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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

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: urn:nbn:de:0183-12dgnn1120

Published: September 11, 2012

© 2012 Grimminger et al.
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Outline

Text

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.