[Myotonia with muscular weakness corrected by exercise. The therapeutic effect of mexiletine]

Abstract

A case of generalized myotonia with autosomal recessive transmission related to Becker's type is reported. A muscular weakness improved by exercise was combined to myotonia. In addition to abundant myotonic discharges, electromyography showed alteration of the voluntary pattern during sustained contraction. The repetitive stimulation showed a marked decrement of the motor potential amplitude with high frequency stimulation. Carbamazepine (800 mg/day) and diphenylhydantoin (300 mg/day) were without effect while myotonia and muscular weakness were considerably and quickly improved by mexiletine (400 mg/day). Tests on ergometric bicycle allowed to quantify this improvement. The physiopathological mechanism of muscular weakness is considered as a depolarization block due to the cumulative depolarization which occurs during myotonic discharge. Most antimyotonic drugs belong to the group of local anesthetics. One of their characteristics is a blocking potency depending on the frequency of membrane activity. Their action is predominant on fibers with repetitive discharges; thus they block the myotonic discharge and prevent the membrane block due to cumulative depolarization. All local anesthetics do not have the same antimyotonic effect. The low molecular weight of mexiletine entails a faster time constant for the block recovery of the sodium channel. It follows that the drug block mainly depends on the frequency of membrane activity and this characteristic could explain the remarkable antimyotonic effect of mexiletine.