title: Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy.
abstract: BACKGROUND
  Recent clinical evidence supports a targeted therapeutic approach for genetic epileptic encephalopathies based on the molecular dysfunction.
  
  
  METHODS
  A 2-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 phosphate and levetiracetam, but a dramatic response to an intravenous loading dose of phenytoin was documented by video-EEG monitoring. 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 developmental delay is evident.
  
  
  CONCLUSIONS
  Sodium channel blockers represent the first-line treatment for confirmed or suspected SCN2A-related epileptic encephalopathies. 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.
authors.affiliation: Service of Pediatric Epileptology - Unit of Clinical Neurophysiology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. Electronic address: robertino.dilena@policlinico.mi.it.
authors.forename: Robertino
authors.initials: R
authors.lastname: Dilena
authors.affiliation: Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Health, Institute "G. Gaslini" University of Genova, Genoa, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.affiliation: Laboratory of Genetics, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gennaro
authors.affiliation: NICU, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bassi
authors.affiliation: Child and Adolescent Neuropsychiatric Service (UONPIA), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Olivotto
authors.affiliation: Service of Pediatric Epileptology - Unit of Clinical Neurophysiology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tadini
authors.affiliation: NICU, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
authors.affiliation: Service of Pediatric Epileptology - Unit of Clinical Neurophysiology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Barbieri
authors.affiliation: Pediatric Neurology and Muscular Diseases Unit, Laboratory of Neurogenetics, Institute "G. Gaslini", Genoa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.affiliation: NICU, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Fumagalli
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D002220:Carbamazepine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics*; D010672:Phenytoin / Q000627:therapeutic use*; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D013036:Spasms, Infantile / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D062551:NAV1.2 Voltage-Gated Sodium Channel; C568251:SCN2A protein, human; D026941:Sodium Channel Blockers; D002220:Carbamazepine; D010672:Phenytoin
keywords: Carbamazepine; Early infantile epileptic encephalopathy; Phenytoin; SCN2A; Sodium channel blockers