title: Cerebrospinal fluid brain injury biomarkers in children: a multicenter study.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) biomarkers reflecting neuronal and astroglial injury, such as total tau (T-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NFL), have been extensively investigated in neurologic diseases in adults, but no large study has investigated these biomarkers in children.
  
  
  METHODS
  This study presents a detailed evaluation of CFS T-tau, GFAP, NFL, and CSF:albumin ratio in a large cohort of pediatric patients. This is a retrospective multicenter study on pediatric patients aged <16 years (n = 607), where neuronal injury biomarkers T-tau, GFAP, NFL, and CSF albumin ratio were analyzed during 2000-2010 at the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Sweden. The patients were grouped into eight categories: epilepsy, infectious and inflammatory central nervous system disorders, progressive encephalopathy, static encephalopathy, tumors, movement disorders, miscellaneous disorders, and a control group.
  
  
  RESULTS
  T-tau, GFAP, and NFL were increased in progressive encephalopathy (P < 0.001), epilepsy (P < 0.001), and infectious and inflammatory central nervous system disorders (P < 0.001) compared with controls. T-tau was the biomarker with the highest diagnostic accuracy with the area under the curve of 0.83 (95% confidence interval (CI), 0.77-0.90; P < 0.0001) for progressive encephalopathy followed by epilepsy 0.80 (95% CI, 0.75-0.87; P < 0.0001). The combination of all four biomarkers further improved the area under the curve for the progressive encephalopathy 0.87 (95% CI, 0.77-0.89; P < 0.0001), followed by epilepsy 0.81 (95% CI, 0.74-0.80; P = 0.030). The combination of the biomarkers also separated progressive from static encephalopathy 0.88 (95% CI, 0.83-0.93; P < 0.0001).
  
  
  CONCLUSIONS
  CSF T-tau, GFAP, and NFL are differently altered across different neurologic diseases in children. Importantly, the biomarker pattern distinguishes between progressive and static neurologic disorders.
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Neurochemistry, Sahlgrenska University Hospital/Mölndal, Sweden. pashtun.shahim@neuro.gu.se
authors.forename: Pashtun
authors.initials: P
authors.lastname: Shahim
authors.forename: Niklas
authors.initials: N
authors.lastname: Darin
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jennions
authors.forename: Johan
authors.initials: J
authors.lastname: Lundgren
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Månsson
authors.forename: Karin
authors.initials: K
authors.lastname: Naess
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Törnhage
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid*; D006801:Humans; D007223:Infant; D008297:Male; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D012189:Retrospective Studies; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; C054369:MAPT protein, human; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D016875:tau Proteins