title: Inflammatory markers in pediatric stroke: An attempt to better understanding the pathophysiology.
abstract: BACKGROUND
  The mechanisms of childhood and perinatal arterial ischemic stroke (AIS) are poorly understood. Multiple risk factors include cerebral arteriopathy, congenital cardiac disease, infection, sickle cell disease, and maternal-fetal conditions in neonates. For infections and parainfectious conditions being the most important a possible inflammatory pathophysiology has long been suspected. This pilot study aims to detect, whether there are any abnormalities of inflammatory markers associated with childhood and neonatal stroke.
  
  
  METHODS
  The concentration of 23 different metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), endothelial factors, vascular cell adhesion proteins, and cytokines in plasma were measured in 12 children with AIS, 7 healthy age matched controls and 6 full term neonates with perinatal AIS.
  
  
  RESULTS
  At the time of the acute event children with AIS had significantly elevated levels of MMP-9, TIMP4, IL-6, IL-8 and CRP compared to controls (p < 0.05). Except for lower IL-6 and CRP levels the pattern of children with a history of varizella-zoster virus (VZV) and other viral infections did not differ to the non-infectious group. Median levels of MMP-1, MMP-2, TIMP-1, TIMP-2, sE-selectin, sICAM-1, sVCAM-1, IL-8, IL-10, TNF-alpha, VEGF, Fetuin A were found to be higher in the neonatal group when compared with older children.
  
  
  CONCLUSIONS
  This pilot study supports the assumption of an inflammatory process and up-regulation of metalloproteinases and their inhibitors, and altered pattern of circulating pro-inflammatory cytokines, CRP and vWF levels in pediatric and neonatal AIS. It highlights the feasibility but also difficulties for similar larger future studies that should aim to clarify childhood stroke etiopathogenesis and consecutive further therapeutic options.
authors.affiliation: Division of Neurology, Department of Pediatrics, Children's Hospital and University of British Columbia, Canada; Department of Neuropediatrics, Development and Rehabilitation, University Children's Hospital, Inselspital, Berne, Switzerland. Electronic address: sarah.buerki@cw.bc.ca.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Buerki
authors.affiliation: Institute for Infectious Diseases, University of Bern, Neuroinfectiology Laboratory, Institute for Infectious Diseases, Postfach 8571, CH-3001 Bern, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Grandgirard
authors.affiliation: University Children's Hospital Basel, Universitäts-Kinderspital beider Basel, Spitalstrasse 33, CH-4056 Basel, Switzerland.
authors.forename: Alexandre N
authors.initials: AN
authors.lastname: Datta
authors.affiliation: University Children's Hospital Zürich, Kinderspital Zürich, University Children's Hospital Zürich, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland.
authors.forename: Annette
authors.initials: A
authors.lastname: Hackenberg
authors.affiliation: Children's Hospital Winterthur, Kantonsspital Winterthur, Brauerstrasse 15, Postfach 834, CH-8401 Winterthur, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Martin
authors.affiliation: Children's Hospital Lucerne, Luzerner Kantonsspital, Kinderspital Luzern, CH-6000 Luzern 16, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitt-Mechelke
authors.affiliation: Institute for Infectious Diseases, University of Bern, Neuroinfectiology Laboratory, Institute for Infectious Diseases, Postfach 8571, CH-3001 Bern, Switzerland; Biology Division, Spiez Laboratory, Swiss Federal Office for Civil Protection, Spiez, Switzerland.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Leib
authors.affiliation: Department of Neuropediatrics, Development and Rehabilitation, University Children's Hospital, Inselspital, Berne, Switzerland.
authors.forename: Maja
authors.initials: M
authors.lastname: Steinlin
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000150:complications; D008297:Male; D010865:Pilot Projects; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers
keywords: Arterial ischemic stroke; Biomarker; Inflammation; Metalloproteinases; Pediatrics