Acta Neuropathologica

, Volume 110, Issue 4, pp 383–392 | Cite as

Cortical neuronal densities and lamination in focal cortical dysplasia

  • M. Thom
  • L. Martinian
  • A. Sen
  • J. H. Cross
  • B. N. Harding
  • S. M. Sisodiya
Regular Paper

Abstract

Focal cortical dysplasia (FCD) is considered to represent a malformation due to abnormal cortical development (MCD) and is an important cause of focal epilepsy. The histopathological features include abnormal laminar architecture, the presence of hypertrophic and dysmorphic neurones in FCD type IIA and additional balloon cells in FCD type IIB. The events causing these sporadic lesions are unknown, but abnormal progenitor cell proliferation occurring late in corticogenesis has been proposed. FCD-like lesions have, however, also been described following a cerebral injury early in life. We carried out a stereological assessment on 15 cases of FCD on NeuN- and Nissl-stained sections from patients with a wide age range, and identified a significant reduction in the neuronal density in all cases in the region of dysplasia compared to the adjacent unaffected cortex (mean neuronal densities 19.2×103/mm3 in the region of dysplasia; 42.8×103/mm3 in the adjacent cortex). Relative differences in neuronal density and size in FCD cases between the superficial (layer I and II) and deep cortical laminae (layer V and VI) were similar to that observed in other pathologies including mild MCD, temporal neocortex adjacent to hippocampal sclerosis as well as in a non-epilepsy surgical control group. The lower overall neuronal densities observed in FCD may reflect neuropil expansion, a local failure of neuronal migration, proliferation or secondary neuronal loss. The preservation of relative differences in neuronal densities between cortical layers and laminar patterns of neurofilament staining in FCD would support the view that the temporal sequence of lamination is not affected.

Keywords

Neuronal density Focal cortical dysplasia Mild malformation due to abnormal cortical development 

References

  1. 1.
    Andres M, Andre VM, Nguyen S, Salamon N, Cepeda C, Levine MS, Leite JP, Neder L, Vinters HV, Mathern GW (2005) Human cortical dysplasia and epilepsy: an ontogenetic hypothesis based on volumetric MRI and NeuN neuronal density and size measurements. Cereb Cortex 15:194–210CrossRefPubMedGoogle Scholar
  2. 2.
    Baybis M, Yu J, Lee A, Golden JA, Weiner H, McKhann G 2nd, Aronica E, Crino PB (2004) mTOR cascade activation distinguishes tubers from focal cortical dysplasia. Ann Neurol 56:478–487CrossRefPubMedGoogle Scholar
  3. 3.
    Cepeda C, Hurst RS, Flores-Hernandez J, Hernandez-Echeagaray E, Klapstein GJ, Boylan MK, Calvert CR, Jocoy EL, Nguyen OK, Andre VM, Vinters HV, Ariano MA, Levine MS, Mathern GW (2003) Morphological and electrophysiological characterization of abnormal cell types in pediatric cortical dysplasia. J Neurosci Res 72:472–486CrossRefPubMedGoogle Scholar
  4. 4.
    Chae T, Kwon YT, Bronson R, Dikkes P, Li E, Tsai LH (1997) Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 18:29–42CrossRefPubMedGoogle Scholar
  5. 5.
    Crino PB, Trojanowski JQ, Eberwine J (1997) Internexin, MAP1B, and nestin in cortical dysplasia as markers of developmental maturity. Acta Neuropathol 93:619–627CrossRefPubMedGoogle Scholar
  6. 6.
    Crino PB, Miyata H, Vinters HV (2002) Neurodevelopmental disorders as a cause of seizures: neuropathologic, genetic, and mechanistic considerations. Brain Pathol 12:212–233PubMedGoogle Scholar
  7. 7.
    Gartner U, Alpar A, Seeger G, Heumann R, Arendt T (2004) Enhanced Ras activity in pyramidal neurons induces cellular hypertrophy and changes in afferent and intrinsic connectivity in synRas mice. Int J Dev Neurosci 22:165–173CrossRefPubMedGoogle Scholar
  8. 8.
    Hevner RF, Daza RA, Rubenstein JL, Stunnenberg H, Olavarria JF, Englund C (2003) Beyond laminar fate: toward a molecular classification of cortical projection/pyramidal neurons. Dev Neurosci 25:139–151CrossRefPubMedGoogle Scholar
  9. 9.
    Howard V, Reed MG (2005) Unbiased stereology: three-dimensional measurement in microscopy, 2nd edn. Garland Science/BIOS, New YorkGoogle Scholar
  10. 10.
    Hua Y, Crino PB (2003) Single cell lineage analysis in human focal cortical dysplasia. Cereb Cortex 13:693–699CrossRefPubMedGoogle Scholar
  11. 11.
    Jacobs B, Schall M, Prather M, Kapler E, Driscoll L, Baca S, Jacobs J, Ford K, Wainwright M, Treml M (2001) Regional dendritic and spine variation in human cerebral cortex: a quantitative golgi study. Cereb Cortex 11:558–571CrossRefPubMedGoogle Scholar
  12. 12.
    Kral T, Clusmann H, Blumcke I, Fimmers R, Ostertun B, Kurthen M, Schramm J (2003) Outcome of epilepsy surgery in focal cortical dysplasia. J Neurol Neurosurg Psychiatry 74:183–188CrossRefPubMedGoogle Scholar
  13. 13.
    Kremer S, De Saint Martin A, Minotti L, Grand S, Benabid AL, Pasquier B, Kahane P (2002) Focal cortical dysplasia possibly related to a probable prenatal ischemic injury. J Neuroradiol 29:200–203PubMedGoogle Scholar
  14. 14.
    Logan MA, Vetter ML (2004) Do-it-yourself tiling: dendritic growth in the absence of homotypic contacts. Neuron 43:439–440CrossRefPubMedGoogle Scholar
  15. 15.
    Lombroso CT (2000) Can early postnatal closed head injury induce cortical dysplasia. Epilepsia 41:245–253CrossRefPubMedGoogle Scholar
  16. 16.
    Marin-Padilla M, Parisi JE, Armstrong DL, Sargent SK, Kaplan JA (2002) Shaken infant syndrome: developmental neuropathology, progressive cortical dysplasia, and epilepsy. Acta Neuropathol 103:321–332CrossRefPubMedGoogle Scholar
  17. 17.
    Palmini A, Najm I, Avanzini G, Babb T, Guerrini R, Foldvary-Schaefer N, Jackson G, Luders HO, Prayson R, Spreafico R, Vinters HV (2004) Terminology and classification of the cortical dysplasias. Neurology 62:S2–S8Google Scholar
  18. 18.
    Sisodiya SM, Thom M, Lin WR, Bajaj NP, Cross JH, Harding BN (2002) Abnormal expression of cdk5 in focal cortical dysplasia in humans. Neurosci Lett 328:217–220CrossRefPubMedGoogle Scholar
  19. 19.
    Spreafico R, Tassi L, Colombo N, Bramerio M, Galli C, Garbelli R, Ferrario A, Lo Russo G, Munari C (2000) Inhibitory circuits in human dysplastic tissue. Epilepsia 41 Suppl 6:S168–S173CrossRefGoogle Scholar
  20. 20.
    Tassi L, Colombo N, Garbelli R, Francione S, Lo Russo G, Mai R, Cardinale F, Cossu M, Ferrario A, Galli C, Bramerio M, Citterio A, Spreafico R (2002) Focal cortical dysplasia: neuropathological subtypes, EEG, neuroimaging and surgical outcome. Brain 125:1719–1732CrossRefPubMedGoogle Scholar
  21. 21.
    Taylor JP, Sater R, French J, Baltuch G, Crino PB (2001) Transcription of intermediate filament genes is enhanced in focal cortical dysplasia. Acta Neuropathol 102:141–148PubMedGoogle Scholar
  22. 22.
    Thom M, Holton JL, D’Arrigo C, Griffin B, Beckett A, Sisodiya S, Alexiou D, Sander JW (2000) Microdysgenesis with abnormal cortical myelinated fibres in temporal lobe epilepsy: a histopathological study with calbindin D-28-K immunohistochemistry. Neuropathol Appl Neurobiol 26:251–257CrossRefPubMedGoogle Scholar
  23. 23.
    Thom M, Harding BN, Lin WR, Martinian L, Cross H, Sisodiya SM (2003) Cajal-Retzius cells, inhibitory interneuronal populations and neuropeptide Y expression in focal cortical dysplasia and microdysgenesis. Acta Neuropathol 105:561–569PubMedGoogle Scholar
  24. 24.
    Urbach H, Scheffler B, Heinrichsmeier T, Oertzen J von, Kral T, Wellmer J, Schramm J, Wiestler OD, Blumcke I (2002) Focal cortical dysplasia of Taylor’s balloon cell type: a clinicopathological entity with characteristic neuroimaging and histopathological features, and favorable postsurgical outcome. Epilepsia 43:33–40CrossRefGoogle Scholar
  25. 25.
    Voelker CC, Garin N, Taylor JS, Gahwiler BH, Hornung JP, Molnar Z (2004) Selective neurofilament (SMI-32, FNP-7 and N200) expression in subpopulations of layer V pyramidal neurons in vivo and in vitro. Cereb Cortex 14:1276–1286CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • M. Thom
    • 1
  • L. Martinian
    • 1
  • A. Sen
    • 1
  • J. H. Cross
    • 2
  • B. N. Harding
    • 3
  • S. M. Sisodiya
    • 1
  1. 1.Division of Neuropathology and Department of Clinical and Experimental EpilepsyInstitute of NeurologyLondonUK
  2. 2.Neuroscience UnitInstitute of Child HealthLondonUK
  3. 3.Department of HistopathologyGreat Ormond Street Hospital for ChildrenLondonUK

Personalised recommendations