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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Developmental Brain Disorders Study Section (DBD)
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Fureman, Brandy E
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University of Wisconsin Madison
Schools of Medicine
United States
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Garcia-Ramos, Camille; Dabbs, Kevin; Lin, Jack J et al. (2018) Progressive dissociation of cortical and subcortical network development in children with new-onset juvenile myoclonic epilepsy. Epilepsia 59:2086-2095
Garcia-Ramos, Camille; Dabbs, Kevin; Meyerand, Elizabeth et al. (2018) Psychomotor slowing is associated with anomalies in baseline and prospective large scale neural networks in youth with epilepsy. Neuroimage Clin 19:222-231
Srnka, Kyle; Seidenberg, Michael; Hermann, Bruce et al. (2018) Intraindividual variability in attentional vigilance in children with epilepsy. Epilepsy Behav 79:42-45
Karrasch, Mira; Tiitta, Petri; Hermann, Bruce et al. (2017) Cognitive Outcome in Childhood-Onset Epilepsy: A Five-Decade Prospective Cohort Study. J Int Neuropsychol Soc 23:332-340
Hermann, Bruce; Loring, David W; Wilson, Sarah (2017) Paradigm Shifts in the Neuropsychology of Epilepsy. J Int Neuropsychol Soc 23:791-805
Garcia-Ramos, Camille; Bobholz, Sam; Dabbs, Kevin et al. (2017) Brain structure and organization five decades after childhood onset epilepsy. Hum Brain Mapp 38:3289-3299
Hanson, Melissa; Morrison, Blaise; Jones, Jana E et al. (2017) Control groups in paediatric epilepsy research: do first-degree cousins show familial effects? Epileptic Disord 19:49-58
Garcia-Ramos, Camille; Lin, Jack J; Bonilha, Leonardo et al. (2016) Disruptions in cortico-subcortical covariance networks associated with anxiety in new-onset childhood epilepsy. Neuroimage Clin 12:815-824
Jones, Jana E; Siddarth, Prabha; Almane, Dace et al. (2016) Identification of risk for severe psychiatric comorbidity in pediatric epilepsy. Epilepsia 57:1817-1825
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

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