Pauline Anderson

December 04, 2017

WASHINGTON, DC — Treating obstructive sleep apnea (OSA) among patients with epilepsy significantly reduced seizures in a study researcher say is the largest of its kind to date.

Dr Thapanee Somboon

"All patients with epilepsy should be screened for OSA, and the condition should be treated, particularly in those with drug-resistant seizures," lead author, Thapanee Somboon, MD, research fellow, Sleep Disorder Center, Cleveland Clinic, Ohio, told Medscape Medical News.

The findings were presented here at the American Epilepsy Society (AES) 71st Annual Meeting 2017.


Common Condition

About 40% of adults with epilepsy also have sleep apnea, and in about 16% the condition is moderate to severe.

In the general population, OSA prevalence increases with age and body mass index (BMI). Compared with the general population, patients with epilepsy are more likely to be more overweight because of more sedentary lifestyle, coupled with the weight-gain side effects of some antiepileptic drugs (AEDs), said Dr Somboon.
OSA interrupts sleep and produces a state of chronic sleep deprivation, which can increase seizures, said Dr Somboon. In addition, OSA is associated with other negative outcomes, including mood and cognitive dysfunction, hypertension, cardiovascular disease, metabolic disorders, and sudden death.

The retrospective study included 197 adults with epilepsy (mean age, 43.9 years; 58% female) who underwent polysomnography (PSG) from 1997 to 2015. Researchers collected demographic information, epilepsy characteristics, PSG data, and adherence to positive airway pressure (PAP) therapy for OSA.

Researchers classified patients as having OSA and receiving PAP therapy, having OSA and not receiving PAP therapy (untreated), and not having OSA. About 62% of the study patients had OSA, of whom 60% were receiving PAP therapy.

The treated and untreated OSA groups did not differ in terms of age, sex, body mass index, or type of standardized AED dose.

As per standard care, all patients with OSA — both untreated patients and those receiving PAP — were educated about conservative therapies at the time of  diagnosis. As part of that education, they were taught the importance of weight loss and avoiding the supine sleep position, alcohol, and other central nervous system depressants.

"While we don't have data regarding the adoption or adherence to these treatments, we suspect that comparable percentages of subjects in both OSA groups would have engaged in these," said Dr Somboon.

She noted that "with the exception of substantial weight loss, these conservative measures rarely produce a meaningful change in OSA severity."

Mechanism Not Clearly Understood

The study included two seizure outcomes: responder rate (a 50% or greater reduction from baseline) and successful outcome (a 50% or greater reduction or being seizure-free at both baseline and follow-up).

The investigators controlled for antiepileptic drug standardized dose, a measure of drug burden, in order to eliminate the impact of drug changes between baseline and follow-up.

At 1 year, the responder rate was significantly greater in patients with PAP-treated OSA (63%; P = .001) and the no-OSA group (44%; P = .11) compared with the untreated OSA group (14%).

Successful outcome was achieved more often in PAP-treated patients (85%) than in those with untreated OSA (55%; P < .001) or the no-OSA group (65%; P = .007).

Although findings were similar at time points beyond 1 year, these analyses were limited to small samples and were not significant, said Dr Somboon.
Neurologists who don't practice sleep medicine and aren't aware of the benefits of sleep therapies may be surprised at the magnitude of seizure improvement with PAP in patients with epilepsy, said Dr Somboon.

How PAP therapy reduces seizures is not clearly understood, she said.

"The most likely explanation is that treatment of OSA consolidates sleep, reducing arousals and awakenings and eliminating oxygen desaturations that might exacerbate epilepsy. Seizures are known to arise surrounding sleep-wake transitions."

This new research is important because it suggests a potentially successful way to reduce seizures in some patients with epilepsy. An estimated 30% of adults with epilepsy have persistent seizures, despite medical and surgical therapies, said Dr Somboon. 

PAP Clearly Works

For a comment on the findings, Medscape Medical News turned to Sanjeev V. Kothare, MBBS, director, Pediatric Neurology, and co-director, Pediatric Sleep Program (Neuro), Cohen Children's Northwell Health, Lake Success, New York.

The new research "reinforces" what he and his colleagues observed in a study published some 7 or 8 years ago, said Dr Kothare.

That study "clearly showed that PAP works" in patients who had both refractory epilepsy and sleep apnea, and the more it was used, the better the results, he said. 

Because so many patients with epilepsy also have OSA, Dr Kothare suggests that clinicians screen for sleep apnea using "a simple questionnaire that can check for snoring," which is the "cardinal symptom" of sleep apnea.

If sleep apnea is uncovered, clinicians should consider PAP, said Dr Kothare.

"PAP will not only improve sleep apnea and fragmented sleep, but it will also improve seizure control, decrease daytime sleepiness, and improve quality of life," including reducing depression.

Clinicians don't always consider sleep problems in their patients with epilepsy, said Dr Kothare. Of the 200 or so delegates who attended a presentation he gave on sleep and epilepsy during the AES 2017 meeting, "I would say that over 100 of them have never thought of using PAP for sleep apnea to improve seizures."

No more than about 30% to 50% of patients in general adhere to PAP therapy, and that percentage is even lower in patients with epilepsy, many of whom have intellectual challenges, said Dr Kothare.

Although PAP is the "gold standard" to treat OSA, a mandibular advancement device that pulls the tongue forward might be "a good alterative" for patients with mild to moderate sleep apnea who can't tolerate PAP, said Dr Kothare.

Also commenting on the study for Medscape Medical News was Rani Sarkis, MD, associate neurologist, Brigham and Women's Hospital, and assistant professor, Harvard Medical School, Boston, Massachusetts. "The new study included one of the largest described cohorts of patients with epilepsy who benefited from treatment of their OSA," said Dr Sarkis, who has investigated the importance of sleep in the consolidation of recently formed memories in patients with epilepsy.

In addition to highlighting the importance of addressing sleep quality in patients with epilepsy, the results should "remind physicians of another nonpharmacologic tool in their armamentarium," he said. 

However, the retrospective nature of the study "creates a bias" because patients were likely referred for a sleep study on the basis of physician judgment rather than using a "systematic approach. Ultimately, a prospective study is badly needed," he added.

Such a study, he noted, could address three important questions: Which patients with epilepsy should be referred for a sleep study? Is there a different threshold for the treatment of OSA in people with epilepsy than in those without epilepsy? Would other therapies affect seizures in people with epilepsy with OSA who don't tolerate PAP?

 Dr Somboon and Dr Kothare have disclosed no relevant financial relationships. Dr Sarkis reports that he has received compensation for activities with DigiTrace/SleepMed.

American Epilepsy Society (AES) 71st Annual Meeting 2017. Abstract  1.201. Presented December 2, 2017.

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