Imaging the Effect of Centrotemporal Spikes and Seizures on Language in Children

Benign Childhood Epilepsy with Centro-Temporal Spikes (BECTS), an extremely common type of childhood epilepsy, is traditionally assumed to have a benign course, but recent studies have shown that cognitive function, especially language, is often impaired in BECTS patients. However, it is not clear whether ithe seizures, the centrotemporal spikes (CTS), or other factors cause the negative cognitive consequences that may impact school performance and social interaction. BECTS patients have scattered seizures but very frequent CTS, and may be suffering with undiagnosed cognitive and language deficits. This suggests a causal role for CTS that has not yet been investigated in detail. This project will examine the impact of seizures and CTS on neurocognitive function in BECTS patients, at diagnosis and after one year. We will gather critical information regarding the effect of the anti-epileptic medication levetiracetam on CTS, which will inform a future Phase III clinical trial aimed at eliminating CTS and improving long term outcome.

This study will explore the interactions between CTS, seizures and neuropsychological outcomes using Functional MRI of language in order to decipher changes in neural circuitry that underlie language deficits found in children with BECTS. Using standardized neuropsychological testing and fMRI at the time of diagnosis, this study will first characterize the nature and incidence of language problems in children with BECTS, separating the effects of CTS and seizures. It is expected that children with BECTS will perform below normative standards on tests of language skill, accompanied by aberrations in the neural circuitry supporting language processing as tested with fMRI. These data will also make it possible to characterize which children with BECTS are most at risk for language problems, by taking into account contributing factors such as number of seizures, age of onset, and frequency and lateralization of CTS.

The proposed exploratory clinical trial will also provide key information needed to properly design and conduct a future double blind Phase III randomized clinical trial (RCT) children aimed at improving language outcome through elimination of CTS. Using an open-label dose-ranging design and 1-year follow up, we will determine the best dose of levetiracetam to control seizures, eliminate CTS and be well tolerated. We will also examine the extent of changes in language function and neural circuitry of language with 1-year follow-up neuropsychological testing and fMRI in LEV-treated and untreated BECTS compared to controls (which will document the natural history of neuropsychological function in untreated BECTS children and give additional information about the effect of LEV). The current study will provide crucial information for a future double blind RCT that will the compare the selected dose of levetiracetam to carbamazepine (the current standard of care) in BECTS. This would change clinical practice by demonstrating the need for AED treatment in BECTS to eliminate CTS, in turn improving long term language and cognitive outcome.