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Increased thalamus levels of glutamate and glutamine (Glx) in patients with idiopathic generalised epilepsy

¹ MR Centre, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
² Division of Neurology, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden

Correspondence to:
Correspondence to:
Ivanka Savic
Department of Clinical Neuroscience, Karolinska Institute, MR Centre, S-171 77 Stockholm, Sweden; ivanka.savic-berglund{at}neuro.ki.se

Objective: Abnormal thalamo-cortical oscillations underlie idiopathic generalised epilepsy (IGE). Although thalamic involvement has long been indicated by electrophysiological data, it has only recently become feasible to test this with independent methods. In this magnetic resonance (MR) study, we investigated the metabolic and structural integrity of the thalamus. Possible changes in glutamine and glutamate concentrations and signs of neuronal damage were of particular interest.

Method: Forty three IGE patients and 38 age and sex matched healthy controls were investigated. Quantitative single volume MR spectroscopy (MRS, 1.5 T) was used to measure concentrations of glutamate and glutamine (Glx) and N-acetyl aspartate (NAA) in thalamus and occipital cortex. We also measured thalamic volumes on high resolution gradient-echo images and estimated fractions of thalamic grey and white matter with voxel based morphometry (VBM).

Results: IGE patients showed elevated Glx and reduced NAA concentrations in the thalamus compared to controls (12.2±2.6 v 8.9±4.1 mM, p = 0.0022 for Glx, and 9.9±1.0 v 10.7±0.9 mM, p = 0.017 for NAA). Thalamic grey matter fraction was reduced in IGE patients, and white matter fraction was increased with the greatest increase in the dorso-medial thalamus. Mean thalamic volume was reduced in patients (6.7±0.7 v 7.2±0.6 ml in controls, p = 0.0001), as was mean cerebral volume (1163±128 v 1250±102 ml, p = 0.0003). Patients’ thalamus/whole brain ratios were normal.

Conclusion: Quantitative MRS and VBM provide further evidence for involvement of the thalamus in IGE. The observed elevation of Glx levels together with reductions in NAA levels and grey matter fractions are consistent with epilepsy related excitoxicity as a possible underlying mechanism.

Abbreviations: EEG, electroencephalography; FSE, fast spin-echo; Glx, glutamate and glutamine; GTCS, generalised tonic-clonic seizures; IGE, idiopathic generalised epilepsy; JME, juvenile myoclonic epilepsy; MNI, Montreal Neurological Institute; MR, magnetic resonance; MRS, MR spectroscopy; NAA, N-acetyl aspartate; SNR, signal to noise ratio; SPGR, spoiled gradient-echo; VBM, voxel based morphometry; VOI, volume of interest

Keywords: glutamate; glutamine; idiopathic generalised epilepsy; MR spectroscopy; thalamo-cortical circuits

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