Abstracts

Rationale: SCN1A mutations have emerged as an important cause of epilepsy syndromes. Disturbances of SCN1A gene lead to a disruption in function of the voltage-gated sodium channel alpha subunit type 1, resulting in abnormal sodium currents. (Strafstrom CE, J Child Neurol 2009, 24:S15).The majority of mutations arise de novo and result in a range of phenotypes from generalized epilepsy with febrile seizures (GEFS ) to severe myoclonic epilepsy in infancy (SMEI or Dravet Syndrome). (Fujiwara T, 2006, 70:S223). The relationships of the phenotypes to the various mutations are still being elucidated. (Lossin C, Brain Dev 2009, 31:114) Management of these patients remains challenging, as many patients remain poorly controlled on multiple antiepileptic drugs (AEDs). To our knowledge there is no literature discussing the usefulness of non-medical interventions such as VNS, corpus callosotomy and cortical resection in patients with SCN1A mutations. Methods: Four children with SCN1A mutations and severe epilepsy were retrospectively reviewed. Type of mutations, age of seizure onset, seizure types, medical and surgical treatments, and outcomes were reviewed. Results: All patients presented with seizures within the first two years of life. Seizure types include myoclonic, complex partial, generalized tonic-clonic (GTCS), absence, and infantile spasms. All patients are developmentally delayed. Genetic mutations include 1 frame shift, 1 splice site disruption, and two missense mutations. The patient with the frame shift mutation suffers only occasional GTCS and is the highest functioning, and has had a positive response to a sodium channel blocker (oxcarbazepine ). Three patients had VNS placement but only one had significant improvement. The other two had subsequent corpus callosotomy (anterior two-thirds in 1 and complete in 1) that resulted in improved seizure control. One of these patients went on to have evaluation with intracranial electrodes and left temporal and orbito-frontal resection, as his seizures became lateralized after callosotomy. Although he has subsequently developed a new seizure focus in the contralateral temporal lobe, his seizure burden remains improved. Conclusions: Surgical intervention including VNS, corpus callosotomy, and cortical resection in selected patients with SCN1A mutations may be a useful adjunct in amelioration of severe epilepsy. Although a theoretical risk of worsening symptoms has been suggested with AEDs that block sodium channels, they should not be eliminated as treatment options. Further study is needed to better elucidate genotype-phenotype correlations between mutations types and clinical presentations, and to determine ideal candidates for surgical interventions. Long-term follow-up is also necessary to document extended benefit.