesity having since gained >60 lb since initiation of Mestinon! Discussion: IEM was redefined by the presence of greater than or equal to 50% liquid swallows with contraction amplitude <30 mm Hg in one of the two distal sites in the lower esophagus. Although antireflux therapy has been the mainstay of IEM treatment, restoration of esophageal smooth muscle contractility by the muscarinic receptor agonist, bethanechol, improved esophageal contraction pressures as well as bolus transit. Recent comparison of oral pyridostygmine (Mestinon), buspirone, and bethanechol was undertaken after short-acting acetylcholinesterase inhibitors were shown to increase esophageal contraction amplitude and duration. After our patient failed to improve with antireflux therapy and a trial of bethanechol, addition of Mestinon was attempted. Although the addition of Mestinon did not change her diagnosis of severe IEM, it did increase distal contraction amplitudes and overall bolus transit of both solids and liquids, but more importantly completely cured the symptom of dysphagia as evidenced by the patient's drastic weight gain over the follow 3 years. Conclusion: The addition of pyridostygmine greatly improved the distal esophageal contraction amplitudes and bolus transit in this patient. Although the degree of improvement was not enough to change her diagnosis of severe IEM, the therapeutic benefit has proven to dramatically improve this woman's quality of life and cure her dysphagia.