Long-term characterization of behavior phenotypes in children with seizures: Analytic approach matters

Behavioral problems in children with new onset epilepsies have been well established in the literature. More recently, the literature indicates the presence of unique behavioral patterns or phenotypes in youth with epilepsy that vary significantly in vulnerability and resilience to behavioral problems. This study contrasts the interpretation of behavioral risk as inferred from cross-sectional versus latent group analytic perspectives, as well as the presence, consistency, stability, and progression of behavioral phenotypes in youth with new onset epilepsy and sibling controls over 3 years.

Three hundred twelve participants (6-16 years old) were recruited within 6 weeks of their first recognized seizure along with 223 unaffected siblings. Each child's behavior was recorded by parents and teachers frequently over 36 months using the Child Behavior Checklist (CBCL), and each child completed self-report measures of depression symptoms over 36 months. Measures were evaluated cross-sectionally and longitudinally to identify clusters with prototypical behavioral trajectories.

Cross-sectional analyses exhibited a pattern of generalized and undifferentiated behavioral problems compared to sibling controls at baseline and prospectively. In contrast, latent trajectory modeling identified three distinct behavior phenotype clusters across all raters (parents, teachers, and youth) over baseline and longitudinal assessments. CBCL Cluster 1 (~30% of youth with epilepsy) exhibited behavior similar to/better than controls, Cluster 2 (~50%) exhibited moderate behavior issues, and Cluster 3 (~20%) exhibited the most pronounced/problematic behavior, falling into Achenbach's clinically relevant behavior range. Behavior within clusters remained stable and consistent. Teachers' and children's behavior assessments corresponded to these cluster groupings consistently over 36 months. Predictors of cluster membership include seizure syndrome type and social determinants of health.

This study demonstrates the varying public health perspectives of behavioral risk in youth with epilepsy that result as a function of analytic approach as well as the presence of distinct latent behavioral trajectory phenotypes over time in youth with new onset epilepsy.