title: Human Parechovirus 3 Meningitis and Fatal Leukoencephalopathy.
abstract: Human parechovirus 3 (HPeV3) is a picornavirus associated with neurologic disease in neonates. Human parechovirus 3 infection of preterm and term infants is associated with seizures and destructive periventricular white matter lesions. Despite unremarkable cerebrospinal fluid (CSF), HPeV3 RNA can be amplified from CSF and nasopharyngeal and rectal swabs. We report pathologic findings in 2 autopsy cases of infants with active HPeV3 infection. Both children were born approximately 1 month premature and were neurologically intact but, after a few weeks, developed seizures and radiologic evidence of white matter lesions. Neuropathologic examination demonstrated classic severe periventricular leukomalacia in the absence of an immune response. Human parechovirus 3 sequences were identified in RNA extracted from CSF, sera, and tissues. Human parechovirus 3 in situ hybridization detection of infected cells was limited to meninges and associated blood vessels in addition to smooth muscle of pulmonary vessels. Ultrastructural evaluation of meninges demonstrated dense core structures compatible with picornavirus virions. These findings suggest that encephalopathic changes are secondary to infection of meninges and potential compromise of vascular perfusion. Thus, parechovirus infection of vascular smooth muscle may be a more general pathogenic process.
authors.affiliation: From the Departments of Pathology (SJB, C-HC, JK, GHM, GW, CAW) and Pediatrics (MP), University of Pittsburgh, Pittsburgh, Pennsylvania; Département de Pathologie, Hôpital Ste-Justine, Université de Montréal, Montréal, Québec, Canada (RA, HS); Polio and Picornavirus Laboratory Branch, Centers for Disease Control and Prevention, Atlanta, Georgia (WAN); and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada (MR).
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Bissel
authors.forename: Roland N
authors.initials: RN
authors.lastname: Auer
authors.forename: Cheng-Hsuan
authors.initials: CH
authors.lastname: Chiang
authors.forename: Julia
authors.initials: J
authors.lastname: Kofler
authors.forename: Geoffrey H
authors.initials: GH
authors.lastname: Murdoch
authors.forename: W Allan
authors.initials: WA
authors.lastname: Nix
authors.forename: Michael
authors.initials: M
authors.lastname: Painter
authors.forename: Maxime
authors.initials: M
authors.lastname: Richer
authors.forename: Hervé
authors.initials: H
authors.lastname: Sartelet
authors.forename: Guoji
authors.initials: G
authors.lastname: Wang
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
mesh_terms: D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007231:Infant, Newborn; D056784:Leukoencephalopathies / Q000473:pathology / Q000821:virology*; D008297:Male; D008587:Meningitis, Viral / Q000473:pathology / Q000821:virology*; D030061:Parechovirus; D010850:Picornaviridae Infections / Q000473:pathology*; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012367:RNA, Viral