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Decrease in Propagation of Interictal Epileptiform Activity After Introduction of Levetiracetam Visualized with Electric Source Imaging

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Abstract

Different neuroimaging techniques (fMRI, spectroscopy, PET) are being used to evaluate candidate drugs in pharmacological development. In patients with epilepsy fast propagation of the epileptiform activity between different brain areas occurs. Electric Source Imaging (ESI), in contrast to the aforementioned techniques, has a millisecond time resolution, allowing visualization of this fast propagation. The purpose of the current project was to use ESI to investigate whether introduction of an antiepileptic drug (levetiracetam, LEV) would change the propagation patterns of the interictal epileptiform activity. Thirty patients with epilepsy were subject to an EEG recording before (pre-LEV) and after (in-LEV) introduction of LEV. Interictal spikes with similar topographic distribution were averaged within each subject, and a distributed source model was used to localize the EEG sources of the epileptiform activity. The temporal development of the activity within 20 regions of interest (ROIs) was determined, and source propagation between different regions was compared between the pre-LEV and in-LEV recordings. Patients with epileptic seizures showed propagation in 22/24 identified spike types in the pre-LEV recordings. In the in-LEV recordings only 7/15 spike types showed propagation, and six of these seven propagating spikes were recorded in patients with poor effect of treatment. Also in patients without seizures LEV tended to suppress propagation. We conclude that the observed suppression of source propagation can be considered as an indicator of effective antiepileptic treatment. ESI might thus become a useful tool in the early clinical evaluation of new candidate drugs in pharmacological development.

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Acknowledgements

We thank Denis Brunet for the development of the analysis software CarTool, and Svein Johannessen for valuable discussions. GL is a part time employee of Electrical Geodesic Inc. MS has received consulting fees from Pfizer and Janssen-Cilag. None of the other authors has any conflict of interest to disclose.

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Authors and Affiliations

  1. Department of Neurosurgery, Oslo University Hospital, Oslo, 0027, Norway

    Pål G. Larsson

  2. Department of Women’s and Children’s Health/Neuropediatrics, Uppsala University, Uppsala, Sweden

    Orvar Eeg-Olofsson

  3. Functional Brain Mapping Laboratory, Department of Neurology, University Hospital, University of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva 14, Switzerland

    Christoph M. Michel & Göran Lantz

  4. Neurology Clinic, University Hospital, Geneva, Switzerland

    Margitta Seeck

  5. The Epilepsy Center, SSE, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway

    Göran Lantz

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  1. Pål G. Larsson
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  2. Orvar Eeg-Olofsson
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  3. Christoph M. Michel
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  4. Margitta Seeck
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  5. Göran Lantz
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Correspondence to Göran Lantz.

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Larsson, P.G., Eeg-Olofsson, O., Michel, C.M. et al. Decrease in Propagation of Interictal Epileptiform Activity After Introduction of Levetiracetam Visualized with Electric Source Imaging. Brain Topogr 23, 269–278 (2010). https://doi.org/10.1007/s10548-010-0150-1

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  • DOI: https://doi.org/10.1007/s10548-010-0150-1

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