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 role of family history to the presence 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), 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS044351-10
Application #
8736015
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Fureman, Brandy E
Project Start
2002-07-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Madison
State
WI
Country
United States
Zip Code
53715
Garcia-Ramos, Camille; Lin, Jack J; Kellermann, Tanja S et al. (2016) Graph theory and cognition: A complementary avenue for examining neuropsychological status in epilepsy. Epilepsy Behav 64:329-335
Garcia-Ramos, C; Song, J; Hermann, B P et al. (2016) Low functional robustness in mesial temporal lobe epilepsy. Epilepsy Res 123:20-8
La, Christian; Garcia-Ramos, Camille; Nair, Veena A et al. (2016) Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions. Front Aging Neurosci 8:110
Hsu, David A; Rayer, Katherine; Jackson, Daren C et al. (2016) Correlation of EEG with neuropsychological status in children with epilepsy. Clin Neurophysiol 127:1196-205
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
Garcia-Ramos, Camille; Lin, Jack J; Prabhakaran, Vivek et al. (2015) Developmental Reorganization of the Cognitive Network in Pediatric Epilepsy. PLoS One 10:e0141186
Almane, Dace; Jones, Jana E; Jackson, Daren C et al. (2015) Brief clinical screening for academic underachievement in new-onset childhood epilepsy: utility and longitudinal results. Epilepsy Behav 43:117-21
Zeng, Hongwu; Ramos, Camille Garcia; Nair, Veena A et al. (2015) Regional homogeneity (ReHo) changes in new onset versus chronic benign epilepsy of childhood with centrotemporal spikes (BECTS): A resting state fMRI study. Epilepsy Res 116:79-85
Garcia-Ramos, Camille; Jackson, Daren C; Lin, Jack J et al. (2015) Cognition and brain development in children with benign epilepsy with centrotemporal spikes. Epilepsia 56:1615-22
Jones, Jana E; Jackson, Daren C; Chambers, Karlee L et al. (2015) Children with epilepsy and anxiety: Subcortical and cortical differences. Epilepsia 56:283-90

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