Focal decreases of cortical GABAA receptor binding remote from the primary seizure focus: What do they indicate?

Abstract

To determine the electroclinical significance and histopathological correlates of cortical gamma-aminobutyric acid(A)(GABA(A)) receptor abnormalities detected in and remote from human neocortical epileptic foci. Cortical areas with decreased(11)C-flumazenil (FMZ) binding were objectively identified on positron emission tomography (PET) images and correlated to intracranial electroencephalography (EEG) findings, clinical seizure variables, histology findings, and surgical outcome in 20 patients (mean age, 9.9 years) with intractable partial epilepsy of neocortical origin and nonlocalizing magnetic resonance imaging (MRI). Focal decrease of cortical FMZ binding was detected in the lobe of seizure onset in 17 (85%) patients. Eleven patients (55%) had 17 remote cortical areas with decreased FMZ binding outside the lobe of seizure onset. Thirteen of those 16 (81%) of the 17 remote cortical regions that were covered by subdural EEG were around cortex showing rapid seizure spread on intracranial EEG. Remote FMZ PET abnormalities were associated with high seizure frequency and, when resected, showed gliosis in all six cases where material was available. Higher number of unresected cortical regions with decreased FMZ binding was associated with poorer surgical outcome. Focal decreases of cortical GABA(A) receptor binding on PET may include cortical regions remote from the primary focus, particularly in patients with high seizure frequency, and these regions are commonly involved in rapid seizure propagation. Although these regions may not always need to be resected to achieve seizure freedom, a careful evaluation of cortex with decreased GABA(A) receptor binding prior to resection using intracranial EEG may facilitate optimal surgical outcome in patients with intractable neocortical epilepsy.