Neurobehavioral comorbidities of pediatric epilepsies are linked to thalamic structural abnormalities

Abstract

Purpose: Neurobehavioral comorbidities are common in pediatric epilepsy with enduring adverse effects on functioning, but their neuroanatomic underpinning is unclear. Striatal and thalamic abnormalities have been associated with childhood-onset epilepsies, suggesting that epilepsy-related changes in the subcortical circuit might be associated with the comorbidities of children with epilepsy. We aimed to compare subcortical volumes and their relationship with age in children with complex partial seizures (CPS), childhood absence epilepsy (CAE), and healthy controls (HC). We examined the shared versus unique structural-functional relationships of these volumes with behavior problems, intelligence, language, peer interaction, and epilepsy variables in these two epilepsy syndromes.

Methods: We investigated volumetric differences of caudate, putamen, pallidum, and thalamus in children with CPS (N = 21), CAE (N = 20), and HC (N = 27). Study subjects underwent structural magnetic resonance imaging (MRI), intelligence, and language testing. Parent-completed Child Behavior Checklists provided behavior problem and peer interaction scores. We examined the association of age, intelligence quotient (IQ), language, behavioral problems, and epilepsy variables with subcortical volumes that were significantly different between the children with epilepsy and HC.

Key findings: Both children with CPS and CAE exhibited significantly smaller left thalamic volume compared to HC. In terms of developmental trajectory, greater thalamic volume was significantly correlated with increasing age in children with CPS and CAE but not in HC. With regard to the comorbidities, reduced left thalamic volumes were related to more social problems in children with CPS and CAE. Smaller left thalamic volumes in children with CPS were also associated with poor attention, lower IQ and language scores, and impaired peer interaction.

Significance: Our study is the first to directly compare and detect shared thalamic structural abnormalities in children with CPS and CAE. These findings highlight the vulnerability of the thalamus and provide important new insights on its possible role in the neurobehavioral comorbidities of childhood-onset epilepsy.

Keywords: Childhood absence epilepsy; Comorbidities; Complex partial seizures; Thalamus.

Figure 1

Subcortical structural volumetric differences among children with complex partial seizures (CPS, red bar), childhood absence epilepsy (CAE, green bar), and healthy controls (blue bar). CPS and CAE group demonstrated significantly reduced thalamic volumes compared to controls. There were no significant volumetric differences in the caudate, putamen, and pallidum. Volumes are expressed in mm³, with error bars representing standard deviations. * denote p ≤ 0.05, controls vs. CPS and controls vs. CAE

Figure 2

Plot of left thalamus volumes versus age for controls, CPS, and CAE. The lines shown were the best fit lines determined by a loess (local regression) procedure.