title: How should children with West syndrome be efficiently and accurately investigated? Results from the National Infantile Spasms Consortium.
abstract: OBJECTIVE
  To prospectively evaluate the etiology of new-onset infantile spasms and evaluate the yield of genetic and metabolic investigations in those without obvious cause after initial clinical evaluation and magnetic resonance imaging (MRI).
  
  
  METHODS
  Twenty-one U.S. pediatric epilepsy centers prospectively enrolled infants with newly diagnosed West syndrome in a central database. Etiology and investigations performed within 3 months of diagnosis were documented.
  
  
  RESULTS
  From June 2012 to June 2014, a total of 251 infants were enrolled (53% male). A cause was identified in 161 (64.4%) of 250 cases (genetic,14.4%; genetic-structural, 10.0%; structural-congenital, 10.8%; structural-acquired, 22.4%; metabolic, 4.8%; and infectious, 2.0%). An obvious cause was found after initial clinical assessment (history and physical examination) and/or MRI in 138 of 161, whereas further genetic and metabolic studies were revealing in another 23 cases. Of 112 subjects without an obvious cause after initial evaluation and MRI, 81 (72.3%) had undergone genetic testing, which showed a causal abnormality in 23.5% and a variant of unknown significance in 14.8%. Although metabolic studies were done in the majority (serum, 79.5%; urine, 69.6%; and cerebrospinal fluid [CSF], 38.4%), these revealed an etiology in only five cases (4.5%). No correlation was found between type of health insurance (public vs. private) and either genetic or metabolic testing.
  
  
  CONCLUSIONS
  Clinical evaluation and MRI provide a specific diagnosis in 55% of children presenting with West syndrome. We propose that a cost-effective workup for those without obvious cause after initial clinical evaluation and MRI includes an array comparative genomic hybridization (aCGH) followed by an epilepsy gene panel if the microarray is not definitive, serum lactate, serum amino acids, and urine organic acids.
authors.affiliation: Child and Adolescent Neurology and Epilepsy, Mayo Clinic, Rochester, Minnesota, U.S.A.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Wirrell
authors.forename: Renée A
authors.initials: RA
authors.lastname: Shellhaas
authors.forename: Charuta
authors.initials: C
authors.lastname: Joshi
authors.forename: Cynthia
authors.initials: C
authors.lastname: Keator
authors.forename: Shilpi
authors.initials: S
authors.lastname: Kumar
authors.forename: Wendy G
authors.initials: WG
authors.lastname: Mitchell
mesh_terms: D002648:Child; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011446:Prospective Studies; D013036:Spasms, Infantile / Q000175:diagnosis* / Q000453:epidemiology*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
keywords: Diagnostic test assessment; Infantile spasms; Observational cohort; Pediatric; West syndrome