title: Increased cerebrospinal fluid cleaved tau protein (C-tau) levels suggest axonal damage in pediatric patients with brain tumors.
abstract: OBJECTIVE
  This study aims to determine if cerebrospinal fluid/serum cleaved tau protein and CSF 9-hydroxyoctadecadienoic acid levels, reflecting potential biomarkers of overall neuronal injury and lipid peroxidation, respectively, are elevated in brain tumor patients compared with controls.
  
  
  METHODS
  This article is a prospective clinical observational study.
  
  
  METHODS
  This study is conducted at a tertiary-care children's hospital.
  
  
  METHODS
  Our participants are children younger than or equal to 18 years of age undergoing brain tumor surgery.
  
  
  RESULTS
  During the study period, 26 consecutive patients newly diagnosed with brain tumors who met the inclusion criteria were prospectively enrolled. Baseline cerebrospinal fluid analysis of cleaved tau and 9-hydroxyoctadecadienoic acid were measured in 15 patients. Cerebrospinal fluid cleaved tau and 9-hydroxyoctadecadienoic acid levels were measured in 22 patients for post-surgery days 1 and 3. Serum cleaved tau levels were measured for 20 and 18 patients for post-surgery days 1 and 3, respectively. The presence of a brain tumor significantly increased the baseline cerebrospinal fluid cleaved tau levels but did not affect cerebrospinal fluid 9-hydroxyoctadecadienoic acid levels. Similarly, there was a significant increase in post-surgery day 1 cerebrospinal fluid cleaved tau levels from baseline (p = 0.01) and a trend toward significant decrease in post-surgery day 3 cerebrospinal fluid cleaved tau from day 1 (p = 0.07). 9-Hydroxyoctadecadienoic acid concentrations remained relatively constant over time with no differences noted between the control and brain tumor patients. There was a trend towards a significant association between cerebrospinal fluid cleaved tau levels and duration of symptoms (p = 0.07).
  
  
  CONCLUSIONS
  Cerebrospinal fluid cleaved tau levels in children with newly diagnosed brain tumors exhibit markedly elevated cerebrospinal fluid cleaved tau levels, suggesting axonal damage. This axonal injury does not seem to correlate with lipid peroxidation at least when as assessed by cerebrospinal fluid 9-hydroxyoctadecadienoic acid levels. There was no association found between the biomarkers and multiple independent variables obtained at pre- and post-tumor resection.
authors.affiliation: Department of Pediatrics, Pediatric Critical Care Medicine, American Family Children's Hospital, University of Wisconsin, Madison, WI, USA, cengiz@wisc.edu.
authors.forename: Pelin
authors.initials: P
authors.lastname: Cengiz
authors.forename: Frank
authors.initials: F
authors.lastname: Zemlan
authors.forename: Jens C
authors.initials: JC
authors.lastname: Eickhoff
authors.forename: Richard
authors.initials: R
authors.lastname: Ellenbogen
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Zimmerman
mesh_terms: D000293:Adolescent; D001369:Axons / Q000473:pathology*; D001932:Brain Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D044243:Linoleic Acids, Conjugated / Q000134:cerebrospinal fluid; D008297:Male; D011446:Prospective Studies; D012189:Retrospective Studies; D013997:Time Factors; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid*
chemical_list: D044243:Linoleic Acids, Conjugated; D016875:tau Proteins; C024347:9-hydroxy-10,12-octadecadienoic acid