Hippocampal N‐acetylaspartate in neocortical epilepsy and mesial temporal lobe epilepsy

Abstract

Previous magnetic resonance spectroscopy (MRS) studies have shown that N-acetylaspartate (NAA) is reduced not only in the ipsilateral but also in the contralateral hippocampus of many patients with mesial temporal lobe epilepsy (mTLE). The reason for the contralateral damage is not clear. To test whether the hippocampus is also damaged if the focus is outside the hippocampus, we have measured patients with neocortical epilepsy (NE). Therefore, the goals of this study were to determine if hippocampal NAA is reduced in NE and if hippocampal NAA discriminates NE from mTLE. MRS imaging (MRSI) studies were performed on 10 NE patients and compared with MRSI results in 23 unilateral mTLE patients and 16 controls. The results show that, in contrast to mTLE, NAA was not reduced in the hippocampus of NE patients, neither ipsilateral nor contralateral to the seizure focus. These results suggest that repeated seizures do not cause secondary damage to the hippocampus. The absence of spectroscopic differences in NE may help to distinguish NE from mTLE.Approximately 30% of epilepsy patients have neocortical epilepsy (NE) [1] in which, in contrast to mesial temporal lobe epilepsy (mTLE), the focus is outside the hippocampus. Although these patients respond much less well than mTLE patients to medical treatment, neurosurgical removal is performed only rarely and with less success than in mTLE [2].This laboratory and others have previously shown that proton magnetic resonance spectroscopy ( 1 H MRS) can be used to lateralize the seizure focus in mTLE [3][4][5][6][7][8][9][10][11]. The correlation to the epileptogenic focus as defined by electroencephalography (EEG) was done on the basis of reduced N-acetylaspartate (NAA) in the hippocampus and/or the temporal lobe. The reduction was reported either in absolute units or as a ratio to choline-containing compounds (Ch) and/ or creatine/phosphocreatine (Cr). Several recent reports have shown that NAA in the contralateral side is also reduced in many mTLE subjects [8,10,11], suggesting contralateral damage. Structural abnormalities of both hippocampi have also been detected in an autopsy study of TLE [12]. Copyright © 1997 The following are the three possible explanations for the contralateral reduction of NAA in mTLE: (1) bilateral presence of mesial tempotal sclerosis, (2) seizures in one hippocampus causing secondary damage to the opposite hippocampus due to preferential pathways, and (3) damage to the contralateral hippocampus as a result of repeated seizure activity. If repeated seizure activity is responsible for reduced contralateral NAA, hippocampal NAA might also be reduced in NE. Therefore, the primary goal of our study was to determine if hippocampal NAA is reduced in NE. The finding may lead to a better understanding of contralateral damage in mTLE, or point to mechanistic differences between mTLE and NE.In some circumstances it can be difficult to distinguish NE from mTLE. Hence, a secondary goal was to test if hippocampal NAA results could be used to discrimina...

Accumulation of N‐Acetyl‐L‐Aspartate in the Brain of the Tremor Rat, a Mutant Exhibiting Absence‐Like Seizure and Spongiform Degeneration in the Central Nervous System

“…Alternatively, several groups have reported decreased NAA levels estimated by proton magnetic resonance spectroscopy in epileptic patients correlating with increased seizure frequency (Vainio et al, 1994;Vermathen et al, 1997;Mendes-Ribeiro et al, 1998), which appears inconsistent with our results. However, this apparent discrepancy might be explained by the different location of NAA between human epileptic patients and NAA-injected rats.…”

Temporal lobectomy for epilepsy: Recovery of the contralateral hippocampus measured by 1 H MRS

“…6 However, it is possible that functional connections exist between the hippocampi and may contribute to seizure propagation, whereas seizures arising from the neocortex do not affect hippocampal metabolism. …”

“…However, in neocortical epilepsy (NE), no MRS imaging (MRSI) changes in the hippocampus were found, suggesting that repeated seizures in NE do not lead to hippocampal impairment. 6 Reductions of NAA are reversible in some diseases. 4,5,7 If the NAA reduction in the contralateral hippocampus is due to secondary alterations caused by repeated seizures, these changes might be reversible with reduction of seizure frequency.…”

1 H MRSI predicts surgical outcome in MRI-negative temporal lobe epilepsy

“…1 1 H MRS imaging (MRSI) measures a number of metabolites, including N-acetyl aspartate (NAA), a marker of neuron viability and density. 2 1 H MRSI has shown NAA is reduced in the epileptogenic hippocampus, [3][4][5] frequently even when the MRI is normal, 3 suggesting NAA can help identify the seizure focus. Previous studies suggested 1 H MRSI may predict surgical outcome, but most of these subjects had MTS on MRI.…”

“…Spectra from 10 patients and 16 control subjects were processed using Siemens LUISE software (Iselin, NJ), 5 whereas spectra from five patients and 12 control subjects were processed using the FITT program. 6 In order to combine these results, standardized z scores were generated for each patient by comparing their NAA ratios with their contemporaneous normal control subjects.…”