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Cerebrospinal Fluid Brain Injury Biomarkers in Children: A Multicenter Study

Shahim, Pashtun; Darin, Niklas; Andreasson, Ulf; Blennow, Kaj; Jennions, Elizabeth; Lundgren, Johan LU ; Mansson, Jan-Eric; Naess, Karin; Tornhage, Carl-Johan and Zetterberg, Henrik, et al. (2013) In Pediatric Neurology 49(1). p.31-39
Abstract
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers reflecting neuronal and astroglial injury, such as total tau (T-tau), glial flbrillary 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... (More)
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers reflecting neuronal and astroglial injury, such as total tau (T-tau), glial flbrillary 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. (c) 2013 Elsevier Inc. All rights reserved. (Less)
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published
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Pediatric Neurology
volume
49
issue
1
pages
31 - 39
publisher
Elsevier
external identifiers
  • wos:000321808700007
  • scopus:84880077757
ISSN
0887-8994
DOI
10.1016/j.pediatrneurol.2013.02.015
language
English
LU publication?
yes
id
00ecf783-b89e-429f-a16e-dafe7fe7b971 (old id 3976052)
date added to LUP
2013-09-02 07:34:25
date last changed
2019-03-05 01:23:11
@article{00ecf783-b89e-429f-a16e-dafe7fe7b971,
  abstract     = {BACKGROUND: Cerebrospinal fluid (CSF) biomarkers reflecting neuronal and astroglial injury, such as total tau (T-tau), glial flbrillary 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 &lt;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 &lt; 0.001), epilepsy (P &lt; 0.001), and infectious and inflammatory central nervous system disorders (P &lt; 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 &lt; 0.0001) for progressive encephalopathy followed by epilepsy 0.80 (95% CI, 0.75-0.87; P &lt; 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 &lt; 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 &lt; 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. (c) 2013 Elsevier Inc. All rights reserved.},
  author       = {Shahim, Pashtun and Darin, Niklas and Andreasson, Ulf and Blennow, Kaj and Jennions, Elizabeth and Lundgren, Johan and Mansson, Jan-Eric and Naess, Karin and Tornhage, Carl-Johan and Zetterberg, Henrik and Mattsson, Nildas},
  issn         = {0887-8994},
  language     = {eng},
  number       = {1},
  pages        = {31--39},
  publisher    = {Elsevier},
  series       = {Pediatric Neurology},
  title        = {Cerebrospinal Fluid Brain Injury Biomarkers in Children: A Multicenter Study},
  url          = {http://dx.doi.org/10.1016/j.pediatrneurol.2013.02.015},
  volume       = {49},
  year         = {2013},
}