Sudden Unexpected Death in Epilepsy (SUDEP) claims approximately 1 in 1,000 lives of epilepsy patients each year.¹  SUDEP occurs when a patient with epilepsy dies suddenly without visible cause, making it virtually impossible to predict.¹  Although researchers and physicians have not identified the precise cause of SUDEP, they have been able to ascertain ailments associated with it including hypoventilation, apnea, respiratory distress, pulmonary hypertension, autonomic dysregulation, and arrhythmia.²  It is believed that the best prevention method is well controlled epilepsy with proper medication and patient adherence.  A healthy diet, exercise, and cardiac evaluation are also believed to reduce a patient’s risk of SUDEP.¹

As the cause of SUDEP is unknown, creating appropriate models to study has been a challenge.  However, researchers have developed models, most commonly using mice, that replicate the cardiovascular and respiratory ailments typically seen in SUDEP patients.²

Publications Citing Use of DSI Technology
Simultaneous cardiac and respiratory inhibition during seizure precedes death in the DBA/1 audiogenic mouse model of SUDEP

This study was designed to evaluate cardiac and respiratory dysfunction in a mouse model of SUDEP.  To do so, the research team simultaneously monitored respiration and ECG in mice using DSI plethysmography and implantable telemetry while monitoring behavior through video recording. The study’s results showed abrupt and simultaneous respiratory and cardiac depression with death occurring due to respiratory arrest.  They also suggest that seizures activate two CNS pathways – one that inhibits respiratory drive, and one that inhibits cardiac function via vagal efferents.  Mechanical ventilation using Harvard Apparatus’ Small Animal Respirator leads to abrupt and simultaneous recovery of both respiration and cardiac function which indicates that the vagal discharge can be rapidly terminated. Further understanding of the mechanism behind the abrupt cardiorespiratory dysfunction and recovery could help uncover therapeutic targets for SUDEP.³

Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy
Cardiac rhythm disturbances, such as changes in heart rate or arrhythmias, caused by seizures can increase risk of SUDEP. This study prescribed a technique to study abnormal brain and cardiac rhythms in which EEG and ECG are measured simultaneously while video is recorded to monitor the animals’ behavior.  This technique utilized a hardwired system to measure EEG and ECG as well as video monitoring technology from DSI.  This study also describes methods for analyzing seizure, EEG spectral power, cardiac function, and heart rate variability data and shows that video-EEG-ECG monitoring in mouse models of epilepsy is a powerful tool for detecting neurological, cardiovascular, or brain-heart interaction dysfunction.⁴

Solutions for SUDEP Research
DSI offers solutions to support studies of neurological, cardiovascular, and respiratory ailments associated with SUDEP.  Implantable telemetry provides the flexibility to measure endpoints such as ECG, EEG, blood pressure, temperature, and activity in conscious, freely moving animals.  ECG and EEG can also be measured using a hardwired system for acute studies.  Plethysmography enables evaluation of respiratory endpoints including respiration, tidal volume, minute volume, and more.  All endpoint collection methods can be combined with video recording to monitor animal behavior and confirm seizure activity. 

Ponemah software offers the flexibility to bring in signals from many different types of equipment (including those listed above) and provides powerful analysis tools to calculate heart rate variability, detect arrhythmia, and more.  Data can be easily exported from Ponemah into NeuroScore software for seizure detection and analysis.

DSI’s sister company, Harvard Apparatus, also offers a small animal respirator commonly used to resuscitate mice once respiratory failure occurs post-seizure.

References
¹Sirven J, Friedman D. (2019). “SUDEP FAQ”. Epilepsy Foundation. https://www.epilepsy.com/learn/early-death-and-sudep/sudep/sudep-faq

²Pansani AP, Colugnati DB, Scorza CA, de Almeida AC, Cavalheiro EA, Scorza FA. (2016). “Furthering our understanding of SUDEP: the role of animal models”. Expert Review of Neurotherapeutics, 16(5). https://doi.org/10.1586/14737175.2016.1169925 

³Schilling WP, McGrath MK, Yang T, Glazebrook PA, Faingold CL, Kunze DL. (2019). “Simultaneous cardiac and respiratory inhibition during seizure precedes death in the DBA/1 audiogenic mouse model of SUDEP”. PLoS One, 14(10). https://doi.org/10.1371/journal.pone.0223468 

⁴Mishra V, Gautier NM, Glasscock E. (2018). “Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy”. Jove. http://dx.doi.org/10.3791/57300.