Longitudinal evolution of electroencephalogram (EEG): Findings over five years of follow-up in children with Zika-related microcephaly from the Microcephaly Epidemic Research Group Pediatric Cohort (2015-2020)

Objective: To assess the longitudinal evolution of EEG findings in children with Zika related-microcephaly (ZRM) and to evaluate the associations of these patterns with the children's clinical and neuroimaging characteristics.Methods: As part of the follow-up of the Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC) in Recife, Brazil, we performed serial EEG recordings in a subgroup of children with ZRM to evaluate changes in background rhythms and epileptiform activity (EA). Latent class analysis was used to identify patterns in the evolution of EA over time; clinical and neuroimaging findings were compared across the identified groups.Results: Out of the 72 children with ZRM who were evaluated during 190 EEGs/videoEEGs, all participants presented with abnormal background activity, 37.5% presented with an alpha-theta rhythmic activity, and 25% presented with sleep spindles, which were less commonly observed in children with epilepsy. EA changed over time in 79.2% of children, and three distinct trajectories were identified: (i) multifocal EA over time, (ii) no discharges/focal EA evolving to focal/multifocal EA, and (iii) focal/multifocal EA evolving to epileptic en-cephalopathy patterns (e.g., hypsarrhythmia or continuous EA in sleep). The multifocal EA over time trajectory was associated with periventricular and thalamus/basal ganglia calcifications, brainstem and corpus callosum atrophy and had less focal epilepsy, whereas the children in the trajectory which evolved to epileptic enceph-alopathy patterns had more frequently focal epilepsy.Significance: These findings suggest that, in most children with ZRM, trajectories of changes in EA can be identified and associated with neuroimaging and clinical features.