Abstracts

Rationale: Mutations in the potassium channel gene KCNT1, typically gain-of-function mutations, cause an epilepsy with a wide phenotypic spectrum, including nocturnal frontal lobe epilepsy (NFLE) in children and adults, a non-specific epileptic encephalopathy (EE) in children, and the most severe form, Epilepsy of Infancy with Migrating Focal Seizures (EIMFS). The epilepsy in these patients is often refractory, presenting clinicians with difficulty in crafting optimal treatment plans. While previous research has suggested that the antiarrhythmic and antimalarial agent, Quinidine, a potassium channel blocker, may be helpful in the treatment of KCNT1-related epilepsy, these data have been conflicting. We sought to evaluate the treatment responsiveness of patients with KCNT1-related epilepsy to conventional therapies, as well as Quinidine. Methods: Data was collected via patient registries at the Children’s Hospital of Philadelphia and the Danish Epilepsy Center, to which patient families and clinicians contributed phenotypic data, including responsiveness to conventional therapies and Quinidine. The registries enroll patients with KCNT1-related epilepsies, including those with a clinical diagnoses of EIMFS. Results: To date, the registries contains data on 44 patients with mutations in KCNT1, the majority of whom have a clinical diagnosis of EIMFS, which to our knowledge, represents the largest cohort to date of patients with KCNT1-related epilepsy. The Ketogenic Diet (KD) was rated as the most effective therapy for KCNT1-related epilepsy, according to a plurality of participants (10/20, 50%), with one child achieving seizure freedom. Quinidine treatment was attempted in 17 patients with EIMFS (mean age 3.9 years, SD 4.0), 9 (53%) of whom reported improvement in seizures, and 8 (47%) of whom reported some improvement in development. Of these 9 responders, 4 experienced temporary seizure freedom and 2 reported sustained seizure freedom of > 1 month. Comparing the effectiveness of KD and Quinidine in patients with at least 3 months of follow-up, the number of patients reporting improvement was comparable (62% KD versus 67% Quinidine, p=0.47). Conclusions: Patients with KCNT1-related epilepsy often experience intractable epilepsy, particularly those with an EIMFS phenotype. Of the therapies evaluated, the Ketogenic Diet and Quinidine were reported as the most effective therapies, and should be considered in patients with KCNT1-related epilepsy. Ongoing work evaluates whether there is a mutation-specific effect that determines responsiveness to Quinidine.