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.
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: Brenda Luna; Sanjiv Bhatia; Changwon Yoo; Quentin Felty; David I Sandberg; Michael Duchowny; Ziad Khatib; Ian Miller; John Ragheb; Jayakar Prasanna; Deodutta Roy Journal: Mol Neurobiol Date: 2014-10-25 Impact factor: 5.590
Authors: Dibyadyuti Datta; Andrea L Conroy; Peter F Castelluccio; John M Ssenkusu; Gregory S Park; Robert O Opoka; Paul Bangirana; Richard Idro; Andrew J Saykin; Chandy C John Journal: Clin Infect Dis Date: 2020-03-03 Impact factor: 9.079
Authors: Henrik Zetterberg; Tobias Skillbäck; Niklas Mattsson; John Q Trojanowski; Erik Portelius; Leslie M Shaw; Michael W Weiner; Kaj Blennow Journal: JAMA Neurol Date: 2016-01 Impact factor: 18.302
Authors: Matthew P Kirschen; Nadir Yehya; Kathryn Graham; Todd Kilbaugh; Robert A Berg; Alexis Topjian; Ramon Diaz-Arrastia Journal: Pediatr Crit Care Med Date: 2020-07 Impact factor: 3.971
Authors: Lina Bergman; Henrik Zetterberg; Helena Kaihola; Henrik Hagberg; Kaj Blennow; Helena Åkerud Journal: PLoS One Date: 2018-05-02 Impact factor: 3.240
Authors: Roos M van der Vuurst de Vries; Yu Yi M Wong; Julia Y Mescheriakova; E Daniëlle van Pelt; Tessel F Runia; Naghmeh Jafari; Theodora Am Siepman; Marie-José Melief; Annet F Wierenga-Wolf; Marvin M van Luijn; Johnny P Samijn; Rinze F Neuteboom; Rogier Q Hintzen Journal: Mult Scler Date: 2018-05-18 Impact factor: 6.312