In:
Brain Communications, Oxford University Press (OUP)
Abstract:
Persistent neurodisability is a known complication in pediatric survivors of cerebral malaria and severe malarial anemia. Tau, ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament-light chain (NF-L), and glial fibrillary acidic protein (GFAP) have proven utility as biomarkers that predict adverse neurologic outcomes in adult and pediatric disorders. In pediatric severe malaria, elevated tau is associated with mortality and neurocognitive complications. We aimed to investigate whether a multi-analyte panel including UCH-L1, NF-L, and GFAP can serve as biomarkers of brain injury associated with mortality and neurodisability in cerebral malaria and severe malarial anemia. In a prospective cohort study of Ugandan children, 18 months-12 years of age with cerebral malaria (n=182), severe malarial anemia (n=158), and asymptomatic community children (n=118), we measured admission blood levels of UCH-L1, NF-L, GFAP. We investigated differences in biomarker levels, associations with mortality, blood-brain barrier integrity, neuro-deficits and cognitive z-scores in survivors up to 24-months follow-up. Admission UCH-L1 levels were elevated & gt;95th percentile of community children in 71% and 51%, and NF-L levels were elevated & gt;95th percentile of community children in 40% and 37% of children with cerebral malaria and severe malarial anemia, respectively. GFAP was not elevated in disease groups compared to controls. In cerebral malaria, elevated NF-L was observed in 16 children who died in-hospital compared to 166 survivors (P=0.01); elevations in UCH-LI levels were associated with degree of blood-brain barrier disruption (P=0.01); and the % predictive value for neuro-deficits over follow-up (discharge, 6-, 12-, 24-months) increased for UCH-L1 (60, 67, 72, 83), but not NF-L (65, 68, 60, 67). In cerebral malaria, elevated UCH-L1 was associated with worse memory scores in children & lt;5 years at malaria episode who crossed to over 5-years old during follow up cognitive testing (β -1.13 [95% CI -2.05, -0.21], P=0.02), and elevated NF-L was associated with worse attention in children ≥5 years at malaria episode and cognitive testing (β -1.08 [95% CI -2.05, -1.05] , P=0.03). In severe malarial anemia, elevated UCH-L1 was associated with worse attention in children & lt;5 years at malaria episode and cognitive testing (β -0.42 [95% CI -0.76, -0.07], P=0.02). UCH-L1 and NF-L levels are elevated in pediatric cerebral malaria and severe malarial anemia. In cerebral malaria, elevated NF-L is associated with mortality whereas elevated UCH-L1 is associated with blood-brain barrier dysfunction and neuro-deficits over follow-up. In cerebral malaria, both markers are associated with worse cognition, while in severe malarial anemia, only UCH-L1 is associated with worse cognition.
Type of Medium:
Online Resource
ISSN:
2632-1297
DOI:
10.1093/braincomms/fcad323
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2023
detail.hit.zdb_id:
3020013-1
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