Magnetic Resonance Spectroscopic Imaging in Temporal Lobe Epilepsy

Kuzniecky, Ruben; Palmer, Cheryl A.; Hugg, James W.; Martin, Roy C.; Sawrie, Steve; Morawetz, Richard B.; Faught, Edward; Knowlton, Robert C.

doi:10.1001/archneur.58.12.2048

Cited by 103 publications

(82 citation statements)

References 34 publications

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“…8,9,35 Several studies have failed to show any significant relationship between content of NAA and cell death in patients with TLE suggesting that NAA loss reflects metabolic dysfunction rather than neuronal loss. 19,26,36,37 Therefore, decreases in NAA content further support our findings of reduced neuronal metabolism. Moreover, alterations of NAD(P)H transients during neuronal activation, a measure of dysfunctional oxidative and/or glycolytic energy metabolism, was revealed by fluorescence recording of hippocampal slices of human tissue from TLE patients.…”

Section: Amino-acid and Neurotransmitter Metabolismsupporting

confidence: 88%

Brain Mitochondrial Metabolic Dysfunction and Glutamate Level Reduction in the Pilocarpine Model of Temporal Lobe Epilepsy in Mice

Smeland

Hadera

McDonald

et al. 2013

J Cereb Blood Flow Metab

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Although certain metabolic characteristics such as interictal glucose hypometabolism are well established for temporal lobe epilepsy (TLE), its pathogenesis still remains unclear. Here, we performed a comprehensive study of brain metabolism in a mouse model of TLE, induced by pilocarpine-status epilepticus (SE). To investigate glucose metabolism, we injected mice 3.5-4 weeks after SE with [1,2-13 C]glucose before microwave fixation of the head. Using 1 H and 13 C nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry and high-pressure liquid chromatography, we quantified metabolites and 13 C labeling in extracts of cortex and hippocampal formation (HF). Hippocampal levels of glutamate, glutathione and alanine were decreased in pilocarpine-SE mice compared with controls. Moreover, the contents of N-acetyl aspartate, succinate and reduced nicotinamide adenine dinucleotide (phosphate) NAD(P)H were decreased in HF indicating impairment of mitochondrial function. In addition, the reduction in 13 C enrichment of hippocampal citrate and malate suggests decreased tricarboxylic acid (TCA) cycle turnover in this region. In cortex, we found reduced 13 C labeling of glutamate, glutamine and aspartate via the pyruvate carboxylation and pyruvate dehydrogenation pathways, suggesting slower turnover of these amino acids and/or the TCA cycle. In conclusion, mitochondrial metabolic dysfunction and altered amino-acid metabolism is found in both cortex and HF in this epilepsy model. Keywords: 13 C isotope; glutamate; mitochondria; neurometabolism; NMR spectroscopy; temporal lobe epilepsy Journal of Cerebral Blood INTRODUCTIONTemporal lobe epilepsy (TLE) is one of the most common forms of human epilepsy and is associated with a high level of drug resistance among patients. The mechanisms underlying the pathogenesis of TLE still remain unclear, although increasing evidence points to a disturbance in amino-acid neurotransmitter homeostasis and energy metabolism, as well as neuronal injury. Metabolic characteristics of human TLE include interictal glucose hypometabolism and a decrease in the levels of the neuronal marker N-acetyl aspartate (NAA) in the epileptogenic region. 1,2 Increased levels of extracellular glutamate in epileptogenic hippocampi have been reported before and during seizures 3 and interictally. 4 Moreover, it has been suggested that the uptake of glutamate from the extracellular space by astrocytes is slower in the epileptic brain as the expression of glutamine synthetase, the glial enzyme that converts glutamate to glutamine, was decreased in the epileptogenic hippocampi from patients with TLE. 5,6 Changes in brain metabolism in rat models of TLE resemble those reported in human TLE such as interictal glucose hypometabolism demonstrated in lithium-pilocarpine rats, 7 as well as alterations in NAA and glutamate reported in post-status epilepticus (SE) models induced by kainic acid and lithiumpilocarpine. [8][9][10] There are, however, few comprehensive studies on brain metabolism in mouse model...

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Section: Amino-acid and Neurotransmitter Metabolismsupporting

confidence: 88%

Brain Mitochondrial Metabolic Dysfunction and Glutamate Level Reduction in the Pilocarpine Model of Temporal Lobe Epilepsy in Mice

Smeland

Hadera

McDonald

et al. 2013

J Cereb Blood Flow Metab

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“…Previous investigations suggest that increased Cr/ NAA ratios in temporal lobe epilepsy are not due solely to cell loss in the hippocampus. 17 Atrophy is an unlikely explanation of our findings because we evaluated the extent of abnormal Cr/NAA ratios in voxels within the hippocampi. Decreased NAA is associated with cerebral regions of interictal spiking and seizure onset, 34,35 which in combination with our results suggests the plausible hypothesis that depression symptoms in temporal lobe epilepsy may be due to the influence of hyperexcitable hippocampal neurons on the limbic network.…”

Section: Methodsmentioning

confidence: 97%

“…[14][15][16][17] The subjects in the current study were a convenience sample who agreed to undergo 1 H-MRSI and were able to obtain transportation at a time when the MR scanner was available. Briefly, all studies were performed in the interictal state, using a 4.1-T whole-body imaging/spectroscopy system and a quadrature-driven, tunable, matchable head coil.…”

Section: Methodsmentioning

confidence: 99%

“…In a detailed comparison of 1 H-MRSI to FDG-PET in temporal lobe epilepsy, hippocampal Cr/NAA measures did not correlate with glucose metabolism; indicating that alterations in glucose uptake and NAA concentrations represent different mechanisms of cellular metabolic dysfunction. 28 Rate of brain glucose metabolism is largely dependent on pyramidal neuron activation and subsequent glutamate release, and recent studies indicate that glucose utilization is directly related to glia uptake of glutamate 32 The wide variability of hippocampal neuron/glia ratios commonly described in temporal lobe epilepsy 17 may explain previous observations of extremes of interictal hyper-and hypometabolism in different regions in mesial temporal sclerosis. 33 This variability may also explain the lack of correlation of hippocampal glucose metabolism with symptoms of depression.…”

Section: Methodsmentioning

confidence: 99%

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Oster¹,

Jones²,

Hildenbrand³

et al. 2007

Neurology

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Abstract-Objective:To investigate the association of an indicator of hippocampal function with severity of depression symptoms in temporal lobe epilepsy. Methods: We evaluated 31 patients with video/EEG-confirmed temporal lobe epilepsy using creatine/N-acetylaspartate ratio maps derived from a previously validated 1 H magnetic resonance spectroscopic imaging ( 1 H-MRSI) technique at 4.1 T. We also assessed depression symptoms, epilepsy-related factors, and self-perceived social and vocational disability. We used conservative nonparametric bivariate procedures to determine the correlation of severity of depression symptoms with imaging and clinical variables. Results: The extent of hippocampal 1 H-MRSI abnormalities correlated with severity of depression (Spearman rho ϭ 0.65, p value Ͻ 0.001), but other clinical factors did not. Conclusion: The extent of hippocampal dysfunction is associated with depression symptoms in temporal lobe epilepsy and may be a more important factor than seizure frequency or degree of disability.

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“…Despite the rapid theoretical and technological progress advances in the field, the robust early diagnosis is still an open problem. Towards this aim various brain imaging approaches have been exploited including Electroencephalographic (EEG) recordings (Goodin et al 1990;Smith 2005;Jan et al 2001;Krause et al 2008;Myatchin et al 2009;Myatchin and Lagae 2011;Yang et al 2012;van Diessen et al 2013), Magnetoencephalography (MEG) (Colon et al 2009), functional Magnetic Resonance Imaging (fMRI) (Gotman et al 2005;Grouiller et al 2011) and Proton MR spectroscopy (Kuzniecky et al 2001) (for a review see also Bano et al (2011)). Whereas well established neuroimaging analysis techniques such as ERP and event-related (de-)synchronization (ERS/ERD) have been applied to the analysis of the brain dynamics of normal and epileptic children (Jiruska et al 2013;Klimesch 1999;Krause et al 2008), significant work remains to be done towards the construction of the underlying anatomical and functional connectivity networks (FCN) (Sargolzaei et al 2015b).…”

Section: Introductionmentioning

confidence: 99%

Children with well controlled epilepsy possess different spatio-temporal patterns of causal network connectivity during a visual working memory task

et al. 2016

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Using spectral Granger causality (GC) we identified distinct spatio-temporal causal connectivity (CC) patterns in groups of control and epileptic children during the execution of a one-back matching visual discrimination working memory task. Differences between control and epileptic groups were determined for both GO and NOGO conditions. The analysis was performed on a set of 19-channel EEG cortical activity signals. We show that for the GO task, the highest brain activity in terms of the density of the CC networks is observed in a band for the control group while for the epileptic group the CC network seems disrupted as reflected by the small number of connections. For the NOGO task, the denser CC network was observed in h band for the control group while widespread differences between the control and the epileptic group were located bilaterally at the left temporal-midline and parietal areas. In order to test the discriminative power of our analysis, we performed a pattern analysis approach based on fuzzy classification techniques. The performance of the classification scheme was evaluated using permutation tests. The analysis demonstrated that, on average, 87.6 % of the subjects were correctly classified in control and epileptic. Thus, our findings may provide a helpful insight on the mechanisms pertaining to the cognitive response of children with well controlled epilepsy and could potentially serve as ''functional'' biomarkers for early diagnosis.

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Magnetic Resonance Spectroscopic Imaging in Temporal Lobe Epilepsy

Cited by 103 publications

References 34 publications

Brain Mitochondrial Metabolic Dysfunction and Glutamate Level Reduction in the Pilocarpine Model of Temporal Lobe Epilepsy in Mice

Brain Mitochondrial Metabolic Dysfunction and Glutamate Level Reduction in the Pilocarpine Model of Temporal Lobe Epilepsy in Mice

Reversible Kernohan notch

Children with well controlled epilepsy possess different spatio-temporal patterns of causal network connectivity during a visual working memory task

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