Cerebrospinal fluid brain injury biomarkers in children: a multicenter study

Pediatr Neurol. 2013 Jul;49(1):31-39.e2. doi: 10.1016/j.pediatrneurol.2013.02.015.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / cerebrospinal fluid
  • Brain Injuries / cerebrospinal fluid*
  • Brain Injuries / diagnosis*
  • Brain Injuries / epidemiology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Glial Fibrillary Acidic Protein / cerebrospinal fluid*
  • Humans
  • Infant
  • Male
  • Neurofilament Proteins / cerebrospinal fluid*
  • Retrospective Studies
  • tau Proteins / cerebrospinal fluid*

Substances

  • Biomarkers
  • Glial Fibrillary Acidic Protein
  • MAPT protein, human
  • Neurofilament Proteins
  • neurofilament protein L
  • tau Proteins