Abstract
Focal Cortical Dysplasias (FCDs) present with a large clinicopathological spectrum. FCDs are believed to relate directly to an epileptogenic condition, although seizure control by surgical resection is variable. This applies in particular to young children with multilobar FCDs, suffering from severe epilepsies and psychomotor retardation. Herein, we performed a comparative analysis of presurgically available data and microscopic inspection of resected cortical specimens to further characterise the pathomorphological spectrum of FCD. Multilobar resection procedures were performed in a consecutive series of 18 young children (mean 7.6 years) with severe pharmaco-resistant epilepsies following extensive presurgical surface-/invasive video-EEG monitoring intraoperative electro-corticography (iECoG), as well as high resolution MRI. In all cases, systematic neuropathological examination of surgical specimens was performed with respect to architectural abnormalities and cell density measurements. These histomorphological data were compared with volumetric MRI analysis. Histopathological examination revealed increased neuronal densities correlating with decreased cortical thickness and abundance of neuronal microcolumns in all cases. Intriguingly, the affected cerebral hemisphere was significantly smaller, relative to the non-epileptogenic contralateral side, in 16 children of our patient series. In conclusion, hypoplastic neocortex and columnar architectural disorganisation point to compromised cortical development, and appear as distinct FCD I subtype in children suffering from severe epilepsies and psychomotor retardation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Barkovich AJ, Kuzniecky RI, Jackson GD, Guerrini R, Dobyns WB. A developmental and genetic classification for malformations of cortical development. Neurology 2005; 65: 1873–1887.
Becker AJ, Chen J, Zien A, et al. Correlated stage- and subfieldassociated hippocampal gene expression patterns in experimental and human temporal lobe epilepsy. Eur J Neurosci 2003; 18: 2792–2802.
Becker AJ, Urbach H, Scheffler B, et al. Focal cortical dysplasia of Taylor’s balloon cell type: Mutational analysis of the TSC1 gene indicates a pathogenic relationship to tuberous sclerosis. Ann Neurol 2002; 52: 29–37.
Bernard C, Anderson A, Becker A, Poolos NP, Beck H, Johnston D. Acquired dendritic channelopathy in temporal lobe epilepsy. Science 2004; 305: 532–535.
Blümcke I, Pauli E, Clusmann H, et al. A new clinico-pathological classification system for mesial temporal sclerosis. Acta Neuropathol 2007; 113: 235–244.
Blümcke I, Vinters HV, Armstrong D, Aronica E, Thom M, Spreafico R. Malformations of cortical development and epilepsies. Epileptic Disord 2009; 11: 181–193.
Briellmann RS, Jackson GD, Kalnins R, Berkovic SF. Hemicranial volume deficits in patients with temporal lobe epilepsy with and without hippocampal sclerosis. Epilepsia 1998; 39: 1174–1181.
Chamberlain WA, Cohen ML, Gyure KA, et al. Interobserver and intraobserver reproducibility in focal cortical dysplasia (malformations of cortical development). Epilepsia 2009; 50: 2593–2598.
Chassoux F, Devaux B, Landre E, et al. Stereoelectroencephalography in focal cortical dysplasia: a 3D approach to delineating the dysplastic cortex. Brain 2000; 123: 1733–1751.
Colombo N, Salamon N, Raybaud C, Ozkara C, Barkovich AJ. Imaging of malformations of cortical development. Epileptic Disord 2009; 11: 194–205.
Crino PB, Becker AJ. Gene profiling in temporal lobe epilepsy tissue and dysplastic lesions. Epilepsia 2006; 47: 1608–1616.
Crino PB, Miyata H, Vinters HV. Neurodevelopmental disorders as a cause of seizures. neuropathologic, genetic and mechanistic considerations. Brain Pathol 2002; 12: 212–233.
Diehl B, Najm I, LaPresto E, et al. Temporal lobe volumes in patients with hippocampal sclerosis with or without cortical dysplasia. Neurology 2004; 62: 1729–1735.
Engel Jr J, Van Ness PC, Rasmussen TB, Ojemann LM. Outcome with respect to epileptic seizures. In: Engel Jr J, ed. Surgical Treatment of the Epilepsies. New York: Raven Press, 1993: 609–621.
Fauser S, Schulze-Bonhage A. Epileptogenicity of cortical dysplasia in temporal lobe dual pathology: an electrophysiological study with invasive recordings. Brain 2006; 129: 82–95.
Hildebrandt M, Amann K, Schroder R, et al. White matter angiopathy is common in pediatric patients with intractable focal epilepsies. Epilepsia 2008; 49: 804–815.
Hildebrandt M, Pieper T, Winkler P, Kolodziejczyk D, Holthausen H, Blümcke I. Neuropathological spectrum of cortical dysplasia in children with severe focal epilepsies. Acta Neuropathol 2005; 110: 1–11.
Holmes GL. Effects of early seizures on later behavior and epileptogenicity. Ment Retard Dev Disabil Res Rev 2004; 10: 101–105.
Krsek P, Maton B, Korman B, et al. Different features of histopathological subtypes of pediatric focal cortical dysplasia. Ann Neurol 2008; 63: 758–769.
Krsek P, Pieper T, Karlmeier A, et al. Different presurgical characteristics and seizure outcomes in children with focal cortical dysplasia type I or II. Epilepsia 2009; 50: 125–137.
Lerner JT, Salamon N, Hauptman JS, et al. Assessment and surgical outcomes for mild type I and severe type II cortical dysplasia: a critical review and the UCLA experience. Epilepsia 2009; 50: 1310–1335.
Majores M, Blumcke I, Urbach H, et al. Distinct allelic variants of TSC1 and TSC2 in epilepsy-associated cortical malformations without balloon cells. J Neuropathol Exp Neurol 2005; 64: 629–637.
Marin-Padilla M. Developmental neuropathology and impact of perinatal brain damage. III: gray matter lesions of the neocortex. J Neuropathol Exp Neurol 1999; 58: 407–429.
Marin-Padilla M, Parisi JE, Armstrong DL, Sargent SK, Kaplan JA. Shaken infant syndrome: developmental neuropathology, progressive cortical dysplasia, and epilepsy. Acta Neuropathol (Berl) 2002; 103: 321–332.
Miller B, Nagy D, Finlay BL, Chance B, Kobayashi A, Nioka S. Consequences of reduced cerebral blood flow in brain development. I. Gross morphology, histology, and callosal connectivity. Exp Neurol 1993; 124: 326–342.
Montenegro MA, Guerreiro MM, Lopes-Cendes I, Guerreiro CA, Cendes F. Interrelationship of genetics and prenatal injury in the genesis of malformations of cortical development. Arch Neurol 2002; 59: 1147–1153.
Moran NF, Lemieux L, Kitchen ND, Fish DR, Shorvon SD. Extrahippocampal temporal lobe atrophy in temporal lobe epilepsy and mesial temporal sclerosis. Brain 2001; 124: 167–175.
Palmini A, Gambardella A, Andermann F, et al. Intrinsic epileptogenicity of human dysplastic cortex as suggested by corticography and surgical results. Ann Neurol 1995; 37: 476–487.
Palmini A, Najm I, Avanzini G, et al. Terminology and classification of the cortical dysplasias. Neurology 2004; 62: S2–S8.
Rakic P. Specification of cerebral cortical areas. Science 1988; 241: 170–176.
Rakic P. Evolution of the neocortex: a perspective from developmental biology. Nat Rev Neurosci 2009; 10: 724–735.
Seidenberg M, Kelly KG, Parrish J, et al. Ipsilateral and contralateral MRI volumetric abnormalities in chronic unilateral temporal lobe epilepsy and their clinical correlates. Epilepsia 2005; 46: 420–430.
Sisodiya SM. Malformations of cortical development: burdens and insights from important causes of human epilepsy. Lancet Neurol 2004; 3: 29–38.
Sutula TP. Mechanisms of epilepsy progression: current theories and perspectives from neuroplasticity in adulthood and development. Epilepsy Res 2004; 60: 161–171.
Tassi L, Colombo N, Garbelli R, et al. Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical outcome. Brain 2002; 125: 1719–1732.
Tassi L, Meroni A, Deleo F, et al. Temporal lobe epilepsy: neuropathological and clinical correlations in 243 surgically treated patients. Epileptic Disord 2009; 11: 281–292.
Taylor DC, Falconer MA, Bruton CJ, Corsellis JA. Focal dysplasia of the cerebral cortex in epilepsy. J Neurol Neurosurg Psychiatry 1971; 34: 369–387.
Thom M, Eriksson S, Martinian L, et al. Temporal Lobe Sclerosis Associated With Hippocampal Sclerosis in Temporal Lobe Epilepsy: Neuropathological Features. J Neuropathol Exp Neurol 2009; 68: 928–938.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Blümcke, I., Pieper, T., Pauli, E. et al. A distinct variant of focal cortical dysplasia type I characterised by magnetic resonance imaging and neuropathological examination in children with severe epilepsies. Epileptic Disord 12, 172–180 (2010). https://doi.org/10.1684/epd.2010.0321
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1684/epd.2010.0321