Cerebral Malaria Retinopathy Predictors of Persisting Neurocognitive Outcomes in Malawian Children

Abstract

Neuropsychological sequelae from pediatric cerebral malaria (CM) have been well-documented. Although malaria-specific retinopathy during acute illness has become a defining criterion for CM, its relationship to neurocognitive sequelae has not been documented. This relationship is important if malaria-specific retinopathy reflects the possible brain neuropathogenesis leading to long-term neurocognitive deficits. From 2008 to 2012, 49 Malawian children 4.5-12 years of age surviving retinopathy-positive CM (CM-R) were tested 1-6 yrs after illness with the Kaufman Assessment Battery for Children, 2 edition, the tests of variables of attention and the Achenbach Child Behavior Checklist. In an observational study of a cohort of cerebral malaria survivors, these neurocognitive and behavioral outcomes were statistically related to types and severity of retinopathy measures, while controlling for age, sex, body mass index, socioeconomic status and time interval between illness and testing. Worse scores for hemorrhages, papilledema, optic disk hyperemia, retinal whitening of macula and foveal annulus were associated with poorer Kaufman Assessment Battery for Children, 2 edition mental processing index and global scale scores. Disk hyperemia was also predictive of tests of variables of attention D prime overall attention performance (inattention) and commission errors (impulsivity). Few associations were found between retinopathy scores and Achenbach Child Behavior Checklist (emotional and behavioral) outcomes. We are the first to report the relationship between severity of malaria-specific retinopathy during acute illness in CM survivors and persisting neurocognitive problems. These findings support earlier studies documenting that severity of retinopathy during acute illness is medically prognostic in CM survivors. We extend these findings to include long-term neurocognitive outcomes.