Background: 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.
Methods: 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, 2nd 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.
Results: Worse scores for hemorrhages, papilledema, optic disk hyperemia, retinal whitening of macula and foveal annulus were associated with poorer Kaufman Assessment Battery for Children, 2nd 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.
Conclusions: 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.
From the *Departments of Psychiatry and Neurology/Ophthalmology, Michigan State University, East Lansing, MI; †Department of Psychiatry, University of Michigan, Ann Arbor, MI; ‡Blantyre Malaria Project, Blantyre, Malawi; §Africa Mental Health Foundation, Mombasa, Kenya; ¶Department of Statistics and Probability; ‖Department of Psychiatry, Michigan State University, East Lansing, MI; and **St Paul’s Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom
Accepted for publication January 24, 2014.
This study was funded by the Michigan State University Department of Psychiatry (J.G.M.), Department of Neurology and Ophthalmology faculty funding (M.J.B.) and Office of the Vice President of Research and Graduate Studies award 07-IRGP-1060 (M.J.B.). Funding support in the recruitment and clinical characterization of the study populations was provided by NIH R01AI34969. The funding sources has no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript and decision to submit the manuscript for publication.
The authors have no other funding or conflicts of interest to disclose.
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Address for correspondence: Michael J. Boivin, PhD, Department of Psychiatry, 965 Fee Road, Room A227 East Fee Hall, Michigan State University, East Lansing, MI 48824. E-mail: firstname.lastname@example.org.