Original Article Citation: Hippocampal Spreading Depolarization as a Driver of Postictal Ambulation Mitlasóczki B, Gutiérrez Gómez A, Kamali M, Babushkina N, Baues M, Kück L, Haubrich AN, Tamiolakis T, Breuer A, Granak S, Schwering Sohnrey M, Gerhauser I, Baumgärtner W, Schwarz MK, Ewell L, Opitz T, Pitsch J, Musall S, Surges R, Mormann F, Beck H, Wenzel M. Sci Transl Med . 2025;17(816):eadv3260. doi:10.1126/scitranslmed.adv3260. PMID: 40961224 Original Article Abstract: Postseizure (postictal) symptoms are regularly encountered in epilepsy and can be life threatening, yet their neurobiological underpinnings remain understudied. Using two-photon or widefield imaging, field potential and unit recordings, optogenetics, and basic behavioral assessment under healthy conditions or viral encephalitis, we studied seizures and postictal symptoms in mice. We show a propensity of the hippocampus for seizure-associated spreading depolarization (sSD). Through optogenetic stimulation, we provide evidence that induced isolated hippocampal spreading depolarization SD is sufficient to elicit postictal ambulation (PIA), whereas induced isolated seizure-like episodes are not. Furthermore, PIA occurred in the absence of SD progression to the neocortex. In addition, we analyzed Behnke-Fried depth-electrode recordings in four patients with focal epilepsy. Of 13 recorded seizures, we observed five slow shifts at seizure termination in the regionwise analysis that could reflect putative sSD. In support of our experiments in mice, we also found an increased vulnerability of the human temporomesial system (hippocampus and amygdala) for this phenomenon and longer recovery times of affected as compared with nonaffected brain regions. This work suggests sSD as a previously underrecognized pathoclinical entity underlying distinct postictal symptoms in epilepsy.
Helen E. Scharfman (2026) studied this question.