Epilepsy and Obstructive Sleep Apnea: Assessing the Risk of SUDEP

Among adverse effects of epilepsy, the potential for sudden unexplained death in epilepsy (SUDEP) is the most dire. Occurring without warning in otherwise healthy-seeming individuals, SUDEP accounts for 15% of epilepsy-related deaths. Adults with epilepsy have a 4.6% to 8% SUDEP risk over their lifetime, and an estimated 70% of SUDEP cases take place during sleep.

Nancy Foldvary-Schaefer, DO, an epilepsy specialist and Director of Cleveland Clinic’s Sleep Disorders Center, researches the bi-directional relationship between sleep apnea and epilepsy. Dr. Foldvary-Schaefer is the corresponding author on a study recently published in Epilepsy & Behavior, which advances the understanding of obstructive sleep apnea (OSA) and SUDEP through the use of gold-standard, in-laboratory polysomnography to accurately assess incidents of OSA in subjects with epilepsy.

Study results underscore the need for physicians to consider sleep as they help their patients manage their epilepsy and related risks.

The work depends on having the most accurate assessment possible of obstructive sleep apnea events.

“These days sleep studies are performed in the laboratory and in the home. Home sleep tests do not include electroencephalogram (EEG) sensors, which prevents the recognition of sleep,” says Dr. Foldvary-Schaefer. “That means the number of upper airway obstructions in sleep will be underestimated compared to the laboratory study. For people with epilepsy, polysomnography performed in the sleep laboratory is preferred and can identify types of obstruction not apparent on home sleep studies. The apnea hypopnea index (AHI) is a much more reliable output of a study than the measurements from a home sleep apnea test. That methodological difference makes our study particularly sound and superior to those previously published.”

Prevalence of apnea in epilepsy

As one of the most feared complications of epilepsy, SUDEP is an area that Dr. Foldvary-Schaefer’s team identifies as needing further research.

“Small studies demonstrate that SUDEP almost always occurs in sleep when people are in the prone — face down — position, sleeping, leading to seizure and death,” she says. “This suggested that there could be a relationship between sleep apnea and SUDEP, since sleep apnea is common in people with epilepsy. Our recent study is an effort to further expand understanding of these relationships.

“Our ultimate goal is to raise awareness among providers who take care of people with epilepsy about the importance of sleep and the risk of sleep disorders in epilepsy, both adults and children,” she adds.

The study

To investigate the relationship between OSA and SUDEP risks, the researchers used the prospectively maintained Cleveland Clinic Sleep Center database to identify 214 adults with epilepsy who had undergone polysomnography (PSG) between 2004 and 2016. Using the AHI, OSA was defined as a patient experiencing five or more apnea-hypopnea events per hour; moderate to severe OSA was defined as AHI ≥ 15.

Investigators used the revised SUDEP-7 risk inventory (rSUDEP-7), a validated tool that scores risk based on answers to seven questions. Scores range from 0 to 7; higher scores indicate greater risks of SUDEP.

The team used Wilcoxon rank-sum tests and multivariable linear models adjusting for age, sex, BMI and smoking status to assess the associations between rSUDEP-7 score and OSA groups (AHI≥15 vs. <15).

The results: Obstructive sleep apnea was present in 134 (62.6%) of the study subjects and was moderate or severe in 75 (35%). Those with AHI ≥15 were more likely to be male, older, have a higher body mass, and have greater frequency of tonic-clonic seizures (TCS). They also tended to have had epilepsy for a longer duration and were more likely to have drug-resistant epilepsy and sleep-related seizures (all p< 0.05).

The median rSUDEP-7 score was 1 (0,3) but 37.4 % of subjects had a score ≥3, indicating high SUDEP risk, and 11.7 % scored ≥5 — the highest SUDEP risk. Scores were higher in those with AHI ≥15 (3 vs. 1, p = 0.001). Higher AHI and oxygen desaturation index of 3% positively correlated with rSUDEP-7 (p=0.002 and p=0.016).

The findings suggest that identifying and treating OSA in epilepsy patients could reduce their risk of SUDEP.

“There may be variables that are predictive of OSA that also may predict sudden death,” says Dr. Foldvary-Schaefer. “Even though we could not control for all potentially relevant factors, our findings suggest that identifying obstructive sleep apnea and treating it may have reduce the risk of sudden death.”

Importantly, she adds, the research indicates that untreated sleep apnea may serve as a comorbid condition that exacerbates the risk of SUDEP.

Challenges and further research

Despite the strong evidence supporting the need for routine OSA screening in epilepsy patients, significant barriers exist. Neurologists and epileptologists are often not trained in sleep medicine, which poses challenges for prioritizing sleep-related issues during patient visits. Yet "it's very easy to ask a few questions to identify people at risk for sleep apnea, and effective treatments are readily available that may reduce these adverse outcomes and improve seizure control," Dr. Foldvary-Schaefer says.

Looking ahead, Dr. Foldvary-Schaefer aims to further study specific patterns of seizure propagation that increase the risk of SUDEP using data from adults with epilepsy undergoing invasive EEG monitoring for purposes of epilepsy surgery. Her research also includes the development of better screening tools for sleep apnea in epilepsy patients. Current screening instruments, which consist of a symptoms including daytime sleepiness or fatigue may not be sufficient.

"The most impactful single question may be whether they have been observed to stop breathing in sleep," says Dr. Foldvary-Schaefer. By refining tools, healthcare providers can more effectively identify and treat sleep apnea in this population.

Conclusion

For clinicians, especially neurologists and primary care physicians, the takeaway is clear.

"People with epilepsy are high risk for sleep apnea,” says Dr. Foldvary-Schaefer. “Identifying and treating obstructive sleep apnea may significantly reduce the risk of adverse outcomes, including SUDEP.”