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Epilepsy in glioblastoma multiforme: correlation with glutamine synthetase levels

  • laboratory Investigation - Human/Animal Tissue
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Abstract

Purpose 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. Discussion 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.

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Authors and Affiliations

  1. Neurology Clinic, University of Brescia, Spedali Civili, Piazzale Spedali Civili 1, 25123, Brescia, Italy

    Anna Rosati & Alessandro Padovani

  2. Department of Neurological Sciences and Vision, Section of Clinical Neurology, University of Verona, Verona, Italy

    Silvia Marconi, Laura Lovato, Nicolò Rizzuto & Bruno Bonetti

  3. Neuropathology Service, Neurological Institute “Carlo Besta”, Milan, Italy

    Bianca Pollo & Emanuela Maderna

  4. Neurosurgery Department, San Maurizio Hospital, Bolzano, Italy

    Alessia Tomassini & Andreas Schwartz

  5. Neuropathology Service, San Maurizio Hospital, San Maurizio, Italy

    Klaus Maier

Authors
  1. Anna Rosati
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  2. Silvia Marconi
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  3. Bianca Pollo
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  4. Alessia Tomassini
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Correspondence to Anna Rosati.

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All Authors confirm that they have read the Journal’s position on issues involved in ethical publication and affirm that the work is consistent with those guidelines. All Authors disclose non conflict of interest. All Authors have been substantively involved in the study and/or the preparation of manuscript. All Authors have seen and approved the submitted version of the paper and accept responsibility for its content.

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Rosati, A., Marconi, S., Pollo, B. et al. Epilepsy in glioblastoma multiforme: correlation with glutamine synthetase levels. J Neurooncol 93, 319–324 (2009). https://doi.org/10.1007/s11060-008-9794-z

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  • DOI: https://doi.org/10.1007/s11060-008-9794-z

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