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: Pashtun Shahim, Niklas Darin, Ulf Andreasson, Kaj Blennow, Elizabeth Jennions, Johan Lundgren, Jan-Eric Månsson, Karin Naess, Carl-Johan Törnhage, Henrik Zetterberg, Niklas Mattsson
• Journal: Pediatric neurology (Pediatr Neurol) Vol. 49 Issue 1 Pg. 31-39.e2 (Jul 2013) ISSN: 1873-5150 [Electronic] United States
• PMID: 23827424 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Adolescent
• Biomarkers (cerebrospinal fluid)
• Brain Injuries (cerebrospinal fluid, diagnosis, 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)