Central Benzodiazepine/γ-Aminobutyric AcidA Receptors in Idiopathic Generalized Epilepsy: An [11C]Flumazenil Positron Emission Tomography Study

Authors

  • Matthias J. Koepp,

    1. MRC Cyclotron Unit, Hammersmith Hospital, Institute of Neurology, Queen Square, London, U.K.
    2. Epilepsy Research Group, Institute of Neurology, Queen Square, London, U.K.
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  • Mark P. Richardson,

    1. MRC Cyclotron Unit, Hammersmith Hospital, Institute of Neurology, Queen Square, London, U.K.
    2. Epilepsy Research Group, Institute of Neurology, Queen Square, London, U.K.
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  • David J. Brooks,

    1. MRC Cyclotron Unit, Hammersmith Hospital, Institute of Neurology, Queen Square, London, U.K.
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  • Vin J. Cunningham,

    1. MRC Cyclotron Unit, Hammersmith Hospital, Institute of Neurology, Queen Square, London, U.K.
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  • John S. Duncan

    Corresponding author
    1. MRC Cyclotron Unit, Hammersmith Hospital, Institute of Neurology, Queen Square, London, U.K.
    2. Epilepsy Research Group, Institute of Neurology, Queen Square, London, U.K.
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Address correspondence and reprint requests to Dr. J. S. Duncan at Epilepsy Research Group, Institute of Neurology, Queen Square, London WClN 3BG, U.K.

Abstract

Summary: Purpose: Previous [11C]flumazenil (FMZ) positron emission tomography (PET) investigations in patients with idiopathic generalized epilepsy (IGE) have demonstrated nonsignificant global cortical decreases in central benzodiazepine γ-aminobutyric acid, (GABAA) receptor (cBZR) binding or focal decreases in the thalamus and increases in the cerebellar nuclei with no changes in cerebral cortex. We previously reported lower [11C]FMZ binding in cerebral cortex of IGE patients treated with valproate (VPA) than in cerebral cortex of controls. We now report high-resolution three-dimensional [11C]FMZ PET studies in a larger number of subjects using an improved method to detect differences in cBZR between IGE patients and controls and a more powerful longitudinal design to determine the functional effect of VPA.

Methods: We compared parametric images of [11C]FMZ volume of distribution (FMZVD) in 10 IGE patients before and after addition of VPA and in 20 normal subjects.

Results: Mean FMZVD was significantly higher in the cerebral cortex (11%, p = 0.009), thalamus (14%, p = 0.018), and cerebellum (15%, p = 0.027) of the 10 IGE patients as compared with that of 20 normal controls. Using statistical parametric mapping, no significant areas of focal abnormality of FMZVD were detected. Addition of VPA was not associated with a significant change in mean FMZVD in any brain area.

Conclusions: Our finding of increased FMZVD in IGE could reflect microdysgenesis or a state of cortical hyperexcitability. Our data suggest that short-term VPA therapy does not affect the number of available cBZR in patients with IGE.

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