Benign Childhood Epilepsy With Centro-Temporal Spikes Clinical Trial
Official title:
Imaging the Effect of Centrotemporal Spikes and Seizures on Language in Children
This project examines how seizures, and abnormal brain activity, affect language skill in children with Benign Childhood Epilepsy with Centro-Temporal Spikes (BECTS). BECTS is a common type of childhood epilepsy, and while BECTS patients stop having seizures by their late teenage years, many studies have shown that these children have language problems that may lead to academic and social difficulties. Using standardized language testing, monitoring of brain activity, and MRI brain imaging, this project aims to determine what particular combination of BECTS symptoms put children most at risk for language problems and whether treatment with anti-epileptic medications may be helpful.
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.
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