Intranasal Seletracetam in a Patient with Reading Epilepsy: First-in-Human Use to Prevent Reflex Seizures

  • Ann Neurol. 2025 Dec 29. doi: 10.1002/ana.78128.
Matthias J Koepp  1  2 ,  Kai-Nicolas Poppert  3 ,  Thomas Felder  4 ,  Aljoscha Thomschewski  3  5 ,  Sandra Lafenthaler  3 ,  Pavel Klein  6 ,  Alexander Rotenberg  7 ,  Wolfgang Löscher  8 ,  Chris Rundfeldt  9 ,  Eugen Trinka  3  5  10
Affiliations
  • 1. Department of Neurology, National Hospital for Neurology and Neurosurgery, Queens Square, London, UK.
  • 2. Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • 3. Department of Neurology, Neurocritical Care and Neurorehabilitation, Christian Doppler University Hospital, Centre of Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Member of EpiCARE, Salzburg, Austria.
  • 4. Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria.
  • 5. Neuroscience Institute, Christian Doppler University Hospital, Centre of Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria.
  • 6. Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD, USA.
  • 7. Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
  • 8. Translational Neuropharmacology Lab, NIFE, Department of Experimental Otology of the ENT Clinics, Hannover Medical School, Hannover, Germany.
  • 9. Drug Consulting Network, Coswig, Germany.
  • 10. Karl Landsteiner Institute for Clinical Neuroscience, Salzburg, Austria.
PMID: 41459805 DOI: 10.1002/ana.78128
Abstract

We report the first human use of intranasal seletracetam (SEL) to prevent reflex seizures. A patient with epilepsy with reading-induced seizures on levetiracetam (3,000 mg/day) continued to experience reading-induced focal seizures with preserved consciousness. Detectable in serum within 2 minutes of intranasal administration, 30 mg seletracetam delayed seizure onset from 1:56 (placebo) to 4:17 minutes post-stimulus onset. A second 30 mg dose fully prevented seizures during 25 minutes of reading. Electroencephalogram (EEG) spike-frequency declined dose-dependently (3.1/min at placebo to 1.6/min after second dose), with reduced spike-propagation on magnetoencephalography (MEG). Our findings support SEL as a promising non-benzodiazepine acute seizure prevention and provide insight into reflex seizure dynamics. ANN NEUROL 2025.

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