Cerebrospinal fluid studies in children with cerebral malaria: An excitotoxic mechanism?

The pathogenesis of cerebral malaria is poorly understood. One hypothesis i s that activation of microglia and astrocytes in the brain might cause the cerebral symptoms by excitotoxic mechanisms. Cerebrospinal fluid was sample d in 97 Kenyan children with cerebral malaria, 85% within 48 hr of admissio n. When compared with an age-matched reference range, there were large incr eases in concentrations of the excitotoxin quinolinic acid (geometric mean ratio cerebral malaria/reference population [95% confidence limits] = 14.1 [9.8-20.4], P < 0.001) and total neopterin (10.9 [9.1-13.0], P < 0.001) and lesser increases in tetra-hydrobiopterin, di-hydrobiopterin, and 5-hydroxy indoleacetic acid. There was no change in tryptophan concentration. In cont rast, nitrate plus nitrite concentrations were decreased (geometric mean ra tio = 0.45 [0.35-0.59], P < 0.001). There was a graded increment in quinoli nic acid concentration across outcome groups of increasing severity. The in creased concentration of quinolinic acid suggests that excitotoxic mechanis ms may contribute to the pathogenesis of cerebral malaria.