Imaging the Effect of Centrotemporal Spikes and Seizures on Language in Children
Condition: Benign Childhood Epilepsy With Centro-Temporal Spikes
MeSH terms: Epilepsy; Seizures; Epilepsy, Rolandic
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Levetiracetam
Intervention type(s): Drug
Intervention description(s): Medication doses are defined on a mg/kg basis. Dosage form, frequency and titration schedule is based on accepted clinical practice.
Other intervention name(s): Keppra
Intervention MeSH terms: Levetiracetam
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Benign Childhood Epilepsy With Centrotemporal Spikes; Benign Rolandic Epilepsy