Decreased binding of [11C]flumazenil in Angelman syndrome patients with GABA(A) receptor beta3 subunit deletions.

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.

Proton spectroscopy in children with epilepsy and febrile convulsions.

An association between complex febrile convulsions and the development of hippocampal atrophy, which is characterized by neuron loss and gliosis, has been suggested but is still controversial. In proton magnetic resonance spectroscopy (1H-MRS) a reduction in N-acetylaspartate (NAA), a neuron marker, or in its ratio to other metabolites, that is, creatine and phospocreatine (Cr) and choline-containing compounds (Cho), is considered a sensitive method for detecting neuron loss. We performed 1H-MRS of mesial temporal regions, including hippocampi, in two different groups of children with epilepsy: in children with a history of complex febrile convulsions (CFCs) (n = 7; mean age 7.1 years) and in children without any history of CFCs, referred to herein as the non-CFC group (n = 6; mean age 7.6 years). Changes in the metabolite ratios were detected in 57% of children in the CFC group and in 67% of children in the non-CFC group. In both groups, NAA/(Cho + Cr), NAA/Cho, and NAA/Cr were significantly decreased ipsilaterally to the seizure focus when compared with the control group, but no significant differences were detected between the CFC and non-CFC groups. Also on the contralateral side, NAA/(Cho + Cr) and NAA/Cr were significantly decreased in both patient groups, but the differences were not significant between the CFC and non-CFC groups. Metabolite abnormalities in the mesial temporal region were detected in children with intractable epilepsy and in children whose epilepsy is well controlled by antiepileptic medication. The noninvasive 1H-MRS can be considered an additional diagnostic method to promote early detection of mesial temporal abnormalities that, in the light of this study, seem to be underdiagnosed in children with either temporal lobe epilepsy or other seizure types.