NeuroVoices: Nancy Foldvary-Schaefer, DO, FAAN, on the Crossover Between Sleep and Epilepsy

Nancy Foldvary-Schaefer, DO, FAAN

Seizure-related respiratory dysfunction may predispose to sudden death in epilepsy (SUDEP), yet existing studies are based largely on scalp recordings and lack of comprehensive polysomnographic (PSG) signals. Presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, held April 22-27, in Boston, Massachusetts, a study assessed respiratory changes in stereoelectroencephalography (SEEG)-recorded perisylvian seizures using a multimodal system that integrated EEG and PSG signals including airflow, effort, SpO2, and CO2.

Conducted by Nancy Foldvary-Schaefer, DO, FAAN, postictal generalized EEG suppression (PGES) seizures (n = 8) were associated with higher central event frequency (median, 3.0 vs 1.0; P <.001) and duration (76 vs 27 sec; P = .010) than seizures without PGES. Despite this, PGES was not associated with sleep state. In contrast, sleep seizures (n = 35) were differentiated from wake seizures only by lower pre-ictal (19.9 [±2.5] vs 24.1 [±3.1] bpm; P <.001), ictal (22.6 [±4.3] vs 28.0 [±2.7] bpm; P <.001) and postictal RR (24.7 [±5.22] vs 8.5 [±4.4] bpm; P = .020) and higher pre-ictal TcpCO2 (40.6 vs 36.8 mmHg; P = .006).

Above all, these findings suggest that PGES in perisylvian seizures are associated with a host of respiratory disturbances, providing further support of its role as a biomarker of SUDEP. Foldvary-Schaefer, director of the Sleep Disorders Center and staff in the Epilepsy Center at Cleveland Clinic, sat down as part of a new iteration of NeuroVoices to discuss the trial, and the growing evidence of the link between sleep and epilepsy. Additionally, she provided insight on the need to raise awareness, the unanswered questions that remain, and whether treating sleep issues early can have a significant long-term impact.

NeurologyLive®: From the findings, what should the clinical community take away?

Certainly, on the epilepsy side, it's important for epileptologists to recognize that some patients with epilepsy have these significant changes or are potentially at risk for these significant changes associated with their seizures. We are not at the point where we’re recording all these sensors while we record seizures, and part of that is because of lack of awareness, technical challenges, but also, patient acceptance. Patients who are recorded in the monitoring units, even with scalping EEG, let alone invasive EEG, are already hooked up to so much stuff that it was challenging for us to even get some of these patients to be recorded for one day. But I think this is part of the research that will help us understand how important it may be to add some of these sensors when we're recording seizures. It's part of the bigger story of these bidirectional relationships between sleep and epilepsy.

What are some of the unanswered questions regarding the link between sleep and epilepsy?

There's a subset of patients who have sleep related epilepsy, or epilepsy that's exclusively or predominantly from sleep; however, understanding the genetic mechanisms and other underlying mechanisms is poorly understood. We don't have specific therapies for sleep-related epilepsy. We are beginning to see clinicians who sort of tailor their therapies to boost antiseizure medication levels at night. We also don't know to what extent people with epilepsy are affected by sleep disorders other than sleep apnea. A lot of the literature in sleep disorders and epilepsy is around sleep apnea, that's where the field kind of began.

But there are many other therapies and sleep disorders, such as primary insomnia disorders, that affect people with epilepsy. We're just beginning to scratch the surface on understanding how well people respond to typical insomnia therapies like cognitive behavioral therapy for insomnia specifically. Can we show that epilepsy outcomes improve when we're lengthening sleep for people with epilepsy? Same for circadian rhythm disorders, and for the overlap of epilepsy and non-REM parasomnias. We have a lot of ways to go in terms of understanding the mechanisms, but also getting to the point of seeing patients in clinic every day, recognizing the symptoms of these disorders, and then moving on to diagnosis and therapies for the sleep side of patients with epilepsy.

Is there evidence of benefit for treating sleep issues early?

We know that the general population has a high prevalence of common sleep disorders, like insomnia and sleep apnea. The prevalence is 30% to 40%, depending on the age and gender. We know these are proven facts. We have long term studies over many years that show the outcomes of treating sleep apnea, the outcomes of treating insomnia. We know that moderate to severe sleep apnea and significant insomnia are real risk factors for cognitive decline as we age, and we know about risk factors of cardiovascular disease for metabolic disease.

We know that treating some of these patients with epilepsy not only improves their quality of life when we address their sleep, but also may improve their epilepsy. What the general level epileptologist may not be as aware of or as skilled in, is simply the diagnosis and treatment of sleep disorders, simply because epileptologists are not always traditionally trained in sleep medicine. One of the goals of having sleep and epilepsy research at a meeting like this is to raise that awareness that every patient with epilepsy can be screened in a small amount of time in your clinic for the most common sleep disorders. Sleep apnea is easy to recognize, insomnia is easy to recognize. If we do more of that, we will be better at enhancing the quality of life of our patients with epilepsy and maybe even improve their underlying condition.

What other types of research would you like to see in this field?

Efforts still need to be at the level of raising awareness of the high comorbidity of sleep disorders so that more epileptologists, more general neurologists immediately work that into their evaluations of patients with epilepsy. We talk a lot about depression and comorbid, psychiatric problems. We know about driving restrictions and its effect on the quality of life, these things we talk to every patient with epilepsy about. But I think adding sleep to those critical things that affect the quality of life of patients is really important.

As a second answer to that question, one of the intriguing things that I'm beginning to work on is the fact that we know this population is very sleepy. They're objectively very sleepy. A couple of years ago, we published the largest paper on objective daytime sleepiness in an unselected group of adults with epilepsy. These are sleepy people, cognitively impaired, have accidents behind the wheel, have poor quality of life, all independent of epilepsy. [We need to] raise awareness of that hypersomnia piece, begin to think about how to test it in clinical trials, and how to identify optimal weight-promoting drugs that might be safe and effective. In this population of patients, this is one of the next things on the horizon.

Transcript edited for clarity. Click here for more NeuroVoices.

REFERENCE
1. Mora-Munoz L, Andrews N, Araujo M, et al. Post ictal generalized EEG suppression, not sleep state, is associated with peri-ictal respiratory disturbances in stereoelectroencephalography recorded perisylvian seizures. Presented at: 2023 AAN Annual Meeting; April 22-27; Boston, MA. Abstract 003054