Sleep Disorders: Differential Diagnosis in Adults

Podcast Transcript

Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.

Glen Stevens, DO, PhD:

Sleep plays a fundamental role in brain health and function as well as overall quality of life, so early identification and treatment of sleep disorders is crucial. However, because there are a myriad of different sleep disorders, of which many can overlap with primary neurologic conditions, diagnosis and development of an effective treatment plan can be challenging. In today's episode, we'll be discussing differential diagnosis of sleep disorders in adults. I'm your host Glen Stevens, neurologist, neuro oncologist in Cleveland Clinic's Neurological Institute. I'm very pleased to have Dr. Nancy Foldvary-Schafer join me for today's conversation. Dr. Foldvary-Schaefer, is director of the Sleep Disorder Center and a staff neurologist in the Epilepsy Center within Cleveland Clinic's Neurological Institute. Nancy, welcome to Neuro Pathways.

Nancy Foldvary-Schaefer, DO, MS:

Thank you. It's my pleasure to be here.

Glen Stevens, DO, PhD:

So Nancy, just for our listeners out there, tell us just a little bit about yourself, where you did your training, how you made your way to Cleveland.

Nancy Foldvary-Schaefer, DO, MS:

Well, I trained in neurology at Loyola in Chicago, and then completed a two year neurophysiology fellowship at Duke, and then came to the Cleveland Clinic. So, I've served in both the epilepsy center and the sleep disorder center since I came many years ago.

Glen Stevens, DO, PhD:

Well, it's our pleasure to have you here, and it's always great to chat with you. So when I'm on hospital service, I always ask the residents, I've started doing this, I always ask the residents, usually the first or second day that I'm on, I go through and I'll ask them and the medical students, how many hours did they sleep the night before. And I think probably the average number that I'm hearing that they tell me is probably six, I think is what the average is. So just as a background, how much sleep should they be getting?

Nancy Foldvary-Schaefer, DO, MS:

Well, sleep needs are actually genetically determined. So, most of us know how much we need because we know how we feel when we don't get that magic number. The National Sleep Foundation a few years ago established new norms. And for adults, especially younger adults, the range is seven to nine hours. But again, there's variation in between individuals. For older adults, that range is seven to eight hours. And certainly under the age of 18, sleep needs are much greater. There was a study a few years ago that demonstrated that in the United States, about 40% of adult Americans were getting six hours or less of sleep, which is significant sleep deprivation. We know that amount of sleep is associated with a host of social issues, as well as medical and psychiatric illnesses.

Glen Stevens, DO, PhD:

So, maybe I shouldn't tell you how many hours I'm sleeping now, but I guess I can just say it's my genetics and I don't need to sleep as much, or maybe I'm just lying to myself and I should sleep more.

Nancy Foldvary-Schaefer, DO, MS:

You are probably lying to yourself, but in fact, sleep need is sort of distributed along a bell-shaped curve. So while most of us fall in that seven to nine hour range, probably one to 2% of the population is genetically short sleeper, four, five hours. And these folks function optimally, and on a measurements of function would be functioning optimally. They don't just think they're functioning optimally. And then one to 2% are long sleepers, genetically wired to need more like nine or 10 hours of sleep. So, you may be in that special one or 2%, Glen, or you may be fooling yourself.

Glen Stevens, DO, PhD:

I'm definitely fooling myself, Nancy. I also... And we're not going to get into it here, but I also ask them if they know who Libby Zion is and why the duty hours are what they are and the rationale and all that behind it. But again, I think that in medicine, we don't always practice what we preach in this regard. And I think the simple answer is probably really listened to your body. And if it seems to be functioning at the level that you're at, then you're probably doing okay.

Nancy Foldvary-Schaefer, DO, MS:

That's right. That's right. Although when people are very sleep deprived or sleep deprived over long periods of time, humans can misperceive how well they're functioning. And so we hear this often where someone, one of our colleagues or someone may be sleep deprived and may become more moody or may become more impaired in doing small finger movements and tasks that require fine finger movements. And sometimes people don't realize that. Their loved ones may realize it, but we as humans are not so smart at recognizing sleep deprivation in ourselves.

Glen Stevens, DO, PhD:

Well, I guess that's good food for thought for everybody listening out there and can reassess, are they really in that special group or are they just fooling themselves? So, everybody out there, take a deep dive and look at yourself.

Nancy Foldvary-Schaefer, DO, MS:

That's right.

Glen Stevens, DO, PhD:

Optimize. So Nancy, I would imagine that most of us have had experienced or have experienced difficulty with sleep at some point, on and off, for many different reasons, but does it really become a sleep problem or a difficulty or a disorder?

Nancy Foldvary-Schaefer, DO, MS:

Well, most sleep disorders are diagnosed when the symptoms have lasted at least three months. And so for example, most adults have had a night or two in their lives of insomnia, just traumatic life events or whatever the case may be, major stressors, and have trouble sleeping. But when that happens on a regular basis, say three days or nights a week, for at least three months, we would consider that a chronic insomnia problem. And you're right that most people know some symptoms of sleep disorders because we've all experienced them, insomnia being most common. The vast majority of adults have had nights of insomnia, and 10% of adults have chronic insomnia. Almost 30% of adults have sleep apnea. So, those are really the two most common, but there are four other major categories of disorders that most people don't even recognize that can also have significant morbidity.

Glen Stevens, DO, PhD:

So, share those with us.

Nancy Foldvary-Schaefer, DO, MS:

Yes. Those are circadian rhythm disorders, the hypersomnia, so the narcolepsy and related disorders, the sleep related movement disorders of which restless leg syndrome is the primary, and then the parasomnias, REM parasomnias, REM behavior disorder and the non-REM parasomnias, which may be a little bit more benign than behavior disorder. And some of these disorders we now recognize are intimately associated with neurological conditions, which is why it's useful for neurologists to have a little sense of how to take a sleep history, at least how to recognize the big ones, the ones that are the severe hypersomnia, which can coexist in the form of narcolepsy or a medically induced hypersomnia in some patients with neurological conditions and importantly run behavior disorder because it's association with subsequent development of the … which is now a well established phenomenon. And so sometimes in the sleep center, sleep doctors see REM behavior disorder, and then now refer to our colleagues in cognitive neurology or movement disorders when we begin to see or hear about other signs and symptoms of neurological disease, because often they'll be a progression into a clearly defined neurological disease.

Glen Stevens, DO, PhD:

And I don't want to get off track here too much, but certainly see a lot of information in the literature these days about sleep and cognitive problems.

Nancy Foldvary-Schaefer, DO, MS:

Absolutely. This is an emerging area of sleep medicine research. Sleep, particularly non-REM sleep, serves the function within the glymphatic system in our brain of clearing neurotoxins. And there have been some very eloquent studies illustrating on PET studies accumulation of beta amyloid, so the Alzheimer's protein when people are routinely sleeping six hours or less, marked contrast to when you're sleeping seven hours or more. And so we need sleep to restore every cell in every organ of our body. And the lack of sleep is having long-term consequences. We may not realize it until way too late in the game, but sleeping regularly, at least seven hours in middle life is now being shown to be associated with preservation of good cognition as one ages, whereas obstructive sleep apnea untreated for many years and short sleep duration for many years is being associated with mild cognitive impairment and increases the risk of Alzheimer's and otherwise predisposed individuals. So, sleep care becomes a part of brain health over the long haul.

Glen Stevens, DO, PhD:

And I think it's just fascinating. I love science in general, but it seems like it was not that long ago that we didn't even know there are actually lymphatics in the brain.

Nancy Foldvary-Schaefer, DO, MS:

Right.

Glen Stevens, DO, PhD:

I mean, 10 years ago I don't think that we knew this.

Nancy Foldvary-Schaefer, DO, MS:

That's right. The RBD story, the REM behavior disorder story began to evolve more like 20 years ago, but rapidly evolved to now, it's a standard. I mean, we now recognize that RBD,,, we're calling it isolated RBD instead of idiopathic RBD because perhaps there are no cases of idiopathic RBD. All of these patients will develop neurodegeneration, unless if it's a drug induced issue. But the cognitive story has evolved just really in the last maybe five to seven years. And it's quite fascinating and critically important for all neurologists who are trying to optimize brain health in our patients of all ages.

Glen Stevens, DO, PhD:

So, I'm going to take a quick little sidebar because I think you might know the answer to this. I noticed you called it restless leg syndrome. And for a short period of time, they called it a different name. So, the official name is back now to restless leg syndrome?

Nancy Foldvary-Schaefer, DO, MS:

I think so. It's gone back and forth, named after the individuals who named it.

Glen Stevens, DO, PhD:

I think it was just too complicated for everybody.

Nancy Foldvary-Schaefer, DO, MS:

Yeah, it was too complicated. It was too complicated and restless leg syndrome resonates with patients. Oftentimes in the clinic, I just ask people do they have restless leg syndrome. Then I go into the diagnostic criteria. But when you have it, you know you have it right.

Glen Stevens, DO, PhD:

Nancy, what's involved in the diagnostic workup for sleep disorders? What do you do?

Nancy Foldvary-Schaefer, DO, MS:

So, it depends on what the presenting symptoms are and where we're going in terms of those six classes of disorders, the insomnias, the sleep disordered breathing, the hypersomnias, the movement disorders, the parasomnias, the circadian rhythm disorders. For example, insomnias a clinical diagnosis, and we may do a test like actigraphy to track movement over time to measure effects of therapy or to classify it. But there's no need for an in laboratory diagnostic test. In fact, it's not needed. Same with restless leg syndrome. We may measure iron levels with restless leg syndrome and other chemistries, but we would not order a sleep study unless if we're thinking of another disorder. So classically, these sleep disorders like sleep apnea require an in laboratory sleep study or a home sleep apnea test. Patients with hypersomnias, that can include the narcolepsy spectrum as well as the circadian rhythm type patients may require more advanced testing overnight polysomnography that can be tailored, followed by a multiple sleep latency test, preceded by two weeks of actigraphy urine toxicology.

And now, we're even in the sleep center doing dim light melatonin onset to measure the onset of melatonin increase in saliva so that we can better confirm circadian rhythm disorders as well as even gene sites so that we can understand for narcolepsy patients, what their genetic metabolism is in terms of picking and choosing medications, since we have many more medications. Now, one important point about your question is that many don't recognize the difference between the home sleep apnea test and the in-lab test. The home sleep test has one indication, and that is to confirm the diagnosis of obstructive sleep apnea, really moderate to severe obstructive sleep apnea, when there are no other sleep disorders suggested or nothing else under consideration. That is the only thing it's good for. You've got it or you don't.

If you're dealing with a patient who snores and may have sleep apnea, but they have a constellation of other symptoms, they also have insomnia or restless legs, or you don't know if they really have sleep apnea, the in-lab test is appropriate because the home test doesn't record EEG. And so we can't stage sleep during the home test. So, the surrogate number that we get for respiratory events is, by definition, underestimated.

Glen Stevens, DO, PhD:

And the benefit of a sleep diary, are people truthful? Is it helpful? Is it overestimated, underestimated, or generally helpful?

Nancy Foldvary-Schaefer, DO, MS:

Yeah, that's a great question. Most of the time when we do actigraphy, which we're doing now only in the last couple of years, and it's evolving in terms of its utility in the sleep center, most of the time actigraphy correlates pretty well with self-reported sleep diaries. We use them all the time in the sleep center. Certainly, our behavioral sleep medicine team, the sleep psychology team relies on them heavily to not only estimate sleep time for patients and then guide care, but they use the diary to actually provide the next recommendation to get the patient to where they're sleeping well again. And so they can be useful. We typically rely on them more for the insomnias than we do for some of the other sleep disorders. But before a sleep study, particularly a comprehensive test, like a PSG and an MSLT for narcolepsy, we would want to see somebody's diary, in addition to actigraphy, to make sure that that test is going to be valid.

Glen Stevens, DO, PhD:

So, you mentioned the big six. So, the treatments are going to depend on which of the big six you have, but go through some of the treatments for us.

Nancy Foldvary-Schaefer, DO, MS:

Yeah. And many people have more than one of the big six. So, sleep apnea-

Glen Stevens, DO, PhD:

It's just like going to sleep in the big six.

Nancy Foldvary-Schaefer, DO, MS:

Sleep apnea commonly coexist with restless legs and insomnia. And sometimes you can't quiet down the restless legs until you've treated the sleep apnea because the patients sleep deprived. Now that they're sleep deprived, their legs are going to be acting up. There are FDA approved medications for the narcolepsy, for sure, and the hypersomnias. And this is one of the most exciting areas. We've seen three new FDA approved drugs for narcolepsy in the last couple of years. Very exciting that they have different mechanisms of action. The newest is pitolisant, a histamine agonist. Never had a histamine agonist before. Certainly we have the oxidates, sodium oxidate and now lower sodium oxidate. The mechanism of action of that is unclear, but it's a game changing agent, as it's pitolisant for narcolepsy with cataplexy. Last year, lower sodium oxidate was the first FDA approved drug for idiopathic hypersomnia. Critically important because this is a population of patients with high morbidity, poor quality of life, cognitive fog because of their persistent daytime sleepiness and there was no FDA approved drug for that population before.

So, lots of options, emerging options for people with narcolepsy. We certainly have medications that are approved for RLS. And the most important thing about RLS is that very often, patients have coexisting deficiency of iron in the brain, which is why we check ferritin and iron levels and really use iron therapy. We're now doing iron infusions for more and more of those patients. For the sleep apnea patients, CPAP has been the gold standard for a long time, but we're increasingly using more oral appliances. And going back a few years ago, the FDA approved hypoglossal nerve stimulation, so we have a growing number of patients getting implanted with hypoglossal nerve stimulation. The FDA indication on age recently reduced to 18, and they're working on a pediatric indication for hypoglossal nerve stimulation. So, exciting stuff there. And gosh, there are no FDA approved drugs for the parasomnias, but we're really learning a lot about the parasomnias, particularly REM behavior disorder. And the AASM, there's a task force that will release new guidelines for therapy around RBD.

Circadian disorders are also difficult to treat, but there's the first ever multicenter trial for a circadian rhythm drug, specifically for delayed sleep phase, and we are actually going to be opening our site for that drug. So, lots of new things happening in sleep. We still have some of the old standards and the insomnia drugs that we've used for a long time and CPAP, but things are really evolving on all fronts.

Glen Stevens, DO, PhD:

Talk a little bit about behavioral therapies.

Nancy Foldvary-Schaefer, DO, MS:

So, behavioral therapies are very important to most patients with sleep disorders, but they've been most well developed for the insomnias. So, we call this team behavioral sleep medicine, BSM. We've got psychologists in our group, and there are psychologists around the country who are BSM certified and most of what they do is behavioral therapy around insomnia. We developed... Actually, Michelle Drerup, who leads our BSM team, developed Go To Sleep, which is a computerized web-based BSM therapy, CBTI, we call it, cognitive behavioral therapy for insomnia. Very effective, probably as effective as individual therapy over a period of time. And this includes a number of different strategies, ranging from simple awareness of sleep hygiene, good sleep hygiene, to things we call cognitive therapy, sort of resetting in the patient's mind what normal sleep is. Many people with chronic insomnia have that perception that I must sleep eight hours again.

And not everybody really is physiologically required to sleep eight hours. And then of course, therapy around, we call stimulus control, managing the bedroom and making sure you're not using your bed for anything other than sleep, and one other thing. Guess what that is, Dr. Stevens. But not reading and not watching TV and not watching your phone because those are all things that then condition the brain to continue to not sleep well. So, this is a very effective treatment. One of our... My other colleagues, Alicia Roth, is now developing cognitive behavioral therapy for hypersomnia disorders because we know that many of our chronic sleep disorder patients have poor quality of life. They're chronically not achieving the milestones that their their friends and their family members are. And so with that comes mood disorders and just challenges functioning optimally every day.

Glen Stevens, DO, PhD:

Well, I'll give a shout out to your group because I had a patient had a very complicated sleep disorder, difficulty, a lot of problems with the sleep wake cycle, and the psychologist change the patient's life.

Nancy Foldvary-Schaefer, DO, MS:

Yeah, it can be very impactful. It actually is hard work. On the surface, might not seem like it's very hard, but our BSM colleagues work very hard over a long period of time. And a motivated patient is almost always going to gain from that experience. But that's what makes our program so strong and unique. We are very fortunate here in the Neurological Institute to have a multidisciplinary sleep program where providers from various different disciplines come together. Most of my colleagues in the Sleep Center have very unique niches. We just talked about the behavioral sleep medicine team. We've got a pulmonary team, a neurology team. And even within that neurology team, we've got specialists in the parasomnias and the hypersomnias, and other medical conditions like the overlap between sleep and epilepsy, which has been my passion for a long time. But not to forget the contributions of our family medicine and internal medicine colleagues, our psychiatry team, along with our psychologists and our pediatric team. And we collaborate closely with our colleagues in the Head and Neck Institute, both dentistry, as well as surgery.

And together, it's really a formidable team capable of managing from the simplest, commonest sleep disorders to very challenging sleep disorders that often coexist with other serious health conditions, including neurological conditions.

Glen Stevens, DO, PhD:

So, maybe there's not a hard or fast rule for these things, but caffeine, when should we cut it off?

Nancy Foldvary-Schaefer, DO, MS:

It really depends on the individual. So, I know patients who, people who can drink caffeine up until 10 o'clock at night and it doesn't bother them at all. But certainly for the patient with any kind of sleep disruption, and certainly for the insomniac, it should be cut off before noon time or by noon time.

Glen Stevens, DO, PhD:

Exercise?

Nancy Foldvary-Schaefer, DO, MS:

Exercise is important for health and wellness. It's important for good sleep too. But rigorous exercise within a couple hours of bedtime is probably going to be stimulating. So, we suggest that that happens before 7:00 PM or so.

Glen Stevens, DO, PhD:

And eating?

Nancy Foldvary-Schaefer, DO, MS:

Eating also is variable, but most of us who eat close to bedtime either get some reflux or have more fragmented sleep. And so it's better... If your biggest meal of the day is going to be dinner, it probably should be three to four hours before bedtime.

Glen Stevens, DO, PhD:

Maybe we need to use the European model where our big meal is at lunch, right?

Nancy Foldvary-Schaefer, DO, MS:

That's right.

Glen Stevens, DO, PhD:

What about our friend melatonin? My patients love the melatonin. What's the data? Is it helpful, not helpful?

Nancy Foldvary-Schaefer, DO, MS:

So, melatonin is not consistently demonstrated to be helpful for insomnia. And most people use it for insomnia or they just use it because they think it's going to help them sleep better. Where melatonin clearly is helpful is in the circadian rhythm disorders. But when it's administered, for example, for people who are night owls, it needs to be administered in a fairly low dose and early, so 3, 4, 5 hours before one's intended bedtime or one's existing bedtime in order to shift sleep. So oftentimes, people who come to the sleep center are taking melatonin incorrectly. Melatonin is not FDA approved because it's not a prescription drug, but it's not approved formally for use for REM behavior disorder, but we'll see in the new guidelines that it is one of the drugs that can be very effective for REM behavior disorder. And then in that case, the doses are higher, up to 15 milligrams at bedtime.

Glen Stevens, DO, PhD:

Wow. So Nancy, I know you mentioned several novel treatments. Any other novel treatments that we bypassed? I know you went through a lot of things. Anything else that I forgot to ask you about that's coming up?

Nancy Foldvary-Schaefer, DO, MS:

Yeah, there's more clinical trials coming up with devices, oral appliance devices for sleep apnea. We will be seeing other modifications of the hypoglossal nerve stimulator for sure. There is data on pediatric down syndrome patients for hypoglossal nerve stimulation. And these multiple clinical trials, a couple of which are orexin agonists... So, for narcolepsy, specifically narcolepsy type one, classic narcolepsy with cataplexy, we know that this is a disease caused by autoimmune destruction of the hypocretin orexin secreting neurons in the hypothalamus. Now, there are trials ongoing with orexin agonists to augment that orexin signaling again, which is an important neurotransmitter that augments or raises the alertness level and augments the neurotransmitters that are already working on wakefulness. And so this probably also will be game changing therapy for people with the hypersomnia, specifically narcolepsy.

Glen Stevens, DO, PhD:

Nancy, thank you so much for joining me today. It's been insightful as always, and we look forward to hearing about all these new applications and medications that are coming up. Thank you very much.

Nancy Foldvary-Schaefer, DO, MS:

It's my pleasure. Thank you.

Conclusion: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's consultqd.clevelandclinic.org/neuro, or follow us on Twitter @CleClinicMD, all one word. And thank you for listening.