Autonomic dysfunction in epilepsy mouse models with implications for SUDEP research

Frontiers in Neurology, vol. 13, pp. 1040648

Abstract

Epilepsy has a high prevalence and can severely impair quality of life and increase the risk of premature death. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in drug-resistant epilepsy and most often results from respiratory and cardiac impairments due to brainstem dysfunction. Epileptic activity can spread widely, influencing neuronal activity in regions outside the epileptic network. The brainstem controls cardiorespiratory activity and arousal and reciprocally connects to cortical, diencephalic, and spinal cord areas. Epileptic activity can propagate trans-synaptically or via spreading depression (SD) to alter brainstem functions and cause cardiorespiratory dysfunction. The mechanisms by which seizures propagate to or otherwise impair brainstem function and trigger the cascading effects that cause SUDEP are poorly understood. We review insights from mouse models combined with new techniques to understand the pathophysiology of epilepsy and SUDEP. These techniques include in vivo, ex vivo, invasive and non-invasive methods in anesthetized and awake mice. Optogenetics combined with electrophysiological and optical manipulation and recording methods offer unique opportunities to study neuronal mechanisms under normal conditions, during and after non-fatal seizures, and in SUDEP. These combined approaches can advance our understanding of brainstem pathophysiology associated with seizures and SUDEP and may suggest strategies to prevent SUDEP.

Authors 4

1. Jennifer Bauer Aachen Department of Epileptology and Neurology

   University of Veterinary Medicine Hannover, Foundation · RWTH Aachen University

   Affiliation as printed

   Department of Epileptology and Neurology, RWTH Aachen University, Aachen, Germany

   Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany

2. Orrin Devinsky

   NYU Langone Health · New York University

   Affiliation as printed

   Departments of Neurology, Neurosurgery and Psychiatry, NYU Langone School of Medicine, New York, NY, United States

3. Markus Rothermel

   University of Veterinary Medicine Hannover, Foundation

   Affiliation as printed

   Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany

4. Henner Koch corresponding Aachen Department of Epileptology and Neurology

   RWTH Aachen University

   Affiliation as printed

   Department of Epileptology and Neurology, RWTH Aachen University, Aachen, Germany