title: Infantile spasms syndrome, West syndrome and related phenotypes: what we know in 2013.
abstract: The current spectrum of disorders associated to clinical spasms with onset in infancy is wider than previously thought; accordingly, its terminology has changed. Nowadays, the term Infantile spasms syndrome (ISs) defines an epileptic syndrome occurring in children younger than 1 year (rarely older than 2 years), with clinical (epileptic: i.e., associated to an epileptiform EEG) spasms usually occurring in clusters whose most characteristic EEG finding is hypsarrhythmia [the spasms are often associated with developmental arrest or regression]. The term West syndrome (WS) refers to a form (a subset) of ISs, characterised by the combination of clustered spasms and hypsarrhythmia on an EEG and delayed brain development or regression [currently, it is no longer required that delayed development occur before the onset of spasms]. Less usually, spasms may occur singly rather than in clusters [infantile spasms single-spasm variant (ISSV)], hypsarrhythmia can be (incidentally) recorded without any evidence of clinical spasms [hypsarrhythmia without infantile spasms (HWIS)] or typical clinical spasms may manifest in absence of hypsarrhythmia [infantile spasms without hypsarrhythmia (ISW)]. There is a growing evidence that ISs and related phenotypes may result, besides from acquired events, from disturbances in key genetic pathways of brain development: specifically, in the gene regulatory network of GABAergic forebrain dorsal-ventral development, and abnormalities in molecules expressed at the synapse. Children with these genetic associations also have phenotypes beyond epilepsy, including dysmorphic features, autism, movement disorders and systemic malformations. The prognosis depends on: (a) the cause, which gives origin to the attacks (the complex malformation forms being more severe); (b) the EEG pattern(s); (c) the appearance of seizures prior to the spasms; and (d) the rapid response to treatment. Currently, the first-line treatment includes the adrenocorticotropic hormone ACTH and vigabatrin. In the near future the gold standard could be the development of new therapies that target specific pathways of pathogenesis. In this article we review the past and growing number of clinical, genetic, molecular and therapeutic discoveries on this expanding topic.
authors.affiliation: Unit of Pediatrics and Pediatric Emergency "Costanza Gravina", University Hospital "Policlinico-Vittorio Emanuele", Catania, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Pavone
authors.affiliation: Unit of Pediatric Neurology and Muscular Diseases, "G. Gaslini" Research Hospital, University of Genoa, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.affiliation: Unit of Pediatrics and Pediatric Emergency "Costanza Gravina", University Hospital "Policlinico-Vittorio Emanuele", Catania, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Falsaperla
authors.affiliation: Unit of Pediatrics and Pediatric Emergency "Costanza Gravina", University Hospital "Policlinico-Vittorio Emanuele", Catania, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pavone
authors.affiliation: Department of Educational Science, Chair of Pediatrics, University of Catania, Italy. Electronic address: m.ruggieri@unict.it.
authors.forename: Martino
authors.initials: M
authors.lastname: Ruggieri
mesh_terms: D001921:Brain / Q000503:physiopathology; D003071:Cognition; D006801:Humans; D007223:Infant; D013036:Spasms, Infantile / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology* / Q000628:therapy
keywords: Genetics; Hypsarrhythmia; Infantile spasms; Treatment; West syndrome