title: Clinical, imaging, and immunohistochemical characteristics of focal cortical dysplasia Type II extratemporal epilepsies in children: analyses of an institutional case series.
abstract: OBJECTIVE Focal cortical dysplasia (FCD) Type II is divided into 2 subgroups based on the absence (IIA) or presence (IIB) of balloon cells. In particular, extratemporal FCD Type IIA and IIB is not completely understood in terms of clinical, imaging, biological, and neuropathological differences. The aim of the authors was to analyze distinctions between these 2 formal entities and address clinical, MRI, and immunohistochemical features of extratemporal epilepsies in children. METHODS Cases formerly classified as Palmini FCD Type II nontemporal epilepsies were identified through the prospectively maintained epilepsy database at the British Columbia Children's Hospital in Vancouver, Canada. Clinical data, including age of seizure onset, age at surgery, seizure type(s) and frequency, affected brain region(s), intraoperative electrocorticographic findings, and outcome defined by Engel's classification were obtained for each patient. Preoperative and postoperative MRI results were reevaluated. H & E-stained tissue sections were reevaluated by using the 2011 International League Against Epilepsy classification system and additional immunostaining for standard cellular markers (neuronal nuclei, neurofilament, glial fibrillary acidic protein, CD68). Two additional established markers of pathology in epilepsy resection, namely, CD34 and α-B crystallin, were applied. RESULTS Seven nontemporal FCD Type IIA and 7 Type B cases were included. Patients with FCD Type IIA presented with an earlier age of epilepsy onset and slightly better Engel outcome. Radiology distinguished FCD Types IIA and IIB, in that Type IIB presented more frequently with characteristic cortical alterations. Nonphosphorylated neurofilament protein staining confirmed dysplastic cells in dyslaminated areas. The white-gray matter junction was focally blurred in patients with FCD Type IIB. α-B crystallin highlighted glial cells in the white matter and subpial layer with either of the 2 FCD Type II subtypes and balloon cells in patients with FCD Type IIB. α-B crystallin positivity proved to be a valuable tool for confirming the histological diagnosis of FCD Type IIB in specimens with rare balloon cells or difficult section orientation. Distinct nonendothelial cellular CD34 staining was found exclusively in tissue from patients with MRI-positive FCD Type IIB. CONCLUSIONS Extratemporal FCD Types IIA and IIB in the pediatric age group exhibited imaging and immunohistochemical characteristics; cellular immunoreactivity to CD34 emerged as an especially potential surrogate marker for lesional FCD Type IIB, providing additional evidence that FCD Types IIA and IIB might differ in their etiology and biology. Although the sample number in this study was small, the results further support the theory that postoperative outcome-defined by Engel's classification-is multifactorial and determined by not only histology but also the extent of the initial lesion, its location in eloquent areas, intraoperative electrocorticographic findings, and achieved resection grade.
authors.affiliation: Department of Neurosurgery, University Hospital of Schleswig-Holstein Campus Kiel, Germany; and.|Divisions of 2 Pediatric Neurosurgery and.|Department of Neurosurgery, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Friederike
authors.initials: F
authors.lastname: Knerlich-Lukoschus
authors.affiliation: Pediatric Neurology, Department of Pediatrics.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Connolly
authors.affiliation: Division of Anatomical Pathology, Department of Pathology and Laboratory Medicine, and.
authors.forename: Glenda
authors.initials: G
authors.lastname: Hendson
authors.affiliation: Divisions of 2 Pediatric Neurosurgery and.|Department of Neurosurgery, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Steinbok
authors.affiliation: Division of Anatomical Pathology, Department of Pathology and Laboratory Medicine, and.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dunham
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D000069279:Drug Resistant Epilepsy / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D064795:Intraoperative Neurophysiological Monitoring / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D054081:Malformations of Cortical Development, Group II / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D019635:Neurosurgical Procedures / Q000379:methods; D011446:Prospective Studies; D012189:Retrospective Studies
keywords: ABC = α-B crystallin; BCCH = British Columbia Children's Hospital; CD34; DRFE = early-onset drug-resistant focal epilepsy; ECoG = electrocorticography; FCD = focal cortical dysplasia; GFAP = glial fibrillary acidic protein; ILAE = International League Against Epilepsy; LFB = Luxol fast blue; NFP = nonphosphorylated neurofilament protein; NeuN = neuronal nuclei; epilepsy; focal cortical dysplasia; immunohistochemistry; intractable seizures; surgical outcome; α-B crystallin