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Peritumoural glutamate correlates with post-operative seizures in supratentorial gliomas

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Abstract

To examine the impact of glutamate on post-operative seizures and survival in a cohort of patients with grade II to IV supratentorial glioma. A retrospective analysis was performed on 216 patients who underwent surgery for supratentorial gliomas. Primary explanatory variables were peritumoural and/or tumoural glutamate concentrations, glutamate transporter expression (EAAT2 and SXC). Univariate and multivariate survival analysis was performed with primary outcomes of time to first post-operative seizure and overall survival. Subgroup analysis was performed in patients with de novo glioblastomas who received adjuvant chemoradiotherapy. 47 (21.8 %), 34 (15.8 %) and 135 (62.5 %) WHO grade II, III and IV gliomas respectively were followed for a median of 15.8 months. Following multivariate analysis, there was a non-significant association between higher peritumoural glutamate concentrations and time to first post-operative seizure (HR 2.07, CI 0.98–4.37, p = 0.06). In subgroup analysis of 81 glioblastoma patients who received adjunct chemoradiotherapy, peritumoural glutamate concentration was significantly associated with time to first post-operative seizure (HR 3.10, CI 1.20–7.97, p = 0.02). In both the overall cohort and subgroup analysis no glutamate cycle biomarkers were predictive of overall survival. Increased concentrations of peritumoural glutamate were significantly associated with shorter periods of post-operative seizure freedom in patients with de novo glioblastomas treated with adjuvant chemoradiotherapy. No glutamate cycle biomarkers were predictive of overall survival. These results suggest that therapies targeting glutamate may be beneficial in tumour associated epilepsy.

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Acknowledgments

Dr. Andrew Neal conducted statistical analysis with the assistance of Mark Tacey from Centre for Clinical Epidemiology, Biostatistics and Health Services Research, Royal Melbourne Hospital, University of Melbourne, VIC 3050.

Funding

Dr. Andrew Neal was supported by an Australian Postgraduate Award Scholarship (University of Melbourne), The UCB Pharma Clinical Scholarship and by the Royal Melbourne Hospital Neuroscience Foundation.

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Authors and Affiliations

  1. Department of Neurology, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia

    Andrew Neal, Patrick Kwan & Terence J. O’Brien

  2. Department of Neurosurgery, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia

    Tanya Yuen & Andrew Morokoff

  3. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia

    Andrew Neal, Patrick Kwan & Terence J. O’Brien

  4. Department of Surgery, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia

    Tanya Yuen & Andrew Morokoff

  5. Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, 3050, Parkville, VIC, Australia

    Andrew R. Bjorksten

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  1. Andrew Neal
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Correspondence to Andrew Neal.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards

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Neal, A., Yuen, T., Bjorksten, A.R. et al. Peritumoural glutamate correlates with post-operative seizures in supratentorial gliomas. J Neurooncol 129, 259–267 (2016). https://doi.org/10.1007/s11060-016-2169-y

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