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Patients with Generalized Epilepsy May Be at Higher Risk for Obstructive Sleep Apnea

Article In Brief

People with generalized epilepsy may be at a higher risk for obstructive sleep apnea than those with focal epilepsy, although all epilepsy patients would likely benefit from screening for sleep disorders.

People with generalized epilepsy may be at a higher risk for obstructive sleep apnea (OSA) than those with focal epilepsy, although all epilepsy patients would likely benefit from screening for sleep disorders, a new study suggests.

While epilepsy is a known risk factor for OSA, the new research examined whether certain epilepsy patients might be particularly at risk. Because the study used a screening questionnaire rather than formal diagnostic testing for OSA, further research is needed to confirm the findings related to generalized versus focal epilepsy, the researchers noted.

“Treatment of OSA may be an important part of treatment for epilepsy, and identification of which [patients] are most at risk for OSA and which are most likely to benefit from OSA treatment is important,” the researchers concluded in a report published in the October 1 issue of Epilepsy & Behavior.

Lead author Matthew T. Scharf, MD, PhD, assistant professor of medicine and neurology at Rutgers Robert Wood Johnson (RWJ) Medical School, said OSA and other sleep problems do not get enough attention in epilepsy care, which tends to be focused mostly on seizure control.

“I think we're getting to the point where screening for OSA should become a routine part of clinical care,” said Dr. Scharf, medical director of the RWJ Sleep Laboratory. “People who have sleep problems often have a poor quality of life.”

Prior research indicates that untreated OSA may increase the incidence of seizures in epilepsy patients and elevate the risk of sudden unexplained death in epilepsy (SUDEP).

Study Details

The new study enrolled 115 patients 18 or older—27 with a diagnosis of generalized epilepsy; 88 with focal epilepsy—who were treated at the Epilepsy Center at Rutgers RWJ Medical School. Participants were assessed for the risk of OSA using the Sleep Apnea Scale of the Sleep Disorders Questionnaire (SA-SDQ), which has been validated as a measure of OSA risk in many studies including those assessing patients with epilepsy, Dr. Scharf said.

Patients were asked a series of sleep-related questions such as “I am told I snore loudly and bother others,” “I am told I stop breathing in sleep,” and “I awake suddenly gasping for breath, unable to breathe.” They also were asked about weight, hypertension, body mass index, smoking history and age. A total score was calculated for each participant, with 12 being the lowest possible total score and 60 the highest.

Unadjusted average SA-SDQ scores were similar for generalized and focal epilepsy (24.4 versus 24.8). Based on previous research, a score of 29 or higher was considered abnormal for male patients and 26 or more for female patients. By that measure, 33.3 percent of patients with generalized epilepsy had an abnormal SA-SDQ score, while 35.2 percent of focal epilepsy patients had an abnormal score.

The researchers then did an adjusted analysis that took into consideration differences in clinical and demographic factors. On average, patients with focal epilepsy had an adjusted SA-SDQ score that was 3.52 points lower than patients with generalized epilepsy, meaning their risk of OSA was lower.

Older age, higher body mass index (BMI), and a history of hypertension were also associated with higher SA-SDQ scores, factors that increase OSA risk in the general population as well. The scores were not significantly affected by whether the patient had seizures in the past month or past six months.

The study also assessed sleepiness using the Epworth Sleepiness Scale and found that scores were fairly similar between the generalized epilepsy group and the focal epilepsy group.

Dr. Scharf said it is not fully understood why epilepsy increases the risk of OSA or why different types of epilepsy (generalized versus focal) may confer varying degrees of risk.

“Possible reasons for higher OSA risk in patients with generalized epilepsy include altered control of the muscles of the upper airway, ventilatory control instability, or differences in upper airway anatomy,” the paper suggested.

“Generalized epilepsy is most often characterized by epileptiform activity involving bilateral thalamocortical circuits. This may cause worse brainstem dysfunction than abnormal activity in focal epilepsy, which may lead to decreased brainstem-mediated respiratory control.”

The duration and types of antiepileptic medication used to treat generalized epilepsy may also be a contributing factor, they said.

Expert Commentary

Sanjeev V. Kothare, MD, FAAN, division director of pediatric neurology at Cohen Children's Medical Center and professor of pediatrics and neurology at Zucker School of Medicine at Hofstra/Northwell, said the study had some limitations that made it difficult to reach firm conclusions.

“The prevalence of OSA was detected in this cohort based on a screening questionnaire. No confirmatory sleep studies were performed,” Dr. Kothare said. “The patients were not followed prospectively to see if treating with continuous positive airway pressure [CPAP] reduced the seizure burden or prevented occurrence of SUDEP [sudden unexpected death in epilepsy].”

“The details of the patients with generalized epilepsy are not specified,” he added. “Were these patients with primary generalized or secondary generalized or symptomatic generalized epilepsy?”

But Dr. Kothare said the study nonetheless provides an important message for clinicians, highlighting the importance of screening for OSA in patients with epilepsy. “By management of the OSA with the use of CPAP and reducing the fragmented sleep, not only would the seizures come under better control, but it may reduce the risk for SUDEP.”

Nancy Foldvary-Schaefer, DO, MS, FAAN, director of the Sleep Disorders Center and staff at the Epilepsy Center at the Cleveland Clinic, said her own studies of OSA in epilepsy have not found that people with generalized epilepsy are more at risk for the sleep disorder than those with focal epilepsy.

She published a study in 2012 in Epilepsy & Behavior of 130 consecutive adult patients with epilepsy who underwent polysomnography. In that study, 30 percent of patients had OSA and 16 percent of the total group had moderate-to-severe disease. Increasing age, antiepileptic drug load, BMI and seizure frequency were associated with elevated OSA severity.

In another study published earlier this year in Behavior & Epilepsy, Dr. Foldvary-Schaefer and colleagues found that excessive daytime sleepiness, a possible sign of OSA, was highly prevalent among 127 epilepsy patients who underwent laboratory testing and even among those who hadn't complained of sleepiness. She said the degree of daytime sleepiness in many of the epilepsy patients was similar to what people with narcolepsy experience.

Dr. Foldvary-Schaefer, professor of neurology at the Cleveland Clinic Lerner College of Medicine, said she believes doctors should screen all epilepsy patients for OSA using a series of simple questions such as those found in the SA-SDQ scale. She makes a habit of asking patients and their bed partners about snoring, pauses in breathing during sleep, and waking up gasping or choking. If a follow-up sleep study confirms a suspicion of OSA, “The treatment of choice is CPAP,” she said. “It is very effective and can reduce seizures in some people with epilepsy.”

Jennifer DeWolfe, DO, who directs the Epilepsy Monitoring Unit at University of Alabama at Birmingham (UAB) and the Sleep Center at Birmingham VA Medical Center, said that epilepsy “as a field needs to focus more on evaluating for obstructive sleep apnea.”

She said that attention is paid to other epilepsy comorbidities, such as mood disorders, but sleepiness and other sleep issues may be dismissed as an unfortunate side effect of AED medications. “You shouldn't just think, ‘It's the medicine,’” she said.

Dr. DeWolfe, associate professor of neurology at UAB, noted that “SUDEP is the leading killer of patients with epilepsy and if sleep apnea could be a contributing factor, we in the field should be paying more attention.”

Dr. DeWolfe said she believes the case is getting stronger to do routine sleep apnea screening in all epilepsy patients, even with something as easy as asking them to answer a short questionnaire ahead of an office visit.

At UAB, “patients admitted for inpatient epilepsy monitoring studies complete standardized screening questionnaires evaluating for daytime sleepiness with the Epworth Sleepiness Scale as well as screening for depression and anxiety. Patients are also evaluated for symptoms of and risk factors for sleep apnea,” Dr. DeWolfe said.

Patients with excessive sleepiness, symptoms for sleep apnea, or risk factors for sleep apnea are then referred for a follow-up sleep clinic evaluation, she said.

Dr. DeWolfe said that improving the quality of sleep for epilepsy patients can improve their overall quality of life, as well as potentially reduce the risk of seizures.

“We have to do a better job of educating our patients on why it's important to get a good night's sleep,” she said.

Disclosures

Drs. Scharf and Kothare reported no disclosures. Dr. Foldvary-Schaefer has received honoraria for serving on the advisory board of Jazz Pharmaceuticals, book royalties from Oxford University Press. Dr. DeWolfe has received research grants from Engage Therapeutics and the NINDS to evaluate antiseizure medications.

Link Up for More Information

• Scharf MT, Greenberg P, Wong S, Mani R. Obstructive sleep apnea risk in patients with focal versus generalized epilepsy https://www.sciencedirect.com/science/article/abs/pii/S1525505020303693. Epilepsy Behav 2020; 111:107190.
• Foldvary-Schaefer N, Andrews ND, Pornsriniyom D, et al. Sleep apnea and epilepsy: Who's at risk https://www.epilepsybehavior.com/article/S1525-5050(12)00558-6/fulltext. Epilepsy Behav 2012;25(3):363–367.
• Grigg-Damberger M, Andrews N, Wang L, et al. Subjective and objective hypersomnia highly prevalent in adults with epilepsy https://www.epilepsybehavior.com/article/S1525-5050(20)30202-X/fulltext. Epilepsy Behav 2020;106:107023.