title: Central benzodiazepine receptors in malformations of cortical development: A quantitative study.
abstract: We calculated [(11)C]flumazenil volume of distribution ([(11)C]FMZ-V(d)) after correction for partial volume effect in 10 patients with malformations of cortical development (MCDs) and partial seizures, to quantify the GABA(A)-central benzodiazepine receptor complex. Abnormal grey matter and adjacent or overlying cortex were outlined individually and added to an individualized anatomical template for correction for partial volume effect. Nine of 10 patients showed single or multiple increases or decreases in [(11)C]FMZ-V(d) in or around MCDs. Two of three patients with band heterotopia showed multiple increases in the overlying cortex. In three of four patients with subependymal nodular heterotopia, nodules had lower [(11)C]FMZ-V(d) than the overlying cortex, which was normal. Decreases in [(11)C]FMZ-V(d) were found in two of three clefts and one of six adjacent regions in one schizencephalic patient; another had normal [(11)C]FMZ-V(d) in the thickened cortex itself but increases in all adjacent regions. Binding was reduced within focal cortical dysplasia but increased in adjacent cortex. [(11)C]FMZ-V(d) was normal within one patient's polymicrogyric cortex but increased in one of six adjacent volumes of interest. The localization of abnormalities correlated with EEG and clinical data in cortical MCDs. Flumazenil binding was decreased in some MCDs with increased grey matter volume and increased in some adjacent or overlying areas of normal-appearing cortex, suggesting functional abnormalities beyond MRI- detectable structural changes.
authors.affiliation: MRC Cyclotron Unit, Clinical Sciences Centre, Hammersmith Hospital and National Society for Epilepsy, Institute of Neurology, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Hammers
authors.forename: M J
authors.initials: MJ
authors.lastname: Koepp
authors.forename: M P
authors.initials: MP
authors.lastname: Richardson
authors.forename: C
authors.initials: C
authors.lastname: Labbé
authors.forename: D J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: V J
authors.initials: VJ
authors.lastname: Cunningham
authors.forename: J S
authors.initials: JS
authors.lastname: Duncan
mesh_terms: D000293:Adolescent; D000328:Adult; D002250:Carbon Radioisotopes; D002490:Central Nervous System / Q000502:physiology; D002540:Cerebral Cortex / Q000002:abnormalities / Q000254:growth & development*; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000503:physiopathology*; D005260:Female; D005442:Flumazenil / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D009421:Nervous System Malformations / Q000503:physiopathology*; D011963:Receptors, GABA-A / Q000502:physiology*; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil