title: Clinical and genetic features of acute encephalopathy in children taking theophylline.
abstract: BACKGROUND
  Theophylline has recently been suspected as a risk factor of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), although there has been no systematic study on the relationship between acute encephalopathy in children taking theophylline (AET) and AESD.
  
  
  METHODS
  We recruited 16 Japanese patients (11 male and 5 female, median age of 2 years and 7 months) with AET from 2008 to 2013. We evaluated their clinical features, such as the duration of first seizure, biphasic clinical course and cranial CT/MRI imaging and compared them with those of AESD. We analyzed the polymorphisms or mutations of genes which are associated with AESD.
  
  
  RESULTS
  Clinically, 12 patients had neurological and/or radiological features of AESD. Only one patient died, whereas all 15 surviving patients were left with motor and/or intellectual deficits. Genetically, 14 patients had at least one of the following polymorphisms or mutations associated with AESD: thermolabile variation of the carnitine palmitoyltransferase 2 (CPT2) gene, polymorphism causing high expression of the adenosine receptor A2A (ADORA2A) gene, and heterozygous missense mutation of the voltage gated sodium channel 1A (SCN1A) and 2A (SCN2A) gene.
  
  
  CONCLUSIONS
  Our results demonstrate that AET overlaps with AESD, and that AET is a multifactorial disorder sharing a genetic background with AESD.
authors.affiliation: Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Japan. Electronic address: makisaito-tky@umin.ac.jp.
authors.forename: Makiko
authors.initials: M
authors.lastname: Saitoh
authors.affiliation: Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Department of Pediatrics, Fukuoka University, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishii
authors.affiliation: Department of Pediatrics, Fukuoka University, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ihara
authors.affiliation: Department of Pediatrics, Fukuoka University, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
authors.affiliation: Department of Pediatrics, Child Medical Center, Osaka City General Hospital, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
authors.affiliation: Department of Pediatric Neurology, Child Medical Center, Osaka City General Hospital, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kawawaki
authors.affiliation: Department of Neurology, National Center for Child Health and Development, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Department of Pediatrics, Jichi Medical University, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamagata
authors.affiliation: Department of Pediatrics, Asahikawa Habilitation Center for Disabled Children, Japan.
authors.forename: Akie
authors.initials: A
authors.lastname: Miyamoto
authors.affiliation: Department of Pediatrics, Tokyo Medical University, Japan.
authors.forename: Gaku
authors.initials: G
authors.lastname: Yamanaka
authors.affiliation: Department of Neurology, Tokyo Metropolitan Hachioji Children's Hospital, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Amemiya
authors.affiliation: Division of Neurology, Saitama Children's Medical Center, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kikuchi
authors.affiliation: Department of Pediatrics, Iwate Medical University, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kamei
authors.affiliation: Department of Pediatrics, Iwate Medical University, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Akasaka
authors.affiliation: Department of Pediatrics, Saiseikai Yokohamashi Tobu Hospital, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Anzai
authors.affiliation: Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuguchi
mesh_terms: D000208:Acute Disease; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001927:Brain Diseases / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics; D043705:Receptor, Adenosine A2A / Q000235:genetics; D013806:Theophylline / Q000008:administration & dosage* / Q000009:adverse effects; D014057:Tomography, X-Ray Computed
chemical_list: D018927:Anti-Asthmatic Agents; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D043705:Receptor, Adenosine A2A; C568242:SCN1A protein, human; C568251:SCN2A protein, human; D013806:Theophylline
keywords: Acute encephalopathy; Adenosine receptors; Status epilepticus; Theophylline