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

• Published in: Journal of neurology, neurosurgery and psychiatry neurosurgery and psychiatry, 2006-04, Vol.77 (4), p.489-494
• Main Authors: Helms, G, Ciumas, C, Kyaga, S, Savic, I
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Clinical Medicine; Convulsions & seizures; EEG; Electroencephalography; Epilepsy; Epilepsy, Generalized - diagnosis; Epilepsy, Generalized - metabolism; Extracellular Space - metabolism; fast spin-echo; Female; FSE; generalised tonic-clonic seizures; glutamate; glutamate and glutamine; Glutamic Acid - metabolism; glutamine; Glutamine - metabolism; Glx; GTCS; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; idiopathic generalised epilepsy; IGE; JME; juvenile myoclonic epilepsy; Klinisk medicin; magnetic resonance; Magnetic Resonance Spectroscopy; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; MNI; Montreal Neurological Institute; MR spectroscopy; MRS; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; N-acetyl aspartate; NAA; Nervous system (semeiology, syndromes); Neurologi; Neurology; Radiologi och bildbehandling; Radiology, Nuclear Medicine and Medical Imaging; Semiotics; signal to noise ratio; SNR; Spectrum analysis; SPGR; spoiled gradient-echo; thalamo-cortical circuits; Thalamus - anatomy & histology; Thalamus - metabolism; VBM; VOI; volume of interest; Volumetric analysis; voxel based morphometry
• ISSN: 0022-3050; 1468-330X; 1468-330X
• DOI: 10.1136/jnnp.2005.074682

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.