"Tectonic" hippocampal malformations in patients with temporal lobe epilepsy

Robert S. Sloviter, Hemant S. Kudrimoti, Kenneth D. Laxer, Nicholas M. Barbaro, Stephen Chan, Lawrence J. Hirsch, Robert R. Goodman, Timothy A. Pedley

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Histological analysis of hippocampi removed en bloc during surgical treatment of temporal lobe epilepsy revealed a subgroup of patients with bulbous expansions of the CA1 pyramidal cell/subicular layers that were consistently accompanied by "tectonic" invaginations of the adjacent dentate gyrus. Most hippocampi containing the CA1/subicular anomaly and the tectonically deformed dentate gyrus exhibited minor cell loss compared to hippocampi with typical hippocampal sclerosis, and retrospective analysis revealed that conventional imaging methods usually failed to detect subtle hippocampal atrophy or abnormal signal characteristics in patients with this anomaly. Cells within the anomaly exhibited the spherical appearance of undifferentiated pyramidal layer neurons, and were immunopositive for the neuronal marker NeuN. Immunostaining for the synaptic marker β-synuclein suggested abnormal dentate gyrus lamination in segments containing the pyramidal cell layer anomaly, but not in unaffected areas of the same specimens. Despite differences in the extent of neuronal loss between patients with hippocampal sclerosis and those with the CA1/subicular anomaly, the incidence of antecedent febrile seizures was similar in both groups. In a comparison group of hippocampi obtained at autopsy, structural irregularities were evident, but were consistently less disruptive to hippocampal architecture than the anomalies observed in epilepsy patients. We hypothesize that developmental malformation of the CA1 pyramidal cell/subicular layers may adversely influence the subsequent development of the adjacent dentate gyrus, and may render temporal lobe structures hyperexcitable and more vulnerable to relatively innocuous seizures and injuries. Thus, these presumably developmental hippocampal anomalies may serve as substrates for early febrile seizures and subsequent epilepsy.

Original languageEnglish (US)
Pages (from-to)123-153
Number of pages31
JournalEpilepsy Research
Volume59
Issue number2-3
DOIs
StatePublished - Apr 1 2004

Keywords

  • Cortical dysplasia
  • Dentate gyrus
  • Development
  • Epileptogenesis
  • Hippocampus
  • Human

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Sloviter, R. S., Kudrimoti, H. S., Laxer, K. D., Barbaro, N. M., Chan, S., Hirsch, L. J., Goodman, R. R., & Pedley, T. A. (2004). "Tectonic" hippocampal malformations in patients with temporal lobe epilepsy. Epilepsy Research, 59(2-3), 123-153. https://doi.org/10.1016/j.eplepsyres.2004.04.001