Abstracts

Rationale: Background: Neonates with unknown etiology of refractory seizures often have an extensive metabolic and genetic evaluation. KCNQ2 encephalopathy is one etiology with distinctive clinical and EEG features that may enable focused testing. Objective : To determine if there are clinical and EEG features that increase the diagnostic yield of KCNQ2 evaluation in early onset neonatal seizures.Methods: All neonates admitted to the NICU have a neurological consultation. Those with EEG confirmed seizures have brain MR imaging. Those with refractory seizures of unknown etiology receive further metabolic and genetic evaluation. We reviewed the medical record for clinical information and laboratory results for patients who developed seizures during NICU admission from January 2011 to May 2015.Results: Total of 218 patients were included. There were 164 patients had seizure in the first week of life. We identified infants with an etiology commensurate with their seizures including perinatal hypoxia ischemia, stroke, structural brain malformations, in utero injury, CNS infection, intracranial hemorrhage and inborn errors of metabolism. After exclusion of these patients, there were 13 patients with unknown cause prior to NICU discharge.Five of them had refractory seizures and four were evaluated with a genetic epilepsy panel. The one patient who refused testing had clonic vs myoclonic seizures and an EEG that was mainly discontinuous with centrotemporal spike wave and was seizure free on oxcarbazepine at last evaluation at 13 months of age. Three of them were positive for KCNQ2 mutation and one for ARX mutation. Tonic seizure or flexor spasm were observed in all KCNQ2 infants. The electrographic features for ARX and KCNQ2 were similar with multifocal spike-waves and brief background suppression. The follow up EEGs were similar to the initial EEGs. Neonates with seizures well-controlled with one medication had clonic, myoclonic or autonomic seizures and no periods of suppression on the EEG in contrast to the refractory group. Two of six patients with no seizure etiology at followup had normal Genedx infantile epilepsy panel testing while the others were lost to followup.Conclusions: Unknown etiology of refractory seizures in the first week of life and an EEG with suppression has a high yield for a genetic diagnosis of KCNQ2 or ARX pathologic mutations and tonic seizure or spasm are typically related with KCNQ2 mutation. This suggests that a genetic epilepsy panel early in the diagnostic pathway may increase early diagnosis and avoid more extensive specialty evaluation.