Abstracts

Rationale: Sodium channel mutations are known to cause various epileptic syndromes. SCN1A mutations have proven to cause loss of function of inhibitory neurons through the NaV1.1 channel and loss of inhibitory tone on excitatory neuron. This knowledge has guided management by avoidance of sodium channel blocking anti-epileptics which may paradoxically potentiate seizure activity. There are few studies of seizure management in patients with SCN2A mutations. Evidence suggests that these mutations range from gain- to loss-of-function. This may explain the wide variety of epileptic syndromes associated with SCN2A mutations (benign familial neonatal-infantile seizures, genetic epilepsy with febrile seizures plus, Dravet syndrome, infantile spasms, autism spectrum disorders, and other infantile and childhood epileptic encephalopathies, including epilepsy of infancy with migrating focal seizures). With such variable phenotypes, there are no established guidelines for anti-epileptic efficacy for patients with SCN2A mutations. There has been some data to support the use of traditional sodium channel-blocking medications such as phenytoin. We propose that lacosamide is also an effective treatment. Methods: We report the clinical course of an ex-36 week gestation newborn who presented with seizures to the neonatal ICU at 6 days of age. She later was found to have the A434P variant of the SCN2A gene on GeneDx Infantile Epilepsy Panel. To our knowledge, this particular mutation not been reported in the literature. Our patient's heterogeneous SCN2A mutation is most likely a pathogenic variant and de novo mutation with parental testing is pending. De novo SCN2A mutations are now being reported in the literature in association with severe infantile epileptic encephalopathies, such as epilepsy of infancy with migrating focal seizures. Prior to her genetic diagnosis, our patient was treated with pharmacologically induced coma with both midazolam and pentobarbital. However, she continued to have alternating hemispheric electrographic seizures. In addition to pentobarbital and midazolam, our patient received fosphenytoin, pyridoxine, leviteracetam, and clobazam, none of which had remarkable clinical efficacy. She then responded well to lacosamide. Results: Our patient's diagnosis and her response to lacosamide may provide clinicians with insight into the management of these patients. Our patient had a good response to lacosamide on repeated trials. She received IV lacosamide and a maintenance dose titrated to 10 mg/kg/day for seizure control. Phenobarbital was not effective, and may have worsened her seizures. Fosphenytoin had minimal effect. This patient is currently on a regimen of lacosamide, leviteracetam and clobazam. Conclusions: Patients with SCN2A mutations may benefit from therapy with lacosamide via slow sodium channel inactivation. A genetic diagnosis can assist in determination of effective treatment for patients with SCN2A mutations and epilepsy of infancy with migrating focal seizures. Funding: none