Effect of local cooling on excitation-contraction coupling in myasthenic muscle: Another mechanism of ice-pack test in myasthenia gravis

•We evaluated the effects of local cooling on muscle twitch in myasthenia gravis.•Local cooling induced amelioration of impaired excitation-contraction coupling in ice-pack-positive myasthenia gravis.•The ice-pack test induces effects on synaptic transmission and excitation-contraction coupling. The ice-pack test is a convenient diagnostic testing procedure for myasthenia gravis (MG). We investigated the underlying mechanism of the ice-pack test performed on bilateral masseters. We performed trigeminal repetitive nerve stimulation (RNS), excitation-contraction (E-C) coupling assessment (Imai’s method) and bite force measurement before and after cooling of the masseters in MG patients and normal controls. After placing the ice-pack on the masseters for 3min, serial recordings of the three tests were performed at various time intervals during 10min after cooling. The bite force increased significantly after cooling in ice-pack-positive MG patients. The acceleration and acceleration ratio (acceleration at a given time to baseline acceleration) of jaw movement increased significantly after cooling of the masseters in ice-pack-positive MG patients compared to ice-pack-negative patients and normal controls. The prolonged effect of cooling continued until the end of recording even though decremental response to RNS had returned to baseline value. Cooling of myasthenic muscle may induce two effects. One is relatively short effect on electrical synaptic transmission at the endplate, and another is prolonged effect on E-C coupling in the muscle. The ice-pack test induces a prolonged effect of ameliorating impaired E-C coupling in MG.