MRI and MRS Markers of Epileptogenesis

DESCRIPTION (provided by applicant): Epilepsy is a common disease, affecting approximately 0.5% of the US population, and disproportionately affecting children. Often, seizures develop months or years - the 'latent period' - following an initial brain injury, such as an episode of SE in early childhood. Not all individuals with comparable early life SE, however, develop epilepsy. Indeed, only a minority of children at risk subsequently develops epilepsy. To prospectively select children most likely to benefit from antiepileptogenic therapy it is necessary to identify surrogate markers. The recent advances in neuroimaging suggest that it may be possible to use neuroimaging tools to identify these surrogate markers. Identification of surrogate markers and would make it possible to initiate antiepileptogenic therapies only in children at risk. Furthermore, since it may take years before seizures develop following an injury, the identification of neuroimaging markers predicting epilepsy can accelerate the discovery of appropriate age-specific treatments to prevent epilepsy Thus, additional surrogate markers must be identified. To be of greatest use, markers either should persist through the latent period or should appear at distinct times within the latent period. It is also desirable that these markers provide insight into the evolution of the biological processes that culminate in epilepsy. To circumvent the problem of long latent periods in the development of human epilepsy, we propose to identify surrogate markers of epileptogenesis in lithium-pilocarpine immature rat model of epilepsy where seizures develop on average ten weeks after status epilepticus. By prospectively studying rats using magnetic resonance imaging and spectroscopy methods, we propose to identify brain changes that precede and predict the development of epilepsy.