Bonn researchers uncover how seizure-related focal spreading depolarization contributes to abnormal post-ictal behaviors in epilepsy.

Bonn, October 12 – Understanding the neurobiological mechanisms underlying post-ictal symptoms in epilepsy such as confusion, aphasia, and unaware wandering, which are most frequently observed in temporal lobe epilepsy (TLE), has long been a challenge for researchers. A pivotal study led by Prof. Wenzel and his team at Bonn University has revealed the critical role of seizure-associated focal spreading depolarization (sSD) as a pathoclinical factor in epilepsy, providing new insights into post-ictal states.

In this comprehensive investigation, the researchers employed advanced imaging techniques, including two-photon and widefield imaging, alongside field potential and single-unit recordings, to study seizures in both murine models and human subjects. The study began with observations of seizures during viral encephalitis in mice and subsequently developed an optogenetic strategy to differentiate between hippocampal seizures and spreading depolarization.

The findings demonstrated that sSD occurs in a region-specific manner, displaying distinct spatial trajectories in relation to preceding seizures. Notably, both seizure-related sSD and isolated hippocampal SD were found to trigger post-ictal wandering behavior, even without the progression of sSD to the neocortex. This unexpected locomotor phenotype highlights a previously unrecognized pathway through which seizures can affect behavior following the ictal state.

Moreover, the researchers confirmed the existence of sSD in human epilepsy patients using Behnke-Fried electrode recordings. The patterns observed in humans were consistent with those identified in murine models, indicating a common neurobiological mechanism.

The implications of these findings are significant for both epilepsy research and clinical practice. Notably, due to the current international EEG standard, sSD is invisible in clinical practice. Thus, by uncovering sSD as a crucial factor underlying post-ictal behavioral abnormalities, this study challenges existing standards in EEG monitoring and raises important questions about the traditional understanding of post-ictal states in epilepsy.

In summary, this groundbreaking work led by Prof. Wenzel opens new avenues for understanding the neurobiology of post-ictal symptoms and may lead to improved diagnostic and therapeutic strategies for individuals suffering from epilepsy.

For further details, please refer to the full publication https://doi.org/10.1101/2024.10.12.618012

Publication: Region-specific spreading depolarization drives aberrant post-ictal behavior; Bence Mitlasoćzki, Adrián Gutiérrez Goméz, Midia Kamali, Natalia Babushkina, Mayan Baues, Laura Kück, André Nathan Haubrich, Theodoros Tamiolakis, Annika Breuer, Simon Granak, Merlin Schwering-Sohnrey, Ingo Gerhauser, Wolfgang Baumgärtner, Laura Ewell, Thoralf Opitz, Julika Pitsch, Simon Musall, Rainer Surges, Florian Mormann, Heinz Beck, Michael Wenzel; bioRxiv 2024.10.12.618012

Scientific contact:
Prof. Michael Wenzel

Department of Epileptology

Bonn University Hospital

E-Mail: michael.wenzel@ukbonn.de

Written by: Dr Michela Barboni, Ph.D