Abstracts

Rationale: To assess the frequency of mutations in the gene for the alpha-1 subunit of the neuronal voltage-gated sodium channel (SCN1A) in patients at a tertiary-care children s hospital, who are strongly considered for resective epilepsy surgery.Methods: Retrospective chart review of patients cared for by the Comprehensive Pediatric Epilepsy Program who had been found to have an SCN1A mutation.Results: Since January 2007, fourteen patients have been found to have an SCN1A mutation. Of those 14 patients, half (7) were strongly considered to be potential candidates for resective epilepsy surgery. Seizure onset occurred between 10 weeks and 7 years of age. Seizure types included febrile, pattern-evoked, apneic, hemiclonic (with varying side of involvement within the same patient), multifocal migrating partial, generalized tonic-clonic (secondarily or primary generalized), complex partial, and myoclonic. Trials of 3 to 11 antiseizure medications had occurred. Ketogenic diet had often been utilized. Physical exam showed a range of abnormalities, including no deficits, dyspraxic or ataxic gait, and impulsivity. Family history revealed a history of febrile seizures or epilepsy in 2 patients. Several patients had undergone several modalities of testing for localization of seizure onset, including continuous video electroencephalogram (vEEG), brain magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), functional MRI (fMRI) and magnetoencephalography (MEG). EEGs showed focal spikes, generalized spike/polyspike and wave discharges, and bilateral independent foci. MRI was most often normal, although focal cortical dysplasia was noted in one patient. Diagnosis of SCN1A mutation was made at a median age of 5 1/2 years (range <9 months to 14 years). Types of mutations include missense, splice, and sequence variants of unknown significance. Conclusions: Fifty percent of patients who were found to have an SCN1A mutation in the last 4 years by the Comprehensive Pediatric Epilepsy Program at our institution were either referred for or being strongly considered for resective epilepsy surgery. The presence of a channelopathy would make likelihood of excellent seizure outcome poor. Testing for channelopathy such as SCN1A mutation should be strongly considered, particularly in patients with multifocal seizure onset or nonlesional MRI. Based on our findings, threshold for testing for channelopathy in patients with typical clinical features should be low, even in the presence of a focal structural lesion.