Benzodiazepine receptors in focal epilepsy with cortical dysgenesis: An C-11-flumazenil PET study

Previous imaging studies using C-11-flumazenil in patients with mesial temporal lobe epilepsy and neocortical partial seizure disorders have found focal decreases in gamma-aminobutyric acid type A/benzodiazepine receptor binding. These studies used subjective visual assessment and a region of interest approach to quantitation. We performed three-dimensional, C-11-flumazenil positron emission tomography in 12 patients with cortical dysgenesis identified by high-resolution volumetric magnetic resonance imaging and in 26 normal subjects. Spectral analysis was used to produce a parametric image of C-11-flumazenil volume of distribution for each subject. Using volumetric normalization and statistical parametric mapping, we compared the entire brain volume of each patient with the brains of the normal group to produce maps of regions of abnormal C-11-flumazenil binding which were then rendered into the volumetric magnetic resonance images. This allowed a correlation of structure and function to be made. Of the 12 patients, 10 showed at least one region of abnormal C-11-flumazenil binding; the abnormal regions were frequently more extensive than were the lesions seen with magnetic resonance imaging. C-11-Flumazenil binding abnormalities were frequently seen in regions of cortex that had a normal magnetic resonance appearance. Lesions were characterized by increases in gamma-aminobutyric acid type A/benzodiazepine receptor availability, and by the decreases found in previous studies. These findings have implications for the neurobiology of seizure disorders associated with cortical dysgenesis and for the management of such patients if surgery is contemplated.