0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Contribution |

In Vivo Hippocampal Metabolic Dysfunction in Human Temporal Lobe Epilepsy FREE

Robert C. Knowlton, MD; Bassel Abou-Khalil, MD; Stephen M. Sawrie, PhD; Roy C. Martin, PhD; R. Edward Faught, MD; Ruben I. Kuzniecky, MD
[+] Author Affiliations

From the UAB Epilepsy Center, Department of Neurology, University of Alabama at Birmingham School of Medicine (Drs Knowlton, Sawrie, Martin, Faught, and Kuzniecky); and Department of Neurology, Vanderbilt University School of Medicine, Nashville, Tenn (Dr Abou-Khalil).


Arch Neurol. 2002;59(12):1882-1886. doi:10.1001/archneur.59.12.1882.
Text Size: A A A
Published online

Background  The nature of functional metabolic disturbances in mesial temporal lobe epilepsy remains unclear.

Objectives  To compare in vivo measures of hippocampal metabolic abnormalities in mesial temporal lobe epilepsy, as acquired with fludeoxyglucose F 18 positron emission tomography and proton magnetic resonance spectroscopic imaging, and to determine the relationship between N-acetylaspartate (NAA) disturbances and well-established derangements of glucose metabolism.

Design  Measures of hippocampal glucose metabolism from fludeoxyglucose F 18 positron emission tomography were normalized to whole brain counts to provide a glucose uptake metabolic index. Proton magnetic resonance spectroscopic imaging was performed at 4.1 T, and measures of creatinine/NAA ratio were made from mostly hippocampal-only voxels. Direct comparisons and correlation analysis of measures were performed.

Setting  Presurgical evaluations for treatment of intractable epilepsy.

Patients  Twenty-nine patients between July 1994 and June 1996 who were candidates for anterior-medial temporal lobectomy at the epilepsy centers of the University of Alabama at Birmingham and Vanderbilt University schools of medicine were studied.

Results  The mean ipsilateral hippocampal glucose metabolic index (0.85) was normal, while the contralateral metabolic index (0.95) was nearly significant for an abnormally elevated measure. The mean ipsilateral hippocampal creatinine/NAA (1.26) was abnormally elevated; the mean contralateral creatinine/NAA (0.88) was normal. Hippocampal glucose and creatinine/NAA measures did not correlate; asymmetry measures also did not correlate.

Conclusions  Hippocampal metabolic disturbances in mesial temporal lobe epilepsy as measured by fludeoxyglucose F 18 positron emission tomography vs proton magnetic resonance spectroscopic imaging reflect different mechanisms of biochemical dysfunction. This lack of correlation is hypothesized to reflect a differential effect of varying degrees of disturbed cellular energy metabolism on mechanisms of glucose use and biosynthesis of NAA.

Figures in this Article

INTERICTAL DISTURBANCES of glucose uptake and N-acetylated compounds (mainly N-acetylaspartate [NAA]) are detected with high sensitivity in the temporal lobes of patients with mesial temporal lobe epilepsy (MTLE).15 However, the causes of interictal hypometabolism and abnormal NAA measures in MTLE remain unknown. Evidence suggests that glucose and NAA disturbances might be related. Both are decreased in the epileptogenic temporal lobes of patients with MTLE1,3,5; both appear to be at least partly independent of hippocampal neuronal cell loss6,7; both reflect dynamic or reversible abnormalities810; and both may be disturbed by abnormal synaptic activity.11,12 Other evidence, however, suggests different underlying mechanisms in the dynamic nature of these metabolic intermediates. Most obvious is the fact that glucose measures may change acutely. For example, glucose uptake increases with seizure activity13 and normal activation of neuronal populations,14 while NAA measures do not appear to change in such settings.15 Furthermore, more specifically in MTLE, interictal glucose uptake appears to be increased in the mesial temporal region contralateral to the side of the epilepsy,16 while NAA measures from the contralateral side are decreased or normal.17

With normative control data from fludeoxyglucose F 18 positron emission tomography (FDG-PET) and proton magnetic resonance spectroscopic imaging (1H MRSI), we addressed questions regarding the relationships between disturbed interictal, predominantly hippocampal glucose and NAA measures in MTLE. Our aims were: (1) to determine whether hippocampal changes in glucose uptake and NAA measures correlate; (2) to determine if the degree of asymmetry measures correlate; and (3) to elucidate any significant differences between hippocampal glucose and NAA measures that may exist. We hypothesized that, although FDG uptake and the relative concentration of NAA may indirectly reflect the same underlying causes of neuronal loss and dysfunction in hippocampi of MTLE, the degree of abnormality for each measure was not correlated. We based this on the understanding that, although neuronal metabolic energy disturbances may affect glucose uptake and NAA concentrations, the biochemical mechanisms leading to the changes in each metabolic intermediate are different.

PATIENTS

Twenty-nine patients between July 1994 and June 1996 who were candidates for anterior-medial temporal lobectomy at the epilepsy centers of the University of Alabama at Birmingham and Vanderbilt University schools of medicine and who were able to complete PET and MRSI examinations were studied. For both procedures, informed consent was obtained according to the guidelines of the universities' institutional review boards. Surgical candidates were excluded if structural imaging revealed pathologic conditions other than evidence for mesial temporal sclerosis. Magnetic resonance imaging evidence of mesial temporal sclerosis was not required. Diagnosis and lateralization of MTLE were based on inpatient interictal and ictal electroencephalographic findings and video monitoring with or without sphenoidal electrodes.

Of the 29 patients in the study, 19 were female. The mean age at evaluation was 34 years (range, 15-44 years). The mean age at seizure onset was 16 years (range, 2-36 years). Nineteen patients had their seizures lateralized to the left temporal lobe and 10 to the right temporal lobe. Twenty-three patients had anterior-medial temporal lobectomy (mean outcome follow-up, >4 years): 17 (74%) are seizure free (Engel18 class I) and 6 (26%) are not seizure free (Engel class II-IV). Histopathologic examination of hippocampal tissue showed a variable degree of astrogliosis and neuronal cell loss in all cases.

CONTROL SUBJECTS

Separate control subjects were studied for PET and MRSI normative data.

Positron emission tomographic scans were performed in 10 neurologically normal subjects (6 women), with a mean age of 31 years (range, 24-37 years). Magnetic resonance spectroscopic imaging studies were performed in 20 normal volunteers (9 women), with a mean age of 35 years (range, 23-50 years).

FDG-PET STUDIES

All PET scans were performed at Vanderbilt University on an ECAT 933/08/16 (Siemens Gammasonics, Knoxville, Tenn). The effective in-plane resolution was 6.5 × 6.5 × 8.0 mm. Fifteen tomographic planes were obtained simultaneously, with a scanning time of 17 minutes. Before emission scans, a transmission scan was obtained and a measured attenuation correction was performed.

All images were reoriented to the midline of the brain to be parallel to the anterior commissure–posterior commissure line. The Talairach and Tournoux atlas19 was used for anatomical localization. Hippocampal regions of interest were manually drawn on axial plane 12 (Figure 1 and Figure 2). Raw counts for individual regions of interest were normalized to whole brain counts (all slices except those that include predominantly temporal lobe regions) to provide a unitless FDG metabolic index that could be compared across subjects.

Place holder to copy figure label and caption
Figure 1.

Oblique transaxial slice of fludeoxyglucose F 18 positron emission tomography scan through the plane of the hippocampi. Manually drawn contours of the hippocampal region are displayed to show the region of sampling for analysis of hippocampal metabolism.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

A, Transaxial magnetic resonance imaging slice along the longitudinal axis of the hippocampi. White outlined boxes illustrate the actual 2-dimensional size of voxels (no other voxels of the spectroscopic image plane are shown). B, Spectroscopic imaging of creatinine–N-acetylaspartate at the same plane as in A. The brighter left hippocampus is the abnormal side with decreased N-acetylaspartate.

Graphic Jump Location
MRI STUDIES

Magnetic resonance imaging studies were performed at the University of Alabama at Birmingham using a standard protocol in an MRI scanner (ACS Unit; Philips; Best, the Netherlands) operating at a field strength of 1.5 T. All patients and controls were studied using the same temporal lobe protocol. For volumetric studies, a volume acquisition (3-dimensional) of the entire brain was acquired using a T1-weighted sequence with an echo time of 6.1 milliseconds, a repetition time of 20.0 milliseconds, a field of view of 23.0 cm, and a flip angle of 28° in a plane perpendicular to the long axis of the hippocampus (1.5-mm-thick slices, 0 gap).

1H MRSI

All 1H-MRSI studies were performed at the University of Alabama at Birmingham before electrode implantation or surgical resection and with approval by the institutional review board. Magnetic resonance spectroscopic imaging data were acquired using a 4.1-T whole body imaging–spectroscopy system and quadrature-driven tunable matchable head coil.20 Sagittal scout images were acquired using a segmented (8 encodes per inversion pulse) inversion recovery gradient echo sequence (repetition time/inversion recovery delay/echo time, 2500/1000/15 milliseconds).21 The details of MRSI acquisition and metabolite analysis have been previously published.22

Table 1 shows the mean values of normalized FDG uptake and creatinine/NAA (Cr/NAA) measured in the hippocampus of normal controls and patients.

Table Graphic Jump LocationMean Hippocampal Values of Normalized Fludeoxyglucose F 18 (FDG) Uptake and Creatinine–N-Acetylaspartate (Cr/NAA)*
HIPPOCAMPAL ABNORMALITIES
Group Data

The mean normalized hippocampal FDG uptake measures for left and right hippocampi were 0.89 and 0.91, respectively. Both values were within normal limits and just slightly greater than the normal mean of 0.88. The mean ipsilateral uptake was 0.85; the contralateral mean uptake was 0.95. Neither value was abnormal (outside the range of 2 SDs); however, the contralateral value was nearly significant for an abnormally elevated measure. The mean asymmetry (ipsilateral minus contralateral, asymmetry index = 11.64%) was significantly greater than the mean of the controls, the direction of asymmetry reflecting a significant relative ipsilateral decrease in glucose uptake. The mean hippocampal Cr/NAA for left and right hippocampi was 1.04 and 1.10, respectively. Both values were abnormally high. The mean ipsilateral Cr/NAA was 1.26; the contralateral measure was 0.88. The ipsilateral value was highly abnormal, while the contralateral value was normal. The mean asymmetry (ipsilateral minus contralateral, asymmetry index = 59.69%) was markedly abnormal, the direction of asymmetry reflecting a significant relative ipsilateral decrease in NAA.

Individual Patients

Ten (34%) of the 29 patients had abnormally decreased ipsilateral hippocampal FDG uptake, while 8 (28%) had abnormally elevated contralateral uptake. Eighteen patients (62%) had significantly asymmetric (asymmetry index >9%) hippocampal uptake. All lateralizing asymmetry was concordant with electroencephalographic lateralization.

Twenty-three patients (79%) had abnormally increased ipsilateral hippocampal Cr/NAA, while 8 patients (28%) had abnormally increased contralateral hippocampal Cr/NAA. Twenty-six patients (90%) had significantly asymmetric (asymmetry index >12%) hippocampal Cr/NAA values. Lateralizing asymmetry was discordant with electroencephalographic findings in 3 patients.

GLUCOSE–Cr/NAA CORRELATION

When all hippocampi were examined (N = 58), no correlation was found between normalized hippocampal FDG uptake and Cr/NAA values (r = −0.009, P = .95). When ipsilateral and contralateral measures were examined separately, neither ipsilateral (r = −0.12, P = .55) nor contralateral (r = 0.25, P = .19) metabolic indexes correlated. The hippocampal FDG and Cr/NAA asymmetry measures (larger-smaller and ipsilateral-contralateral) did not correlate (r = 0.11, P = .59 and r = −0.07, P = .74); however, left-right asymmetry was strongly correlated (r = −0.51, P = .005).

The major finding of this work was the lack of individual and group correlation between in vivo hippocampal glucose uptake and Cr/NAA concentration in patients with MTLE. Also notable was that the sensitivity of detecting ipsilateral hippocampal abnormality of Cr/NAA concentration (79%) was much greater than that of hippocampal FDG uptake (34%).

The absence of an association between hippocampal FDG uptake and NAA concentration has 2 explanations, which are not mutually exclusive: (1) the differences in sensitivity between the techniques are incongruent over the range of abnormality and (2) the underlying mechanisms for these disturbances are different, whether or not they are directly or indirectly related to the same pathogenesis. This is not necessarily an unexpected finding, yet prior FDG-PET and MRSI studies1,5 have suggested that glucose and NAA disturbances may be related. At the same time, these studies acknowledge the complementary nature of epilepsy lateralization provided by the different modalities. Furthermore, the high sensitivity of FDG-PET lateralization, which may parallel that demonstrated with 1H MRSI, reflects much more extensive temporal lobe metabolic disturbances, specifically as seen in the extrahippocampal regions of the temporal pole and anterior-lateral neocortex. In contrast, our findings involving measures predominantly from the hippocampus reveal that abnormal NAA concentration is detected with a greater sensitivity compared with abnormal glucose metabolism.

In further contrast between glucose uptake and NAA disturbances, contralateral hippocampal FDG uptake appears to change in a direction opposite that of the relative concentration of NAA. Our normalized measures of hippocampal-specific FDG uptake are comparable to those measured by Rubin et al,16 who found increased mesiobasal temporal metabolic indexes. We did not find abnormally elevated ipsilateral hippocampal glucose metabolism; however, our mean value was normal (not abnormally low). Although our contralateral hippocampal metabolic measurement with FDG was not outside 2 SDs of normal, it was nearly so in the direction of being elevated. Therefore, if actual FDG uptake in the hippocampus is normal or elevated, it should not be expected that hippocampal glucose metabolism would correlate with the established expectation of relative decreases in NAA concentration of the same region.

This observed difference in apparent direction of contralateral abnormality is of particular interest. Proton magnetic resonance spectroscopic temporal lobe epilepsy studies2,17,2225 have consistently demonstrated a high sensitivity to detect abnormally low measures of NAA in the contralateral mesial temporal lobe regions. The high sensitivity has been explained by the likelihood of contralateral cryptic hippocampal sclerosis, as reported in one autopsy series.26 However, this simple explanation does not hold up after demonstration that contralateral decreases in NAA measures are reversible, as seen in patients who became seizure free after surgery.9,10 This important finding has emphasized the functional or dynamic component of NAA measurement—most important, that it is not simply a measure of irreversible neuronal loss.

Of separate issue in the examination of relationships between PET measurement of glucose uptake and 1H MRSI measurement of NAA is the problem that the basic mechanisms responsible for these disturbances in MTLE remain unclear. Glucose is effectively the sole energy substrate for the human brain, and its uptake as measured by FDG-PET is believed to predominantly reflect synaptic activity.27 Neuronal loss in mesial temporal sclerosis may affect glucose metabolism, but increased synaptic activity (excitatory and inhibitory) and energy associated with synaptic reorganization may unpredictably offset the net glucose use in sclerotic hippocampi. In contrast, the measurement of decreased NAA may reflect multiple causes, including a decrease in neuronal cell density, neuronal or axonal shrinkage with a relative increase in tissue water, or metabolic dysfunction.28 The latter may reflect a decrease in NAA synthesis, an increase in its catabolism, or a combination of both.

Before further discussion of any putative hypothesis or interpretation of our findings, limitations of the work, mostly regarding methods, must be emphasized. In a region as small as the hippocampus, partial volume effects compromise our measurements from PET29 and 1H MRSI.30,31 As such, it is difficult to determine whether estimates of the hippocampal gray matter component in the different measures were roughly equal (with respect to proportion and distribution of instrument sampling). If the measures are grossly unequal, then tests of correlation will not be valid. We attempted to minimize partial volume effects by designating contours of the PET hippocampal regions of interest clearly within the outer margins of the hippocampal tracer activity. For 1H MRSI, the exclusion of voxels not involving hippocampal tissue and high resolution provided by the improved signal to noise from our 4.1-T magnet allowed maximal measurement of predominantly hippocampal gray matter and minimized the partial volume effect as much as possible without tissue segmentation.32

Another issue is our assumption that the measure of Cr/NAA is a reliable measure of NAA change. Although it is ideal to measure the actual concentration of NAA, the methods are particularly complex and not always practical. Fortunately, prior work that measured the concentration of hippocampal creatinine in MTLE showed that it was not significantly different from the mean of control subjects.17 Therefore, until efficient and reliable measures of actual concentration of NAA become more routine, relative values such as the measure of NAA to Cr or NAA to (choline plus Cr) remain commonly used practical measures of relative NAA change.

Our hypothesis that these measures of metabolic disturbance were not related was based mainly on the expectation that mechanisms underlying interictal changes in glucose uptake and relative NAA concentration have a differential dependence on the neuronal cellular energy state. It would be expected that, in the progression of disturbed neuronal energy maintenance, NAA concentration would decrease at a time when glucose uptake would not. This would occur early, at a time when mitochondrial function is compromised but when other mechanisms of cellular energy maintenance are preserved. N-acetylaspartate synthesis by the mitochondrial enzyme L-aspartate N-acetyltransferase is dependent on the mitochondrial concentration of acetyl coenzyme A.33 When the tricarboxylic acid cycle is operating normally, sufficient acetyl coenzyme A should be produced for normal synthesis of NAA. When mitochondrial enzymes—either the enzyme complexes of oxidative phosphorylation or the regulated pyruvate dehydrogenase complex—begin to dysfunction, acetyl coenzyme A production would diminish such that NAA synthesis is affected. Early in this process of dysfunction, before occurrence of cellular energy failure, glucose uptake would remain normal or elevated, because glycolysis would still be functioning to maintain cellular energy charge. Such a proposed explanation, although without many of the mechanistic details elucidated, allows for the disassociation between glucose uptake and NAA measures in MTLE, as well as their reversibility or dynamic nature and the possibility for a normal or relative net increase in glucose metabolism. Furthermore, preliminary work with phosphorus P 31 MRSI shows no net change in energy charge occurring in the interictal state, based on the observation that the adenosine triphosphate concentration does not change significantly.34 Finally, 1H MRSI studies35,36 of lactate provide evidence that an elevation of lactate may exist interictally in epileptogenic tissue, supporting the possibility that some degree of anaerobic glycolysis may occur in an attempt to maintain cellular energy charge.

Two important questions remain: (1) What pathogenesis associated with epilepsy causes glucose hypometabolism that is reversible without irreversible neuronal injury or death? and (2) What causes reversible neuronal cellular dysfunction in and around epileptogenic tissue? The first may in part be simply explained by net changes in regional neuronal synaptic activity. This is an important variable that appears to be mostly independent of NAA changes, for neuronal activity changes associated with seizures and the postictal state appear to cause no significant change in MRSI measures of NAA.15 The second question remains unanswered on 2 levels: (1) What might be responsible for long-term decreased interictal neuronal synaptic activity? and (2) What might be the cause of reversible mitochondrial dysfunction? In vitro rat brain studies37,38 show decreased concentration of NAA (due to decreased synthesis) with inhibition of mitochondrial respiratory chain enzymes, including inhibition that is not to such a degree that the cells become irreversibly injured. Further supporting a hypothesis that proposes dysfunctional mitochondrial synthesis of NAA as a cause for its decreased measure in epileptogenic tissue is evidence from human PET and MRSI investigations of mitochondrial encephalomyelopathies that demonstrates a connection between chronic defects in oxidative phosphorylation and epileptogenesis.39 Moreover, recent work provides direct evidence that mitochondrial dysfunction exists in epileptogenic tissue of human temporal lobe epilepsy.40

Accepted for publication August 20, 2002.

This work was supported by grant R01 NS33919 from the National Institutes of Health, Bethesda, Md.

Author contributions: Study concept and design (Drs Knowlton, Martin, and Kuzniecky); acquisition of data (Dr Abou-Khalil); analysis and interpretation of data (Drs Knowlton, Abou-Khalil, and Sawrie); drafting of the manuscript (Dr Knowlton); critical revision of the manuscript for important intellectual content (Drs Knowlton, Abou-Khalil, Sawrie, Martin, Faught, and Kuzniecky); statistical expertise (Drs Sawrie and Martin); obtained funding (Dr Kuzniecky); administrative, technical, or material support (Drs Knowlton, Abou-Khalil, Faught, and Kuzniecky); study supervision (Dr Knowlton).

Corresponding author and reprints: Robert C. Knowlton, MD, UAB Epilepsy Center, Department of Neurology, University of Alabama at Birmingham School of Medicine, 312 Civitan International Research Center, 1719 Sixth Ave S, Birmingham, AL 35294-0021 (e-mail: knowlton@uab.edu).

Achten  ESantens  PBoon  P  et al Single-voxel proton MR spectroscopy and positron emission tomography for lateralization of refractory temporal lobe epilepsy. AJNR Am J Neuroradiol.1998;19:1-8.
Cendes  FCaramanos  ZAndermann  FDubeau  FArnold  DL Proton magnetic resonance spectroscopic imaging and magnetic resonance imaging volumetry in the lateralization of temporal lobe epilepsy: a series of 100 patients. Ann Neurol.1997;42:737-746.
Knowlton  RCLaxer  KDEnde  G  et al Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy. Ann Neurol.1997;42:829-837.
Kuzniecky  RHugg  JWHetherington  H  et al Relative utility of 1H spectroscopic imaging and hippocampal volumetry in the lateralization of mesial temporal lobe epilepsy. Neurology.1998;51:66-71.
Lu  DMargouleff  CRubin  E  et al Temporal lobe epilepsy: correlation of proton magnetic resonance spectroscopy and 18F-fluorodeoxyglucose positron emission tomography. Magn Reson Med.1997;37:18-23.
Henry  TRBabb  TLEngel Jr  J  et al Hippocampal neuronal loss and regional hypometabolism in temporal lobe epilepsy. Ann Neurol.1994;36:925-927.
Kuzniecky  RKnowlton  RHug  J  et al Hippocampal 1H spectroscopic imaging in mesial temporal lobe epilepsy: correlation with histopathology of mesial temporal sclerosis [abstract]. Neurology.2000;54(suppl 3):A4.
Hajek  MWieser  HGKhan  N  et al Preoperative and postoperative glucose consumption in mesiobasal and lateral temporal lobe epilepsy. Neurology.1994;44:2125-2132.
Hugg  JWKuzniecky  RIGilliam  FG  et al Normalization of contralateral metabolic function following temporal lobectomy demonstrated by 1H magnetic resonance spectroscopic imaging. Ann Neurol.1996;40:236-239.
Cendes  FAndermann  FDubeau  FMatthews  PMArnold  DL Normalization of neuronal metabolic dysfunction after surgery for temporal lobe epilepsy: evidence from proton MR spectroscopic imaging. Neurology.1997;49:1525-1533.
Rango  MSpangnoli  DTomei  GBamonti  FScarlato  GZetta  L Central nervous system trans-synaptic effects of acute axonal injury: a 1H magnetic resonance spectroscopy study. Magn Reson Med.1995;33:595-600.
Magistretti  PJPellerin  L Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci.1999;354:1155-1163.
Engel  JJKuhl  DEPhelps  ME Patterns of human local cerebral glucose metabolism during epileptic seizures. Science.1982;218:64-66.
Fox  PTRaichle  MEMintun  MADence  C Nonoxidative glucose consumption during focal physiologic neural activity. Science.1988;241:462-464.
Cendes  FStanley  JADubeau  FAndermann  FArnold  DL Proton magnetic resonance spectroscopic imaging for discrimination of absence and complex partial seizures. Ann Neurol.1997;41:74-81.
Rubin  EDhawan  VMoeller  JR  et al Cerebral metabolic topography in unilateral temporal lobe epilepsy. Neurology.1995;45:2212-2223.
Ende  GLaxer  KDKnowlton  RCMatson  GBWeiner  MW Quantitative 1H-SI shows bilateral metabolite changes in unilateral TLE patients with and without hippocampal atrophy.  In: Proceedings of the Third Annual Meeting of the Society of Magnetic Resonance; August 19-25, 1995; Nice, France.
Engel  JJ Outcome with respect to epileptic seizures.  In: Engel  JJ, ed. Surgical Treatment of the Epilepsies. New York, NY: Raven Press; 1987:553-571.
Talairach  JTournoux  P Coplanar Stereotaxic Atlas of the Human Brain.  New York, NY: Thieme-Stratton Inc; 1988.
Vaughan  JTHetherington  HPOtu  JOPan  JWPohost  GM High frequency volume coils for clinical NMR imaging and spectroscopy. Magn Reson Med.1994;32:206-218.
Pan  JWVaughan  JTKuzniecky  RIPohost  GMHetherington  HP High resolution neuroimaging at 4.1T. Magn Reson Imaging.1995;13:915-921.
Hetherington  HKuzniecky  RPan  J  et al Proton nuclear magnetic resonance spectroscopic imaging of human temporal lobe epilepsy at 4.1 T. Ann Neurol.1995;38:396-404.
Connelly  AJackson  GDDuncan  JSKing  MDGadian  DG Magnetic resonance spectroscopy in temporal lobe epilepsy. Neurology.1994;44:1411-1417.
Ng  TCComair  YGXue  M  et al Temporal lobe epilepsy: presurgical localization with proton chemical shift imaging. Radiology.1994;193:465-472.
Cross  JHConnelly  AJackson  GD  et al Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy. Ann Neurol.1996;39:107-113.
Margerison  JHCorsellis  JAN Epilepsy and the temporal lobes: a clinical, electroencephalographic and neuropathological study of the brain in epilepsy, with particular reference to the temporal lobes. Brain.1966;89:499-530.
Bruehl  CWitte  OW Cellular activity underlying altered brain metabolism during focal epileptic activity. Ann Neurol.1995;38:414-420.
Tsai  GCoyle  JT N-acetylaspartate in neuropsychiatric disorders. Prog Neurobiol.1995;46:531-540.
Labbe  CFroment  JCKennedy  AAshburner  JCinotti  L Positron emission tomography metabolic data corrected for cortical atrophy using magnetic resonance imaging. Alzheimer Dis Assoc Disord.1996;10:141-170.
Strauss  WLTsuruda  JSRichards  TL Partial volume effects in volume-localized phased-array proton spectroscopy of the temporal lobe. J Magn Reson Imaging.1995;5:433-436.
O'Neill  JEberling  JLSchuff  N  et al Method to correlate 1H MRSI and 18FDG-PET. Magn Reson Med.2000;43:244-250.
Hetherington  HPPan  JWChu  WJMason  GFNewcomer  BR Biological and clinical MRS at ultra-high field. NMR Biomed.1997;10:360-371.
Berlinguet  LLaliberte  M Biosynthesis of N-acetyl-L-aspartic acid in vivo and in brain homogenates. Can J Biochem.1970;48:207-211.
Hugg  JWLaxer  KDMatson  GBMaudsley  AAHusted  CAWeinger  MW Lateralization of human focal epilepsy by 31P magnetic resonance spectroscopic imaging. Neurology.1992;42:2011-2018.
Aasly  JSilfvenius  HAas  TC  et al Proton magnetic resonance spectroscopy of brain biopsies from patients with intractable epilepsy. Epilepsy Res.1999;35:211-217.
Hill  RAChiappa  KHHuang-Hellinger  FJenkins  BG Hemodynamic and metabolic aspects of photosensitive epilepsy revealed by functional magnetic resonance imaging and magnetic resonance spectroscopy. Epilepsia.1999;40:912-920.
Bates  TEStrangward  MKeelan  J  et al Inhibition of N-acetylaspartate production: implications for 1H MRS studies in vivo. Neuroreport.1996;7:1397-1400.
Dautry  CVaufrey  FBrouillet  E  et al Early N-acetylaspartate depletion is a marker of neuronal dysfunction in rats and primates chronically treated with the mitochondrial toxin 3-nitropropionic acid. J Cereb Blood Flow Metab.2000;20:789-799.
Berkovic  SFCarpenter  SEvans  A  et al Myoclonus epilepsy and ragged-red fibres (MERRF), I: a clinical, pathological, biochemical, magnetic resonance spectrographic and positron emission tomographic study. Brain.1989;112:1231-1260.
Kunz  WSKudin  APVielhaber  S  et al Mitochondrial complex I deficiency in the epileptic focus of patients with temporal lobe epilepsy. Ann Neurol.2000;48:766-773.

Figures

Place holder to copy figure label and caption
Figure 1.

Oblique transaxial slice of fludeoxyglucose F 18 positron emission tomography scan through the plane of the hippocampi. Manually drawn contours of the hippocampal region are displayed to show the region of sampling for analysis of hippocampal metabolism.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

A, Transaxial magnetic resonance imaging slice along the longitudinal axis of the hippocampi. White outlined boxes illustrate the actual 2-dimensional size of voxels (no other voxels of the spectroscopic image plane are shown). B, Spectroscopic imaging of creatinine–N-acetylaspartate at the same plane as in A. The brighter left hippocampus is the abnormal side with decreased N-acetylaspartate.

Graphic Jump Location

Tables

Table Graphic Jump LocationMean Hippocampal Values of Normalized Fludeoxyglucose F 18 (FDG) Uptake and Creatinine–N-Acetylaspartate (Cr/NAA)*

References

Achten  ESantens  PBoon  P  et al Single-voxel proton MR spectroscopy and positron emission tomography for lateralization of refractory temporal lobe epilepsy. AJNR Am J Neuroradiol.1998;19:1-8.
Cendes  FCaramanos  ZAndermann  FDubeau  FArnold  DL Proton magnetic resonance spectroscopic imaging and magnetic resonance imaging volumetry in the lateralization of temporal lobe epilepsy: a series of 100 patients. Ann Neurol.1997;42:737-746.
Knowlton  RCLaxer  KDEnde  G  et al Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy. Ann Neurol.1997;42:829-837.
Kuzniecky  RHugg  JWHetherington  H  et al Relative utility of 1H spectroscopic imaging and hippocampal volumetry in the lateralization of mesial temporal lobe epilepsy. Neurology.1998;51:66-71.
Lu  DMargouleff  CRubin  E  et al Temporal lobe epilepsy: correlation of proton magnetic resonance spectroscopy and 18F-fluorodeoxyglucose positron emission tomography. Magn Reson Med.1997;37:18-23.
Henry  TRBabb  TLEngel Jr  J  et al Hippocampal neuronal loss and regional hypometabolism in temporal lobe epilepsy. Ann Neurol.1994;36:925-927.
Kuzniecky  RKnowlton  RHug  J  et al Hippocampal 1H spectroscopic imaging in mesial temporal lobe epilepsy: correlation with histopathology of mesial temporal sclerosis [abstract]. Neurology.2000;54(suppl 3):A4.
Hajek  MWieser  HGKhan  N  et al Preoperative and postoperative glucose consumption in mesiobasal and lateral temporal lobe epilepsy. Neurology.1994;44:2125-2132.
Hugg  JWKuzniecky  RIGilliam  FG  et al Normalization of contralateral metabolic function following temporal lobectomy demonstrated by 1H magnetic resonance spectroscopic imaging. Ann Neurol.1996;40:236-239.
Cendes  FAndermann  FDubeau  FMatthews  PMArnold  DL Normalization of neuronal metabolic dysfunction after surgery for temporal lobe epilepsy: evidence from proton MR spectroscopic imaging. Neurology.1997;49:1525-1533.
Rango  MSpangnoli  DTomei  GBamonti  FScarlato  GZetta  L Central nervous system trans-synaptic effects of acute axonal injury: a 1H magnetic resonance spectroscopy study. Magn Reson Med.1995;33:595-600.
Magistretti  PJPellerin  L Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos Trans R Soc Lond B Biol Sci.1999;354:1155-1163.
Engel  JJKuhl  DEPhelps  ME Patterns of human local cerebral glucose metabolism during epileptic seizures. Science.1982;218:64-66.
Fox  PTRaichle  MEMintun  MADence  C Nonoxidative glucose consumption during focal physiologic neural activity. Science.1988;241:462-464.
Cendes  FStanley  JADubeau  FAndermann  FArnold  DL Proton magnetic resonance spectroscopic imaging for discrimination of absence and complex partial seizures. Ann Neurol.1997;41:74-81.
Rubin  EDhawan  VMoeller  JR  et al Cerebral metabolic topography in unilateral temporal lobe epilepsy. Neurology.1995;45:2212-2223.
Ende  GLaxer  KDKnowlton  RCMatson  GBWeiner  MW Quantitative 1H-SI shows bilateral metabolite changes in unilateral TLE patients with and without hippocampal atrophy.  In: Proceedings of the Third Annual Meeting of the Society of Magnetic Resonance; August 19-25, 1995; Nice, France.
Engel  JJ Outcome with respect to epileptic seizures.  In: Engel  JJ, ed. Surgical Treatment of the Epilepsies. New York, NY: Raven Press; 1987:553-571.
Talairach  JTournoux  P Coplanar Stereotaxic Atlas of the Human Brain.  New York, NY: Thieme-Stratton Inc; 1988.
Vaughan  JTHetherington  HPOtu  JOPan  JWPohost  GM High frequency volume coils for clinical NMR imaging and spectroscopy. Magn Reson Med.1994;32:206-218.
Pan  JWVaughan  JTKuzniecky  RIPohost  GMHetherington  HP High resolution neuroimaging at 4.1T. Magn Reson Imaging.1995;13:915-921.
Hetherington  HKuzniecky  RPan  J  et al Proton nuclear magnetic resonance spectroscopic imaging of human temporal lobe epilepsy at 4.1 T. Ann Neurol.1995;38:396-404.
Connelly  AJackson  GDDuncan  JSKing  MDGadian  DG Magnetic resonance spectroscopy in temporal lobe epilepsy. Neurology.1994;44:1411-1417.
Ng  TCComair  YGXue  M  et al Temporal lobe epilepsy: presurgical localization with proton chemical shift imaging. Radiology.1994;193:465-472.
Cross  JHConnelly  AJackson  GD  et al Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy. Ann Neurol.1996;39:107-113.
Margerison  JHCorsellis  JAN Epilepsy and the temporal lobes: a clinical, electroencephalographic and neuropathological study of the brain in epilepsy, with particular reference to the temporal lobes. Brain.1966;89:499-530.
Bruehl  CWitte  OW Cellular activity underlying altered brain metabolism during focal epileptic activity. Ann Neurol.1995;38:414-420.
Tsai  GCoyle  JT N-acetylaspartate in neuropsychiatric disorders. Prog Neurobiol.1995;46:531-540.
Labbe  CFroment  JCKennedy  AAshburner  JCinotti  L Positron emission tomography metabolic data corrected for cortical atrophy using magnetic resonance imaging. Alzheimer Dis Assoc Disord.1996;10:141-170.
Strauss  WLTsuruda  JSRichards  TL Partial volume effects in volume-localized phased-array proton spectroscopy of the temporal lobe. J Magn Reson Imaging.1995;5:433-436.
O'Neill  JEberling  JLSchuff  N  et al Method to correlate 1H MRSI and 18FDG-PET. Magn Reson Med.2000;43:244-250.
Hetherington  HPPan  JWChu  WJMason  GFNewcomer  BR Biological and clinical MRS at ultra-high field. NMR Biomed.1997;10:360-371.
Berlinguet  LLaliberte  M Biosynthesis of N-acetyl-L-aspartic acid in vivo and in brain homogenates. Can J Biochem.1970;48:207-211.
Hugg  JWLaxer  KDMatson  GBMaudsley  AAHusted  CAWeinger  MW Lateralization of human focal epilepsy by 31P magnetic resonance spectroscopic imaging. Neurology.1992;42:2011-2018.
Aasly  JSilfvenius  HAas  TC  et al Proton magnetic resonance spectroscopy of brain biopsies from patients with intractable epilepsy. Epilepsy Res.1999;35:211-217.
Hill  RAChiappa  KHHuang-Hellinger  FJenkins  BG Hemodynamic and metabolic aspects of photosensitive epilepsy revealed by functional magnetic resonance imaging and magnetic resonance spectroscopy. Epilepsia.1999;40:912-920.
Bates  TEStrangward  MKeelan  J  et al Inhibition of N-acetylaspartate production: implications for 1H MRS studies in vivo. Neuroreport.1996;7:1397-1400.
Dautry  CVaufrey  FBrouillet  E  et al Early N-acetylaspartate depletion is a marker of neuronal dysfunction in rats and primates chronically treated with the mitochondrial toxin 3-nitropropionic acid. J Cereb Blood Flow Metab.2000;20:789-799.
Berkovic  SFCarpenter  SEvans  A  et al Myoclonus epilepsy and ragged-red fibres (MERRF), I: a clinical, pathological, biochemical, magnetic resonance spectrographic and positron emission tomographic study. Brain.1989;112:1231-1260.
Kunz  WSKudin  APVielhaber  S  et al Mitochondrial complex I deficiency in the epileptic focus of patients with temporal lobe epilepsy. Ann Neurol.2000;48:766-773.

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 16

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics
PubMed Articles