Quinidine therapy and therapeutic drug monitoring in four patients with KCNT1 mutations.

Several recent studies have reported potassium sodium-activated channel subfamily T member 1 (KCNT1) mutations in epilepsy patients on quinidine therapy. The efficacy and safety of quinidine for epilepsy treatment, however, remains controversial. We herein report the cases of four patients with KCNT1 mutations treated with quinidine. A reduction in seizures of more than 50% after quinidine treatment was observed in one patient with epilepsy of infancy with migrating focal seizures (EIMFS), whereas two patients with EIMFS and one with focal epilepsy did not achieve apparent seizure reduction. The relationship between quinidine dose and serum quinidine concentration was inconsistent, particularly at high quinidine doses. One patient with EIMFS developed ventricular tachycardia the day after an increase in quinidine dose from 114 to 126 mg/kg/day. The serum trough quinidine concentration and the corrected QT interval (QTc) before arrhythmia onset were 2.4 μg/ml and 420 ms, respectively, and peak serum quinidine concentration after arrhythmia onset was 9.4 μg/ml. Another patient with EIMFS showed aberrant intraventricular conduction with a quinidine dose of 74.5 mg/kg/day and a serum trough concentration of 3.2 μg/ml. Given that serum quinidine levels may elevate sharply after a dose increase, careful monitoring of electrocardiographs and serum concentrations is required. Based on a review of previous reports and our experience with this case, quinidine should be considered as a promising drug for patients with EIMFS harbouring KCNT1 mutations, however, its efficacy remains controversial due to the limited number of cases, and more information on optimal serum concentrations and appropriate titration methods is required.