Determinants of IQ outcome after focal epilepsy surgery in childhood: A longitudinal case-control neuroimaging study

Objective: Intelligence quotient (IQ) outcomes after pediatric epilepsy surgery show significant individual variation. Clinical factors such as seizure cessation or antiepileptic medication discontinuation have been implicated, but do not fully account for the heterogeneity seen. Less is known about the impact of neurobiological factors, such as brain development and resection location. This study examines clinical and neuroimaging factors associated with cognitive outcome after epilepsy surgery in childhood. Methods: Fifty-two children (28 boys, 24 girls) were evaluated for epilepsy surgery and reassessed on average 7.7 years later. In the intervening time, 13 were treated pharmacologically and 39 underwent focal surgery (17 temporal, 16 extratemporal, six multilobar; mean age at surgery = 14.0 years). Pre- and postsurgical assessments included IQ tests and T1-weighted brain images. Predictors of IQ change were investigated, including voxel-based analyses of resection location, and gray and white matter volume change. Results: Overall modest IQ improvement was seen in children treated surgically, but not in those treated pharmacologically only. Applying a ≥10-point change threshold, 39% of the surgically treated children improved, whereas 10% declined. Clinical factors associated with IQ increases were lower preoperative IQ and longer follow-up duration, whereas seizure and antiepileptic medication cessation were not predictive. Among neuroimaging factors, we observed that left anterior temporal resections impacted negatively on verbal reasoning, linked to full-scale IQ decline. In contrast, gray matter volume change in ipsi- and contralesional hemispheres was positively correlated with IQ change. Voxel-based morphometry identified the gray matter volume change in the contralesional dorsolateral frontal cortex as most strongly associated with IQ improvement. Significance: We show that a variety of factors are likely to contribute to patterns of postsurgical change in IQ. Neuroimaging results indicate that left anterior temporal resections constrain development of verbal cognition, whereas simultaneously cortical growth after surgical treatment can support improvements in IQ.