Stefan Rampp1, Karl Rössler2, Hajo Hamer3, Margit Illek4, Michael Buchfelder4, Arnd Doerfler5, Tom Pieper6, Till Hartlieb6, Manfred Kudernatsch7, Konrad Koelble8, Jose Eduardo Peixoto-Santos9, Ingmar Blümcke8, Roland Coras8. 1. Department of Neurosurgery, University Hospital Erlangen, Germany; Department of Neurosurgery, University Hospital Halle, Germany. Electronic address: Stefan.rampp@uk-erlangen.de. 2. Department of Neurosurgery, University Hospital Erlangen, Germany; Department of Neurosurgery, University Hospital Vienna, Austria. 3. Epilepsy Center, Department of Neurology, University Hospital Erlangen, Germany. 4. Department of Neurosurgery, University Hospital Erlangen, Germany. 5. Department of Neuroradiology, University Hospital Erlangen, Germany. 6. Hospital for Neuropediatrics and Neurological Rehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany. 7. Epilepsy Center and Department of Neurosurgery, Schön Klinik Vogtareuth, Germany; Research Institute, Rehabilitation, Transition, Palliation, PMU Salzburg, Salzburg, Austria. 8. Department of Neuropathology, University Hospital Erlangen, Germany. 9. Department of Neuropathology, University Hospital Erlangen, Germany; Department of Neurology and Neurosurgery, Paulista School of Medicine, UNIFESP, Brazil.
Abstract
OBJECTIVE: Reliable localization of the epileptogenic zone is necessary for successful epilepsy surgery. Neurophysiological biomarkers include ictal onsets and interictal spikes. Furthermore, the epileptic network shows oscillations with potential localization value and pathomechanistic implications. The cellular origin of such markers in invasive EEG in vivo remains to be clarified. METHODS: In the presented pilot study, surgical brain samples and invasive EEG recordings of seven patients with surgically treated Focal Cortical Dysplasia (FCD) type II were coregistered using a novel protocol. Dysmorphic neurons and balloon cells were immunohistochemically quantified. Evaluated markers included seizure onset, spikes, and oscillatory activity in delta, theta, gamma and ripple frequency bands, as well as sample entropy and phase-amplitude coupling between delta, theta, alpha and beta phase and gamma amplitude. RESULTS: Correlations between histopathology and neurophysiology provided evidence for a contribution of dysmorphic neurons to interictal spikes, fast gamma activity and ripples. Furthermore, seizure onset and phase-amplitude coupling in areas with dysmorphic neurons suggests preserved connectivity is related to seizure initiation. Balloon cells showed no association. CONCLUSIONS: Phase-amplitude coupling, spikes, fast gamma and ripples are related to the density of dysmorphic neurons and localize the seizure onset zone. SIGNIFICANCE: The results of our pilot study provide a new powerful tool to address the cellular source of abnormal neurophysiology signals to leverage current and novel biomarkers for the localization of epileptic activity in the human brain.
OBJECTIVE: Reliable localization of the epileptogenic zone is necessary for successful epilepsy surgery. Neurophysiological biomarkers include ictal onsets and interictal spikes. Furthermore, the epileptic network shows oscillations with potential localization value and pathomechanistic implications. The cellular origin of such markers in invasive EEG in vivo remains to be clarified. METHODS: In the presented pilot study, surgical brain samples and invasive EEG recordings of seven patients with surgically treated Focal Cortical Dysplasia (FCD) type II were coregistered using a novel protocol. Dysmorphic neurons and balloon cells were immunohistochemically quantified. Evaluated markers included seizure onset, spikes, and oscillatory activity in delta, theta, gamma and ripple frequency bands, as well as sample entropy and phase-amplitude coupling between delta, theta, alpha and beta phase and gamma amplitude. RESULTS: Correlations between histopathology and neurophysiology provided evidence for a contribution of dysmorphic neurons to interictal spikes, fast gamma activity and ripples. Furthermore, seizure onset and phase-amplitude coupling in areas with dysmorphic neurons suggests preserved connectivity is related to seizure initiation. Balloon cells showed no association. CONCLUSIONS: Phase-amplitude coupling, spikes, fast gamma and ripples are related to the density of dysmorphic neurons and localize the seizure onset zone. SIGNIFICANCE: The results of our pilot study provide a new powerful tool to address the cellular source of abnormal neurophysiology signals to leverage current and novel biomarkers for the localization of epileptic activity in the human brain.
Authors: Pablo Cuesta; Manuela Ochoa-Urrea; Michael Funke; Omar Hasan; Ping Zhu; Alberto Marcos; Maria Eugenia López; Paul E Schulz; Samden Lhatoo; Dimitrios Pantazis; John C Mosher; Fernando Maestu Journal: Brain Commun Date: 2022-02-03
Authors: Imad Najm; Dennis Lal; Mario Alonso Vanegas; Fernando Cendes; Iscia Lopes-Cendes; Andre Palmini; Eliseu Paglioli; Harvey B Sarnat; Christopher A Walsh; Samuel Wiebe; Eleonora Aronica; Stéphanie Baulac; Roland Coras; Katja Kobow; J Helen Cross; Rita Garbelli; Hans Holthausen; Karl Rössler; Maria Thom; Assam El-Osta; Jeong Ho Lee; Hajime Miyata; Renzo Guerrini; Yue-Shan Piao; Dong Zhou; Ingmar Blümcke Journal: Epilepsia Date: 2022-06-15 Impact factor: 6.740
Authors: Stephan Vogel; Martin Kaltenhäuser; Cora Kim; Nadia Müller-Voggel; Karl Rössler; Arnd Dörfler; Stefan Schwab; Hajo Hamer; Michael Buchfelder; Stefan Rampp Journal: Brain Sci Date: 2021-11-30