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Open Access 01-12-2013 | Research

Disorganization of neocortical lamination in focal cortical dysplasia is brain-region dependent: evidence from layer-specific marker expression

Authors: Susanne Fauser, Ute Häussler, Catharina Donkels, Susanne Huber, Julia Nakagawa, Marco Prinz, Andreas Schulze-Bonhage, Josef Zentner, Carola A Haas

Published in: Acta Neuropathologica Communications | Issue 1/2013

Abstract

Background

Focal cortical dysplasias (FCD) are local disturbances of neocortical architecture and a common cause of pharmaco-resistant focal epilepsy. Little is known about the pathomechanisms leading to architectural abnormalities associated with FCD.

Results

In the present study we compared 52 FCD cases originating from the frontal or temporal lobe with or without Ammon’s horn sclerosis (AHS) with regard to structural and molecular differences. We applied layer-specific (ER81, RORß, SMI32, TLE4) and interneuron (calbindin, parvalbumin) markers by means of immunohistochemistry, in situ hybridization (ISH), and real time RT-PCR and correlated our findings with clinical parameters. We found that: (1) Structural abnormalities were most prominent in layers III-VI including changed morphology of individual neurons or dispersion, blurring and thinning of layers. These alterations were most pronounced in isolated frontal FCD, whereas the most homogeneous group was FCD IIIa. (2) Numbers of calbindin- and parvalbumin-positive interneurons varied considerably within the different FCD groups, but were not generally reduced. A significant decrease was only found for calbindin-positive interneurons in frontal FCD, and for parvalbumin-positive interneurons in FCD IIIa. (3) Interestingly, FCD IIIa presented with significant changes in the numbers of calbindin- or TLE4-positive neurons when compared to isolated FCD or controls. (4) Correlations between clinical and cellular parameters strongly depended on FCD localisation and age of the patients.

Conclusions

In summary, our data suggest that late cortical development is disturbed in FCD, yet most likely by different causes depending on brain region, FCD type and FCD severity.

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Palmini A, Andermann F, Olivier A, Tampieri D, Robitaille Y, Melanson D, Ethier R: Neuronal migration disorders: a contribution of modern neuroimaging to the etiologic diagnosis of epilepsy. Can J Neurol Sci 1991, 18: 580–587.PubMed

Chan S, Chin SS, Nordli DR, Goodman RR, DeLaPaz RL, Pedley TA: Prospective magnetic resonance imaging identification of focal cortical dysplasia, including the non-balloon cell subtype. Ann Neurol 1998, 44: 749–757. 10.1002/ana.410440508CrossRefPubMed

Bastos AC, Comeau RM, Andermann F, Melanson D, Cendes F, Dubeau F, Fontaine S, Tampieri D, Olivier A: Diagnosis of subtle focal dysplastic lesions: curvilinear reformatting from three-dimensional magnetic resonance imaging. Ann Neurol 1999, 46: 88–94. 10.1002/1531-8249(199907)46:1<88::AID-ANA13>3.0.CO;2-4CrossRefPubMed

Kassubek J, Huppertz HJ, Spreer J, Schulze-Bonhage A: Detection and localization of focal cortical dysplasia by voxel-based 3-D MRI analysis. Epilepsia 2002, 43: 596–602. 10.1046/j.1528-1157.2002.41401.xCrossRefPubMed

Wilke M, Kassubek J, Ziyeh S, Schulze-Bonhage A, Huppertz HJ: Automated detection of gray matter malformations using optimized voxel-based morphometry: a systematic approach. Neuroimage 2003, 20: 330–343. 10.1016/S1053-8119(03)00296-9CrossRefPubMed

Huppertz HJ, Grimm C, Fauser S, Kassubek J, Mader I, Hochmuth A, Spreer J, Schulze-Bonhage A: Enhanced visualization of blurred gray-white matter junctions in focal cortical dysplasia by voxel-based 3D MRI analysis. Epilepsy Res 2005, 67: 35–50. 10.1016/j.eplepsyres.2005.07.009CrossRefPubMed

Kuzniecky R, Murro A, King D, Morawetz R, Smith J, Powers R, Yaghmai F, Faught E, Gallagher B, Snead OC: Magnetic resonance imaging in childhood intractable partial epilepsies: pathologic correlations. Neurology 1993, 43: 681–687. 10.1212/WNL.43.4.681CrossRefPubMed

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. 10.1212/01.wnl.0000183747.05269.2dCrossRefPubMed

Mischel PS, Nguyen LP, Vinters HV: Cerebral cortical dysplasia associated with pediatric epilepsy. Review of neuropathologic features and proposal for a grading system. J Neuropathol Exp Neurol 1995, 54: 137–153. 10.1097/00005072-199503000-00001CrossRefPubMed

10.

Crino PB, Miyata H, Vinters HV: Neurodevelopmental disorders as a cause of seizures: neuropathologic, genetic, and mechanistic considerations. Brain Pathol 2002, 12: 212–233.CrossRefPubMed

11.

Tassi L, Colombo N, Garbelli R, Francione S, Lo Russo G, Mai R, Cardinale F, Cossu M, Ferrario A, Galli C, et al.: Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical outcome. Brain 2002, 125: 1719–1732. 10.1093/brain/awf175CrossRefPubMed

12.

Palmini A, Najm I, Avanzini G, Babb T, Guerrini R, Foldvary-Schaefer N, Jackson G, Luders HO, Prayson R, Spreafico R, Vinters HV: Terminology and classification of the cortical dysplasias. Neurology 2004, 62: S2-S8.CrossRefPubMed

13.

Kloss S, Pieper T, Pannek H, Holthausen H, Tuxhorn I: Epilepsy surgery in children with focal cortical dysplasia (FCD): results of long-term seizure outcome. Neuropediatrics 2002, 33: 21–26. 10.1055/s-2002-23595CrossRefPubMed

14.

Kral T, Clusmann H, Blümcke I, Fimmers R, Ostertun B, Kurthen M, Schramm J: Outcome of epilepsy surgery in focal cortical dysplasia. J Neurol Neurosurg Psychiatry 2003, 74: 183–188. 10.1136/jnnp.74.2.183PubMedCentralCrossRefPubMed

15.

Fauser S, Bast T, Altenmüller DM, Schulte-Monting J, Strobl K, Steinhoff BJ, Zentner J, Schulze-Bonhage A: Factors influencing surgical outcome in patients with focal cortical dysplasia. J Neurol Neurosurg Psychiatry 2008, 79: 103–105. 10.1136/jnnp.2007.116038CrossRefPubMed

16.

Semah F, Picot MC, Adam C, Broglin D, Arzimanoglou A, Bazin B, Cavalcanti D, Baulac M: Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology 1998, 51: 1256–1262. 10.1212/WNL.51.5.1256CrossRefPubMed

17.

Fauser S, Schulze-Bonhage A, Honegger J, Carmona H, Huppertz HJ, Pantazis G, Rona S, Bast T, Strobl K, Steinhoff BJ, et al.: Focal cortical dysplasias: surgical outcome in 67 patients in relation to histological subtypes and dual pathology. Brain 2004, 127: 2406–2418. 10.1093/brain/awh277CrossRefPubMed

18.

Fauser S, Huppertz HJ, Bast T, Strobl K, Pantazis G, Altenmüller DM, Feil B, Rona S, Kurth C, Rating D, et al.: Clinical characteristics in focal cortical dysplasia: a retrospective evaluation in a series of 120 patients. Brain 2006, 129: 1907–1916. 10.1093/brain/awl133CrossRefPubMed

19.

Blümcke I, Thom M, Aronica E, Armstrong DD, Vinters HV, Palmini A, Jacques TS, Avanzini G, Barkovich AJ, Battaglia G, et al.: The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia 2011, 52: 158–174. 10.1111/j.1528-1167.2010.02777.xPubMedCentralCrossRefPubMed

20.

Sheen VL, Ferland RJ, Neal J, Harney M, Hill RS, Banham A, Brown P, Chenn A, Corbo J, Hecht J, et al.: Neocortical neuronal arrangement in Miller Dieker syndrome. Acta Neuropathol 2006, 111: 489–496. 10.1007/s00401-005-0010-3CrossRefPubMed

21.

Hevner RF: Layer-specific markers as probes for neuron type identity in human neocortex and malformations of cortical development. J Neuropathol Exp Neurol 2007, 66: 101–109. 10.1097/nen.0b013e3180301c06CrossRefPubMed

22.

Garbelli R, Rossini L, Moroni RF, Watakabe A, Yamamori T, Tassi L, Bramerio M, Russo GL, Frassoni C, Spreafico R: Layer-specific genes reveal a rudimentary laminar pattern in human nodular heterotopia. Neurology 2009, 73: 746–753. 10.1212/WNL.0b013e3181af3397CrossRefPubMed

23.

McConnell SK: Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation. J Neurosci 1988, 8: 945–974.PubMed

24.

McConnell SK, Kaznowski CE: Cell cycle dependence of laminar determination in developing neocortex. Science 1991, 254: 282–285. 10.1126/science.1925583CrossRefPubMed

25.

Caviness VS Jr: Neocortical histogenesis in normal and reeler mice: a developmental study based upon [3H]thymidine autoradiography. Brain Res 1982, 256: 293–302.CrossRefPubMed

26.

Hevner RF, Shi L, Justice N, Hsueh Y, Sheng M, Smiga S, Bulfone A, Goffinet AM, Campagnoni AT, Rubenstein JL: Tbr1 regulates differentiation of the preplate and layer 6. Neuron 2001, 29: 353–366. 10.1016/S0896-6273(01)00211-2CrossRefPubMed

27.

Arlotta P, Molyneaux BJ, Chen J, Inoue J, Kominami R, Macklis JD: Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo. Neuron 2005, 45: 207–221. 10.1016/j.neuron.2004.12.036CrossRefPubMed

28.

Molyneaux BJ, Arlotta P, Hirata T, Hibi M, Macklis JD: Fezl is required for the birth and specification of corticospinal motor neurons. Neuron 2005, 47: 817–831. 10.1016/j.neuron.2005.08.030CrossRefPubMed

29.

Hadjivassiliou G, Martinian L, Squier W, Blumcke I, Aronica E, Sisodiya SM, Thom M: The application of cortical layer markers in the evaluation of cortical dysplasias in epilepsy. Acta Neuropathol 2010, 120: 517–528. 10.1007/s00401-010-0686-xPubMedCentralCrossRefPubMed

30.

Rossini L, Moroni RF, Tassi L, Watakabe A, Yamamori T, Spreafico R, Garbelli R: Altered layer-specific gene expression in cortical samples from patients with temporal lobe epilepsy. Epilepsia 2011, 52: 1928–1937. 10.1111/j.1528-1167.2011.03246.xCrossRefPubMed

31.

Sakakibara T, Sukigara S, Saito T, Otsuki T, Takahashi A, Kaneko Y, Kaido T, Saito Y, Sato N, Kimura Y, et al.: Delayed maturation and differentiation of neurons in focal cortical dysplasia with the transmantle sign: analysis of layer-specific marker expression. J Neuropathol Exp Neurol 2012, 71: 741–749. 10.1097/NEN.0b013e318262e41aCrossRefPubMed

32.

Ferrer I, Tunon T, Soriano E, del Rio A, Iraizoz I, Fonseca M, Guionnet N: Calbindin immunoreactivity in normal human temporal neocortex. Brain Res 1992, 572: 33–41. 10.1016/0006-8993(92)90447-HCrossRefPubMed

33.

Bourne JA, Rosa MG: Hierarchical development of the primate visual cortex, as revealed by neurofilament immunoreactivity: early maturation of the middle temporal area (MT). Cereb Cortex 2006, 16: 405–414.CrossRefPubMed

34.

Nakagawa Y, O’Leary DD: Dynamic patterned expression of orphan nuclear receptor genes RORalpha and RORbeta in developing mouse forebrain. Dev Neurosci 2003, 25: 234–244. 10.1159/000072271CrossRefPubMed

35.

Zamecnik J, Krsek P, Druga R, Marusic P, Benes V, Tichy M, Komarek V: Densities of parvalbumin-immunoreactive neurons in non-malformed hippocampal sclerosis-temporal neocortex and in cortical dysplasias. Brain Res Bull 2006, 68: 474–481. 10.1016/j.brainresbull.2005.10.008CrossRefPubMed

36.

Yoneshima H, Yamasaki S, Voelker CC, Molnar Z, Christophe E, Audinat E, Takemoto M, Nishiwaki M, Tsuji S, Fujita I, Yamamoto N: Er81 is expressed in a subpopulation of layer 5 neurons in rodent and primate neocortices. Neuroscience 2006, 137: 401–412. 10.1016/j.neuroscience.2005.08.075CrossRefPubMed

37.

Whitford KL, Dijkhuizen P, Polleux F, Ghosh A: Molecular control of cortical dendrite development. Annu Rev Neurosci 2002, 25: 127–149. 10.1146/annurev.neuro.25.112701.142932CrossRefPubMed

38.

Andres M, Andre VM, Nguyen S, Salamon N, Cepeda C, Levine MS, Leite JP, Neder L, Vinters HV, Mathern GW: Human cortical dysplasia and epilepsy: an ontogenetic hypothesis based on volumetric MRI and NeuN neuronal density and size measurements. Cereb Cortex 2005, 15: 194–210.CrossRefPubMed

39.

Rakic P: Evolution of the neocortex: a perspective from developmental biology. Nat Rev Neurosci 2009, 10: 724–735. 10.1038/nrn2719PubMedCentralCrossRefPubMed

40.

O’Leary DD, Chou SJ, Sahara S: Area patterning of the mammalian cortex. Neuron 2007, 56: 252–269. 10.1016/j.neuron.2007.10.010CrossRefPubMed

41.

Spreafico R, Tassi L, Colombo N, Bramerio M, Galli C, Garbelli R, Ferrario A, Lo Russo G, Munari C: Inhibitory circuits in human dysplastic tissue. Epilepsia 2000,41(Suppl 6):S168-S173.CrossRefPubMed

42.

Thom M, Harding BN, Lin WR, Martinian L, Cross H, Sisodiya SM: Cajal-Retzius cells, inhibitory interneuronal populations and neuropeptide Y expression in focal cortical dysplasia and microdysgenesis. Acta Neuropathol 2003, 105: 561–569.PubMed

43.

Garbelli R, Meroni A, Magnaghi G, Beolchi MS, Ferrario A, Tassi L, Bramerio M, Spreafico R: Architectural (Type IA) focal cortical dysplasia and parvalbumin immunostaining in temporal lobe epilepsy. Epilepsia 2006, 47: 1074–1078. 10.1111/j.1528-1167.2006.00577.xCrossRefPubMed

44.

Wyllie E, Comair YG, Kotagal P, Raja S, Ruggieri P: Epilepsy surgery in infants. Epilepsia 1996, 37: 625–637. 10.1111/j.1528-1157.1996.tb00626.xCrossRefPubMed

45.

Tassi L, Garbelli R, Colombo N, Bramerio M, Lo Russo G, Deleo F, Milesi G, Spreafico R: Type I focal cortical dysplasia: surgical outcome is related to histopathology. Epileptic Disord 2010, 12: 181–191.PubMed

46.

Wyler AR, Dohan FC Jr, Schweitzer JB, Berry AD III: A grading system for mesial temporal pathology (hippocampal sclerosis) from anterior temporal lobectomy. J Epilepsy 1992, 5: 220–225. 10.1016/S0896-6974(05)80120-3CrossRef

47.

Wagener RJ, David C, Zhao S, Haas CA, Staiger JF: The somatosensory cortex of reeler mutant mice shows absent layering but intact formation and behavioral activation of columnar somatotopic maps. J Neurosci 2010, 30: 15700–15709. 10.1523/JNEUROSCI.3707-10.2010CrossRefPubMed

Title: Disorganization of neocortical lamination in focal cortical dysplasia is brain-region dependent: evidence from layer-specific marker expression
Authors: Susanne Fauser
Ute Häussler
Catharina Donkels
Susanne Huber
Julia Nakagawa
Marco Prinz
Andreas Schulze-Bonhage
Josef Zentner
Carola A Haas
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2013
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/2051-5960-1-47

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Disorganization of neocortical lamination in focal cortical dysplasia is brain-region dependent: evidence from layer-specific marker expression

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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