Redefining periodic paralysis with CACNA1S mutation in a Spanish cohort.

Introduction: Muscle MRI and electrophysiological exercise testing have been reported as useful techniques in hypokalemic periodic paralysis (HypoPP). Striking clinical differences between men and women with this disorder are well known; however, little information is available on complementary tests in the asymptomatic population.

Methods: We recruited 11 individuals with HypoPP from 4 independent families, carrying the frequent p.R528H mutation in the calcium channel gene CACNA1S; the sample included 8 symptomatic men and 3 asymptomatic women, together with 9 controls recruited from the same families. Muscle MRI and electrophysiological long exercise test results were evaluated in this homogeneous cohort.

Results: Muscle MRI showed a consistent pattern of atrophy and fatty infiltration mainly involving posterior compartment muscles of the thigh, with first involvement of the adductor magnus and semimembranosus, both in symptomatic and all the asymptomatic carriers, associated with age. The long exercise test showed a delayed decrement in compound muscle action potential amplitude and area in all carriers, regardless of the symptoms, with results becoming 100% sensitive after 35min.

Conclusions: Our findings redefine the exercise test and muscle imaging findings in HypoPP due to the p.R528H CACNA1S mutation, with a particular focus on asymptomatic carriers, who displayed the same alterations as those described in symptomatic patients, thus highlighting their value as screening tools.