Neurologic sequelae of cerebral malaria and other forms of severe malaria in children

Background: Neurologic sequelae occur after cerebral malaria (CM) but are less well described after non-cerebral severe malaria (NCSM). Methods: In a prospective cohort study, we determined the presence, type and outcomes of neurologic sequelae (persistent neurologic deficits and/or development of epilepsy over 12-month follow-up) in Ugandan children admitted with CM (n = 54) or NCSM (severe malarial anemia, respiratory distress, malaria with multiple seizures, or prostration, n = 495). Results: At hospital discharge, neurologic deficits were more frequent in children with CM (21/54 [38.9%]) than children with NCSM (45/495 [9.1%], P < 0.001). At 12-month follow-up, persistent neurologic deficits did not differ significantly between children with CM or NCSM (1/47 (2.1%) vs. 2/449 (0.4%), OR [95% CI], 5.8 [0.8, 44.7]). However, development of epilepsy, and consequently presence of neurologic sequelae, at 12-month follow-up were more frequent in children with CM than NCSM (3/47 (6.4%) vs. 3/449 (0.7%), OR [95% CI] 10.0 [2.2, 45.6], and 3/47 (6.4%) vs. 5/449 (1.1%), OR [95% CI] 6.4 [1.6, 25.1], respectively). Seven children with no neurologic deficits at discharge had new deficits at 12 months. Conclusion: Neurologic sequelae, particularly epilepsy, are more common in CM than other forms of severe malaria, but occur rarely in non-cerebral severe malaria. Impact: Long-term neurologic sequelae in children after forms of severe malaria other than cerebral malaria (e.g., severe malarial anemia, respiratory distress, malaria with multiple seizures, and prostration) are not well-characterized. In the present study, long-term neurologic sequelae (persistent neurological deficits and/or development of epilepsy after discharge over 12- month follow-up) were more common in children with cerebral malaria (6%) than in children with non-cerebral severe malaria (1%). Epilepsy was the primary driver of the differences between groups (cerebral malaria, 6%, non-cerebral severe malaria 0.7%). Long-term neurologic sequelae are rare in children with non-cerebral severe malaria.