Acta Neuropathologica

, 117:535

Towards a clinico-pathological classification of granule cell dispersion in human mesial temporal lobe epilepsies

  • Ingmar Blümcke
  • Iris Kistner
  • Hans Clusmann
  • Johannes Schramm
  • Albert J. Becker
  • Christian E. Elger
  • Christian G. Bien
  • Martin Merschhemke
  • Heinz-Joachim Meencke
  • Thomas Lehmann
  • Michael Buchfelder
  • Daniel Weigel
  • Rolf Buslei
  • Hermann Stefan
  • Elisabeth Pauli
  • Michelle Hildebrandt
Original Paper

DOI: 10.1007/s00401-009-0512-5

Cite this article as:
Blümcke, I., Kistner, I., Clusmann, H. et al. Acta Neuropathol (2009) 117: 535. doi:10.1007/s00401-009-0512-5

Abstract

The dentate gyrus (DG) plays a pivotal role in the functional and anatomical organization of the hippocampus and is involved in learning and memory formation. However, the impact of structural DG abnormalities, i.e., granule cell dispersion (GCD), for hippocampal seizure susceptibility and its association with distinct lesion patterns in epileptic disorders, such as mesial temporal sclerosis (MTS) remains enigmatic and a large spectrum of pathological changes has been recognized. Here, we propose a clinico-pathological classification of DG pathology based on the examination of 96 surgically resected hippocampal specimens obtained from patients with chronic temporal lobe epilepsy (TLE). We observed three different histological patterns. (1) A normal granule cell layer was identified in 11 patients (no-GCP; 18.7%). (2) Substantial granule cell loss was evident in 36 patients (referred to as granule cell pathology (GCP) Type 1; 37.5%). (3) Architectural abnormalities were observed in 49 specimens, including one or more of the following features: granule cell dispersion, ectopic neurons or clusters of neurons in the molecular layer, or bi-lamination (GCP Type 2; 51%). Cell loss was always encountered in this latter cohort. Seventy-eight patients of our present series suffered from MTS (81.3%). Intriguingly, all MTS patients displayed a compromised DG, 31 (40%) with significant cell loss (Type 1) and 47 (60%) with GCD (Type 2). In 18 patients without MTS (18.7%), seven displayed focally restricted DG abnormalities, either cell loss (n = 5) or GCD (n = 2). Clinical histories revealed a significant association between DG pathology patterns and higher age at epilepsy surgery (p = 0.008), longer epilepsy duration (p = 0.004), but also with learning dysfunction (p < 0.05). There was no correlation with the extent of pyramidal cell loss in adjacent hippocampal segments nor with postsurgical seizure relief. The association with long-term seizure histories and cognitive dysfunction is remarkable and may point to a compromised regenerative capacity of the DG in this cohort of TLE patients.

Keywords

HippocampusDentate gyrusEpilepsySeizureClassification

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ingmar Blümcke
    • 1
  • Iris Kistner
    • 1
  • Hans Clusmann
    • 2
  • Johannes Schramm
    • 2
  • Albert J. Becker
    • 3
  • Christian E. Elger
    • 4
  • Christian G. Bien
    • 4
  • Martin Merschhemke
    • 5
  • Heinz-Joachim Meencke
    • 5
  • Thomas Lehmann
    • 6
  • Michael Buchfelder
    • 7
  • Daniel Weigel
    • 7
  • Rolf Buslei
    • 1
  • Hermann Stefan
    • 8
  • Elisabeth Pauli
    • 8
  • Michelle Hildebrandt
    • 1
  1. 1.Department of NeuropathologyUniversity Hospital ErlangenErlangenGermany
  2. 2.Department of NeurosurgeryUniversity of Bonn Medical CenterBonnGermany
  3. 3.Department of NeuropathologyUniversity of Bonn Medical CenterBonnGermany
  4. 4.Department of EpileptologyUniversity of Bonn Medical CenterBonnGermany
  5. 5.Epilepsy Center Berlin-BrandenburgBerlinGermany
  6. 6.Department of NeurosurgeryCharité-University Medicine BerlinBerlinGermany
  7. 7.Department of NeurosurgeryUniversity Hospital ErlangenErlangenGermany
  8. 8.Department of NeurologyUniversity Hospital ErlangenErlangenGermany