Children with Rolandic epilepsy have micro- and macrostructural abnormalities in white matter constituting networks...

Self-limited epilepsy with centrotemporal spikes is a transient developmental epilepsy with a seizure onset zone localized to the centrotemporal cortex that commonly impacts aspects of language function. To better understand the relationship between these anatomical findings and symptoms, we characterized the language profile and white matter microstructural and macrostructural features in a cohort of children with SeLECTS.

Children with active SeLECTS (n = 13), resolved SeLECTS (n = 12), and controls (n = 17) underwent high-resolution MRIs including diffusion tensor imaging sequences and multiple standardized neuropsychological measures of language function. We identified the superficial white matter abutting the inferior rolandic cortex and superior temporal gyrus using a cortical parcellation atlas and derived the arcuate fasciculus connecting them using probabilistic tractography. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region, and tested for linear relationships between diffusivity metrics in these regions and language scores on neuropsychological testing.

We found significant differences in several language modalities in children with SeLECTS compared to controls. Children with SeLECTS performed worse on assessments of phonological awareness (p = 0.045) and verbal comprehension (p = 0.050). Reduced performance was more pronounced in children with active SeLECTS compared to controls, namely, phonological awareness (p = 0.028), verbal comprehension (p = 0.028), and verbal category fluency (p = 0.031), with trends toward worse performance also observed in verbal letter fluency (p = 0.052), and the expressive one-word picture vocabulary test (p = 0.068). Children with active SeLECTS perform worse than children with SeLECTS in remission on tests of verbal category fluency (p = 0.009), verbal letter fluency (p = 0.006), and the expressive one-word picture vocabulary test (p = 0.045). We also found abnormal superficial white matter microstructure in centrotemporal ROIs in children with SeLECTS, characterized by increased diffusivity and fractional anisotropy compared to controls (AD p = 0.014, RD p = 0.028, MD p = 0.020, and FA p = 0.024). Structural connectivity of the arcuate fasciculus connecting perisylvian cortical regions was lower in children with SeLECTS (p = 0.045), and in the arcuate fasciculus children with SeLECTS had increased diffusivity (AD p = 0.007, RD p = 0.006, MD p = 0.016), with no difference in fractional anisotropy (p = 0.22). However, linear tests comparing white matter microstructure in areas constituting language networks and language performance did not withstand correction for multiple comparisons in this sample, although a trend was seen between FA in the arcuate fasciculus and verbal category fluency (p = 0.047) and the expressive one-word picture vocabulary test (p = 0.036).

We found impaired language development in children with SeLECTS, particularly in those with active SeLECTS, as well as abnormalities in the superficial centrotemporal white matter as well as the fibers connecting these regions, the arcuate fasciculus. Although relationships between language performance and white matter abnormalities did not pass correction for multiple comparisons, taken together, these results provide evidence of atypical white matter maturation in fibers involved in language processing, which may contribute to the aspects of language function that are commonly affected by the disorder.