Overview

Overview

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in patients with epilepsy, and, among neurological disorders, is second only to stroke in the number of potential life years lost. Cardiac and respiratory physiology dysregulation, systemic and cerebral circulation dysfunction, and seizure-induced hormonal and metabolic changes all may contribute to SUDEP. However, a particular area that remains understudied are influences of respiratory physiologic derangements as a trigger or product of epileptic seizures. Analyses of SUDEP cases recorded in epilepsy monitoring units have revealed a consistent pattern of generalized tonic-clonic seizure (GTCS)-induced postictal generalized EEG suppression and tachypnea, followed within minutes by cardiorespiratory collapse with terminal apnea and subsequent terminal asystole typically occurring during sleep in the prone position.

A critical gap in or knowledge, however, is the lack of information on key respiratory parameters including airflow, respiratory effort, oxygen saturation (SpO2), and carbon dioxide (CO2) in SUDEP cases. A potential causal role for such respiratory influences on seizures is highlighted by commonly observed associated apnea and hypopnea often resulting in significant exposure to hypoxia and hypercapnia, with end tidal CO2 (EtCO2) elevations lasting over 15 minutes after scalp-recorded generalized and focal seizures. The only invasive EEG study involved 10 subjects with bi-temporal recordings and found that apnea occurred only with contralateral spread. The importance of respiratory physiology is underscored by evidence that peri-ictal hypoventilation may contribute to cardiac abnormalities, the latter of which have been the primary focus of investigation of SUDEP mechanistic underpinnings. Further, in the largest polysomnographic (PSG) study thus far, we identified obstructive sleep apnea (OSA) in 30% of adults with epilepsy, including 16% with moderate-to-severe OSA. The rates exceed general population estimates and raise the possibility of bidirectional relationships between seizures and respiratory dysfunction.

Integration of stereo-electroencephalography (SEEG) with sleep and respiratory recordings offers the possibility of characterizing relationships between seizures and key respiratory markers and delineating functional connectivity of epileptic network activation with peri-ictal respiratory modulation, which may be insightful for understanding SUDEP. Our experience maintaining PSG signal integrity during seizures and access to a high volume of SEEG cases support the feasibility of the proposed research. Our group with expertise in neurophysiology, epileptology, sleep medicine, respiratory physiology, signal processing, and dynamical systems analyses will accomplish the following aims:

Aim 1. Characterize Relationships among Classical Ictal EEG Landmarks and Respiratory Parameters.

Aim 2. Investigate the Impact of Sleep-Wake State on Peri-ictal Respiratory Parameters.

Aim 3. Correlate Peri-Ictal Respiratory Involvement and Seizure Localization/Network Activation.

Contact Information

Nancy Foldvary-Schaefer, DO, MS
foldvan@ccf.org

Funding Sources

CTSC CSR SUDEP Pilot Award 2015-2016: Peri-lctal Respiratory Dysfunction: A Multi-modality Analysis of Sleep and Breathing in Adults with Pharmacoresistant Epilepsy, PI: N Foldvary-Schaefer

Publications

Publications

  1. Epilepsy and Sleep-Related Breathing Disturbances. Somboon T, Grigg-Damberger MM, Foldvary-Schaefer N. Chest. 2019 Jul;156(1):172-181.
  2. Continuous Positive Airway Pressure Therapy for Obstructive Sleep Apnea Reduces Interictal Epileptiform Discharges in Adults with Epilepsy.Pornsriniyom D, Shinlapawittayatorn K, Fong J, Andrews ND, Foldvary-Schaefer N.  Epilepsy Behav. 2014; 37:171–4. doi.org/10.1016/j.yebeh.2014.06.025.
  3. Effect of Positive Airway Pressure Therapy on Seizure Control in Epilepsy Patients with Obstructive Sleep Apnea. Pornsriniyom D, Kim H, Bena J, Andrews N , Moul D, Foldvary-Schaefer N. Epilepsy Behav. 2014; 37: 270–75.
  4. Continuous Positive Airway Pressure Therapy for Obstructive Sleep Apnea Reduces Interictal Epileptiform Discharges in Adults with Epilepsy.Pornsriniyom D, Shinlapawittayatorn K, Fong J, Andrews ND, Foldvary-Schaefer N.  Epilepsy Behav. 2014; 37:171–4. doi.org/10.1016/j.yebeh.2014.06.025.
  5. Sleep Apnea and Epilepsy: Who's at Risk? Foldvary-Schaefer N, Andrews ND, Pornsriniyom D, Moul DE, Sun Z, Bena J. Epilepsy Behav. 2012; 25: 363–7.
Members & Collaborations

Members & Collaborations

Members

Nancy Foldvary-Schaefer, DO, MS
Noah Andrews, RPSGT
James Bena BS

Cleveland Clinic Affiliations

William Bingaman, MD
Patrick Chauvel, MD, PhD
Juan Bulacio, MD
Jorge Gonzalez, MD

External Relationships & Collaborations

John Mosher, PhD