title: Molecular neuropathology of epilepsy-associated glioneuronal malformations.
abstract: Glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) as well as highly differentiated glioneuronal tumors (i.e. gangliogliomas) and constitute frequent findings in patients with pharmacoresistent focal epilepsies. Tailored resection strategies evolved as promising treatment options and allow a systematic neuropathologic and molecular biologic examination of the epileptogenic area in these patients. The histopathologic appearance and immunophenotype of glioneuronal lesions are, however, characterized by numerous similarities and suggest impaired proliferation, migration, and differentiation of neural precursor cells to play a pathogenetic role. Recent studies point toward molecular alterations within a variety of genes and pathways involved in development of the central nervous system, neuronal growth, and maturation. Compromised signaling within insulin- or reelin-transduction cascades are common findings and were associated with specific MCD entities. Unraveling pathogenic mechanisms may advance refined classification systems for epilepsy-associated malformations and open new avenues for the development of targeted treatment strategies in pharmacoresistent focal epilepsies associated with cortical malformations.
authors.affiliation: Department of Neuropathology, Bonn University Medical Center, Sigmund-Freud Strasse 25, D-53105 Bonn, Germany. albert_becker@uni-bonn.de
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.forename: Ingmar
authors.initials: I
authors.lastname: Blümcke
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.forename: Volkmar
authors.initials: V
authors.lastname: Hans
authors.forename: Michael
authors.initials: M
authors.lastname: Majores
mesh_terms: D001932:Brain Neoplasms / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002540:Cerebral Cortex / Q000254:growth & development / Q000473:pathology; D004827:Epilepsy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D018303:Ganglioglioma / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009421:Nervous System Malformations / Q000150:complications / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014402:Tuberous Sclerosis / Q000150:complications / Q000473:pathology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D000091042:Reelin Protein; D012697:Serine Endopeptidases; C000717127:RELN protein, human