Cognitive, academic, social and psychiatric abnormalities are common in childhood onset epilepsy, with enduring adverse consequences into adulthood, even among those with uncomplicated and remitted epilepsies. To understand the natural history of these lifespan issues, the initial funding cycle of our prospective cohort study (RO1-44351) examined children (ages 8-18) with newly diagnosed idiopathic epilepsies (n=75) and healthy controls (n=62), and followed them for 2 years with neuropsychological, psychiatric, and neuroimaging techniques. While informing the early natural history of cognitive, anatomic, and psychiatric abnormalities of childhood epilepsy, we also identified risk factors at the time of epilepsy diagnosis that predicted developmental trajectories two years following diagnosis. We hypothesize these same abnormalities will predict longer term outcomes in important areas of life performance (e.g., employment, independent living, educational attainment). In this competing renewal application, we propose to follow our original cohort to characterize and predict young adulthood outcomes, enrich the cohort with new onset epilepsy and control participants (n=150), and incorporate new procedures to test hypotheses regarding the effects of family history, disrupted neural circuitry and epilepsy syndrome on life course.
The specific aims of this competing renewal application are as follows: 1) Characterize the longer-term (10- year) social, educational, vocational, and psychiatric trajectories of childhood onset epilepsy and identify predictors of favorable and unfavorable young adult outcomes; 2) Clarify the contribution of family history to the risk of cognitive and psychiatric comorbidities in children with new onset epilepsy; 3) Characterize the relationship between abnormalities in brain volume, shape and connectivity with disordered cognition and psychiatric status; and 4) Identify syndrome-specific cognitive, psychiatric, and imaging abnormalities.

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), and 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56NS044351-08
Application #
8329899
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Fureman, Brandy E
Project Start
2002-07-01
Project End
2012-09-29
Budget Start
2011-09-30
Budget End
2012-09-29
Support Year
8
Fiscal Year
2011
Total Cost
$506,045
Indirect Cost
Name
University of Wisconsin Madison
Department
Neurology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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