Abstracts

Rationale: Four prevalent comorbidities in youth with new onset epilepsy have been detected at the time of diagnosis including Academic Difficulties, ADHD, Anxiety and Depressive disorders. There is controversy regarding whether these issues are brain based or caused by other factors (e.g., psychosocial or medication causes). We interrogated whether these complications were associated with anatomic brain differences at/near the time of diagnosis as well as developmental anomalies prospectively (2 years later). In order to contrast the core comorbidity we compared the epilepsy neurobehavioral comorbidity groups to controls on an understudied gyrification index of brain anatomy. ()  The Local Gyrification Index from FreeSurfer is a metric that quantifies the amount of cortex buried within the sulcal folds compared with the amount of cortex on the outer visible cortex. Cortex with extensive folding has a larger gyrification index while cortex with limited folding has a smaller gyrification index. Methods: Children (aged 8-18) with new onset epilepsy (N=39) and healthy controls (N=57) participated in comprehensive psychiatric assessments. Parents were interviewed regarding their child’s status through a structured psychiatric interview and completion of questionnaires and behavioral rating scales at baseline and 2-year follow-up. All participants had a 1.5T MRI scanning sessions at each time point, including anatomical 3D T1-weighted MRI.  MR images were processed with Freesurfer version 5.3, including the longitudinal pipeline and supplemental generation of the Local Gyrification Index (LGI) at baseline and the annualized symmetric percent change (SPC) of the LGI across the cortical surface.  Cortical surface analysis of local gyrification values were conducted with Freesurfer’s vertex-based statistical toolbox, Qdec, employing a Monte Carlo null-Z cluster correction. Results: No group differences survived cluster correction in the Depression group. Figure 2 shows regions where prospective change in gyrification differs for each comorbidity group compared to controls. Blue colors indicate where the gyrification change is more negative in the comorbid epilepsy groups.  Yellow regions indicate higher gyrification change over two years in the comorbidity groups.   No group differences survived cluster correction in the Academic Problems group.Figure 1 shows anomalous areas of cortical gyrification at baseline in the comorbidity groups. Blue colors indicate significant clusters where gyrification is lower in the comorbid epilepsy groups while yellowy regions indicate higher gyrification values in comorbidity groups.  No group differences survived cluster correction in the Depression group. Figure 22 shows regions where prospective  change in gyrification  differs for each comorbidity group compared to controls. Blue colors indicate where the gyrification change is more negative in the comorbid epilepsy groups.  Yellow regions indicate higher gyrification change over two years in the comorbidity groups.   No group differences survived cluster correction in the Academic Problems group. Conclusions: Areas of abnormal cortical gyrification are evident at baseline as well as propectively in groups of children with new onset epilepsy with common neurobehavioral comorbidities of childhood epilepsy. These abnormalities are evident at baseline and prospectively suggesting abnormal antecedent and prospective development.  Importantly, children with epilepsy without these comorbidities are most akin to normally developing children without epilepsy. Funding: NINDS 3RO1 44351