title: A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease?
abstract: OBJECTIVE
  The purpose of this study was to review the experience with herpes simplex encephalitis at the Hospital for Sick Children over the past 12 years.
  
  
  METHODS
  All patients who were admitted to our institution with acute encephalitis between January 1994 and December 2005 were enrolled prospectively in an encephalitis registry. Children from the registry with herpes simplex encephalitis were included in this study; we detailed the clinical presentations, laboratory findings, electroencephalographic findings, diagnostic imaging findings, treatments, and outcomes for all cases.
  
  
  RESULTS
  Of 322 cases of acute encephalitis, 5% were caused by herpes simplex virus. Initially negative herpes simplex virus cerebrospinal fluid polymerase chain reaction results were found in 2 cases (13%), but results became positive in repeat cerebrospinal fluid analyses. Classic clinical presentations were seen in 75% of cases, cerebrospinal fluid pleocytosis was found in 94%, elevated cerebrospinal fluid protein levels were found in 50%, electroencephalographic changes were observed in 94%, and diagnostic imaging abnormalities were noted in 88%. All patients were treated with intravenous acyclovir. Neurologic sequelae occurred in 63% of cases, including seizures in 44% and developmental delays in 25%. There were no deaths in this study group.
  
  
  CONCLUSIONS
  Herpes simplex encephalitis continues to be associated with poor long-term neurologic outcomes despite appropriate therapy. Cerebrospinal fluid polymerase chain reaction results may be negative early in the course of herpes simplex encephalitis; therefore, repeat cerebrospinal fluid analysis should be considered if herpes simplex encephalitis is suspected. Atypical forms of herpes simplex virus central nervous system disease may occur in children.
authors.affiliation: Division of Neurology, Hospital for Sick Children and University of Toronto, Toronto, Ontario, M5G 1X8, Canada.
authors.forename: Jorina M
authors.initials: JM
authors.lastname: Elbers
authors.forename: Ari
authors.initials: A
authors.lastname: Bitnun
authors.forename: Susan E
authors.initials: SE
authors.lastname: Richardson
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Ford-Jones
authors.forename: Raymond
authors.initials: R
authors.lastname: Tellier
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Wald
authors.forename: Martin
authors.initials: M
authors.lastname: Petric
authors.forename: Hanna
authors.initials: H
authors.lastname: Kolski
authors.forename: Helen
authors.initials: H
authors.lastname: Heurter
authors.forename: Daune
authors.initials: D
authors.lastname: MacGregor
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D020803:Encephalitis, Herpes Simplex / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D013997:Time Factors