Abstracts

Rationale: In a proportion of patients, typical absence seizures remain refractory to treatment with ethosuximide, divalproex sodium, and other currently available antiepileptic drugs (AEDs). Ezogabine (retigabine), a potassium channel opener, is approved for the treatment of focal-onset seizures. We report the case of an adult in whom rapid and complete elimination of multiple daily generalized-onset absence seizures occurred with adjunctive ezogabine use.Methods: A 59-year old woman with a family history of epilepsy developed typical absence seizures at age 6 years. These seizures were refractory to succinimides, phenytoin, phenobarbital and the ketogenic diet as a child and young adult, but remitted at about age 25 years. Absence seizures returned at about age 47 and were associated with bursts of 3 to 4 /second generalized spike-and-slow-wave complexes. They were refractory to succinimides, divalproex, lamotrigine, levetiracetam, topiramate, zonisamide, acetazolamide, rufinamide and lacosamide. Between ages 47 and 58 years, she averaged 3-10 absence seizures daily with a seizure-free day no more than a few times a year, and she had 6 generalized tonic-clonic seizures. Results: While taking lamotrigine 200 mg BID and zonisamide 200 mg BID, she was started on ezogabine 50 mg daily, and increased by 50 mg increments at 14 day intervals. Once reaching an ezogabine dose of 50 mg in the morning, 50 mg at mid-day and 100 mg at night her absence seizures stopped and she remained seizure free for 3 months. Absences later returned 7 days after subsequently discontinuing zonisamide. Further increasing the ezogabine to a total daily dose of 400 mg in addition to lamotrigine did not eliminate the daily absences, but restarting the zonisamide at lower dose again reduced her absence seizures. Conclusions: Ezogabine at low dose combined with lamotrigine and zonisamide, AEDs which predominantly enhance rapid inactivation of sodium channels, produced seizure-freedom in a patient with decades of medically-refractory typical absence seizures. Combination AEDs with mechanisms of action other than inhibition of T-type calcium currents may have efficacy in the treatment of absence seizures.