Neuromuscular excitability changes produced by sustained voluntary contraction and response to mexiletine in myotonia congenita

Objective: To investigate the cause of transient weakness in myotonia congenita (MC) and the mechanism of action of mexiletine in reducing weakness. Methods: The changes in neuromuscular excitability produced by 1. min of maximal voluntary contractions (MVC) were measured on the amplitude of compound muscle action potentials (CMAP) in two patients with either recessive or dominant MC, compared to control values obtained in 20 healthy subjects. Measurements were performed again in MC patients after mexiletine therapy. Results: Transient reduction in maximal CMAP amplitude lasting several minutes after MVC was evident in MC patients, whereas no change was observed in controls. Mexiletine efficiently reduced this transient CMAP depression in both patients. Discussion: Transient CMAP depression following sustained MVC may represent the electrophysiological correlate of the weakness clinically experienced by the patients. In MC, the low chloride conductance could induce self-sustaining action potentials after MVC, determining progressive membrane depolarization and a loss of excitability of muscle fibers, thus resulting in transient paresis. Mexiletine may prevent conduction block due to excessive membrane depolarization, thus reducing the transient CMAP depression following sustained MVC.