Behavioral phenotypes of childhood idiopathic epilepsies

Abstract

ObjectiveTo characterize the presence and nature of discrete behavioral phenotypes and their correlates in a cohort of youth with new and recent onset focal and generalized epilepsies.MethodsThe parents of 290 youth (age = 8‐18 years) with epilepsy (n = 183) and typically developing participants (n = 107) completed the Child Behavior Checklist for children aged 6‐18 from the Achenbach System of Empirically Based Assessment. The eight behavior problem scales were subjected to hierarchical clustering analytics to identify behavioral subgroups. To characterize the external validity and co‐occurring comorbidities of the identified subgroups, we examined demographic features (age, gender, handedness), cognition (language, perception, attention, executive function, speed), academic problems (present/absent), clinical epilepsy characteristics (epilepsy syndrome, medications), familial factors (parental intelligence quotient, education, employment), neuroimaging features (cortical thickness), parent‐observed day‐to‐day executive function, and number of lifetime‐to‐date Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM‐IV) diagnoses.ResultsHierarchical clustering identified three behavioral phenotypes, which included no behavioral complications (Cluster 1, 67% of epilepsy cohort [n = 122]), nonexternalizing problems (Cluster 2, 11% of cohort [n = 21]), and combined internalizing and externalizing problems (Cluster 3, 22% of cohort [n = 40]). These behavioral phenotypes were characterized by orderly differences in personal characteristics, neuropsychological status, history of academic problems, parental status, cortical thickness, daily executive function, and number of lifetime‐to‐date DSM‐IV diagnoses. Cluster 1 was most similar to controls across most metrics, whereas Cluster 3 was the most abnormal compared to controls. Epilepsy syndrome was not a predictor of cluster membership.SignificanceYouth with new and recent onset epilepsy fall into three distinct behavioral phenotypes associated with a variety of co‐occurring features and comorbidities. This approach identifies important phenotypes of behavior problem presentations and their accompanying factors that serve to advance clinical and theoretical understanding of the behavioral complications of children with epilepsy and the complex conditions with which they co‐occur.

Behavioral phenotypes of temporal lobe epilepsy

“…Neuroimaging research has shown concomitant abnormalities consistent with the presence and degree of impairment across the cognitive phenotypes reflected in brain structure, connectivity (diffusion and resting state fMRI), and large‐scale covariance analyses of cortical/subcortical gray and white matter—the findings overall consistent with the hypothesis that disrupted networks rather than focal pathology primarily underlie the heterogeneous cognitive presentations of TLE 11,15‐18 …”

“…In the larger epilepsy neurobehavioral phenotype literature, the patterns shown here have been observed in cross-sectional and/or prospective investigations of quality of life, 43,44 cognitive trajectories of children treated surgically or medically, 45 and most patterns of depression in mothers of children with new onset epilepsy. 46 Cognitive phenotype investigations of adults with temporal lobe epilepsy have more typically identified varying patterns of abnormality across groups 10,9,17,11,13,14,16 as well as in patterns of executive function in children with epilepsy (Modi et al, 2019). That said, as this is the first attempt to characterize behavioral phenotype groups in temporal lobe epilepsy, more research is needed using other behavioral metrics and extension to other epilepsy syndromes to derive a fuller understanding of the taxonomy of behavioral abnormality in epilepsy and its associated patterns.…”

“…Regional analyses of cortical volume and thickness have been variably linked to the cognitive phenotypes of temporal lobe epilepsy, with more consistent positive relationships reported using diffusion MRI or resting state fMRI. 9,17,11,13,16 Our inability to identify stepwise abnormalities in regional analyses of cortical volume or thickness across the behavioral phenotypes should be addressed in future research with larger sample sizes, more contemporary imaging platforms, alternative analytics (eg network science), and other neuroimaging approaches that are more sensitive to detecting network abnormalities.…”

“…[9][10][11][12][13][14] Neuroimaging research has shown concomitant abnormalities consistent with the presence and degree of impairment across the cognitive phenotypes reflected in brain structure, connectivity (diffusion and resting state fMRI), and largescale covariance analyses of cortical/subcortical gray and white matter-the findings overall consistent with the hypothesis that disrupted networks rather than focal pathology primarily underlie the heterogeneous cognitive presentations of TLE. 11,[15][16][17][18] The issue of heterogeneity in the psychiatric complications of the epilepsies and a related taxonomy of psychopathological phenotypes has been investigated less often. In youth with new and recent onset epilepsies using a standard parent-completed rating scale (Child Behavior Checklist), three behavioral phenotypes were identified that ranged from comparable to normally developing youth, to an intermediate group characterized by nonexternalizing behavioral problems (eg depression, anxiety), to a generally behaviorally disrupted group of clinical significance.…”

“…These behavioral phenotypes were associated with diverse sociodemographic, clinical epilepsy, and neuroimaging correlates. 17 In adults with focal epilepsies, distinct symptom-based phenotypes of depression along with their accompanying cognitive complications have been identified. 19 To date, a comparable approach has not been undertaken in regard to the behavioral complications of adults with epilepsy which is the purpose here.…”