Abstract
Gangliogliomas (GG) constitute the most frequent tumor entity in young patients undergoing surgery for intractable epilepsy. Surgery provides the best chance for curing epilepsy and preventing malignant transformation. GG consist of a mixture of dysplastic neurons and neoplastic astroglial cells. Although malignant transformation of GG is rare, it has been documented in their astroglial component. The characteristic histopathological features of GG together with the coexistence with cortical dysplasia and the expression of stem cell markers (such as CD34) suggest a developmental origin for these lesions. The malformative nature of GG is also supported by the detection of molecular alterations common to other developmental glioneuronal lesions. In particular, recent studies suggest a role for the phosphatidyl-inositol 3-kinase (PI3K)-mTOR pathway in the molecular pathogenesis of glioneuronal lesions. The cellular mechanism(s) underlying the epileptogenicity of GG is still not clearly defined. Several mechanisms are possibly involved. Recent studies support the role of alterations of the balance between excitation and inhibition, and neuron-glia interactions may also play a critical role in the generation of seizures. Astroglial cells express functional receptors for a variety of neurotransmitters and may critically modulate synaptic transmission. In addition, an increasing number of observations indicate that specific inflammatory pathways are activated in GG and may contribute to the onset of seizures and epileptogenesis.
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References
Aronica E, Gorter JA, Jansen GH, van Veelen CW, van Rijen PC, Leenstra S, Ramkema M, Scheffer GL, Scheper RJ, Troost D (2003) Expression and cellular distribution of multidrug transporter proteins in two major causes of medically intractable epilepsy: focal cortical dysplasia and glioneuronal tumors. Neuroscience 118:417–429
Aronica E, Boer K, Becker A, Redeker S, Spliet WG, van Rijen PC, Wittink F, Breit T, Wadman WJ, Lopes da Silva FH, Troost D, Gorter JA (2008) Gene expression profile analysis of epilepsy-associated gangliogliomas. Neuroscience 151:272–292
Aronica E, Leenstra S, van Veelen CW, van Rijen PC, Hulsebos TJ, Tersmette AC, Yankaya B, Troost D (2001a) Glioneuronal tumors and medically intractable epilepsy: a clinical study with long-term follow-up of seizure outcome after surgery. Epilepsy Res 43:179–191
Aronica E, Yankaya B, Jansen GH, Leenstra S, van Veelen CW, Gorter JA, Troost D (2001b) Ionotropic and metabotropic glutamate receptor protein expression in glioneuronal tumors from patients with intractable epilepsy. Neuropathol Appl Neurobiol 27:1–16
Aronica E, Redeker S, Boer K, Spliet WG, van Rijen PC, Gorter JA, Troost D (2007) Inhibitory networks in epilepsy-associated gangliogliomas and in the perilesional epileptic cortex. Epilepsy Res 74:33–44
Becker AJ, Klein H, Baden T, Aigner L, Normann S, Elger CE, Schramm J, Wiestler OD, Blumcke I (2002) Mutational and expression analysis of the reelin pathway components CDK5 and doublecortin in gangliogliomas. Acta Neuropathol 104:403–408
Becker AJ, Blumcke I, Urbach H, Hans V, Majores M (2006) Molecular neuropathology of epilepsy-associated glioneuronal malformations. J Neuropathol Exp Neurol 65:99–108
Blumcke I (2009) Neuropathology of focal epilepsies: a critical review. Epilepsy Behav 15:34–39
Blumcke I, Wiestler OD (2002) Gangliogliomas: an intriguing tumor entity associated with focal epilepsies. J Neuropathol Exp Neurol 61:575–584
Blümcke I, Vinters HV, Armstrong D, Aronica E, Thom M, Spreafico R (2009) Malformations of Cortical Development and Epilepsies: Neuropathological findings with emphasis on Focal Cortical Dysplasia. Epileptic Disord 11:181–193
Boer K, Troost D, Timmerman W, Spliet WGM, van Rijen PC, Aronica E (2009) Pi3K-mTOR signaling and AMOG expression in epilepsy-associated glioneuronal tumors. Brain Pathol Apr 7. [Epub ahead of print]
Clusmann H, Schramm J, Kral T, Helmstaedter C, Ostertun B, Fimmers R, Haun D, Elger CE (2002) Prognostic factors and outcome after different types of resection for temporal lobe epilepsy. J Neurosurg 97:1131–1141
Evans AJ, Fayaz I, Cusimano MD, Laperriere N, Bilbao. JM (2000) Combined pleomorphic xanthoastrocytoma-ganglioglioma of the cerebellum. Arch Pathol Lab Med 124:1707–1709
Fassunke J, Majores M, Tresch A, Niehusmann P, Grote A, Schoch S, Becker AJ (2008) Array analysis of epilepsy-associated gangliogliomas reveals expression patterns related to aberrant development of neuronal precursors. Brain 131:3034–3050
Fauser S, Becker A, Schulze-Bonhage A, Hildebrandt M, Tuxhorn I, Pannek HW, Lahl R, Schramm J, Blumcke I (2004) CD34-immunoreactive balloon cells in cortical malformations. Acta Neuropathol 108:272–278
Ferrier CH, Aronica E, Leijten FS, Spliet WGM, van Huffelen AC, van Rijen PC, Binnie CD (2006) Electrocorticographic discharge patterns in glioneuronal tumors and focal cortical dysplasia. Epilepsia 47:1477–1486
Giulioni M, Gardella E, Rubboli G, Roncaroli F, Zucchelli M, Bernardi B, Tassinari CA, Calbucci F (2006) Lesionectomy in epileptogenic gangliogliomas: seizure outcome and surgical results. J Clin Neurosci 13:529–535
Hoischen A, Ehrler M, Fassunke J, Simon M, Baudis M, Landwehr C, Radlwimmer B, Lichter P, Schramm J, Becker AJ, Weber RG (2008) Comprehensive characterization of genomic aberrations in gangliogliomas by CGH, array-based CGH and interphase FISH. Brain Pathol 18:326–337
Im SH, Chung CK, Cho BK, Wang KC, Yu IK, Song IC, Cheon GJ, Lee DS, Kim NR, Chi JG (2002) Intracranial ganglioglioma: preoperative characteristics and oncologic outcome after surgery. J Neuro Oncol 59:173–183
Jackson JH (1882) Localized convulsions from tumor of the brain. Brain 5:364–374
Kam R, Chen J, Blumcke I, Normann S, Fassunke J, Elger CE, Schramm J, Wiestler OD, Becker AJ (2004) The reelin pathway components disabled-1 and p35 in gangliogliomas–a mutation and expression analysis. Neuropatho Appl Neurobiol 30:225–232
Kohling R, Senner V, Paulus W, Speckmann EJ (2006) Epileptiform activity preferentially arises outside tumor invasion zone in glioma xenotransplants. Neurobiol Dis 22:64–75
Louis, DN, Ohgaki, H, Wiestler, OD and Cavanee, WK (eds) (2007) WHO classification of tumours of the central nervous system. IARC, Lyon
Luyken C, Blumcke I, Fimmers R, Urbach H, Wiestler ODand, Schramm J (2004) Supratentorial gangliogliomas: histopathologic grading and tumor recurrence in 184 patients with a median follow-up of 8 years. Cancer 101:146–155
Majores M, von Lehe M, Fassunke J, Schramm J, Becker AJ, Simon M (2008) Tumor recurrence and malignant progression of gangliogliomas. Cancer 113:3355–3363
Morris HH, Matkovic Z, Estes ML, Prayson RA, Comair YG, Turnbull J, Najm I, Kotagal Pand, Wyllie E (1998) Ganglioglioma and intractable epilepsy: clinical and neurophysiologic features and predictors of outcome after surgery. Epilepsia 39:307–313
Ogiwara H, Nordli DR, DiPatri AJ, Alden TD, Bowman RM, Tomita T (2010) Pediatric epileptogenic gangliogliomas: seizure outcome and surgical results. J Neurosur Pediatr 5:271–276
Palmini A, Najm I, Avanzini G, Babb T, Guerrini R, Foldvary-Schaefer N, Jackson G, Luders HO, Prayson R, Spreafico R, Vinters HV (2004) Terminology and classification of the cortical dysplasias. Neurology 62:S2–8
Pandita A, Balasubramaniam A, Perrin R, Shannon P, Guha A (2007) Malignant and benign ganglioglioma: a pathological and molecular study. Neuro Oncol 9:124–134
Potter CJ, Huang Hand, Xu T (2001) Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105:357–368
Quinn B (1998) Synaptophysin staining in normal brain: importance for diagnosis of ganglioglioma. Am J Surg Pathol 22:550–556
Samadani U, Judkins AR, Akpalu A, Aronica E, Crino PB (2007) Differential cellular gene expression in ganglioglioma. Epilepsia 48:646–653
Schick V, Majores M, Koch A, Elger CE, Schramm J, Urbach H, Becker AJ (2007) Alterations of phosphatidylinositol 3-kinase pathway components in epilepsy-associated glioneuronal lesions. Epilepsia 48(Suppl 5):65–73
Shamji MF, Fric-Shamji ECand, Benoit BG (2009) Brain tumors and epilepsy: pathophysiology of peritumoral changes. Neurosurg Rev 32:275–284
Squire JA, Arab S, Marrano P, Bayani J, Karaskova J, Taylor M, Becker L, Rutka J, Zielenska M (2001) Molecular cytogenetic analysis of glial tumors using spectral karyotyping and comparative genomic hybridization. Mol Diagn 6:93–108
van Breemen MS, Wilms EB, Vecht CJ (2007) Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol 6:421–430
Vezzani A, Granata T (2005) Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46:1724–1743
Yamada J, Okabe A, Toyoda H, Kilb W, Luhmann HJ, Fukuda A (2004) Cl- uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1. J Physiol 557:829–841
Yin XL, Hui AB, Pang JC, Poon WS, Ng HK (2002) Genome-wide survey for chromosomal imbalances in ganglioglioma using comparative genomic hybridization. Cancer Genet Cytogenet 134:71–76
Zeng LH, Xu L, Gutmann DH, Wong M (2008) Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann Neurol 63:444–453
Acknowledgments
We thank Dr. Albert Becker (Dept. of Neuropathology, University of Bonn Medical Center) for his input in the final version of this chapter.
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Aronica, E., Niehusmann, P. (2012). Gangliogliomas: Molecular Pathogenesis and Epileptogenesis. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 5. Tumors of the Central Nervous System, vol 5. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2019-0_29
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