title: Epilepsy in glioblastoma multiforme: correlation with glutamine synthetase levels.
abstract: OBJECTIVE
  The hypothesis addressed by this study is that a glutamine synthetase (GS) deficiency in neoplastic astrocytes is a possible molecular basis associated with seizure generation in glioblastoma multiforme (GBM).
  
  
  METHODS
  Quantitative Western blot analysis of GS was performed in 20 individuals operated for malignant glioma.
  
  
  RESULTS
  The levels of GS in patients with GBM and epilepsy were significantly lower (range 0.04-1.15; mean 0.35 +/- 0.36; median 0.25) than in non-epileptic GBM individuals (range 0.78-3.97; mean 1.64 +/- 0.99; median 1.25; P = 0.002). No relationship has been found between histological features (i.e. necrosis, gliosis, stroma, inflammatory cells, giant cells, and haemosiderine) and GS expression or epilepsy.
  
  
  CONCLUSIONS
  Even though the epileptogenesis in glioma is multifactorial, it is conceivable that a down-regulation of GS may have an important pro-epileptogenic role in GBM, through the slowing of glutamate-glutamine cycle. This study suggests that seizures in GBM are coupled with a highly localized enzyme deficiency. The manipulation of GS activity might constitute a novel principle for inhibiting seizures in patients with glioma epilepsy.
authors.affiliation: Neurology Clinic, University of Brescia, Italy. anna.rosati@libero.it
authors.forename: Anna
authors.initials: A
authors.lastname: Rosati
authors.forename: Silvia
authors.initials: S
authors.lastname: Marconi
authors.forename: Bianca
authors.initials: B
authors.lastname: Pollo
authors.forename: Alessia
authors.initials: A
authors.lastname: Tomassini
authors.forename: Laura
authors.initials: L
authors.lastname: Lovato
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maderna
authors.forename: Klaus
authors.initials: K
authors.lastname: Maier
authors.forename: Andreas
authors.initials: A
authors.lastname: Schwartz
authors.forename: Nicolò
authors.initials: N
authors.lastname: Rizzuto
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Bruno
authors.initials: B
authors.lastname: Bonetti
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000150:complications / Q000201:enzymology*; D004827:Epilepsy / Q000201:enzymology* / Q000209:etiology*; D005260:Female; D005909:Glioblastoma / Q000150:complications* / Q000201:enzymology* / Q000473:pathology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D005974:Glutamate-Ammonia Ligase