Peritumoural glutamate correlates with post-operative seizures in supratentorial gliomas.
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.
Department of Neurology, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia. neala@student.unimelb.edu.au.|Department of Medicine, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia. neala@student.unimelb.edu.au.
Andrew
0000-0001-9251-5471
A
Neal
Department of Neurosurgery, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia.|Department of Surgery, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia.
Tanya
T
Yuen
Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, 3050, Parkville, VIC, Australia.
Andrew R
AR
Bjorksten
Department of Neurology, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia.|Department of Medicine, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia.
Patrick
P
Kwan
Department of Neurology, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia.|Department of Medicine, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia.
Terence J
TJ
O'Brien
Department of Neurosurgery, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia.|Department of Surgery, Royal Melbourne Hospital, University of Melbourne, 3050, Parkville, VIC, Australia.
Andrew
A
Morokoff
D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects; D015331:Cohort Studies; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000601:surgery; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures / Q000009:adverse effects*; D011183:Postoperative Complications / Q000378:metabolism*; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology*; D015173:Supratentorial Neoplasms / Q000601:surgery; D016019:Survival Analysis
D000927:Anticonvulsants; D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid
Epilepsy; Glioma; Glutamate; Seizure; Tumour