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Abstract
Objective: To investigate the relationship of glutamate and glutamate transporter expression in human gliomas and surrounding peritumoral brain to the presence of tumor-associated seizures (TAS).
Methods: We studied a retrospective (group 1: 190 patients) and then a prospective (group 2: 98 patients) cohort of patients who underwent a craniotomy for a supratentorial glioma. Tumor and peritumor tissue specimens were assayed for glutamate concentration and expression of glial glutamate transporters. Differences between the seizure (TAS) and seizure-free (non-TAS) groups were compared.
Results: A total of 42% of patients had TAS, with 95% of seizures first occurring preoperatively. Clinical factors independently associated with risk of TAS were younger age, temporal lobe location, and tumors with oligodendroglial components. Molecular features in tumor specimens associated with TAS were higher glutamate concentrations, reduced EAAT2 expression, and increased system Xc− expression. In group 2, these results were also replicated in the peritumor tissue. Logistic regression analysis identified raised glutamate concentrations in tumor and peritumor tissue, increased expression of peritumor system Xc−, younger age, temporal lobe location, and tumors with oligodendroglial components as independently predictive of preoperative seizures.
Conclusion: Relative increased glutamate concentration in gliomas, and altered glutamate transporter expression, are associated with the presence of TAS and may play a mechanistic role in their pathogenesis.
GLOSSARY
- AED=
- antiepileptic drug;
- CI=
- confidence interval;
- EAAT=
- excitatory amino acid transporter;
- GBM=
- glioblastoma multiforme;
- MPH=
- Melbourne Private Hospital;
- OR=
- odds ratio;
- RMH=
- Royal Melbourne Hospital;
- TAS=
- tumor-associated seizures
Footnotes
Study funding: Supported by the National Health and Medical Research Council of Australia (628301); The Melville Hughes Scholarship (to T.Y.); the John Lowenthal Surgical Scholarship, Royal Australasian College of Surgeons (to T.Y.); and the Royal Melbourne Hospital Neuroscience Foundation.
Editorial, page 844
Supplemental data at www.neurology.org
Presented in part at the 23rd annual scientific meeting of the Epilepsy Society of Australasia, Sydney, Australia, November 5–7, 2008; and the annual scientific meeting of Neurosurgical society of Australasia, Alice Springs, Australia, November 17–20, 2009.
- Received November 2, 2011.
- Accepted February 29, 2012.
- Copyright © 2012 by AAN Enterprises, Inc.
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