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JOHN WHYTE: Welcome, everyone. I'm Dr. John Whyte, Chief Medical Officer at WebMD. Narcolepsy is a chronic sleep condition that impacts hundreds of thousands of people here in the United States. It can significantly impact their quality of life and impact their day to day functioning. So today, I want to talk about the signs and symptoms of narcolepsy. What's the diagnostic criteria? What are the current treatments? And what may be on the horizon?

And to help me do that, I've called upon to experts. Dr. Luis Ortiz, he's a sleep expert, an internist, a pediatrician, a pulmonologist at Johns Hopkins. And Dr. Lois Krahn, she's also a sleep expert and a professor of psychiatry at Mayo. Thanks for joining me.

LUIS ORTIZ: Thank you for having us.

LOIS KRAHN: Thank you.

JOHN WHYTE: Dr. Krahn, let's start off and remind people-- what do we mean by narcolepsy? What are the signs and symptoms?

LOIS KRAHN: Narcolepsy is a disorder where patients have excessive daytime sleepiness often associated with poor nighttime sleep, episodes of weakness, and vivid dreams. And it's a lifelong condition once it develops.

JOHN WHYTE: And Dr. Ortiz, what about people that are listening, saying, I'm sleepy. Maybe I have narcolepsy. Or I have sleep apnea. Is that the same thing? Help us understand those differences.

LUIS ORTIZ: So narcolepsy is more than just being sleepy. A person with narcolepsy who gets an adequate amount of sleep every night, they may wake up refreshed. They may feel great. And they may be feeling ready to take on the day. But a few hours later, they feel as if they hadn't slept in a day. And they desperately need that sleep before they can function again. They may take that nap. They may wake up 20 minutes later. They may wake up 40 minutes later. When they wake up, they usually feel good. They usually feel refreshed. Only for a certain time later, they feel that same feeling as if they hadn't slept in a day returns. And they have to drop everything to sleep again.

JOHN WHYTE: And it's a condition that can occur in children and adults. How do we recognize it in children?

LUIS ORTIZ: And it's very difficult to recognize it in children. And that what is usually what leads to such a long delay in diagnosis. On average, it takes about 10 years from onset of symptoms to actual diagnosis. In children, one sign could be return of napping. So typically in the United States, children stop taking naps at around age five. And when you see it in children, the parent may say, well, my child had stopped napping at age five. He's now nine or 10 years old. He's starting to nap again.

JOHN WHYTE: So why is it taking 10 years for the average person to be diagnosed?

LOIS KRAHN: There is a fundamental problem in that if someone has sleepiness, the first assumption is that they aren't going to bed on time and are burning the candle at both ends. And unfortunately, that is what is assumed rather than the possibility of a medical disorder like narcolepsy. And that has been a very hard hurdle to overcome.

JOHN WHYTE: Do we see epidemiologic differences around the world?

LUIS ORTIZ: So yeah, actually, there is a very-- so in the United States, it's estimated to be one in 2000. There seems to be a higher-- it's more frequent at least in Japan where it was estimated to be like one in 500, whereas in the Middle East, it seems to be rarer. However, if you're looking at just the United States or North America, it affects the second decade of life and then at the end of the third decade of life. And then but ages, genders, and races-- it doesn't seem to have a preference.

LOIS KRAHN: And I'll just say, because this is chronic disease, there are people who are in their 80s and 90s who have lived with narcolepsy since they were teenagers.

LUIS ORTIZ: Yeah, and they lived their whole lives, and they never know. And some of them are more fortunate. They have really good support systems, and they're able to overcome it without medications. They're able to find a job that can support their need for napping, whereas others, they live their whole lives thinking that they were failures because they can't keep a job. They can't raise their family well. And that's what we want to prevent. That's really what the end goal of treatment of narcolepsy. You can still feel sleepy. You may still feel like you wish you can be more awake. By the end of the day, we want people to be able to say that they're able to live a life that they're happy with. And if a patient says that they're not there yet, that means we still have more work to do.

JOHN WHYTE: Walk us through the diagnosis of narcolepsy. Someone is watching the show and thinking maybe they have it. Maybe a member of their family does. What are the diagnostic tests that should be done?

LUIS ORTIZ: So after being evaluated by a sleep physician, the patient would typically undergo two weeks of actigraphy monitoring. It's a device that tracks movement of the arm. And so, as you can expect when you're awake, there'll be more movement than compared to when you're asleep. That way, we can correlate that to wake and sleep. So this way, we can actually correlate if they're actually getting sufficient amount of sleep at night and through the week. The next portion of the evaluation involves an overnight polysomnogram. A polysomnogram, sometimes called a sleep test, measures different aspects of physociology, brainwave activity, heart rate, respiratory rate, airflow going in and out of the nose and mouth, oxygen levels, carbon dioxide levels in children, and physical movement during sleep. And we also video it at the same time. This has been the standard method of evaluation for narcolepsy for several years. However, recently, a commercial lab has been developed for evaluation of type 1 narcolepsy in that we can perform a cerebral spinal fluid analysis for hypocretin. Hypocretin is a neural hormone that is deficient in people with narcolepsy.

JOHN WHYTE: So there's type 1. Is there also a type 2? Type 1 narcolepsy is also known as narcolepsy with cataplexy. However, the actual etiology and way of diagnosing it is a deficiency of hypocretin. And so, below two standard deviations of what is expected of normal, you have type 1 narcolepsy regardless if you ever manifested symptoms of cataplexy. Type 2 narcolepsy is otherwise known as narcolepsy without cataplexy. So if you were to do a spinal fluid analysis of their hypocretin levels, they may have normal or maybe low normal levels but they don't have a very severely low levels of hypocretin. And they don't have cataplexy as well.

JOHN WHYTE: Dr. Krahn, is hypocretin the cause of narcolepsy? Do we know enough? We know that hypocretin levels are decreased in patients with narcolepsy cataplexy. Whether that's the cause or just an indicator of the disease is unknown. However, hypocretin plays an important role. And it's been an area of research that's ongoing. Can you help our audience understand what we mean by cataplexy and how that's often a symptom associated with narcolepsy?

LOIS KRAHN: So cataplexy is abrupt muscle weakness triggered by an emotion. I'll give an example. Someone is very excited. They're running in a race. They're about to win. And the feeling causes them to become awkward. They can't move their legs in the way they would before. And instead of running, they stumble.

JOHN WHYTE: Do we know the triggers for cataplexy?

LOIS KRAHN: So they tend to be strong emotions, interestingly, more commonly, positive emotions like laughter, humor. But sometimes, it can be surprise, fear, and anger. And a person gets upset or has the strong emotion, and then very abruptly cannot control all of their muscles.

JOHN WHYTE: Dr. Ortiz, what are the current treatment options? LUIS ORTIZ: So there are a wide variety of different treatment options. However, they are categorically mostly in the stimulant class of medications. We have the very older medications such as amphetamines and methylphenidate. But we also have newer medications that target the dopamine and norepinephrine systems of the brain to activate the circuits in the brain that promote wakefulness. We also have oxybate medications, oxybate products, that do the inverse. They actually stimulate gaba systems that actually promote sleep. The thought process with this medication is that it can potentially correct the sleep aberrations that we see in people with narcolepsy. And then, during the daytime, it kind of improves the activity of the wakefulness systems in the brain during the day. And most recently, there's been research into using orexin or hypocretin agonists as a way of replacing what was lost in narcolepsy.

JOHN WHYTE: And how effective are these current treatments? LUIS ORTIZ: So it varies from person to person, unfortunately. Some patients may do absolutely fine with amphetamines or methylphenidate. And their functionality is perfect for them. Other people, the only thing they get is side effects. And they need to go on to some of the newer medications. And a lot of it is, when working with patients with narcolepsy, it's a matter of trying to balance the effectiveness with side effects.

JOHN WHYTE: Dr. Krahn, what about the role of lifestyle? You do diet, exercise. Lifestyle, does that have a role in the treatment of narcolepsy either as a primary treatment or as an adjunct? What's the latest on it?

LOIS KRAHN: So lifestyle is important. It's rarely enough by itself. And the key thing is that patients need to make getting enough sleep a high priority. Narcolepsy patients sometimes struggle to stay asleep at night. Sometimes medications can be used to help them sleep better. They have to make sure that they have created the opportunity to get to bed, to stay in bed. Also, exercise has been proven to be helpful in combination with medications. There are some reports of dietary manipulations, but that likely is not as powerful as getting enough sleep and using exercise strategically.

JOHN WHYTE: So how do we make sleep a priority? Sleep always seems to be the last thing that people pay attention to. I'll do it later. Can we catch up on the weekends? Why aren't we having a priority on sleep?

LOIS KRAHN: So I would offer that many people don't understand the value of sleep. I think we have to appreciate that the brain is active during sleep. There's a rinsing process that allows us to wake up and feel refreshed. And if we shortchange ourselves on sleep, we're going to shortchange our brain in going through that cycle. And it's not surprising that when people wake up in the morning, they can feel pretty dreadful. And that can persist during the entire day as they struggle.

JOHN WHYTE: Dr. Ortiz, we always like to talk about the latest research. What might be on the horizon? Do you see more effective therapies coming on board soon, or a wider range of therapies?

LUIS ORTIZ: Last year, there was already two new products specifically to treat narcolepsy released and many more on the horizon. Specifically, there's some nighttime medication, oxybate products. Typically, these are medications that have high sodium content, which is a limiting factor for certain patients. But there's already been, this year, released a low sodium oxybate product that can be taken by people with hypertension. So those are some that's in the near future. In a little, not so near future, but still coming up pretty soon are the orexin agonist that basically will stimulate the receptors that are tied to orexin, which is what is assumed to be missing in narcolepsy. And so the thought is that you give the patient this product, and it's going to significantly improve their sleepiness. As the landscape expands, the idea is that there will be something for everyone with narcolepsy so that they can live effective lives.

JOHN WHYTE: Well, we know that narcolepsy impacts people's quality of life. We know that it's undiagnosed. We know we have effective therapies and more therapies coming on the horizon. What do you both want to leave our listeners with?

LUIS ORTIZ: So with evaluation and good treatment, it is possible to live a full and productive life. I myself have type 1 narcolepsy. It was a struggle. It was a struggle finding what worked best for me. It was definitely a struggle to go through medical school. But working with your physician and being able to achieve a good balance of lifestyle and medications, you can achieve what you want in life.

LOIS KRAHN: Well, I would just like to focus on excessive sleepiness. If someone is sleepy all the time, think about it. It may be a medical disorder. And that is a sign to go get evaluated. That's the single symptom that all patients with narcolepsy as well as people with other sleep disorders have. And that's not normal.

JOHN WHYTE: Dr. Ortiz, where can listeners go to get more information and support about narcolepsy?

LUIS ORTIZ: Narcolepsy Network is the largest patient advocacy organization for people with narcolepsy. We provide support groups, education, and resources for, not only for people with narcolepsy, but their support network and also physicians. We do a lot of online support groups so that people with narcolepsy can meet other people with narcolepsy. A lot of times, someone with narcolepsy, they're the only one they know that has narcolepsy. And so it's the most validating feeling in the world to be able to tell your story to someone, and someone else says, "I know. I do the exact same thing. That's happened to me, too." And there's so many of us out there that just connecting can make a big difference.

JOHN WHYTE: Well, I want to thank you both for taking time to share your insights about narcolepsy and how we can get people diagnosed and treated. Thanks for taking the time today.

LUIS ORTIZ: Thanks for having me.

LOIS KRAHN: Thank you.