Epilepsy in glioblastoma multiforme: correlation with glutamine synthetase levels.
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.
Rosati
Anna
A
Neurology Clinic, University of Brescia, Italy. anna.rosati@libero.it
Marconi
Silvia
S
Pollo
Bianca
B
Tomassini
Alessia
A
Lovato
Laura
L
Maderna
Emanuela
E
Maier
Klaus
K
Schwartz
Andreas
A
Rizzuto
Nicolò
N
Padovani
Alessandro
A
Bonetti
Bruno
B
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
D005974:Glutamate-Ammonia Ligase