title: Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation.
abstract: BACKGROUND
  Syntaxin Binding Protein 1 (STXBP1) mutations determine a central neurotransmission dysfunction through impairment of the synaptic vesicle release, thus causing a spectrum of phenotypes varying from syndromic and non-syndromic epilepsy to intellectual disability of variable degree. Among the antiepileptic drugs, levetiracetam has a unique mechanism of action binding SV2A, a glycoprotein of the synaptic vesicle release machinery.
  
  
  METHODS
  We report a 1-month-old boy manifesting an epileptic encephalopathy with clonic seizures refractory to phenobarbital, pyridoxine and phenytoin that presented a dramatic response to levetiracetam with full epilepsy control and EEG normalization. Genetic analysis identified a novel de novo heterozygous mutation (c.[922A>T]p.[Lys308(∗)]) in the STXBP1 gene that severely affects the protein.
  
  
  CONCLUSIONS
  The observation of a dramatic efficacy of levetiracetam in a case of STXBP1 epileptic encephalopathy refractory to other antiepileptic drugs and considerations regarding the specific mechanism of action of levetiracetam modulating the same system affected by STXBP1 mutations support the hypothesis that this drug may be able to reverse specifically the disease epileptogenic abnormalities. Further clinical observations and laboratory studies are needed to confirm this hypothesis and eventually lead to consider levetiracetam as the first choice treatment of patients with suspected or confirmed STXBP1-related epilepsies.
authors.affiliation: Unit of Clinical Neurophysiology, Department of Neuroscience and Mental Health, 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, Ophthalmology, Genetics, Maternal and Child Health, Institute "G. Gaslini", University of Genova, Genoa, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.affiliation: Pediatric Neurology and Muscular Diseases Unit, Laboratory of Neurogenetics, Institute "G. Gaslini", Genoa, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Traverso
authors.affiliation: Pediatric Neurology Unit and Epilepsy Center, Department of Neuroscience, "Fatebenefratelli e Oftalmico" Hospital, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viri
authors.affiliation: Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Cristofori
authors.affiliation: Unit of Clinical Neurophysiology, Department of Neuroscience and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tadini
authors.affiliation: Unit of Clinical Neurophysiology, Department of Neuroscience and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Barbieri
authors.affiliation: Pediatric Neurology Unit and Epilepsy Center, Department of Neuroscience, "Fatebenefratelli e Oftalmico" Hospital, Milan, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Romeo
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
mesh_terms: D017668:Age of Onset; D000927:Anticonvulsants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D000077287:Levetiracetam; D008297:Male; D051938:Munc18 Proteins / Q000235:genetics*; D009154:Mutation; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D051938:Munc18 Proteins; C497937:STXBP1 protein, human; D000077287:Levetiracetam; D010889:Piracetam
keywords: Antiepileptic drugs; Early onset epileptic encephalopathy; Levetiracetam; Pharmacogenetics; STXBP1 mutation