Case Report Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy Robertino Dilena a,⇑ , Pasquale Striano b , Elena Gennaro c , Laura Bassi d , Sara Olivotto e , Laura Tadini a , Fabio Mosca d , Sergio Barbieri a , Federico Zara f , Monica Fumagalli d a Service of Pediatric Epileptology – Unit of Clinical Neurophysiology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy b Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Health, Institute ‘‘G. Gaslini” University of Genova, Genoa, Italy c Laboratory of Genetics, E.O. Ospedali Galliera, Genova, Italy d NICU, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milano, Universita ` degli Studi di Milano, Milan, Italy e Child and Adolescent Neuropsychiatric Service (UONPIA), Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy f Pediatric Neurology and Muscular Diseases Unit, Laboratory of Neurogenetics, Institute ‘‘G. Gaslini”, Genoa, Italy Received 12 July 2016; received in revised form 15 October 2016; accepted 29 October 2016 Abstract Background: Recent clinical evidence supports a targeted therapeutic approach for genetic epileptic encephalopathies based on the molecular dysfunction. Patient description: A2-day-old male infant presented with epileptic encephalopathy characterized by burst-suppression EEG background and tonic-clonic migrating partial seizures. The condition was refractory to phenobarbital, pyridoxine, pyridoxal phos- phate and levetiracetam, but a dramatic response to an intravenous loading dose of phenytoin was documented by video-EEG mon- itoring. Over weeks phenytoin was successfully switched to carbamazepine to prevent seizure relapses associated with difficulty in maintaining proper blood levels of phenytoin. Genetic analysis identified a novel de novo heterozygous mutation (c.[4633A>G]p. [Met1545Val]) in SCN2A. At two years and three months of age the patient is still seizure-free on carbamazepine, although a devel- opmental delay is evident. Conclusions: Sodium channel blockers represent the first-line treatment for confirmed or suspected SCN2A-related epileptic ence- phalopathies. In severe cases with compatible electro-clinical features we propose a treatment algorithm based on a test trial with high dose intravenous phenytoin followed in case of a positive response by carbamazepine, more suitable for long-term maintenance treatment. Because of their rarity, collaborative studies are needed to delineate shared therapeutic protocols for EIEE based on the electro-clinical features and the presumed underlying genetic substrate. Ó 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: SCN2A; Early infantile epileptic encephalopathy; Sodium channel blockers; Carbamazepine; Phenytoin 1. Introduction Early infantile epileptic encephalopathy (EIEE) due to SCN2A mutations (EIEE 11) is attributed to dysfunction of the brain sodium channel Na(V)1.2 [1,2]. In some patients with EIEE 11 in vitro http://dx.doi.org/10.1016/j.braindev.2016.10.015 0387-7604/Ó 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. ⇑ Corresponding author at: Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Servizio di Epilettologia e Neurofisiopatologia Pediatrica, Clinica Mangiagalli, via Commenda 12, 20122 Milan, Italy. Fax: +39 0255032155. E-mail address: robertino.dilena@policlinico.mi.it (R. Dilena). www.elsevier.com/locate/braindev Brain & Development xxx (2016) xxx–xxx Please cite this article in press as: Dilena R et al. Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy. Brain Dev (2016), http://dx.doi.org/10.1016/j.braindev.2016.10.015