title: Glutamate is associated with a higher risk of seizures in patients with gliomas.
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 X(c)(-) 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 X(c)(-), younger age, temporal lobe location, and tumors with oligodendroglial components as independently predictive of preoperative seizures.
  
  
  CONCLUSIONS
  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.
authors: Departments of Surgery, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
authors: Tanya I
authors: TI
authors: Yuen
authors: Andrew P
authors: AP
authors: Morokoff
authors: Andrew
authors: A
authors: Bjorksten
authors: Giovanna
authors: G
authors: D'Abaco
authors: Lucy
authors: L
authors: Paradiso
authors: Sue
authors: S
authors: Finch
authors: Daniel
authors: D
authors: Wong
authors: Christopher A
authors: CA
authors: Reid
authors: Kim L
authors: KL
authors: Powell
authors: Kate J
authors: KJ
authors: Drummond
authors: Mark A
authors: MA
authors: Rosenthal
authors: Andrew H
authors: AH
authors: Kaye
authors: Terence J
authors: TJ
authors: O'Brien
mesh_terms: D000328:Adult; D027182:Amino Acid Transport System y+ / Q000235:genetics; D001254:Astrocytoma / Q000150:complications / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D015331:Cohort Studies; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D005909:Glioblastoma / Q000150:complications / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D012640:Seizures / Q000453:epidemiology* / Q000209:etiology*; D015173:Supratentorial Neoplasms / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D027182:Amino Acid Transport System y+; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human; C118895:SLC7A11 protein, human; D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid