Abstracts

We previously reported that tissue N-acetyl aspartate content correlates with tissue glutamate and creatine content in the epileptogenic human hippocampus [Ann Neurol 2002;52:635-642, Neurology 2003;60:1646-1651]. There were no significant associations among these three metabolites and hippocampal neuron loss nor glial density. We now investigate what associations are present among these metabolites in the middle temporal gyrus and hippocampus of patients with hippocampal sclerosis. Fourteen patients, who agreed to temporal lobectomy, participated in this study after informed consent was obtained using a protocol approved by the Yale IRB. All tissues were resected for therapeutic reasons, not experimental ones. With the blood supply intact, paired biopsy samples of the middle temporal gyrus and pes of the hippocampus were removed and frozen. As described previously, metabolite content was analyzed after perchloric acid extraction by high-resolution magnetic resonance spectroscopy. Intracellular glutamate and N-acetyl aspartate (NAA) content were slightly lower in the pes, which reached trend significance (p[sim]0.08) for NAA, but not glutamate (p[sim]0.24). Total creatine content was slightly higher in the pes (p[sim]0.23). Hippocampal neuron density was 36% (se 3%) and glial density was 180% (se 9%) of autopsy controls. Highly significant associations (p[lt]0.001) were seen among NAA, glutamate, and total creatine in the middle temporal gyrus. Similar, highly significant associations were seen among NAA, glutamate, and total creatine in the hippocampus. There is a significant association (p[lt]0.01) between the NAA content of the middle temporal gyrus and the hippocampus. Trends, which failed to reach the 0.05 significance level, were present for the intracellular content of glutamate (p[sim]0.08) and total creatine (p[sim]0.09) between the lateral temporal neocortex and hippocampus. Our study provides further support for the concept that N-acetyl-aspartate levels reflect mitochondrial function and thus energy state rather than neuronal or axonal loss in mesial temporal lobe epilepsy. (Supported by NIH-NINDS NS39092.)