Admission Clinical and EEG Features Associated With Mortality and Long-term Neurologic and Cognitive Outcomes in Pediatric Cerebral Malaria

Background For children with cerebral malaria, mortality is high, and, in survivors, long-term neurologic and cognitive dysfunction are common. While specific clinical factors are associated with death or long-term neurocognitive morbidity in cerebral malaria, the association of EEG features with these outcomes, particularly neurocognitive outcomes, is less well characterized.

Methods In this prospective cohort study of 149 children 6 months to 12 years of age who survived cerebral malaria in Kampala, Uganda, we evaluated whether depth of coma, number of clinical seizures, or EEG features during hospitalization were associated with mortality during hospitalization, short and long-term neurologic deficits, or long-term cognitive outcomes (overall cognition, attention, memory) over 2-year follow-up.

Results Higher Blantyre or Glasgow coma scores (BCS and GCS, respectively), higher background voltage, and presence of normal reactivity on EEG were each associated with lower mortality. Among clinical and EEG features, the presence of >4 seizures on admission had the best combination of negative and positive predictive values for neurologic deficits in follow-up. In multivariable modeling of cognitive outcomes, number of seizures and specific EEG features showed independent association with better outcomes. In children <5 years throughout the study, seizure number and presence of vertex sharp waves were independently associated with better post-hospitalization cognitive performance; faster dominant frequency with better attention; and higher average background voltage and faster dominant background frequency with better associative memory. In children <5 years at CM episode but ≥5 years at cognitive testing, seizure number, background dominant frequency, and the presence of vertex sharp waves were each associated with changes in cognition; seizure number and variability with attention; and seizure number with working memory.

Conclusions In children with cerebral malaria, seizure number is strongly associated with risk of long-term neurologic deficits, while seizure number and specific EEG features (average background voltage, dominant rhythm frequency, presence of vertex sharp waves, presence of variability) are independently associated with cognitive outcomes. Future studies should evaluate the predictive value of these findings.