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Brain Advance Access published online on April 8, 2003
Brain, doi:10.1093/brain/awg138
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© 2003 The Guarantors of Brain

Article

Grey and white matter flumazenil binding in neocortical epilepsy with normal MRI. A PET study of 44 patients

Alexander Hammers 1, Matthias J. Koepp 1, Mark P. Richardson 1, René Hurlemann 2, David J. Brooks 3, John S. Duncan 4*

1 MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK; National Society for Epilepsy MRI Unit, Chalfont St Peter; Department of Clinical and Experimental Epilepsy, Institute of Neurology, Queen Square, London, UK
2 National Society for Epilepsy MRI Unit, Chalfont St Peter; Department of Clinical and Experimental Epilepsy, Institute of Neurology, Queen Square, London, UK
3 MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK
4 National Society for Epilepsy MRI Unit, Chalfont St Peter; Department of Clinical and Experimental Epilepsy, Institute of Neurology, Queen Square, London, UK

* Corresponding author. E-mail: j.duncan{at}ion.ucl.ac.uk.

Received 5 August 2002 ; revised 19 December 2002 ; accepted 13 January 2003

Abstract

In 20-30% of potential surgical candidates with refractory focal epilepsy, standard MRI does not identify the cause. {gamma}-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. [11C]Flumazenil (FMZ) PET images most subtypes of GABAA receptors, present on most neurons. We investigated [11C]FMZ binding in grey and white matter in 16 normal controls and in 44 patients with refractory neocortical focal epilepsy and normal optimal MRI. Fourteen patients had unilateral frontal lobe epilepsy, five occipital lobe epilepsy (OLE), six parietal lobe epilepsy (PLE) and 19 neocortical epilepsy that was not clearly lobar. Parametric images of FMZ volume of distribution (FMZ-Vd) were computed. Statistical parametric mapping (SPM99) with explicit masking, including the white matter, was used to analyse individual patients and groups. Thirty-three of the 44 patients showed focal abnormal FMZ-Vd; increases in 16, decreases in eight, and both increases and decreases in nine. In seven patients, the increases in FMZ binding were periventricular, in locations normally seen in periventricular nodular heterotopia on MRI. There were frontal and parietal increases in FMZ binding in grey and white matter in the PLE group and decreases in the cingulate gyrus in the OLE group. FMZ binding increases, particularly periventricular increases, were a prominent feature of MRI-negative focal epilepsies and may represent neuronal migration disturbances.

Keywords: SPM99; localization-related epilepsy; frontal lobe epilepsy; parietal lobe epilepsy; occipital lobe epilepsy
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