Abstract
INTRODUCTION: Seizures are common in patients with a Glioblastoma. Although the epileptogenic mechanism remains unclear, it is suggested to be dependent upon peritumoural changes. Histological analysis of human intratumoural and peritumoural glioma tissue demonstrated that glutamate concentrations in tissue from both sites were increased in patients with seizures when compared to those without. It would be advantageous to have a non-invasive method for predicting which patients are most likely to be affected by seizures. METHOD: 80 patients with a Glioblastoma were imaged pre-operatively at 3T with sequences including anatomical and multivoxel spectroscopy. Regions of interest (ROIs) were selected in a circumferential consecutive pattern from the border of the T1-weighted enhancing region to normal appearing brain. Glutamate parameters (Glu + Gln/Cr) were calculated per voxel and expressed as a ratio to normal brain. Clinical variables were analysed in relation to tumour progression and survival. RESULTS: The mean Glu + Gln/Cr concentration remained more than 1.5 times higher compared to normal brain at a 3 cm radial distance from the T1-weighted enhancing margin in the seizure group. At this distance, the mean Glu + Gln/Cr concentration ratio had returned to 1 in the non-seizure group (Seizures 1.56 ± 0.1 vs. non-seizures 0.92 ± 0.06, p < 0.001). The presence of seizures was associated with a shorter time to progression on multivariate analysis (HR = 7.55; p = 0.01). CONCLUSION: We demonstrate that the presence of seizures is associated with elevated tumour and peritumoural glutamate concentrations and a shortened time to tumour progression in Glioblastomas. Glutamate may play a role in the pathogenesis of seizures and represent a potential biomarker for tumour progression.
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