We are proposing the first prospective investigation designed to detect progressive adverse effects of chronic early onset (less than age 14) temporal lobe epilepsy (TLE) on brain structure and function. This proposed study will combine high- resolution quantitative MRI volumetrics, comprehensive neuropsychological assessment, and an fMRI memory activation task. The purpose of this investigation is to test the hypothesis that early onset TLE is associated with a generalized adverse neurodevelopmental impact on both brain structure and function, an impact that may constitute an early-acquired neurobiological vulnerability for progressive cognitive decline in the face of ongoing chronic epilepsy. In this competing renewal application, we propose a longitudinal examination of 80 early onset TLE subjects and 80 age and gender matched controls that were initially seen for baseline testing four to five years earlier. All subjects will again undergo cognitive assessment and whole brain quantitative MRI volumetrics and a subset of subjects will undergo an fMRI object memory task. It is predicted that: 1) cognitive decline in this four-five year interval will be greater for early onset TLE subjects compared to controls, 2) decline will be most evident among those with longer duration of epilepsy, and for measures of memory function, speeded cognitive processing and non-verbal abilities compared to language based tasks, and 3) test-retest cognitive decline shown by early onset TLE subjects will be predicted by time total brain tissue volume and proportional brain tissue lost over the test- retest interval, and 4) increasing chronicity of epilepsy will be associated with decreasing mesial temporal lobe activation on an fMRI object memory task. Additional analyses will examine the impact of specific epilepsy course variables, depression, and associated chronic medical illness on longitudinal changes in TLE. The proposed study addresses an important and unresolved question concerning the possibility of progression in humans with TLE and the predictors of that decline. The findings will have potential implications for treatment as well as the understanding of the pathophysiology and natural history of TLE.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Special Emphasis Panel (ZRG1-BDCN-5 (01))
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Fureman, Brandy E
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University of Wisconsin Madison
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