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dc.contributor.authorLimbrick, David D.en_US
dc.contributor.authorBaksh, Brandonen_US
dc.contributor.authorMorgan, Clinton D.en_US
dc.contributor.authorHabiyaremye, Gakwayaen_US
dc.contributor.authorMcAllister, James P.en_US
dc.contributor.authorInder, Terrie E.en_US
dc.contributor.authorMercer, Deannaen_US
dc.contributor.authorHoltzman, David M.en_US
dc.contributor.authorStrahle, Jenniferen_US
dc.contributor.authorWallendorf, Michael J.en_US
dc.contributor.authorMorales, Diego M.en_US
dc.date.accessioned2017-04-06T03:18:32Z
dc.date.issued2017en_US
dc.identifier.citationLimbrick, D. D., B. Baksh, C. D. Morgan, G. Habiyaremye, J. P. McAllister, T. E. Inder, D. Mercer, et al. 2017. “Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus.” PLoS ONE 12 (2): e0172353. doi:10.1371/journal.pone.0172353. http://dx.doi.org/10.1371/journal.pone.0172353.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32071947
dc.description.abstractIntroduction: Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value. Methods: CSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPPα, sAPPβ, Aβ42), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC. Results: CSF levels of APP, sAPPα, sAPPβ, Aβ42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age (p<0.0001 and AUC = 0.99), followed by normalized sAPPβ (p = 0.0001, AUC = 0.95), tau, APP, and L1CAM. Among subjects ≤12 months, a normalized CSF sAPPα cut-point of 0.41 provided the best prediction of CHC (odds ratio = 528, sensitivity = 0.94, specificity = 0.97); these infants were 32 times more likely to have CHC. Conclusions: CSF proteins such as sAPPα and related proteins hold promise as biomarkers of CHC in infants and young children, and provide insight into the pathophysiology of CHC during this critical period in neurodevelopment.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0172353en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315300/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectAnatomyen
dc.subjectBody Fluidsen
dc.subjectCerebrospinal Fluiden
dc.subjectMedicine and Health Sciencesen
dc.subjectPhysiologyen
dc.subjectNervous Systemen
dc.subjectNeurologyen
dc.subjectHydrocephalusen
dc.subjectBiochemistryen
dc.subjectBiomarkersen
dc.subjectDiagnostic Medicineen
dc.subjectSigns and Symptomsen
dc.subjectStenosisen
dc.subjectPathology and Laboratory Medicineen
dc.subjectCongenital Disordersen
dc.subjectCentral Nervous Systemen
dc.subjectPeople and Placesen
dc.subjectPopulation Groupingsen
dc.subjectAge Groupsen
dc.subjectChildrenen
dc.subjectInfantsen
dc.subjectFamiliesen
dc.titleCerebrospinal fluid biomarkers of infantile congenital hydrocephalusen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorInder, Terrie E.en_US
dc.date.available2017-04-06T03:18:32Z
dc.identifier.doi10.1371/journal.pone.0172353*
dash.authorsorderedfalse
dash.contributor.affiliatedInder, Terrie


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