Are developmental dysplastic lesions epileptogenic?

Philip A Schwartzkroin, H. Jürgen Wenzel

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cortical dysplasia of various types, reflecting abnormalities of brain development, have been closely associated with epileptic activities. Yet, there remains considerable discussion about if/how these structural lesions give rise to seizure phenomenology. Animal models have been used to investigate the cause-effect relationships between aberrant cortical structure and epilepsy. In this article, we discuss three such models: (1) the Eker rat model of tuberous sclerosis, in which a gene mutation gives rise to cortical disorganization and cytologically abnormal cellular elements; (2) the p35 knockout mouse, in which the genetic dysfunction gives rise to compromised cortical organization and lamination, but in which the cellular elements appear normal; and (3) the methylazoxymethanol-exposed rat, in which time-specific chemical DNA disruption leads to abnormal patterns of cell formation and migration, resulting in heterotopic neuronal clusters. Integrating data from studies of these animal models with related clinical observations, we propose that the neuropathologic features of these cortical dysplastic lesions are insufficient to determine the seizure-initiating process. Rather, it is their interaction with a more subtly disrupted cortical "surround" that constitutes the circuitry underlying epileptiform activities as well as seizure propensity and ictogenesis.

Original languageEnglish (US)
Pages (from-to)35-44
Number of pages10
JournalEpilepsia
Volume53
Issue numberSUPPL. 1
DOIs
StatePublished - Jun 2012

Fingerprint

Seizures
Animal Models
Malformations of Cortical Development
Tuberous Sclerosis
Knockout Mice
Cell Movement
Epilepsy
Mutation
DNA
Brain
Genes
methylazoxymethanol

Keywords

  • Eker rat
  • Granule cell dispersion
  • Methylazoxymethanol
  • Nodular heterotopia
  • p35 knockout mouse
  • Tuber

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Are developmental dysplastic lesions epileptogenic? / Schwartzkroin, Philip A; Wenzel, H. Jürgen.

In: Epilepsia, Vol. 53, No. SUPPL. 1, 06.2012, p. 35-44.

Research output: Contribution to journalArticle

Schwartzkroin, Philip A ; Wenzel, H. Jürgen. / Are developmental dysplastic lesions epileptogenic?. In: Epilepsia. 2012 ; Vol. 53, No. SUPPL. 1. pp. 35-44.
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