title: Elevated cerebrospinal fluid endothelin 1 associated with neurogenic pulmonary edema in children with enterovirus 71 encephalitis.
abstract: OBJECTIVE
  Neurogenic pulmonary edema (NPE) is a fatal complication in children with enterovirus 71 (EV71) encephalitis. Endothelin 1 (ET-1), a potent vasoconstrictor, can induce pulmonary edema in rats via intrathecal injections. Thus, it was hypothesized that ET-1 in the central nervous system may correlate with NPE in children with EV71 encephalitis.
  
  
  METHODS
  Clinical data and ET-1 in the cerebrospinal fluid (CSF) were compared between three groups: (1) EV71 encephalitis with NPE; (2) EV71 encephalitis without NPE; and (3) non-EV71 aseptic meningitis. ET-1 immunostaining was performed on the brainstem of autopsy patients.
  
  
  RESULTS
  The EV71 with NPE group showed significantly increased CSF levels of ET-1 compared to the EV71 without NPE and the non-EV71 aseptic meningitis groups (both p<0.01). The optimum cut-off point of ET-1 to predict NPE in EV71 patients, based on the receiver operating characteristic curve, was 0.5 pg/ml (sensitivity 83%, specificity 100%). Immunostaining in the brainstem showed increased ET-1 expression, mainly in the oligodendrocytes, in EV71 with NPE patients compared with control patients.
  
  
  CONCLUSIONS
  ET-1 in the central nervous system may play a role in the development of NPE in children with EV71 infection and could be used as a biomarker or therapeutic target for NPE in EV71 encephalitis.
authors.affiliation: Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan. Electronic address: nckutu@gmail.com.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Tu
authors.affiliation: Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Anatomy and Cell Biology, National Yang Ming University, Taipei, Taiwan.
authors.forename: Hsueh-Te
authors.initials: HT
authors.lastname: Lee
authors.affiliation: Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jing-Jou
authors.initials: JJ
authors.lastname: Yan
authors.affiliation: Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chun-I
authors.initials: CI
authors.lastname: Sze
authors.affiliation: Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Chou
authors.affiliation: Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan.
authors.forename: Chien-Jung
authors.initials: CJ
authors.lastname: Ho
authors.affiliation: Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan; Department of Pediatrics, Wan-Fang Hospital, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chao-Ching
authors.initials: CC
authors.lastname: Huang
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002675:Child, Preschool; D018792:Encephalitis, Viral / Q000150:complications*; D019332:Endothelin-1 / Q000134:cerebrospinal fluid* / Q000378:metabolism; D029821:Enterovirus A, Human / Q000302:isolation & purification*; D004769:Enterovirus Infections / Q000150:complications*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008582:Meningitis, Aseptic / Q000134:cerebrospinal fluid; D011654:Pulmonary Edema / Q000134:cerebrospinal fluid* / Q000821:virology*; D051381:Rats
chemical_list: D019332:Endothelin-1
keywords: Encephalitis; Endothelin 1; Enterovirus 71; Neurogenic pulmonary edema