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57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

12. - 15.09.2012, Erlangen

Banner: 57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie

Large-scale gene expression analysis in hippocampal tissue of epileptic patients stratified according to levetiracetam responsiveness

Meeting Abstract

  • presenting/speaker Tanja Grimminger - University, Neuropathology, Bonn, Germany
  • Katharina Pernhorst - University, Neuropathology, Bonn, Germany
  • Rainer Surges - University, Epileptology, Bonn, Germany
  • Karen M.J. van Loo - University, Neuropathology, Bonn, Germany
  • Marec von Lehe - University, Neurosurgery, Bonn, Germany
  • Per Hoffmann - University, Human Genetics, Bonn, Germany
  • Sven Cichon - University, Human Genetics, Bonn, Germany
  • Susanne Schoch - University, Epileptology, Bonn, Germany
  • Albert J. Becker - University, Neuropathology, Bonn, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP6.1

doi: 10.3205/12dgnn112, urn:nbn:de:0183-12dgnn1120

Veröffentlicht: 11. September 2012

© 2012 Grimminger et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



Focal epilepsies represent severe neurological disorders, which frequently originate in the temporal lobe (temporal lobe epilepsy; TLE). TLE is often associated with pharmacoresistance and in many TLE patients only neurosurgical removal of the seizure focus results in seizure control. Levetiracetam (LEV) represents a unique type of anti epileptic drug (AED) as it is the only one known so far whose high-affinity binding site, the synaptic vesicle protein SV2A, is a component of the presynaptic release machinery and as it generally leads to excellent seizure control even in previously refractory patients. However, a subgroup of LEV-treated TLE patients (approximately 20–30% of individuals) does not reveal any response to LEV from the beginning of treatment, i.e., a priori non-responders. This unexpected phenomenon is in contrast to the well known secondary, acquired pharmacoresistance that is observed in a high number of patients.

Using human hippocampal tissue derived from epilepsy surgery (n=52) we established a genome wide expression array analysis, which provides differential hippocampal gene expression patterns in LEV-responders versus a priori non-responders. Subsequent promoter analysis revealed individual single nucleotide polymorphisms (SNPs) that are strong candidates to influence the respective gene expression, for example of the molecule PIGP an elementary component of Wnt-signaling. Our results suggest distinct SNPs, transcription factors and presynapse-associated molecules as new factors in LEV-response of TLE patients, which will need further assessment as diagnostic markers or therapeutic targets in the future.

Our work is supported by DFG, BMBF, Else Kröner-Fresenius-Stiftung & BONFOR program of the University of Bonn Medical Center.