West Syndrome Treatment: New Roads for an Old Syndrome

tuberous sclerosis) (11–13). Therefore, most recently the treatment of WS with valproate has been overtaken and overlooked (14, 15). Overall, the treatment strategies in WS [either the first-line treatments (e.g., ACTH and vigabatrin) or the more classical nongolden treatments (e.g., valproate or other newer anticonvulsants)] are based on the assumption that an early initiation of therapy coupled with a rapid control of seizures in these patients may prevent the arrest or the decline in cognitive development. However, the spectrum of disorders associated to clinical spasms with onset in infancy is wider than previously thought and is currently comprised under the umbrella term of Infantile Spasms syndrome (ISs), which 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). WS refers to a form (a subset) of ISs, characterized by the combination of clustered spasms and hypsarrhythmia on an EEG. Additional (less common) phenotypes falling within the ISs include the so-called infantile spasms single-spasm variant (ISSV: in which spasms may occur singly rather than in clusters), hypsarrhythmia without infantile spasms [HWIS: in which hypsarrhythmia can be (incidentally) recorded without any evidence of clinical spasms], and infantile spasms without hypsarrhythmia (ISW: in which typical clinical spasms may manifest in absence of hypsarrhythmia) [reviewed in Lux and Osborne (11)]. 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 A commentary on