Serum 8,12-iso-iPF2α-VI Isoprostane Marker of Oxidative Damage and Cognition Deficits in Children with Konzo

We sought to determine whether motor and cognitive deficits associated with cassava (food) cyanogenic poisoning were associated with high concentrations of F2-isoprostanes, well-established indicators of oxidative damage. Concentrations of serum F2-isoprostanes were quantified by LC-MS/MS and anchored to measures of motor proficiency and cognitive performance, which were respectively assessed through BOT-2 (Bruininks/Oseretsky Test, 2nd Edition) and KABC-II (Kaufman Assessment Battery for Children, 2nd edition) testing of 40 Congolese children (21 with konzo and 19 presumably healthy controls, overall mean age (SD): 9.3 (3.2) years). Exposure to cyanide was ascertained by concentrations of its main metabolite thiocyanate (SCN) in plasma and urine. Overall, SCN concentrations ranged from 91 to 325 and 172 to 1032 µmol/l in plasma and urine, respectively. Serum isoprostanes ranged from 0.1 to 0.8 (Isoprostane-III), 0.8 to 8.3 (total Isoprostane-III), 0.1 to 1.5 (Isoprostane-VI), 2.0 to 9.0 (total Isoprostane-VI), or 0.2 to 1.3 ng/ml (8,12-iso-iPF2α-VI isoprostane). Children with konzo poorly performed at the BOT-2 and KABC-II testing relative to presumably healthy children (p<0.01). Within regression models adjusting for age, gender, motor proficiency, and other biochemical variables, 8,12-iso-iPF2α-VI isoprostane was significantly associated with the overall cognitive performance (β = -32.36 (95% CI: -51.59 to -13.03; P<0.001). This model explained over 85% of variation of the KABC-II score in children with konzo, but was not significant in explaining the motor proficiency impairment. These findings suggest that cognitive deficits and, possibly, brain injury associated with cassava poisoning is mediated in part by oxidative damage in children with konzo. 8,12-iso-iPF2α-VI isoprostane appears to be a good marker of the neuropathogenic mechanisms of konzo and may be used to monitor the impact of interventional trials to prevent the neurotoxic effects of cassava cyanogenic poisoning.