Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated with coma duration and long-term neurocognitive impairment in Ugandan children with cerebral malaria.

Malar J
Authors
Keywords
Abstract

BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated.

METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were compared to CSF cytokine levels, acute and long-term neurologic complications, and long-term cognitive impairments. CSF kynurenine and KYNA from eight Swedish children without neurological or infectious disease admitted to Astrid Lindgren's Children's Hospital were quantified and used for comparison.

RESULTS: Children with CM had significantly higher CSF concentration of kynurenine and KYNA than Swedish children (P 

CONCLUSIONS: CSF KYNA and kynurenine are elevated in children with CM, indicating an inhibition of glutamatergic and cholinergic signaling. This inhibition may lead acutely to prolonged coma and long-term to impairment of attention and cognition.

Year of Publication
2017
Journal
Malar J
Volume
16
Issue
1
Pages
303
Date Published
2017 07 28
ISSN
1475-2875
DOI
10.1186/s12936-017-1954-1
PubMed ID
28754152
PubMed Central ID
PMC5534063
Links
Grant list
D43 NS078280 / NS / NINDS NIH HHS / United States
R01 NS055349 / NS / NINDS NIH HHS / United States