Our controlled prospective cohort study (RO1-44351) examined children (ages 8-18) with newly diagnosed childhood epilepsies (n=183) and healthy controls (n=107) with neuropsychological, neuroimaging and psychiatric assessments. This competing renewal application proposes that four prevalent neurobehavioral comorbidities (Academic Problems, ADHD, Anxiety, Depression) are not merely consequences of epilepsy syndrome type, course, treatment, or societal stigma, but represent fundamental phenotypes of the childhood epilepsies. These phenotypes are associated with altered neurodevelopmental processes occurring antecedent to seizure onset and at epilepsy diagnosis. We posit that neurobehavioral comorbidities are associated with abnormal baseline and prospective cognitive and neuroimaging findings and are predictive of long-term psychosocial outcomes. A critical corollary is that children with epilepsy who at epilepsy diagnosis are without these four neurobehavioral comorbidities are comparable to healthy peers in cognition and brain structure, prospective cognitive and brain development, and long term life outcomes. This view challenges the conventional wisdom regarding what constitutes the ?benign? epilepsies (i.e., not epilepsy syndrome and course but the presence/absence of key comorbidities). This view carries fundamental implications for clinical care, and offers to merge two disparate lines of research in the childhood epilepsies by proposing that the problematic long term psychosocial outcomes of the idiopathic childhood epilepsies are linked primarily to the neurobehavioral comorbidities. In this competing renewal application we propose to complete the follow-up of our entire cohort (n=290) in order to characterize the pattern of shared and unique risk of neurobehavioral comorbidities across epilepsy syndromes from baseline to 5-years after diagnosis (Aim 1), determine patterns of brain and cognitive development associated with neurobehavioral comorbidities from baseline to 5-years after diagnosis (Aim 2); and determine whether divergent psychosocial outcomes in young adulthood, 10-years after diagnosis, are predicted by baseline neurobehavioral comorbidity status compared to epilepsy syndrome (Aim 3).

Public Health Relevance

Childhood epilepsy is a prevalent neurological disorder associated with poor outcomes in key aspects of adult life (e.g., employment and finances; marriage and family; social and psychiatric status), but the predictors of these outcomes remain poorly understood. The results of this controlled prospective cohort investigation will provide what we believe are the earliest insights into the natural history of these problematic lifespan outcomes.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
High Priority, Short Term Project Award (R56)
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Developmental Brain Disorders Study Section (DBD)
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Whittemore, Vicky R
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University of Wisconsin Madison
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United States
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Kellermann, Tanja S; Bonilha, Leonardo; Lin, Jack J et al. (2015) Mapping the landscape of cognitive development in children with epilepsy. Cortex 66:1-8
Dabbs, Kevin; Jones, Jana E; Jackson, Daren C et al. (2013) Patterns of cortical thickness and the Child Behavior Checklist in childhood epilepsy. Epilepsy Behav 29:198-204
Amarreh, Ishmael; Dabbs, Kevin; Jackson, Daren C et al. (2013) Cerebral white matter integrity in children with active versus remitted epilepsy 5 years after diagnosis. Epilepsy Res 107:263-71
Lin, Jack J; Riley, Jeff D; Hsu, David A et al. (2012) Striatal hypertrophy and its cognitive effects in new-onset benign epilepsy with centrotemporal spikes. Epilepsia 53:677-85
Tosun, Duygu; Siddarth, Prabha; Toga, Arthur W et al. (2011) Effects of childhood absence epilepsy on associations between regional cortical morphometry and aging and cognitive abilities. Hum Brain Mapp 32:580-91