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.