title: Parechovirus Encephalitis and Neurodevelopmental Outcomes.
abstract: OBJECTIVE
  We aimed to describe the clinical features and outcome of human parechovirus (HPeV) encephalitis cases identified by the Australian Childhood Encephalitis (ACE) study.
  
  
  METHODS
  Infants with suspected encephalitis were prospectively identified in 5 hospitals through the (ACE) study. Cases of confirmed HPeV infection had comprehensive demographic, clinical, laboratory, imaging, and outcome at discharge data reviewed by an expert panel and were categorized by using predetermined case definitions. Twelve months after discharge, neurodevelopment was assessed by using the Ages and Stages Questionnaire (ASQ).
  
  
  RESULTS
  We identified thirteen cases of suspected encephalitis with HPeV infection between May 2013 and December 2014. Nine infants had confirmed encephalitis; median age was 13 days, including a twin pair. All had HPeV detected in cerebrospinal fluid with absent pleocytosis. Most were girls (7), admitted to ICU (8), and had seizures (8). Many were born preterm (5). Seven patients had white matter diffusion restriction on MRI; 3 with normal cranial ultrasounds. At discharge, 3 of 9 were assessed to have sequelae; however, at 12 months' follow-up, by using the ASQ, 5 of 8 infants showed neurodevelopmental sequelae: 3 severe (2 cerebral palsy, 1 central visual impairment). A further 2 showed concern in gross motor development.
  
  
  CONCLUSIONS
  Children with HPeV encephalitis were predominantly young, female infants with seizures and diffusion restriction on MRI. Cranial ultrasound is inadequately sensitive. HPeV encephalitis is associated with neurodevelopmental sequelae despite reassuring short-term outcomes. Given the absent cerebrospinal fluid pleocytosis and need for specific testing, HPeV could be missed as a cause of neonatal encephalopathy and subsequent cerebral palsy.
authors.affiliation: Sydney Medical School, Sydney, Australia; Marie Bashir Institute of Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia; Department of Infectious Diseases and Microbiology, The Children's Hospital at Westmead, Sydney, Australia; philip.britton@health.nsw.gov.au.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Britton
authors.affiliation: Sydney Medical School, Sydney, Australia; Department of Neurology, The Children's Hospital at Westmead, Sydney, Australia;
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
authors.affiliation: Department of Infectious Diseases, Royal Children's Hospital, Brisbane, Australia;
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nissen
authors.affiliation: SAEFVIC, Murdoch Children's Research Institute, Melbourne, Australia; Department of General Medicine, Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia;
authors.forename: Nigel
authors.initials: N
authors.lastname: Crawford
authors.affiliation: Sydney Medical School, Sydney, Australia; Department of Infectious Diseases and Microbiology, The Children's Hospital at Westmead, Sydney, Australia; Australian Paediatric Surveillance Unit, Sydney, Australia; and.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Elliott
authors.affiliation: Sydney Medical School, Sydney, Australia; Department of Infectious Diseases and Microbiology, The Children's Hospital at Westmead, Sydney, Australia; National Centre for Immunization Research and Surveillance, Sydney, Australia.
authors.forename: Kristine
authors.initials: K
authors.lastname: Macartney
authors.affiliation: Sydney Medical School, Sydney, Australia; National Centre for Immunization Research and Surveillance, Sydney, Australia.
authors.forename: Gulam
authors.initials: G
authors.lastname: Khandaker
authors.affiliation: Sydney Medical School, Sydney, Australia; Marie Bashir Institute of Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia; Department of Infectious Diseases and Microbiology, The Children's Hospital at Westmead, Sydney, Australia; National Centre for Immunization Research and Surveillance, Sydney, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Booy
authors.affiliation: Sydney Medical School, Sydney, Australia; Marie Bashir Institute of Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia; Department of Infectious Diseases and Microbiology, The Children's Hospital at Westmead, Sydney, Australia;
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Jones
mesh_terms: D002547:Cerebral Palsy / Q000209:etiology*; D002658:Developmental Disabilities / Q000209:etiology*; D038524:Diffusion Magnetic Resonance Imaging; D004569:Electroencephalography; D018792:Encephalitis, Viral / Q000150:complications*; D005076:Exanthema / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D000068079:Motor Disorders / Q000209:etiology*; D010850:Picornaviridae Infections / Q000150:complications*; D011446:Prospective Studies; D012640:Seizures / Q000209:etiology; D011795:Surveys and Questionnaires; D014786:Vision Disorders / Q000209:etiology*; D066127:White Matter / Q000473:pathology