title: Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Frontal Lobe Epilepsy: A New Clinico-Pathological Entity.
abstract: The histopathological spectrum of human epileptogenic brain lesions is widespread including common and rare variants of cortical malformations. However, 2-26% of epilepsy surgery specimens are histopathologically classified as nonlesional. We hypothesized that these specimens include also new diagnostic entities, in particular when presurgical magnetic resonance imaging (MRI) can identify abnormal signal intensities within the anatomical region of seizure onset. In our series of 1381 en bloc resected epilepsy surgery brain specimens, 52 cases could not be histopathologically classified and were considered nonlesional (3.7%). An increase of Olig2-, and PDGFR-alpha-immunoreactive oligodendroglia was observed in white matter and deep cortical layers in 22 of these patients (42%). Increased proliferation activity as well as heterotopic neurons in white matter were additional histopathological hallmarks. All patients suffered from frontal lobe epilepsy (FLE) with a median age of epilepsy onset at 4 years and 16 years at epilepsy surgery. Presurgical MRI suggested focal cortical dysplasia (FCD) in all patients. We suggest to classify this characteristic histopathology pattern as "mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE)." Further insights into pathomechanisms of MOGHE may help to bridge the diagnostic gap in children and young adults with difficult-to-treat FLE.
authors.affiliation: Department of Neuropathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schurr
authors.affiliation: Department of Neuropathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Coras
authors.affiliation: Department of Neurosurgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Rössler
authors.affiliation: Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schoen-Klinik Vogtareuth, Vogtareuth, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Pieper
authors.affiliation: Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schoen-Klinik Vogtareuth, Vogtareuth, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kudernatsch
authors.affiliation: Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schoen-Klinik Vogtareuth, Vogtareuth, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Holthausen
authors.affiliation: Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schoen-Klinik Vogtareuth, Vogtareuth, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Winkler
authors.affiliation: Epilepsy Center Bethel, Hospital Mara, Bielefeld, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Woermann
authors.affiliation: Epilepsy Center Bethel, Hospital Mara, Bielefeld, Germany.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bien
authors.affiliation: Epilepsy Center Bethel, Hospital Mara, Bielefeld, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Polster
authors.affiliation: Epilepsy Center Bethel, Hospital Mara, Bielefeld, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schulz
authors.affiliation: Department of Neurosurgery, Evangelisches Krankenhaus Bielefeld, Kantensiek 11, 33617 Bielefeld, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Kalbhenn
authors.affiliation: Department of Radiology, University Hospital Bonn, 53127 Bonn, Germany.|Department of Radiology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.affiliation: Department of Neuropathology, University Hospital Bonn, 53127 Bonn, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Becker
authors.affiliation: Swiss Epilepsy Center, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grunwald
authors.affiliation: Swiss Epilepsy Center, Zurich, Switzerland.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Huppertz
authors.affiliation: Servicio de Neurología, Hospital Ruber International, C/La Masó n 38, 28034 Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gil-Nagel
authors.affiliation: Servicio de Neurología, Hospital Ruber International, C/La Masó n 38, 28034 Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Toledano
authors.affiliation: Department of Pediatrics, Medical University Vienna, 1090 Vienna, Austria.
authors.forename: Martha
authors.initials: M
authors.lastname: Feucht
authors.affiliation: Department of Pediatrics, Medical University Vienna, 1090 Vienna, Austria.|Institute of Neurology, Medical University Vienna, 1090 Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Mühlebner
authors.affiliation: Department of Neurosurgery, Medical University Vienna, 1090 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Czech
authors.affiliation: Department of Neuropathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Blümcke
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D000069279:Drug Resistant Epilepsy / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D017034:Epilepsy, Frontal Lobe / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D006965:Hyperplasia; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000000981:diagnostic imaging / Q000473:pathology*; D008875:Middle Aged; D059906:Neuroimaging; D000076104:Oligodendrocyte Transcription Factor 2 / Q000032:analysis; D009836:Oligodendroglia / Q000473:pathology*; D055815:Young Adult
chemical_list: C405708:OLIG2 protein, human; D000076104:Oligodendrocyte Transcription Factor 2
keywords: epilepsy; frontal lobe; hyperplasia; neuropathology; oligodendrocytes