Abstracts

Rationale: Epilepsy with centrotemporal spikes (ECTS) is a common focal childhood epilepsy. Children with ECTS exhibit abnormalities in cognition and brain structure, although comprehensive prospective studies are lacking. We investigated cortical thickness and cognition in children with ECTS and healthy controls (HC), cross-sectionally and longitudinally. Methods: Participants were aged 8-18, including 24 with ECTS and 57 HC. All ECTS participants were assessed within 12 months of epilepsy diagnosis, had normal neurological examinations, and normal clinical MRI. Controls were age- and gender-matched first-degree cousins. All participants completed comprehensive cognitive assessment across multiple functional domains (IQ, academic achievement, language, motor, executive, attention, and memory) while a subset (14 ECTS, 36 HC) underwent T1 volumetric MRI scans. To correct for multiple comparisons, a Monte Carlo simulation was implemented with an initial cluster-forming threshold set to p < 0.05. Age and sex were used as covariates in all analyses. Two-year follow-up assessments were identical to baseline sessions. Results: At baseline, cognition in ECTS participants compared to HC exhibited deficits in psychomotor speed, confrontation naming, arithmetic, immediate verbal memory, attention, and inhibition. Longitudinally, rates of cognitive development in ECTS paralleled those of HC for all tests except confrontation naming, in which ECTS participants improved significantly more than HC from baseline to follow-up. At follow-up, children with ECTS continued to perform below controls in tests of motor function, immediate verbal memory, attention, and inhibition. ECTS participants also had lower verbal IQ scores compared to HC at follow-up but not at baseline. On imaging children with ECTS demonstrated cortical areas of both decreased thickness (left lateral occipital, left superior frontal, right middle frontal, and right inferior parietal cortex) and increased thickness (right precentral gyrus; Figure 1). Longitudinally, HC showed widespread cortical thinning in both hemispheres, while ECTS participants showed no cortical thinning and regions of cortical thickening in the right hemisphere (precentral and superior frontal areas; Figure 2). Conclusions: This is the first longitudinal investigation of combined changes in cognition and cortical thickness in children with ECTS. The first major finding is that the cognitive abnormalities associated with ECTS largely persist over time: both groups show significant cognitive development over time but in most functional domains, ECTS participants do not catch up to HC after 2 years. The second major finding is an absence of cortical thinning in children with ECTS over time. Although at baseline, children with ECTS showed both increased and decreased cortical thickness in several regions compared to HC, longitudinal analysis showed that the diffuse cortical thinning that takes place in HC is absent in ECTS participants, and in fact there are areas of increasing thickness compared to baseline measurements within the ECTS group.