1H-MRS profile in MRI positive- versus MRI negative patients with temporal lobe epilepsy

INTRODUCTION The objective of this study was to quantitate and compare ipsilateral total N-acetyl aspartate (tNAA), creatine (Cr), choline (Cho), myo-inositol (m-Ins) and glutamate plus glutamine (Glx) levels in the hippocampi of patients with temporal lobe epilepsy (TLE) with and without magnetic resonance imaging (MRI) evidence for mesial temporal sclerosis (MRI positive/negative). PATIENTS AND METHODS Twenty-three age matched healthy controls and 26 consecutive patients with unilateral TLE, based on intensive 24h video-EEG, were investigated with proton magnetic resonance spectroscopy ((1)H-MRS) (17 with unilateral hippocampal sclerosis (HS) in MRI-MRI positive; 9 MRI negative). For statistical analysis one-way analysis of variance (ANOVA) with post hoc multiple comparisons and Bonferroni correction was applied. The significance level was based on p<0.05. RESULTS The mean tNAA level ipsilateral to the seizure focus was significantly decreased in MRI negative, respectively MRI positive patients in comparison to healthy controls (p<0.001). The lowest tNAA level was noticed in the MRI positive group (p<0.001). Statistical analysis highlighted a clear "tNAA cut-off" (95% confidence interval) between MRI positive- and MRI negative patients and healthy controls. Mean level of Glx and m-Ins was not significantly elevated or reduced. However, in individual cases a significant elevation was noticed for Glx in MRI negative patients, respectively for m-Ins in MRI positive patients. CONCLUSION MRI negative TLE patients have a different MRS profile than MRI positive patients (HS) with marginal but significant decrease of tNAA. Our results reveal a clear "tNAA cut-off" between the groups. The value of m-Ins and Glx in focus detection in TLE patients remains controversy.

[1]  Stephen K Fisher,et al.  Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance , 2002, Journal of neurochemistry.

[2]  A. Connelly,et al.  The amygdala and intractable temporal lobe epilepsy , 1996, Neurology.

[3]  Dennis D. Spencer,et al.  N-acetyl-aspartate, total creatine, and myo-inositol in the epileptogenic human hippocampus , 2003, Neurology.

[4]  R. Kuzniecky,et al.  Magnetic resonance spectroscopic imaging in temporal lobe epilepsy: neuronal dysfunction or cell loss? , 2001, Archives of neurology.

[5]  Ari Syngeniotis,et al.  Myoinositol Abnormalities in Temporal Lobe Epilepsy , 2003, Epilepsia.

[6]  P. Boesiger,et al.  Quantitative 1H MRS in the evaluation of mesial temporal lobe epilepsy in vivo. , 1998, Magnetic resonance imaging.

[7]  C. Hanstock,et al.  Chronic lithium and sodium valproate both decrease the concentration of myo-inositol and increase the concentration of inositol monophosphates in rat brain , 2000, Brain Research.

[8]  Tae Joo Jeon,et al.  Evaluation of ictal brain SPET using statistical parametric mapping in temporal lobe epilepsy , 2000, European Journal of Nuclear Medicine.

[9]  J S Duncan,et al.  Imaging and epilepsy. , 1997, Brain : a journal of neurology.

[10]  J S Duncan,et al.  Short echo time single‐voxel 1H magnetic resonance spectroscopy in magnetic resonance imaging–negative temporal lobe epilepsy: Different biochemical profile compared with hippocampal sclerosis , 1999, Annals of neurology.

[11]  Christopher Nimsky,et al.  Non‐invasive detection of hippocampal sclerosis: correlation between metabolite alterations detected by 1H‐MRS and neuropathology , 2008, NMR in biomedicine.

[12]  D. Arnold,et al.  Lateralization of temporal lobe epilepsy based on regional metabolic abnormalities in proton magnetic resonance spectroscopic images , 1994, Annals of neurology.

[13]  E. Moser,et al.  1H magnetic resonance spectroscopy at 3 T in cryptogenic and mesial temporal lobe epilepsy , 2006, NMR in biomedicine.

[14]  D. Gadian,et al.  Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  D. Rothman,et al.  Neuronal and glial metabolite content of the epileptogenic human hippocampus , 2002, Annals of neurology.

[16]  F. Woermann,et al.  A Short‐echo‐time Proton Magnetic Resonance Spectroscopic Imaging Study of Temporal Lobe Epilepsy , 2002, Epilepsia.

[17]  H. Stefan,et al.  A new approach in anti‐epileptic drug evaluation , 2004, European journal of neurology.

[18]  P M Matthews,et al.  Normalization of neuronal metabolic dysfunction after surgery for temporal lobe epilepsy , 1997, Neurology.

[19]  Dennis D Spencer,et al.  Glutamate–glutamine Cycling in the Epileptic Human Hippocampus , 2002, Epilepsia.

[20]  M. During,et al.  Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain , 1993, The Lancet.

[21]  O Ganslandt,et al.  Identifying the affected hemisphere by 1H‐MR spectroscopy in patients with temporal lobe epilepsy and no pathological findings in high resolution MRI , 2006, European journal of neurology.

[22]  C R Jack,et al.  Epilepsy: surgery and imaging. , 1993, Radiology.

[23]  Michael W Weiner,et al.  Spectroscopic Metabolic Abnormalities in mTLE with and without MRI Evidence for Mesial Temporal Sclerosis Using Hippocampal Short‐TE MRSI , 2003, Epilepsia.

[24]  Donald H. Lee,et al.  MR in temporal lobe epilepsy: analysis with pathologic confirmation. , 1998, AJNR. American journal of neuroradiology.

[25]  G. Jackson,et al.  Preoperative MRI predicts outcome of temporal lobectomy , 1995, Neurology.

[26]  G. Matson,et al.  Neuron loss localizes human temporal lobe epilepsy by in vivo proton magnetic resonance spectroscopic imaging , 1993, Annals of neurology.

[27]  O Ganslandt,et al.  Multimodal coregistration in patients with temporal lobe epilepsy--results of different imaging modalities in lateralization of the affected hemisphere in MR imaging positive and negative subgroups. , 2007, AJNR. American journal of neuroradiology.

[28]  B. Tomandl,et al.  Clinical applications of 1H‐MR spectroscopy in the evaluation of epilepsies – What do pathological spectra stand for with regard to current results and what answers do they give to common clinical questions concerning the treatment of epilepsies? , 2003, Acta neurologica Scandinavica.

[29]  I. Fried,et al.  Comparison of seizure related amino acid release in human epileptic hippocampus versus a chronic, kainate rat model of hippocampal epilepsy , 1996, Epilepsy Research.

[30]  M. Han,et al.  Lateralizing ability of single-voxel proton mr spectroscopy in hippocampal sclerosis: comparison with mr imaging and positron emission tomography. , 2001, AJNR. American journal of neuroradiology.

[31]  G Helms,et al.  A precise and user‐independent quantification technique for regional comparison of single volume proton MR spectroscopy of the human brain , 2000, NMR in biomedicine.

[32]  Terence J. O'Brien,et al.  “Magnetic Resonance Imaging Negative Positron Emission Tomography Positive” Temporal Lobe Epilepsy: FDG-PET Pattern Differs from Mesial Temporal Lobe Epilepsy , 2006, Molecular Imaging and Biology.

[33]  K Scheffler,et al.  Effect of diffusion in inhomogeneous magnetic fields on balanced steady‐state free precession , 2007, NMR in biomedicine.

[34]  S. Provencher Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[35]  O Ganslandt,et al.  Short TE single‐voxel 1H‐MR spectroscopy of hippocampal structures in healthy adults at 1.5 Tesla—how reproducible are the results? , 2005, NMR in biomedicine.

[36]  G. Fein,et al.  Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy , 1997, Annals of neurology.

[37]  S. Provencher Automatic quantitation of localized in vivo 1H spectra with LCModel , 2001, NMR in biomedicine.

[38]  T. Yoshimine,et al.  Kainic acid-induced seizure upregulates Na(+)/myo-inositol cotransporter mRNA in rat brain. , 1999, Brain research. Molecular brain research.

[39]  I. Fried,et al.  In vivo measurements of glutamine+ glutamate (Glx) and N‐acetyl aspartate (NAA) levels in human partial epilepsy , 2000, Acta neurologica Scandinavica.