title: Decrease in propagation of interictal epileptiform activity after introduction of levetiracetam visualized with electric source imaging.
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.
authors.affiliation: Department of Neurosurgery, Oslo University Hospital, Oslo, 0027, Norway.
authors.forename: Pål G
authors.initials: PG
authors.lastname: Larsson
authors.forename: Orvar
authors.initials: O
authors.lastname: Eeg-Olofsson
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Michel
authors.forename: Margitta
authors.initials: M
authors.lastname: Seeck
authors.forename: Göran
authors.initials: G
authors.lastname: Lantz
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D001931:Brain Mapping; D002648:Child; D002675:Child, Preschool; D003952:Diagnostic Imaging / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam