ABSTRACT
We used positron emission tomography (PET) to study brain [11C]flumazenil (FMZ) binding in four Angelman syndrome (AS) patients. Patients 1 to 3 had a maternal deletion of 15q11-q13 leading to the loss of beta3 subunit of gamma-aminobutyric acidA/benzodiazepine (GABA(A)/BZ) receptor, whereas Patient 4 had a mutation in the ubiquitin protein ligase (UBE3A) saving the beta3 subunit gene. [11C]FMZ binding potential in the frontal, parietal, hippocampal, and cerebellar regions was significantly lower in Patients 1 to 3 than in Patient 4. We propose that the 15q11-q13 deletion leads to a reduced number of GABA(A)/BZ receptors, which could partly explain the neurological deficits of the AS patients.
Subject(s)
Angelman Syndrome/genetics , Angelman Syndrome/metabolism , Gene Deletion , Receptors, GABA-A/genetics , Adolescent , Adult , Angelman Syndrome/diagnostic imaging , Brain/diagnostic imaging , Brain/metabolism , Child , Child, Preschool , Female , Humans , Male , Tomography, Emission-ComputedABSTRACT
Hippocampal atrophy characterized by neuronal loss is a common feature in intractable temporal lobe epilepsy in adults. In proton magnetic resonance spectroscopy, a reduction in N-acetylaspartate or in its ratio to other metabolites is considered a sensitive method for detecting neuronal loss. This noninvasive approach was used to study the temporal lobes, especially the hippocampal regions of children with partial epilepsy. In all cases, 2-[18F]fluoro-2-deoxy-D-glucose scans were studied to verify the extension of the hypometabolic area. Five children manifested temporal lobe epilepsy; in 2 of them, epilepsy was intractable. Both manifested temporal hypometabolism on positron emission tomography, hippocampal atrophy on magnetic resonance imaging, and significant reductions in the metabolite ratios on spectroscopy ipsilateral to the seizure focus, as verified by EEG. Three children with temporal lobe epilepsy had infrequent seizures. One of them had a reduction in metabolite ratios in the hippocampus and hippocampal atrophy on magnetic resonance imaging ipsilateral to the seizure focus. The results show that the value of proton spectroscopy lies not only in lateralizing hippocampal atrophy but also in detecting bilaterality and the extent of neuronal loss outside hippocampi. This noninvasive preoperative diagnostic method can be considered an additional technique to be used in conjunction with other imaging techniques for clinical assessment of children with intractable temporal lobe epilepsy.
