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Central sleep apnea is a complex and often underrecognized sleep-related breathing disorder that differs from obstructive sleep apnea by involving reduced respiratory drive rather than upper airway obstruction. In this episode, Dr. Ran Liu reviews the underlying mechanisms of central sleep apnea, including the role of ventilatory control instability, discusses its association with neurologic conditions such as stroke, multiple sclerosis, ALS, and myasthenic disorders, and highlights key considerations for diagnosis and management. Learn how emerging technologies, personalized treatment strategies, and advances in sleep medicine are improving outcomes for patients with this heterogeneous group of disorders. In this episode, Teshamae Monteith, MD, FAAN, speaks with Ran R. Liu, MD, FRCPC, MSc, author of the article "Central Sleep Apnea" in the Continuum® August 2026 Sleep Neurology issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Liu is an Adjunct Clinical Assistant Professor at McMaster University in Hamilton, Canada, and an Adjunct Lecturer at the University of Toronto in Toronto, Canada. Additional Resources Read the article: Central Sleep Apnea Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @headacheMD Guest: @SleepyNeuroDoc Full episode transcript available here Dr Monteith: You may be familiar with obstructive sleep apnea, but central sleep apnea is often less understood and frequently underdiagnosed. In this podcast, we break down the key clinical pearls to sharpen your diagnostic reasoning, discuss why central sleep apnea matters, and to explore some of the fascinating advances transforming the field. Dr Jones: This is Dr. Lyell Jones, editor-in-chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Monteith: This is Dr. Teshamae Monteith. Today, I'm interviewing Dr. Richard Liu about his article on central sleep apnea. This article appears in the August 2026 Continuum issue on Neurology of Sleep. Welcome to our podcast. How are you? Dr Liu: Good. Thank you, Dr. Monteith, for having me today. Dr Monteith: Please introduce yourself to our audience. Dr Liu: Hello, everybody. My name is Richard Liu. I am a sleep neurologist. I am working out of Toronto at both Sunnybrook Health Science Center and MedSleep. I did my residency at Queen's for neurology and my sleep medicine fellowship at Harvard University. Dr Monteith: Great. And what got you interested in sleep? Dr Liu: Thank you very much for asking. For me, sleep medicine is a field where essentially everything is connected. Certainly, impaired sleep can affect many other conditions, including many neurological conditions. And even within sleep medicine, when somebody has a sleep disorder, often the entire system is connected. So as an example, if you have insomnia and fragmented sleep and periodic limb movements of sleep, certainly these conditions can impact sleep apnea. And certainly, for today's topic of central sleep apnea, this is an extremely complicated disorder where it's a very in-depth integration between neurological and respiratory physiology, among other systems as well. Dr Monteith: So, I guess you're kind of like the cornerstone, sleep being the cornerstone of neurology. Everyone has to sleep. That's for sure. Great. So why don't we talk about what central sleep apnea is, and how prevalent is it as a collective group of disorders compared to obstructive sleep apnea? Dr Liu: So, one way to think about central sleep apnea is that this is a heterogeneous group of etiology. But the primary concept here for central sleep apnea is that there's a reduction in respiratory drive. This is in contrast to obstructive sleep apnea, where essentially this is some form of airway obstruction in the presence of relatively intact respiratory drive. And of course, there's mixed apneas where they may contain features of both. But of course, now we know that even obstructive sleep apnea, there's a certain degree of drive dependence somewhat blurring these distinctions. The overall prevalence of central sleep apnea is about five to ten percent of all patients with sleep- disorder breathing. And certainly, it could be higher in some neurological conditions, such as things like stroke, multiple sclerosis, and multisystem atrophy. Dr Monteith: Great. So certainly, it's out there. Why don't you tell us about the objectives of your article? Dr Liu: Absolutely. Thank you for asking. I think the main objective of this article is really to highlight that central sleep apnea is a complex syndrome resulting from a large group of heterogeneous etiologies. And of course, again, it could be associated with many neurological conditions. And really here, I want to highlight advancements, both medicine and technology, on both the side of diagnosis of central sleep apnea, as well as the multimodal targeted treatment. Dr Monteith: And what do you want our listeners to take away from this talk and certainly your article? What are the key essential points? Dr Liu: Thank you very much for asking. I think that one way of looking at central sleep apnea to etiologically divide this into both hypocapnic and hypercapnic central sleep apnea. And of course, loop gain being a major driver for a hypocapnic central sleep apnea, and that one can actually think about hypocapnic central sleep apnea beyond a phenotypic spectrum with obstructive sleep apnea, with many patients having overlapping features of both obstruction and central component. On the other hand, hypercapnic central sleep apnea, often also known as hyperventilation syndrome, can span etiology from chemoreflex dysfunction to a broad range of neuroanatomical localization, such as central nervous system, peripheral nervous system, neuromuscular junction, and muscle disorders. Dr Monteith: And what are some of the symptoms of central sleep apnea? Do any of them differ from obstructive sleep apnea? Dr Liu: Thank you for asking, that's an excellent question. So certainly, central sleep apnea symptoms can overlap with obstructive sleep apnea symptoms. And of course, given the large range of underlying etiology, often the CSA symptoms depend on the underlying etiology. There may be less snoring compared to obstructive sleep apnea patients, especially the hypocapnic CSA patients. Of course, these patients, like OSA, may have frequent awakenings, gasping and choking their sleep, and nocturia, and so on.These patients may have daytime sleepiness, insomnia-like symptoms, or they could be asymptomatic. Interestingly, the hypocarbnic central sleep apnea patients, they're a bit more prone to have the insomnia-like symptoms, whereas the hypercarbnic central sleep apnea patients, they tend to have a bit more of the daytime sleepiness and morning headaches. Dr Monteith: You spoke about some of the neurological disorders that might be associated with central sleep apnea, like stroke and multiple sclerosis. What about some of the more traditional risk factors associated with obstructive sleep apnea or conditions associated with it, like obesity and hypertension? Or does that just mix the picture? Dr Liu: There is many overlap between risk factors between obstructive sleep apnea and central sleep apnea, and certainly one of the things that I highlight in this article is really that often it's not just black and white, that this could be a spectrum with overlapping disease between both conditions. So certainly, in our neurological world, stroke is the most common thing that may be associated with central sleep apnea. But overall, cardiovascular issues such as heart failure, atrial fibrillation, these things can also be associated with central sleep apnea. And again, from the neurological perspective, if we were to divide from hypocarbnic versus hypercarbnic central sleep apnea, by thinking about the hypercarbic central sleep apnea, again, this is where we're thinking about hypoventilation syndromes. You know, anything that can cause neuromuscular weakness, this is something that we should have a high alarm for, that potentially there may be a hypoventilation component. So, things like any myasthenic syndromes and ALS. Dr Monteith: Great. Why don't we also talk about the classification? When was the last time central sleep apnea's classification was updated, and what should we know about the classification? Dr Liu: The most recent classification for central sleep apnea is written in the International Classification of Sleep Disorders, third edition. In this edition, it's classified with six central sleep apnea syndromes. So, these are the CSA with Cheyne-Stoke breathing, CSA due to high altitude periodic breathing, primary CSA, CSA due to medication or substance, CSA due to medical disorder without Cheyne-Stoke breathing, and treatment-emergent central sleep apnea. These classifications more so describe the circumstance of when CSA occurs. A more etiological classification that we can consider would be classifying them by the underlying pathophysiology, which is dividing this from hypercarbnic central sleep apnea versus a hypocarbnic central sleep apnea. Certainly, both set of classification are discussed in this article. Dr Monteith: Yeah. You discussed at length, the major physiological factors that our audience is just going to have to read. I don't want them to hear this too much while they're driving or on the treadmill, cause its super high level. But why don't we just start with some very basic factors that we need to know about this circuitry? Dr Liu: Perhaps I can start with this concept of loop gain, which is the most important concept under hypocarbnic central sleep apnea. For any one of my colleagues who's listening to this, they're probably laughing right now cause they think that loop gain is my favorite word. So, loop gain is an engineering term referring to the sensitivity of a feedback loop. So, in the context of sleep medicine, this is an overly sensitive respiratory control to carbon dioxide and oxygen fluctuation. There are three components. The main one is controller gain. This is a chemosensitivity predominant to CO2. The second is plant gain, which is the lung's effectiveness for carbon dioxide excretion. And the last is what's called the mixing gain. This is circuitry delay from the time the signal travels from the pulmonary artery to the peripheral and central chemoreceptors. So conceptually, one may think, let's say something decreases your ventilation, so for example, apnea or hypopnea. With this, as you can imagine, when you stop breathing, your CO2 builds up, and this builds up according to the curve of the plant gain. And of course, this build of CO2 signal takes time to go from your lung to your chemoreceptor. That's your mixing gain. And of course, here it meets the overly sensitive chemoreceptors. This is your controller gain. As a result, this results in amplification of your ventilation to the initial respiratory disturbance. So, you have a overshoot of ventilation. All of a sudden, you're blowing out too much carbon dioxide, then you become hypocarbnic. At one point, if you blow out way too much carbon dioxide, your CO2 goes below what's called a PCO2 apneic threshold. After this, if your CO2's below, you essentially stop breathing. And of course, after that, you can imagine your CO2s are building up again. So, when this loop goes over and over, you generate what's called a chemoreflex-driven respiratory oscillation, where you create a crescendo, decrescendo-like flow pattern, which is underneath what we see in periodic breathing in central sleep apnea. Dr Monteith: So, without going into too much detail, what is the key way to target restoration of equilibrium? Are there anatomical targets, physiologic targets that we're trying to manipulate here? Dr Liu: Again, thank you very much for that wonderful question. There's certainly many approaches that we could do to improve the stability of the system. Certainly, there are treatments for ventilation, either CPAP or in the case of hypocarbon central sleep apnea, things like adaptive servo ventilation. There is also medications that we can certainly discuss later that can double down the entire system for loop gain. Positional therapy can help for many of these patients. For the appropriate patient, improving their arousal threshold can actually reduce arousal-induced amplification of loop gain. Many of these patients, again, if appropriate, certainly weight loss may be helpful, and these are among many things that we can potentially do to improve the ventilatory stability of these patients. Dr Monteith: Okay, great. But let's also talk about the general overall approach to diagnosing, and much of it is by history, as you mentioned. There's also sometimes a need, as you say, to differentiate out how much is obstructive. So, what is the thinking process there when you're approaching a patient? Dr Liu: So perhaps I can start with in terms of the diagnostic modalities that we could use for this. So, the gold standard for diagnosis of central sleep apnea is still our polysonogram. The home sleep apnea test sometimes may be harder to distinguish between obstructive and central events. In addition, on a PSG, you have EEG. This allows you to assess for sleep quality and arousals, as well as the EMGs, which can help you pick up periodic limb movements of sleep. And of course, all of these things themselves can affect the central sleep apnea and can be a potential treatment factor. Dr Monteith: Before we get into treatment, can you just give us, like, the top five or six drugs or drug classes we need to look for so that, you know, we can discontinue or try something else for our patients that might be complicating their presentation? Dr Liu: Certainly medications, in some cases, can help central sleep apnea, but other cases can certainly be a precipitant of central sleep apnea. So, one thing to consider would be opioid medication. They can certainly cause very complicated central sleep apnea, something called ataxic breathing, where you have irregularity to the tidal volume and the rate of breathing. Other medications such as Oxybate, baclofen, valproic acid, gabapentin, all of which can certainly contribute to central sleep apnea. And of course, in the stroke world, something that we should always think about is that Tetagelor can also contribute to central sleep apnea. And outside of this, things like muscle relaxants, anesthetic agents can also be a contributor. Dr Monteith: Great. Now let's get into some of the treatment. Dr Liu: I like to divide treatment into targeting a hypercarbnic central sleep apnea and a hypocarbonic central sleep apnea. For hypocarbonic central sleep apnea, the first line is CPAP treatment. But for many patients, CPAP therapy is insufficient. There's also adaptive servo ventilation, which is an advanced device designed for hypocarbonic central sleep apnea. For hypercarbic central sleep apnea, again, first line is CPAP treatment, with more advanced devices being a bilevel therapy as well as volume-assured pressure support ventilation. There are also medications that can reduce loop gain, with the most researched one being acetazolamide. We can also reduce arousal thresholds, which could be appropriate for certain patients. And for certain patients, improving arousal threshold can be helpful as, especially in hypocarbic central sleep apnea, that arousals can amplify loop gain. Weight loss can be helpful for both hyper- and hypocarbonic central sleep apnea, and we have great new medication on the market for this. Other therapy can include supplemental oxygen that can be added to PAP devices, as well as phrenic nerve stimulation, positional therapy, as well as carbon dioxide modulation. Dr Monteith: Excellent. So, it sounds like there's a lot of opportunity to help patients. Now, what are you most excited about in terms of latest development for detection as well as for intervention? Dr Liu: Thank you very much. I'm actually excited about many things in sleep medicine. Perhaps the thing that I'm most excited about in detection in sleep medicine would be the wearable technologies. So, these technologies may use photoplethysmography to detect peripheral artertonometry. This is where we're measuring the pulsatile arterial volume signals as a surrogate of cardiac and respiratory function. And when paired, that was often desaturation. With these technologies, we can actually detect the staging, autonomic arousals, and HI. So of course, these technologies do not have flow, and they do not have EEG. But they're very powerful technology that allows us to do multi-night testing from home. And of course, understanding both the potential limitation of these technology in the context of patients can be very useful. In terms of treatment-wise, we're learning so much about the underlying contributing drivers of different forms of central sleep apnea. So again, this is highlighted in my article that many of these patients needs multimodal targeted treatment, both between either a PAP device in addition to other things such as medication, oxygen, positional therapy, and so on. Dr Monteith: Great. So, I mean, I think there's so much to this field. Your article is very extensive. Thank you very much for writing this. I know it may have taken a bit of time, and I appreciate you being on our podcast. Dr Liu: Thank you very much. Dr Monteith: Again today, I've been interviewing Dr. Richard Liu about his article on central sleep apnea. This article appears in the August 2026 Continuum issue on Neurology of Sleep. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Central Sleep Apnea With Dr. Ran R. Liu

Sleep Diagnostics and Monitoring Technology in Obstructive Sleep Apnea With Dr. Joyce K. Lee-Iannotti

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Continuum Audio features conversations with the guest editors and authors of Continuum: Lifelong Learning in Neurology, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. AAN members can earn CME for listening to interviews for review articles and completing the evaluation on the AAN's Online Learning Center.

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