Child's Nervous System

, Volume 22, Issue 8, pp 821–826 | Cite as

Cortical dysplasia: neuropathological aspects

  • Christian H. RickertEmail author
Special Annual Issue



Malformations of the cerebral cortex are a frequent cause of pharmacoresistant epilepsies and developmental disorders.

Epidemiology and genetics

The incidence of cortical dysplasias in epilepsy surgical series varies from 12 to 40% and focal cortical dysplasias (FCD) are one of the most common neuropathological findings in resection specimens from pediatric patients undergoing cortical resections for the treatment of refractory epilepsy.

Macroscopy and histopathology

Surgical specimens in FCD may appear normal macroscopically, but in some cases, widening of the cortex with poor demarcation from the underlying white matter is noted. In milder dysplasias, the main pathological feature is disorganization of the cortical architecture (“dislamination”) with less striking neuronal and glial cytopathology. Histopathology shows an excess of neurons in layer I, including Cajal–Retzius cells, clusters of neurons, marginal glioneuronal heterotopias, and a persistent subpial granule cell layer. The hallmarks of FCD are disorganization of the laminar architecture and of the cytology of individual neurons. In many cases, layer I remains hypocellular and distinct from deeper laminae, but lower cortical layers may be ill-defined or broken up by the presence of many large and randomly located abnormal and cytomegalic neurons; depending on their morphology, referred to as “giant neurons,” “immature neurons,” or “dysmorphic neurons.” The other pathognomonic cell type associated with FCD is the “balloon cell.” These cells were originally considered to be of astrocytic lineage; however, there is evidence that they are in effect “balloon neurons.”

Immunohistochemistry and structural findings

Immunohistochemistry is not essential in making the diagnosis of FCD or microdysgenesis but allows further characterization of cell types.


Balloon cell Cortical malformation Dysmorphic neuron Focal cortical dysplasia Hamartia Heterotopia Microdysgenesis 


  1. 1.
    Aronica E, Gorter JA, Jansen GH, van Veelen CW, van Rijen PC, Ramkema M, Troost D (2003) Expression and cell distribution of group I and group II metabotropic glutamate receptor subtypes in Taylor-type focal cortical dysplasia. Epilepsia 44:785–795PubMedCrossRefGoogle Scholar
  2. 2.
    Barkovich AJ, Kuzniecky RI, Dobyns WB, Jackson GD, Becker LE, Evrard P (1996) A classification scheme for malformations of cortical development. Neuropediatrics 27:59–63PubMedCrossRefGoogle Scholar
  3. 3.
    Barkovich AJ, Kuzniecky RI, Jackson GD, Guerrini R, Dobyns WB (2001) Classification system for malformations of cortical development: update. Neurology 57:2168–2178PubMedGoogle Scholar
  4. 4.
    Barkovich AJ, Kuzniecky RI, Jackson GD, Guerrini R, Dobyns WB (2005) A developmental and genetic classification for malformations of cortical development. Neurology 65:1873–1887PubMedCrossRefGoogle Scholar
  5. 5.
    Blumcke I, Lobach M, Wolf HK, Wiestler OD (1999) Evidence for developmental precursor lesions in epilepsy-associated glioneuronal tumors. Microsc Res Tech 46:53–58PubMedCrossRefGoogle Scholar
  6. 6.
    Blumcke I, Thom M, Wiestler OD (2002) Ammon’s horn sclerosis: a maldevelopmental disorder associated with temporal lobe epilepsy. Brain Pathol 12:199–211PubMedGoogle Scholar
  7. 7.
    Bocti C, Robitaille Y, Diadori P, Lortie A, Mercier C, Bouthillier A, Carmant L (2003) The pathological basis of temporal lobe epilepsy in childhood. Neurology 60:191–195PubMedCrossRefGoogle Scholar
  8. 8.
    Briellmann RS, Torn-Broers Y, Berkovic SF (2001) Idiopathic generalized epilepsies: do sporadic and familial cases differ? Epilepsia 42:1399–1402PubMedCrossRefGoogle Scholar
  9. 9.
    Cepeda C, Andre VM, Flores-Hernandez J, Nguyen OK, Wu N, Klapstein GJ, Nguyen S, Koh S, Vinters HV, Levine MS, Mathern GW (2005) Pediatric cortical dysplasia: correlations between neuroimaging, electrophysiology and location of cytomegalic neurons and balloon cells and glutamate/GABA synaptic circuits. Dev Neurosci 27:59–76PubMedCrossRefGoogle Scholar
  10. 10.
    Crino PB (2005) Molecular pathogenesis of focal cortical dysplasia and hemimegalencephaly. J Child Neurol 20:330–336PubMedCrossRefGoogle Scholar
  11. 11.
    Crino PB, Miyata H, Vinters HV (2002) Neurodevelopmental disorders as a cause of seizures: neuropathologic, genetic, and mechanistic considerations. Brain Pathol 12:212–233PubMedCrossRefGoogle Scholar
  12. 12.
    Crino PB, Trojanowski JQ, Eberwine J (1997) Internexin, MAP1B, and nestin in cortical dysplasia as markers of developmental maturity. Acta Neuropathol 93:619–627PubMedCrossRefGoogle Scholar
  13. 13.
    Daumas-Duport C, Varlet P, Bacha S, Beuvon F, Cervera-Pierot P, Chodkiewicz JP (1999) Dysembryoplastic neuroepithelial tumors: nonspecific histological forms—a study of 40 cases. J Neurooncol 41:267–280PubMedCrossRefGoogle Scholar
  14. 14.
    Eriksson SH, Rydenhag B, Uvebrant P, Malmgren K, Nordborg C (2002) Widespread microdysgenesis in therapy-resistant epilepsy—a case report on post-mortem findings. Acta Neuropathol 103:74–77PubMedCrossRefGoogle Scholar
  15. 15.
    Garbelli R, Munari C, De Biasi S, Vitellaro-Zuccarello L, Galli C, Bramerio M, Mai R, Battaglia G, Spreafico R (1999) Taylor’s cortical dysplasia: a confocal and ultrastructural immunohistochemical study. Brain Pathol 9:445–461PubMedCrossRefGoogle Scholar
  16. 16.
    Hildebrandt M, Pieper TP, Winkler Kolodziejczyk D, Holthausen H, Blumcke I (2005) Neuropathological spectrum of cortical dysplasia in children with severe focal epilepsies. Acta Neuropathol 110:1–11PubMedCrossRefGoogle Scholar
  17. 17.
    Hua Y, Crino PB (2003) Single cell lineage analysis in human focal cortical dysplasia. Cereb Cortex 13:693–699PubMedCrossRefGoogle Scholar
  18. 18.
    Kakita A, Kameyama S, Hayashi S, Masuda H, Takahashi H (2005) Pathologic features of dysplasia and accompanying alterations observed in surgical specimens from patients with intractable epilepsy. J Child Neurol 20:341–350PubMedCrossRefGoogle Scholar
  19. 19.
    Kasper BS, Stefan H, Buchfelder M, Paulus W (1999) Temporal lobe microdysgenesis in epilepsy versus control brains. J Neuropathol Exp Neurol 58:22–28PubMedCrossRefGoogle Scholar
  20. 20.
    Kerfoot C, Vinters HV, Mathern GW (1999) Cerebral cortical dysplasia: giant neurons show potential for increased excitation and axonal plasticity. Dev Neurosci 21:260–270PubMedCrossRefGoogle Scholar
  21. 21.
    Kim JY, Roh JK, Lee SK, Chung CK (2002) Neurotrophin receptor immunoreactivity in severe cerebral cortical dysplasia. Epilepsia 43(Suppl 5):220–226PubMedCrossRefGoogle Scholar
  22. 22.
    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
  23. 23.
    Marin-Padilla M, Parisi JE, Armstrong DL, Sargent SK, Kaplan JA (2002) Shaken infant syndrome: developmental neuropathology, progressive cortical dysplasia, and epilepsy. Acta Neuropathol 103:321–332PubMedCrossRefGoogle Scholar
  24. 24.
    Meencke HJ, Janz D (1985) The significance of microdysgenesia in primary generalized epilepsy: an answer to the considerations of Lyon and Gastaut. Epilepsia 26:368–371PubMedCrossRefGoogle Scholar
  25. 25.
    Mikuni N, Babb TL, Ying Z, Najm I, Nishiyama K, Wylie C, Yacubova K, Okamoto T, Bingaman W (1999) NMDA-receptors 1 and 2A/B coassembly increased in human epileptic focal cortical dysplasia. Epilepsia 40:1683–1687PubMedCrossRefGoogle Scholar
  26. 26.
    Mischel PS, Nguyen LP, Vinters HV (1995) Cerebral cortical dysplasia associated with pediatric epilepsy. Review of neuropathologic features and proposal for a grading system. J Neuropathol Exp Neurol l4:137–153CrossRefGoogle Scholar
  27. 27.
    Mizuguchi M, Yamanouchi H, Becker LE, Itoh M, Takashima S (2002) Doublecortin immunoreactivity in giant cells of tuberous sclerosis and focal cortical dysplasia. Acta Neuropathol 104:418–424PubMedGoogle Scholar
  28. 28.
    Nordborg C, Eriksson S, Rydenhag B, Uvebrant P, Malmgren K (1999) Microdysgenesis in surgical specimens from patients with epilepsy: occurrence and clinical correlations. J Neurol Neurosurg Psychiatry 67:521–524PubMedCrossRefGoogle Scholar
  29. 29.
    Palmini A, Luders HO (2002) Classification issues in malformations caused by abnormalities of cortical development. Neurosurg Clin N Am 13:1–16PubMedCrossRefGoogle Scholar
  30. 30.
    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 23(62):S2–S8Google Scholar
  31. 31.
    Pilz D, Stoodley N, Golden JA (2002) Neuronal migration, cerebral cortical development, and cerebral cortical anomalies. J Neuropathol Exp Neurol 61:1–11PubMedGoogle Scholar
  32. 32.
    Prayson RA, Spreafico R, Vinters HV (2002) Pathologic characteristics of the cortical dysplasias. Neurosurg Clin N Am 13:17–25PubMedCrossRefGoogle Scholar
  33. 33.
    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 125:1719–1732PubMedCrossRefGoogle Scholar
  34. 34.
    Tassi L, Pasquier B, Minotti L, Garbelli R, Kahane P, Benabid AL, Battaglia G, Munari C, Spreafico R (2001) Cortical dysplasia: electroclinical, imaging, and neuropathologic study of 13 patients. Epilepsia 42:1112–1123PubMedCrossRefGoogle Scholar
  35. 35.
    Taylor DC, Falconar MA, Bruton CJ, Corsellis JA (1971) Focal dysplasia of the cerebral cortex in epilepsy. J Neurol Neurosurg Psychiatry 34:369–387PubMedCrossRefGoogle Scholar
  36. 36.
    Thom M (2004) Epilepsy part I: cortical dysplasia. In: Golden JA, Harding BN (eds) Pathology & Genetics. Developmental neuropathology. ISN Neuropath, Basel, pp 61–66Google Scholar
  37. 37.
    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
  38. 38.
    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 26:251–257PubMedCrossRefGoogle Scholar
  39. 39.
    Thom M, Martinian L, Sen A, Cross JH, Harding BN, Sisodiya SM (2005) Cortical neuronal densities and lamination in focal cortical dysplasia. Acta Neuropathol 110:383–392PubMedCrossRefGoogle Scholar
  40. 40.
    Thom M, Sisodiya S, Harkness W, Scaravilli F (2001) Microdysgenesis in temporal lobe epilepsy. A quantitative and immunohistochemical study of white matter neurones. Brain 124:2299–2309PubMedCrossRefGoogle Scholar
  41. 41.
    Urbach H, Scheffler B, Heinrichsmeier T, von Oertzen J, 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 43:33–40PubMedCrossRefGoogle Scholar
  42. 42.
    Vinters HV (2002) Histopathology of brain tissue from patients with infantile spasms. Int Rev Neurobiol 49:63–76PubMedGoogle Scholar
  43. 43.
    Walsh CA (1999) Genetic malformations of the human cerebral cortex. Neuron 23:19–29PubMedCrossRefGoogle Scholar
  44. 44.
    Yamanouchi H, Jay V, Otsubo H, Kaga M, Becker LE, Takashima S (1998) Early forms of microtubule-associated protein are strongly expressed in cortical dysplasia. Acta Neuropathol 95:466–470PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Anatomical PathologyRoyal Children’s HospitalParkville VicAustralia

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