Subfield-specific Loss of Hippocampal N-acetyl Aspartate in Temporal Lobe Epilepsy

Authors


  • Stefan Vielhaber and Heiko G. Niessen contributed equally to this publication

Address correspondence and reprint requests to Wolfram S. Kunz, NeuroCognition, Life & Brain Center, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany. E-mail: wolfram.kunz@ukb.uni-bonn.de

Summary

Purpose: In patients with mesial temporal lobe epilepsy (MTLE) it remains an unresolved issue whether the interictal decrease in N-acetyl aspartate (NAA) detected by proton magnetic resonance spectroscopy (1H-MRS) reflects the epilepsy-associated loss of hippocampal pyramidal neurons or metabolic dysfunction.

Methods: To address this problem, we applied high-resolution 1H-MRS at 14.1 Tesla to measure metabolite concentrations in ex vivo tissue slices from three hippocampal subfields (CA1, CA3, dentate gyrus) as well as from the parahippocampal region of 12 patients with MTLE.

Results: In contrast to four patients with lesion-caused MTLE, we found a large variance of NAA concentrations in the individual hippocampal regions of patients with Ammon's horn sclerosis (AHS). Specifically, in subfield CA3 of AHS patients despite of a moderate preservation of neuronal cell densities the concentration of NAA was significantly lowered, while the concentrations of lactate, glucose, and succinate were elevated. We suggest that these subfield-specific alterations of metabolite concentrations in AHS are very likely caused by impairment of mitochondrial function and not related to neuronal cell loss.

Conclusions: A subfield-specific impairment of energy metabolism is the probable cause for lowered NAA concentrations in sclerotic hippocampi of MTLE patients.

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