title: Neuropathologic measurements in focal cortical dysplasias: validation of the ILAE 2011 classification system and diagnostic implications for MRI.
abstract: Focal cortical dysplasias (FCD) which represent a composite group of cortical malformations are increasingly recognized as morphological substrate for severe therapy-refractory epilepsy in children and young adults. However, presurgical evaluation remains challenging as not all FCD variants can be reliably detected by high-resolution magnetic resonance imaging (MRI). Here, we studied a cohort of 52 epilepsy patients with neuropathological evidence for FCD using the 2011 classification of the International League against Epilepsy (ILAE) and systematically analysed those histopathologic features applicable also for MRI diagnostics. Histopathologic parameters included quantitative measurements of cellular profiles, cortical thickness, heterotopic neurons in white matter, and myelination that were compared between FCD subtypes and age-/localization-matched controls (n = 36) using multivariate analysis. Dysmorphic neurons in both FCD Type II variants showed significantly increased diameter of their cell bodies and nuclei. Cortical thickness was also increased with a distinct loss of myelin content specifying FCD Type IIb from IIa. The data further suggested that myelination deficits in FCD Type IIb result from compromised oligodendroglial lineage differentiation and we concluded that the "transmantle sign" is a unique finding in FCD Type IIb. In contrast, FCD Type Ia was characterized by a smaller cortical ribbon and higher neuronal densities, but these parameters failed to reach statistical significance (considering age- and location-dependent variability in controls). All FCD variants showed abnormal grey-white matter boundaries with increased numbers of heterotopic neurons. Similar results were obtained also at deep white matter location. Thus, many FCD variants may indeed escape visual MRI inspection, but suspicious areas with increased or decreased cortical thickness as well as grey-white matter blurring may be uncovered using post-processing protocols of neuroimaging data. The systematic analysis of well-specified histopathological features could be helpful to improve sensitivity and specificity in MRI detection during pre-surgical work-up of patients with drug-resistant focal epilepsies.
authors: Department of Neuropathology, University Hospital Erlangen, Germany.
authors: Angelika
authors: A
authors: Mühlebner
authors: Roland
authors: R
authors: Coras
authors: Katja
authors: K
authors: Kobow
authors: Martha
authors: M
authors: Feucht
authors: Thomas
authors: T
authors: Czech
authors: Hermann
authors: H
authors: Stefan
authors: Daniel
authors: D
authors: Weigel
authors: Michael
authors: M
authors: Buchfelder
authors: Hans
authors: H
authors: Holthausen
authors: Tom
authors: T
authors: Pieper
authors: Manfred
authors: M
authors: Kudernatsch
authors: Ingmar
authors: I
authors: Blümcke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001927:Brain Diseases / Q000145:classification* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000145:classification / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D038801:International Classification of Diseases / Q000592:standards*; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards*; D008297:Male; D054220:Malformations of Cortical Development / Q000145:classification* / Q000473:pathology*; D065703:Malformations of Cortical Development, Group I; D008875:Middle Aged; D055815:Young Adult