Subfield-specific loss of hippocampal N-acetyl aspartate in temporal lobe epilepsy.
OBJECTIVE
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 ((1)H-MRS) reflects the epilepsy-associated loss of hippocampal pyramidal neurons or metabolic dysfunction.


METHODS
To address this problem, we applied high-resolution (1)H-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.
Vielhaber
Stefan
S
Department of Neurology II, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
Niessen
Heiko G
HG
Debska-Vielhaber
Grazyna
G
Kudin
Alexei P
AP
Wellmer
Jörg
J
Kaufmann
Jörn
J
Schönfeld
Mircea Ariel
MA
Fendrich
Robert
R
Willker
Wieland
W
Leibfritz
Dieter
D
Schramm
Johannes
J
Elger
Christian E
CE
Heinze
Hans-Jochen
HJ
Kunz
Wolfram S
WS
D000154:Aconitate Hydratase / Q000032:analysis; D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D002452:Cell Count; D004569:Electroencephalography / Q000706:statistics & numerical data; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007773:Lactates / Q000032:analysis / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D009682:Magnetic Resonance Spectroscopy / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000473:pathology; D020534:Parahippocampal Gyrus / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D011300:Preoperative Care; D017966:Pyramidal Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D012598:Sclerosis; D013386:Succinates / Q000032:analysis / Q000378:metabolism