A female patient with paramyotonia congenita. Part 1: Combination therapy of lacosamide and topiramate

Paramyotonia congenita (PMC) is a congenital disorder characterized by non-dystrophic myotonia due to variants of SCN4A . SCN4A encodes the α-subunit of the voltage-gated sodium channel Na V 1.4, which is responsible for the generation of action potentials and excitation of skeletal muscle fibers. Despite some reduction of myotonia by sodium channel blockers, a more effective treatment is still being sought. We herein report a patient whose myotonia was ameliorated by combination therapy with topiramate, mexiletine and lacosamide. The patient was a 20-year-old woman. A few days after birth, laryngospasm and cyanosis had appeared repeatedly on crying, gradually followed by local myotonia in various parts of the body. Exposure to both hot and cold, exercise, and mental stress induced myotonia in her fingers, orbicularis oculi, neck, trunk, and limbs, lasting for several minutes to hours, several times a day. We diagnosed her with PMC by detecting a c.3917G>A, p.(Gly1306Glu) variant in SCN4A. She also had epilepsy with tonic-clonic seizure since 1 year old. Combination therapy of topiramate and lacosamide in addition to mexiletine reduced the myotonia markedly. A sodium channel blocker, the combination of fast inactivation by topiramate and mexiletine, and slow inactivation by lacosamide may be effective in reducing myotonia in PMC. The further accumulation of data concerning this treatment is required.