Abstracts

Rationale: Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the human brain. In patients with chronic intractable partial epilepsy not associated with a structural lesion, decreased GABA_A receptor binding in the epileptogenic hippocampus and/or cortex is a common finding on [¹¹C]flumazenil positron emission tomography (PET). Previous cross-sectional studies suggested that some of these GABA_A receptor abnormalities may develop after the onset of initial seizures. However, the natural course of GABA_A receptor abnormalities in the epileptic brain remains unclear. Therefore, we have designed a prospective, longitudinal study applying [¹¹C]flumazenil PET to detect and quantify focal GABA_A receptor binding abnormalities and track their longitudinal changes in children with recent onset epilepsy. We report now the preliminary findings of this study.Methods: Twelve children (mean age: 8.6 years; range: 1.4-15.1 years) with a recent onset partial epilepsy (at least 2 seizures before PET) and normal MRI underwent [¹¹C]flumazenil PET scanning at an average of 11 months (range: 2-24 months) after their initial seizure. The total seizure number ranged between 2 and 12 for the group (median: 3 seizures). MRI-co-registered PET images were used to measure [¹¹C]flumazenil binding asymmetries in the cortex as well as the whole hippocampus and three (anterior, middle, and posterior) hippocampal subregions. Normal asymmetry limits were defined by [¹¹C]flumazenil PET scans obtained in a control group of 8 healthy adult controls. Results: Abnormal [¹¹C]flumazenil binding asymmetry (>3 SD above control mean asymmetry) was found in the whole hippocampus in one child, with decreased binding on the left side and most severe involvement in the anterior portion of the hippocampus. Another five children showed abnormal [¹¹C]flumazenil binding asymmetry in the anterior (N=4; lower binding on the left in all subjects) or posterior (N=1, lower binding on the right) hippocampus only. In a group comparison, the anterior hippocampus showed a significant left < right binding asymmetry as compared to the controls (p = .011). Abnormal cortical binding asymmetries (>10% asymmetry in small cortical segments present in at least three consecutive image planes) were found in three patients (including two with hippocampal abnormality), involving one region in two and multiple cortical regions in one child. Conclusions: Abnormal cortical and/or hippocampal GABA_A receptor binding can be present in some children (7of 12 in this series) with recent onset partial epilepsy even if MRI shows no lesion. The left anterior hippocampus appears to be most commonly involved during the early course of epilepsy. Whether early focal GABA_A receptor abnormalities represent epileptogenic regions, and if they indicate an increased risk for intractable epilepsy, needs to be determined by future studies. (This work was supported by NIH grant #NS34488 to Dr. H.T. Chugani)