The relationship between the localization of the generalized spike and wave discharge generators and the response to valproate

Authors

  • Jerzy P. Szaflarski,

    Corresponding author
    1. Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, U.S.A
    Current affiliation:
    1. Department of Neurology and, UAB Epilepsy Center, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A
    • Department of Neurology and the Cincinnati Epilepsy Center, University of Cincinnati, Cincinnati, Ohio, U.S.A
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  • Benjamin Kay,

    1. Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio, U.S.A
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  • Jean Gotman,

    1. Montreal Neurological Institute, Montreal, Quebec, Canada
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  • Michael D. Privitera,

    1. Department of Neurology and the Cincinnati Epilepsy Center, University of Cincinnati, Cincinnati, Ohio, U.S.A
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  • Scott K. Holland

    1. Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, U.S.A
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Address correspondence to Jerzy P. Szaflarski, Department of Neurology, UAB Epilepsy Center University of Alabama at Birmingham, 312 Civitan International Research Center, 1719 6th Avenue South Birmingham, AL 35294, U.S.A. E-mail: szaflaj@uab.edu

Summary

Purpose

Up to 30% of patients with idiopathic generalized epilepsy (IGE) have seizures that are refractory to medication despite appropriate therapy that commonly includes valproate (VPA). The aim of this study was to compare patients with VPA-refractory and VPA-responsive IGE in order to determine whether there are group differences in generalized spike and wave discharge (GSWD) generators that may be associated with VPA resistance.

Methods

Of 89 IGE patients who underwent electroencephalography (EEG) combined with functional magnetic resonance imaging (fMRI; EEG/fMRI), 25 with GSWDs identified in EEG/fMRI data were included. Simultaneous acquisition of 64 channels of EEG data at 10 kHz was performed using an MRI-compatible EEG cap and amplifier at 4T. VPA resistance was defined as lack of seizure control despite therapeutic dose of VPA.

Key Findings

The fMRI blood oxygen–level dependent (BOLD) correlates of GSWD in the entire group involved midline thalamus, frontal regions comprising Brodmann areas 6, 24, and 32, and temporal lobes diffusely. When VPA-responsive and VPA-resistant patients were compared, BOLD signal increases were noted in the VPA-resistant patients in medial frontal cortex, along the paracingulate gyrus (Montreal Neurological Institute; MNI x = 2, y = 13.6, z = 45.9), and anterior insula bilaterally (right MNI x = 37.6, y = 7.8, z = 0.6, left MNI x = −35.3, y = 13.6, z = −5.3).

Significance

Our findings support the hypothesis that VPA-resistant and VPA-responsive patients may have different GSWD generators. Furthermore, we hypothesize that these differences in GSWD generators may be the reason for different responses to VPA.

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