Elevated Cerebrospinal Fluid Tau Protein Concentrations on Admission Are Associated With Long-term Neurologic and Cognitive Impairment in Ugandan Children With Cerebral Malaria

Author:

Datta Dibyadyuti1ORCID,Conroy Andrea L1,Castelluccio Peter F2,Ssenkusu John M3,Park Gregory S4,Opoka Robert O5,Bangirana Paul6,Idro Richard5,Saykin Andrew J7,John Chandy C14

Affiliation:

1. Department of Pediatrics, Ryan White Center for Pediatric Infectious Disease and Global Health, Indianapolis

2. Department of Biostatistics, Indiana University School of Medicine, Indianapolis

3. Department of Epidemiology and Biostatistics, Makerere University, Kampala, Uganda

4. University of Minnesota Medical School, Minneapolis

5. Departments of Paediatrics and Child Health, Kampala, Uganda

6. Departments of Psychiatry, Makerere University, Kampala, Uganda

7. Indiana Alzheimer Disease Center and Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis

Abstract

Abstract Background Elevated concentrations of cerebrospinal fluid (CSF) tau, a marker of axonal injury, have been associated with coma in severe malaria (cerebral malaria [CM]). However, it is unknown whether axonal injury is related to long-term neurologic deficits and cognitive impairment in children with CM. Methods Admission CSF tau concentrations were measured in 145 Ugandan children with CM and compared to clinical and laboratory factors and acute and chronic neurologic and cognitive outcomes. Results Elevated CSF tau concentrations were associated with younger age, increased disease severity (lower glucose and hemoglobin concentrations, malaria retinopathy, acute kidney injury, and prolonged coma duration, all P < .05), and an increased CSF:plasma albumin ratio, a marker of blood–brain barrier breakdown (P < .001). Admission CSF tau concentrations were associated with the presence of neurologic deficits at hospital discharge, and at 6, 12, and 24 months postdischarge (all P ≤ .02). After adjustment for potential confounding factors, elevated log10-transformed CSF tau concentrations correlated with worse cognitive outcome z scores over 2-year follow-up for associative memory (β coefficient, –0.31 [95% confidence interval [CI], –.53 to –.10]) in children <5 years of age, and for overall cognition (–0.69 [95% CI, –1.19 to –.21]), attention (–0.78 [95% CI, –1.34 to –.23]), and working memory (–1.0 [95% CI, –1.68 to –.31]) in children ≥5 years of age (all P < .006). Conclusions Acute axonal injury in children with CM is associated with long-term neurologic deficits and cognitive impairment. CSF tau concentrations at the time of the CM episode may identify children at high risk of long-term neurocognitive impairment.

Funder

National Institutes of Health

National Institute of Neurological Disorders and Stroke

Fogarty International Center

Indiana Alzheimer Disease Center

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

Reference39 articles.

1. Severe malaria;World Health Organization;Trop Med Int Health,2014

2. The clinical features of cerebral malaria in children;Molyneux;Med Trop (Mars),1990

3. Pathogenesis, clinical features, and neurological outcome of cerebral malaria;Idro;Lancet Neurol,2005

4. A protein factor essential for microtubule assembly;Weingarten;Proc Natl Acad Sci U S A,1975

5. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders;Buée;Brain Res Brain Res Rev,2000

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