# Breathing Rescue for SUDEP Prevention (BreatheS)

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $597,611

## Abstract

PROJECT SUMMARY
Sudden unexpected death in epilepsy (SUDEP) is a devastating complication of epilepsy and a leading cause
of premature death in persons with chronic uncontrolled epilepsy. Despite the major impact on life expectancy
in these individuals, no targeted SUDEP preventive strategies currently exist. Most SUDEPs occur after a
generalized convulsive seizure, and victims are typically found in bed in the prone position. Until recently, SUDEP
was thought to be due to cardiovascular failure, but research on patients who died while being monitored in
hospital epilepsy units reveal that most SUDEP is due to post-convulsive central apnea. Crucially, a three-minute
post convulsive window of opportunity was identified, beyond which the terminal cascade of respiratory and
cardiac failure appears irrevocable. By advancing our understanding of forebrain breathing networks, we can
develop neuromodulatory strategies for respiratory facilitation and apnea rescue that may prevent SUDEP during
this critical time window. The objective of this project is to understand forebrain modulation of breathing by using
anatomically precise intracranial stereotactic electroencephalography (SEEG) data that can determine optimal
stimulation paradigms for breathing enhancement. The study population are patients with medically refractory
epilepsy undergoing 1) intracranial SEEG evaluation with implanted depth electrodes for epilepsy surgery, and
2) simultaneous polygraphic cardiorespiratory monitoring of thoracoabdominal excursions, nasal and oral
airflow, oxygen saturation, carbon dioxide, plethysmography and EKG. To achieve this goal, in Aim 1, we will
identify forebrain regions in which electrical activity is coupled with respiratory activity by using spontaneous and
task-related breathing data and monitoring simultaneous brain signal dynamics. We will further analyze functional
connectivity to graph networks as a function of breathing tasks, in order to establish network hubs as candidate
regions for stimulation targets and in order to reveal a comprehensive cortical connectome. In Aim 2, we will
apply electrical stimulus to these regions to assess neuromodulatory effects on respiration. Effective stimulation
paradigms/sites will be tested in the immediate post-convulsive state in the latter part of this study, to prove
feasibility of neuromodulation in this state, and these seizures will be compared with non-stimulated seizures
obtained from the NINDS Center for SUDEP Research, using 1:5 matching (matched for age, sex, SUDEP risk
factors-duration of epilepsy and GCS frequency). Our project will identify effective stimulation sites and
paradigms for breathing rescue as well as will establish feasibility of stimulation approaches in the post-
convulsive state. Our results will set the stage for a clinical trial of efficacy of neuromodulation for apnea rescue
as potential anti-SUDEP therapy, in individuals who at high SUDEP risk. This work will also provide insights i...

## Key facts

- **NIH application ID:** 10889976
- **Project number:** 5R01NS133743-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Nuria Lacuey Lecumberri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $597,611
- **Award type:** 5
- **Project period:** 2023-07-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889976

## Citation

> US National Institutes of Health, RePORTER application 10889976, Breathing Rescue for SUDEP Prevention (BreatheS) (5R01NS133743-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10889976. Licensed CC0.

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