Anna Maria Buccoliero1, Chiara Caporalini2, Mirko Scagnet3, Federico Mussa3, Flavio Giordano3, Iacopo Sardi4, Irene Migliastro2, Selene Moscardi2, Valerio Conti5, Carmen Barba6, Manila Antonelli7, Francesca Gianno7, Sabrina Rossi8, Francesca Diomedi-Camassei8, Marco Gessi9, Vittoria Donofrio10, Luca Bertero11, Felice Giangaspero7, Mariarita Santi12, Eleonora Aronica13, Lorenzo Genitori3, Renzo Guerrini5. 1. Pathology Unit, Children's Hospital A. Meyer-University of Florence, Italy. Electronic address: ambuccoliero@unifi.it. 2. Pathology Unit, Children's Hospital A. Meyer-University of Florence, Italy. 3. Department of Neurosurgery, Children's Hospital A. Meyer-University of Florence, Italy. 4. Neuro-oncology Unit, Children's Hospital A. Meyer-University of Florence, Italy. 5. Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Children's Hospital A. Meyer-University of Florence, Italy. 6. Pediatric Neurology, Neuroscience Department, Children's Hospital A. Meyer-University of Florence, Italy. 7. Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy. 8. Pathology Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 9. Institute of Pathology, Fondazione Policlinico Universitario 'Agostino Gemelli', Università Cattolica del Sacro Cuore, Rome, Italy. 10. Pathology Unit, Ospedale Santobono-Pausilipon, Naples, Italy. 11. Pathology Unit, Department of Medical Sciences, University of Turin, Italy. 12. Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, PA, USA. 13. Department of Neuropathology, AMC, University of Amsterdam, Amsterdam, the Netherlands.
Abstract
PURPOSE: Our purpose was to better understand the pathogenesis of seizures associated with angiocentric glioma. Angiocentric glioma is an indolent and rare low-grade glioma. Its typical clinical presentation is with epileptic seizures. The pathogenesis of tumor-associated seizures is poorly understood. Among the possible pathomechanisms, the increased neurotoxic concentrations of the glutamate has been proposed. Glutamate transporters, pyruvate carboxylase and glutamine synthetase are involved in maintaining the physiological concentration of glutamate in the inter synaptic spaces. METHODS: We evaluated the immunohistochemical expression of EAAT2 (the most important glutamate transporter), pyruvate carboxylase and glutamine synthetase in 17 angiocentric gliomas. RESULTS: EAAT2 was never expressed (0%) in the neoplastic cells in none of the cases studied. Pyruvate carboxylase was expressed in the cytoplasm of the neoplastic cells in 16/17 cases (94 %). Glutamine synthetase was expressed in the cytoplasm of the neoplastic cells in 15/17 cases (88 %). CONCLUSION: The net result of this enzymatic expression, in particular considering the loss of EAAT2, could be an increased glutamate concentration in the synaptic clef, which might increase local network excitability initially involving intratumoral neurons. The observation that the angiocentric glioma-associated epilepsy might be at least in part related to EAAT2 deficiency opens up interesting therapeutic perspectives.
PURPOSE: Our purpose was to better understand the pathogenesis of seizures associated with angiocentric glioma. Angiocentric glioma is an indolent and rare low-grade glioma. Its typical clinical presentation is with epileptic seizures. The pathogenesis of tumor-associated seizures is poorly understood. Among the possible pathomechanisms, the increased neurotoxic concentrations of the glutamate has been proposed. Glutamate transporters, pyruvate carboxylase and glutamine synthetase are involved in maintaining the physiological concentration of glutamate in the inter synaptic spaces. METHODS: We evaluated the immunohistochemical expression of EAAT2 (the most important glutamate transporter), pyruvate carboxylase and glutamine synthetase in 17 angiocentric gliomas. RESULTS:EAAT2 was never expressed (0%) in the neoplastic cells in none of the cases studied. Pyruvate carboxylase was expressed in the cytoplasm of the neoplastic cells in 16/17 cases (94 %). Glutamine synthetase was expressed in the cytoplasm of the neoplastic cells in 15/17 cases (88 %). CONCLUSION: The net result of this enzymatic expression, in particular considering the loss of EAAT2, could be an increased glutamate concentration in the synaptic clef, which might increase local network excitability initially involving intratumoral neurons. The observation that the angiocentric glioma-associated epilepsy might be at least in part related to EAAT2deficiency opens up interesting therapeutic perspectives.