Induced myotonia in man and goat.

Abstract

Abstract Treatment of 41 hypercholesterolemic patients with the cholesterol-lowering agent, diazacholesterol, an analogue of cholesterol, was associated with the development of muscular spasms in 30 individuals; electromyography (EMG) disclosed myotonia in 27 of 28 patients so tested. Associated with the clinical and EMG myotonia were alterations in the body sterol composition, as determined by gas-liquid chromatography (GLC). The plasma of all but one of the 36 patients so studied showed a fall in total sterols, while the plasma, erythrocyte membrane, and the one muscle sample examined were marked by the appearance of desmosterol, the immediate precursor of cholesterol. Discontinuation of diazacholesterol therapy was accompanied by the disappearance of clinical and EMG manifestations of myotonia, a marked reduction in plasma and erythrocyte desmosterol, and a concomitant rise in total sterol levels. Administration of diazacholesterol to normal, myotonic, and hybrid goats was associated with the appearance of myotonia or the worsening of pre-existing myotonia, a decline in plasma total sterols, and the appearance of desmosterol in plasma, erythrocyte membrane, and muscle. The findings suggest that diazacholesterol may cause clinical and electromyographic findings similar to those observed in the human myotonic disorders and in myotonic goats. The role of altered sterol synthesis in the pathogenesis of the findings is now being investigated.