Idiopathic Hypersomnia: Diagnosis & Management

Nancy Foldvary-Schaefer, DO, discusses the often missed or delayed diagnosis of idiopathic hypersomnia and management of this elusive sleep disorder.

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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: Although the reliability of the multiple sleep latency tests, the MSLT, for assessing non-cataplectic central disorders of hypersomnolence is not established, it is the tool most often utilized for individuals suspected of having these debilitating conditions. Some 30 to 40% of idiopathic hypersomnia patients have normal results, which often leads to missed or delayed diagnosis of a specific sleep disorder. In this episode of Neuro Pathways, we're discussing the diagnosis and management of idiopathic hypersomnia and the need for wider acceptance of alternate diagnostic modalities. 

I'm your host Glenn Stevens, neurologist, neuro oncologist in Cleveland Clinic's Neurological Institute. I'm very pleased to have Dr. Nancy Foldvary-Schaefer join me for today's conversation. Dr. Foldvary-Schaefer is the 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: Thanks. Thanks for having me.

Glen Stevens, DO, PhD: Nancy, it's always great to have you here, but for those that don't know you, tell us a little bit about your background and how you made your way to the Cleveland Clinic and what you do on a daily basis.

Nancy Foldvary-Schaefer, DO: Yeah. Sure. So I trained in neurology years and years ago at Loyola in Chicago, and then went to Duke for a neurophysiology fellowship where I spent two years doing EEG epilepsy and sleep disorders. And so ultimately I became board-certified in epilepsy medicine, neurophysiology, brainwave reading, EEG, as well as sleep medicine. So I've to some extent combined my neurophysiology skills and there's a lot of overlap between epilepsy and sleep. And so we've really built a sleep medicine program that has a neurology and neurophysiology expertise, which differentiates us a bit from most other sleep programs.

Glen Stevens, DO, PhD: Yeah, I think that's one of the great things about the sleep program. It's neurologists, it's internists, it's psychiatrists, it's pulmonary people. I mean, it really is a nice multidisciplinary look at things. So somebody comes to see you, they have a specific problem. In one of those areas, you can deviate to the specialist in that area, which makes it very one-stop shopping for patients is very nice. So in my simplistic way, when I look at the word idiopathic hypersomnolence, to me it's, we're not sure what causes it, but I'm sleeping all the time. That's how I look at it. But I know that you're more educated than I. So give me the educated definition of idiopathic hypersomnolence.

Nancy Foldvary-Schaefer, DO: So idiopathic hypersomnolence or idiopathic hypersomnia is one of the primary central nervous system hypersomnia disorders that's classified by the International Classification of Sleep Disorders, which is in its third edition. And in some ways it is... Well, it's one of those disorders. And the other ones, the ones that people might know more about are narcolepsy type I and narcolepsy type II. And over time now, in fact, and I know we'll speak to this, we've got the first FDA approved drug for idiopathic hypersomnia. We've seen many more patients presenting with a question about idiopathic hypersomnia. And there's, as a result of that much more research happening in the scientific community about IH and how to differentiate IH from the narcolepsies and how to better understand the underlying pathophysiology of IH, which is very much poorly understood. What we do know is that there is a clinical phenotype that meets criteria for idiopathic hypersomnia. There are diagnostic testing that can confirm it. We'll talk about the limitations of that. What we don't understand is what's the underlying biology of it relative to narcolepsy, which is much better elucidated.

Glen Stevens, DO, PhD: Well, I'm very confident that you're going to figure that out for us, at some point.

Nancy Foldvary-Schaefer, DO: We're going to crack the case.

Glen Stevens, DO, PhD: And you need to stay on staff until that is done. So we talked a little bit in the intro about this thing called the multiple sleep latency test, the MSLT. Tell us a little bit about what that is and why you believe or feel that it's probably not the ideal test to use for diagnosing these idiopathic hypersomnia cases.

Nancy Foldvary-Schaefer, DO: Well, a polysomnogram, an overnight sleep study followed by the next morning by a multiple sleep latency test is the gold standard test for confirmation of the diagnosis of narcolepsy, specifically narcolepsy type I. It was developed for narcolepsy. It's been extrapolated... Because of the lack of other better tests, it's been extrapolated in the U.S. for use for any person coming for an objective evaluation of hypersomnia or excessive daytime sleepiness, excessive need to sleep. But what we've learned in some recent studies, including looking at our own data, is that patients with idiopathic hypersomnia, about a third of them, can have a negative MSLT and therefore tend to not get a diagnosis. And they may come back and they may come back again and again. 

And one of the cases that we've talked about recently here was a patient who had three series of PSG followed by an MSLT, which is almost a 24-hour test. It's a labor and intensive test and a costly test that was negative three times until we tried a different type of test and confirmed the diagnosis that way. And the big challenge here is that these are patients who are very disabled often by their sleep-wake complaints. And so lack of a diagnosis can lead to years of poor school performance, poor work performance, depression, just very poor quality of life. And we've seen this over and over again. And I think the scientific community is really beginning to recognize that we're really missing the boat here in terms of finding more accurate ways of diagnosing these patients earlier so that we can treat them now that we have medications and reduce their disability.

Glen Stevens, DO, PhD: So in a simple term, this test, this sleep latency test, tells you what? It tells you how quickly you fall asleep? Or is that what it primarily tells you?

Nancy Foldvary-Schaefer, DO: The MSLT is a test that's done on our very rigorous circumstances inside the sleep laboratory. It consists of five naps at two hour intervals. So a patient having this is going to be in the lab for most of the day after the overnight sleep study, and they're allowed to be comfortable in the lab. The lights get dimmed, there's a standard process and they're allowed to dose. And then each nap trial will end after generally a 20-minute period of time, unless if the patient falls asleep earlier. So we are measuring the latency, the time it takes for someone to achieve sleep on the sleep study. And then we average that over the five naps and we get a mean sleep latency. And then we measure whether or not a sleep onset REM periods, whether we see REM on the MSLT, which is the hallmark of narcolepsy, but not of idiopathic hypersomnia.

Glen Stevens, DO, PhD: Right. So with the IH, you would not see the early REM, how fast or how long does it take them typically to fall asleep?

Nancy Foldvary-Schaefer, DO: Well, the American Academy of Sleep Medicine standards require a mean sleep latency of eight minutes or less. But the interesting thing about idiopathic hypersomnia patients is that they often talk about being able to sleep anytime, but not having that sleep attack like the narcolepsy patient has, where their narcolepsy patients fighting off sleep, maybe dozing without even realizing it. IH patients feel sleepy but may not fall asleep on a 20-minute nap. And that's the difference, which is why probably many of these MSLTs are unremarkable or barely meet criteria, whereas the narcolepsy patient, especially narcolepsy type I, often has an abnormal study the first time they're ever in the sleep lab.

Glen Stevens, DO, PhD: So it sounds like a very good test to differentiate that group.

Nancy Foldvary-Schaefer, DO: Yes.

Glen Stevens, DO, PhD: But maybe not so much for the IH group. Now, I know that in the Sleep Center there's been a lot of movement of doing home testing, those types things. Can you do the MSLT at home or no?

Nancy Foldvary-Schaefer, DO: No. The MSLT is done under very standard circumstances. There's a lights out and then it has to end at a certain time. Patient can't have distractions. There should be meals at standard time, so the patient's not hungry. So it really needs to be done in the sleep laboratory and it needs to be preceded by an overnight polysomnogram that rules out sleep apnea, ensures there's enough sleep time to make it a valid test, ensures that there aren't other disorders in a home sleep test. Even if we could do an MSLT or a version of an MSLT at home, the home sleep test as we know it, which is just sensors for breathing and oximeter would not be adequate. So it's really a labor-intensive test and it should be preceded by, and we've been doing actigraphy now for years at the Cleveland Clinic. Actigraphy, or at least a sleep log for seven days before testing should be done even before the patient comes in for the overnight polysomnogram.

Glen Stevens, DO, PhD: So we'll get to the actigraphy in a second. One of the things that I've been irritated by is I can never sleep on a long flight.

Nancy Foldvary-Schaefer, DO: Oh.

Glen Stevens, DO, PhD: I know, I know. But now that I've gone through this information, I'm feeling better because when I look over and the guy's asleep right away on the plane, he's probably got IH.

Nancy Foldvary-Schaefer, DO: Or narcolepsy.

Glen Stevens, DO, PhD: Or narcolepsy. So I should feel bad for him and I should be happy that I'm not falling asleep right away. So if I have IH, how much sleep is too much sleep? How many hours? And I guess I have to feel not rested when I wake up. What's the definition?

Nancy Foldvary-Schaefer, DO: Well, on testing, the requirement for testing, which would be on actigraphy or an expanded polysomnogram, if the MSLT is not abnormal, would be 11 hours. But the clinical criteria have changed over time. And of course laboratory criteria have changed, too. There is a subset of idiopathic hypersomnia patients that have what we call long sleep time. And these are the 10-hour plus sleepers - 10, 12, 14 hours at a 24-hour period. There are patients who otherwise have the phenotype of idiopathic hypersomnia and objective abnormalities in the laboratory who sleep less, who sleep eight, nine hours. It doesn't seem like there are significant differences between these groups.

And in fact, in clinical trials of one of the medications that we'll discuss, both groups responded well to medication. But we generally think of the IH patient as being a deeper, longer sleeper than the narcoleptic. And when IH patients nap during the day, in fact many choose not to nap because their naps make them feel more groggy and they wake up with this sleep inertia or sleep drunkenness, which is one of the key clinical criteria that differentiates IH from narcolepsy, which is really miserable to have to kind of be in that groggy state and then kind of work yourself awake, which can take many minutes or even hours for IH patients.

Glen Stevens, DO, PhD: So if you look at the IH's PSG, can you look at that and determine what level of sleep they're in? Can that give you a clue or it's not part of the criteria?

Nancy Foldvary-Schaefer, DO: It's really not part of the criteria. The IH patient has a higher sleep efficiency in the sleep lab, so I look for that. I look for more deeper sleep and less arousals. In fact, we've got a computer scientist now in our group who is a machine learning expert and he's doing machine learning on our polysomnogram/EEGs and others have done this earlier too, to see if we can find biomarkers in the sleep lab that would help us differentiate IH, yeah, from narcolepsy and from other undifferentiated hypersomnias to advance the field. And this is where we're all going with our data, but this is an area of interest for AI using the many, many, many signals we acquire in a polysomnogram to try to make smarter diagnoses, combining it with clinical data and other types of data that we collect on sleep patients.

Glen Stevens, DO, PhD: You mentioned the actigraphy. Tell us a little bit about that. That's a sensor that's monitoring motion.

Nancy Foldvary-Schaefer, DO: Yes.

Glen Stevens, DO, PhD: Right?

Nancy Foldvary-Schaefer, DO: Yes. So our actigraphs are watches and they collect data over 7, 14, 21 days. We tend to record two weeks of actigraphy before these hypersomnia evaluations. And by that I mean the overnight sleep study followed by the MSLT.

Glen Stevens, DO, PhD: So you do that first?

Nancy Foldvary-Schaefer, DO: We do it immediately before that. And we're doing this for a couple of reasons. We're doing it because even though patients may report to us that they are not chronically sleep-deprived, we know that in our country, 30 to 40% of adults are chronically sleep-deprived. So a hypersomnia evaluation in the setting of chronic sleep deprivation is really invalid. So we really need to address chronic sleep deprivation. The other thing we need to do is identify circadian rhythm disorders. So some people in this hypersomnia category are going to be sort of night owls, delayed sleep phase patients or patients who have otherwise abnormal circadian rhythms and they're in a separate sleep disorder category. And we would not make a diagnosis of IH or narcolepsy in the setting of one of those disorders. And so we're using actigraphy for both of those reasons. 

We found really interesting things. We found a significant number of patients whose sleep log and actigraph do not match where the actigraphy is leading to a diagnosis that would be different if we didn't have the actigraphy. And this is a challenge. I mean, we're pleased to be doing these. We think it's adding to the quality of care we provide. Most centers don't. A few do. And the challenge with that currently is that while actigraphy has a CPT code, most payers are not reimbursing for it. We make it very reasonable financially for patients. So the need for actigraphy doesn't turn them away from getting a diagnostic evaluation, but it's not yet something that's accepted by payers, that's accepted to be part of the evaluation, although it should be.

Glen Stevens, DO, PhD: Is there any data to support dominant versus non-dominant arm or arm versus leg?

Nancy Foldvary-Schaefer, DO: It's by definition put on the non-dominant arm and we're quantifying the kind of amount of time that the watch is very inactive at night and assuming that that's sleep time. And then our psychologist in the sleep lab also will quantify the amount of time during the wake period where there is no motion. And we use that as a surrogate for napping. And one of the diagnostic criteria for IH is having at least 11 hours in a 24-hour period on average of assumed to be sleep time by actigraphy. So sometimes we make the diagnosis based on the actigraph when the MSLT was negative.

Glen Stevens, DO, PhD: And there's a test called a psychomotor vigilance test that you can also utilize. Tell us about that.

Nancy Foldvary-Schaefer, DO: Yeah, so we don't use this in our lab and it's really done for research purposes, but the Europeans have done a lot of work on idiopathic hypersomnia and narcolepsy, and there is a study that showed that testing people with PVT at periods associated with the MSLT more reliably identified idiopathic hypersomnia than the MSLT. So it's just moving us toward thinking about alternative ways to diagnose these patients. The other thing that the French have done, which we've dabbled with a little bit here, is they've developed an expanded polysomnography protocol whereby people come into the sleep lab and have a PSG and an MSLT, and then they go into a 32-hour, which is an extended polysomnogram protocol. I've done this on two patients who had classic IH phenotype, repeated negative MSLTs who both met the cut point for idiopathic hypersomnia, which is sleep for at least 19 hours in a 32-hour period. And that test led them toward effective therapy that they otherwise were not getting because of the classic negative MSLT.

Glen Stevens, DO, PhD: So with your experience, if you are going to test me for IH, insurance isn't an issue, how should I be tested? What would you-

Nancy Foldvary-Schaefer, DO: We'd probably just stick you in the lab for like a week and close the door.

If insurance was not an issue, I think we would be doing extended polysomnography, so we would be doing more longer recordings. And instead of the MSLT where you tell the patient they can go to sleep and then wake them up and then make them stay awake and then they do it all over again, we would probably be doing 24-hour polysomnography where the test is done at night as usual. But then the daytime recording is sort of a sleep ad lib sort of thing. The technologists don't interrupt the patients. You can kind of rest as you'd like, and we'd probably be identifying these patients much more effectively.

Glen Stevens, DO, PhD: And is this pie in the sky or is this something that would be possible? Are there advocate groups out there? Is there anybody pushing for this?

Nancy Foldvary-Schaefer, DO: Well, this is something that our European colleagues have developed very elaborate protocols in some cases, I think because of the fixed criteria that is recognized by the American Academy of Sleep Medicine, although there's been some modification of the definitions in recent years, and then our payers in the United States, this is something that I think is going to take a lot of effort to shift. But there are foundations and funding organizations that are now requesting applications for alternative test measures. There's a recognition in the scientific community, undoubtedly in the sleep field that this is an area where there's a huge gap and that we need to explore, not only the neurophysiology behind this, but also the neurobiology and new pharmacological therapies because this is an unmet need in the sleep field.

Glen Stevens, DO, PhD: Epworth Sleepiness Scale, is that helpful? I mean, can you just look at that and you can see what someone has put down? You could say just based on the information they provide, I have a 50% sensitivity or specificity, is it helpful, not helpful?

Nancy Foldvary-Schaefer, DO: Well, the Epworth Sleepiness Scale is helpful in a few situations. It tends to have very high scores for people with narcolepsy. Scores are more variable, but they can be high in people with idiopathic hypersomnia. There's a scale developed by the French that's called idiopathic hypersomnia severity scale that is a little bit more labor-intensive than the Epworth Sleepiness Scale. We're going to be adopting it inside our patient enter data here at Cleveland Clinic soon. But that really tests the specific, not just how fast you dose, which is the Epworth Sleepiness Scale, but this other questionnaire really gets to the specific diagnostic criteria of idiopathic hypersomnia. Which is this sort of excessive need to sleep, sleep inertia, the cognitive impairment that's associated with idiopathic hypersomnia. So those are features of IH that differentiate it from narcolepsy, and that often can be missed in a very quick clinical interview. Patients with IH have also autonomic dysfunction, and so they'll report a lot of headache and dysautonomia, brain fog during the day. And as I mentioned, the sleep inertia. And so those things can be captured by other instruments that really aren't widely used clinically yet. But I think we'll be shifting toward developing more subjective information that is going to be more specific to IH than the Epworth Sleepiness Scale is.

Glen Stevens, DO, PhD: So the French seem to be doing pretty well, why?

Nancy Foldvary-Schaefer, DO: The French are doing really well.

Glen Stevens, DO, PhD: Is it the system, the insurance? Is it more freedom to do things, less regulation?

Why are they doing well?

Nancy Foldvary-Schaefer, DO: I think there's a European narcolepsy network with outstanding people that have been dedicated to this kind of work for decades. They've really, in many ways led this area of sleep research in many ways. There's groups in the United States that are very strong as well. I think that there is freedom to establish these protocols where people are in the test environment, in the laboratory environment for a long period of time. We're not used to that. When I've done these 32 hour protocols here, you need to have a technologist who's at least available for the patient, and that's a bed that otherwise might be used for a different kind of study, and the patient stays a second night, which we can't bill for. So we're just dabbling with this here. But I think our payment structure is such that it's impacted our ability to really be innovative in this test environment.

Glen Stevens, DO, PhD: So let's say we have the diagnosis, let's move to treatment.

Nancy Foldvary-Schaefer, DO: Okay.

Glen Stevens, DO, PhD: How do we treat?

Nancy Foldvary-Schaefer, DO: So historically we treated IH like we treated narcolepsy, provided that the insurance company would allow us to use certain medications. But since the traditional stimulants are inexpensive, generally methylphenidate, amphetamines and then Modafinil and armodafinil have been in the market now for 40 years. This was the standard of care until 2021 when lower sodium oxybate, which is one of the two oxybate medications on the market became FDA approved. And the data, it really is very robust and the outcomes were not just daytime sleepiness, but it was instruments specific to idiopathic hypersomnia as well as laboratory evaluations. So lower sodium Oxybate is lower salt oxybate, Xywav made by Jazz Pharmaceuticals. Xyrem was the first drug made by Jazz Pharmaceuticals that came on the market in 2005 or sodium oxybate. And it has obviously a lot of sodium salt in it. Lower sodium oxybate has 92% sodium. And so this became the particular formulation that was FDA approved for idiopathic hypersomnia.

Glen Stevens, DO, PhD: And it's stimulating the noradrenergic system or what's the mechanism?

Nancy Foldvary-Schaefer, DO: Yeah, it's interesting. Not completely understood, but it has an effect on probably the dopamine system, the serotonergic system. It probably modulates GABA, specifically GABA-B. It is a derivative of gamma-hydroxybutyrate, which is the date rape drug. And it's formulated and it was developed in collaboration with Jazz Pharmaceuticals and the FDA over a long period of time to be liquid formulation that is not dissolvable, so it's not able to be misused, and it's actually very safe. Its Class III, its Schedule III, whereas methylphenidate and amphetamine are Schedule II drugs. So potentially more concerning in terms of tolerance. And so this is a drug that has been proven to be very effective over a long period of time, safe despite the background of the development of this drug. And it's really the drug of choice. But in the United States, we have payers that require that patients have tried other things first, which is usually a traditional stimulant or modafinil, armodafinil.

Glen Stevens, DO, PhD: And do patients self-medicate? And if so, what do they use?

Nancy Foldvary-Schaefer, DO: I think most patients who self-medicate with any of the hypersomnias are using caffeine, but caffeine doesn't... Many of these patients are also... The IH patients have a little dysautonomia. So some of them can't tolerate a lot of traditional stimulant anyway. And so in the end of the day, people often are changing their lifestyles a little bit to fit their sleep disorder. In fact, my colleague Alicia Roth, who's a psychologist in the Sleep Disorders Center is developing cognitive behavioral therapy for hypersomnia. So we've long had CBT-I, cognitive behavioral therapy for insomnia. Now, there's a shift toward developing behavioral strategies, CBT for this population of patients because they tend to be presenting in their second, third decade of life. They tend to be socially adversely affected by this disorder. They don't have really the energy to socialize and do much more than what the core requirements are for the day, whether it's school or work. And so there's a lot of probably psychosocial support that we can develop, some of which can be evidence-based that can also enhance the care of these patients.

Glen Stevens, DO, PhD: So I probably should ask you this at a start, but what percentage of population probably has this type of disorder?

Nancy Foldvary-Schaefer, DO: Well, it's probably estimated that maybe one or two in a thousand people have narcolepsy, and IH is estimated to be about a fifth of that. But I think we really don't know. There was a large American adult questionnaire several years ago that was published that I think included 16,000 adults who did some subjective assessments of sleepiness. And in the end, after excluding sleep disorders that are other sleep disorders, sleep apnea, and maybe circadian rhythm disorders, things like shift work, it was estimated that maybe 1% of the population would meet criteria for a central nervous system disorder of hypersomnolence, which is huge. 

It's quite prevalent, but I think we're missing a lot of these cases. They're costly evaluations. People don't know much about these sleep disorders, referring providers like primary care may miss it. And in the end of the day, many of these people come and they say, "I've been talking to my doctor for years or I've seen other sleep doctors," and they feel they've been written off as lazy or just not motivated. And so it really is a difficult diagnosis to pin down, and we don't understand the prevalence for that reason.

Glen Stevens, DO, PhD: Is there a higher incidence of accidental death in these patients?

Nancy Foldvary-Schaefer, DO: That I don't know. But there's emerging data in the narcolepsy subset, and this might be due to the lack of orexin in the hypothalamus, that there is a comorbidity of cardiovascular disease that is now recognized that wasn't. Obesity, that presents kind of rapidly in the course of narcolepsy presentation. But I think we're just beginning to sort of begin to understand over observational studies really what the natural history of IH is.

Glen Stevens, DO, PhD: Yeah, that was actually going to be my next question. Does it co-mingle with other disorders?

Nancy Foldvary-Schaefer, DO: Well, we certainly know that there's a high prevalence of psychiatric disease, anxiety, depression, and other kinds of substance abuse with all the hypersomnias. But I don't think we really have good established data on other organ systems.

Glen Stevens, DO, PhD: And other novel treatments on the horizon.

Nancy Foldvary-Schaefer, DO: There are a few, so clinical trials ended last year for pitolisant, which is a histamine agonist drug that's FDA approved for narcolepsy. So the FDA is reviewing those multicenter trials. And then we are in the midst now, probably soon to be wrapping up studiesm with an orexin agonist drug. And those were including initially, not just narcolepsy, but also idiopathic hypersomnia. So what's been very interesting is that since the FDA approval of lower sodium oxybate for IH, there has been a lot more interest in idiopathic hypersomnia and other pharmaceutical companies who are developing other kinds of wake promoting agents have recognized this huge unmet need for IH. And so generally, while they develop protocols for narcolepsy, we're also seeing protocols developed for IH.

Glen Stevens, DO, PhD: Final words of advice for our listeners? Key points you want to highlight?

Nancy Foldvary-Schaefer, DO: Yeah. I think one of the key points is that patients will present with excessive daytime sleepiness. And there are disorders other than narcolepsy, probably rarer than narcolepsy, but they exist. And it's important to really take a comprehensive history and make sure that you're tailoring your sleep studies. I think this is a really important point. All sleep labs aren't the same. And so we're fortunate here at the Cleveland Clinic to have really expert technologists and facilities that allow us to do these more elaborate kind of evaluations. Most of the time when I see results from other places, and I think that the diagnosis might've been missed, it was perhaps a flaw in the way the test was planned. And so it's important these patients have very planned tests. They need to be off medicines that are affecting the test. They should have actigraphy or a sleep log in advance. And so search out for the right sleep program that's closest to you to make sure that your patients are getting optimal recordings.

Glen Stevens, DO, PhD: Okay. Well, Nancy, thanks for sharing your insights with us today. I'm sure it's been very helpful for those who see these patients, and it's good to see that there's some hope on the horizon as it moves forward. And as always, I enjoy our time together. Thank you very much.

Nancy Foldvary-Schaefer, DO: Thank you. I'll hold that bed for you.

Closing: 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 podcast. And don't forget, you can access realtime 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.