Selects: How Narcolepsy Works

Choosing narcolepsy for this week

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1:37McCormick's signature seasonings make it easier to add bold flavors that make each bite of your meal more delicious. Try the chimichurri blend that elevates grilled meats. Explore the full array of blends and find your favorite at mccormick.com. Hey guys, it's me, Josh. And for this week's Select, I'm going with our May 2020 episode on narcolepsy. It's one of those S-Y-S-K-esque episodes that covers something we've all heard of but really know nothing about. And it's deeply satisfying because it all makes sense and it fits together

2:11once you understand it. Good stuff. I hope you enjoy it.

2:20Welcome to Stuff You Should Know, a production of iHeartRadio.

2:30Hey, and welcome to the podcast. I'm Josh Clark, and there's Charles W. Chuck Bryan over there. And, uh, still know Jerry. Chuck, wake up. Huh? We're going to get some mail for that right off of the bat. I feel quite refreshed. So, Chuck, you might have narcolepsy then. If you just fell asleep, were you able to resist that urge to sleep just now? No. As soon as I heard, hey, welcome to the podcast, I went, lights out. I think that happens to a lot of people.

3:03Have you ever known anyone with narcolepsy? I haven't. The closest I've come to that is, um, watching my own private Idaho. What? Do you find that, uh, sleep-inducing? No, no. There's, uh, I think... Oh, right. It's River Phoenix or Keanu Reeves has narcolepsy. No, that's right. I forgot about that. I thought you were saying it's so boring you can't stay awake. No, no. No, that's Cats. Did you see that? No, don't you remember that I tried to make myself go to sleep in Cats in the middle of Cats?

3:36Oh, that's right. No, I have not seen the movie, no. Yeah, that's what I was wondering about. After having been on Movie Crush, I, um, now I can't tell what's what anymore, what I said where. Uh, so my great-aunt Laura had narcolepsy, which is my paternal grandmother's sister. And, uh, I only met her a few times. This is from my, my dad's side of the, like, the Mississippi clan. So, I think I only, I only remember going to Mississippi, like, once when I was a kid and visiting her.

4:08And I just remember my brother and I, this is my only memory of the visit, is Scott and I sitting in a room talking with her, and her being in the middle of a sentence, and then her head falling down. And then ten seconds later, she would pick her head up and continue that sentence. Wow, like, like, without missing a beat? Or was there like a, oh, you know, was she aware that she had just fallen asleep and woken up? In my memory, from being like ten years old, she didn't miss a beat and just finished her sentence, like, right in the middle of a sentence,

4:39and didn't mention it. And my brother and I were just like, what is going on here? Oh, wait, your dad didn't prepare you for it? I don't remember. I blocked out, you know, purposely blocked out a lot of my childhood. Right, for sure. So, I don't know. And that got folded into the shuffle? That's the only thing I remember. It may be a child's memory that is a little trumped up, but that's how I remember it. Wow, man. Well, yeah, I've never known anybody with narcolepsy, and based on that, going into this whole episode,

5:15like, I was just basically going in like I'm sure most of our listeners are, where it's just like, yeah, if somebody falls asleep in the middle of the day, they can't help it, and then they wake back up, and who cares, basically, you know? But the more that I've researched this, the more I'm like, you know, even if it were just that alone, it would be pretty disruptive to your normal life, depending on how often it happened to you, you know, every day. But the fact is, it's not just that alone, and there's a lot of extra symptoms to it that make it frightening,

5:47or terrifying, or depressing, or just completely disruptive, or make it so that you are maybe unable to hold down a job, or go to school. It's actually a much sadder condition than I think most people think of, because it seems innocuous. It's just like, hey, you fall asleep here or there. It's fine, you know? And it's not. There's a lot more to it than that. Yeah, for sure. I should also mention, too, that something that should not be confused with narcolepsy is something that Emily's family has.

6:18And I saw this when we would go to visit when they lived in Ohio, when we would stay at her parents' house. Eating too much turkey? Well, you know, eating, drinking during the day, such that by 7 to 8 o'clock at night, every night, I would, Emily and I would look around, we're watching TV, and there are four, usually three, sleeping adults. And I dubbed it the gas leak, which everyone in their family thought was hysterical. Right. Now that's just plain old funny.

6:49Yeah, that's not narcolepsy at all. That's just, you know, at what age does that start happening, is what I want to know, because I'm creeping up there. 21. Because I can still jam late into the night. I'm still, you know, I might be sleepy the next day, but that's my only time when I don't have a five-year-old. So I use that time. I can stay up still till midnight, one in the morning if I am doing something. That's really neat. You must have a lot of testosterone left.

7:19I don't think so. Well, I mean, well, no, I mean, like, to have energy after, you know, a certain time of day is, I think you have a lot of testosterone, Chuck. I would bet. We're going to take you in for a test after this. Well, I feel like it kicks back in. Like, I'm sleepy sometimes during the day, but then when the night comes and my daughter's asleep, I'm like, all right, this is my time to shine. No, that's very fortunate, man, that you're not just like, this is my time to Netflix and chill.

7:51Like, you're getting stuff done. I'm envious of you for that because I get a little tired. But I definitely don't have narcolepsy. I'm just kind of like, I'm somewhere between you and Emily's family. The gas leak, right?

Defining the sleep disorder

8:05Yeah. So narcolepsy is, it's a chronic disorder. It's a sleep disorder. And I know we've talked a little bit about this in some of our other sleep disorder episodes, so much so that I thought we might have actually covered this, but I quadruple checked, and we have not. But it's characterized by a few things. One of the main tenets that basically everybody that has narcolepsy has what's called excessive daytime sleepiness. Right. That's what everybody thinks about when you think of narcolepsy.

8:36Somebody just falling asleep, they can't help it, they're just suddenly out. That's right. Yeah. They also call those sleep attacks, which is pretty cute. And no matter what variation of narcolepsy you have, you have excessive daytime sleepiness, EDS, right? That's right. And this is not, you know, this is nothing new. We're just now sort of figuring it out a little bit since the 90s, which we'll get to. But obviously, this has been happening since there have been people.

9:07They've probably been suffering from narcolepsy. You know, a small percentage of people. But it was first described in 1880 by a French physician named Jean-Baptiste Édouard Gelleneau. Not bad. How would you have said it? Jean-Baptiste Édouard Gelleneau. Gelleneau? You have to put that little uptick on the end. I think that's called an accent agou. Right. Right.

9:37So, yeah, that's how I would have said it. But either way, I think we basically got it across. He was a French physician from 1880. That's the important part. Yeah, and the origin of the actual term is from Greek, narca, which is numbness or stupor. Stupor is one of my favorite words. It's a good one. And lepsis, to attack or to seize. Right. So, it's an attack of stupor, basically, is what he meant when he coined that term. And the reason Jean-Baptiste Édouard Gelleneau came up with this is because a 36-year-old wine

10:13cask maker came to him and said, hey, I think there might be something wrong with me. I fall asleep suddenly out of nowhere for one to five minutes, 200 times a day, every day. What do you think? And Gelleneau said, I think I'm going to make my career on you, buddy. I did the math there. If you average about two and a half minutes between the one to five, that's about eight hours of dozing. Okay. I'm really glad you said that, Chuck, because this was something that I had no idea about.

10:45But if you take over a 24-hour period, somebody with narcolepsy, and put their amount of sleep next to somebody without narcolepsy, over 24 hours, it's going to wash out to roughly the same. Did you know that? I didn't know that. But does that mean that this guy dozed eight hours a day and then stayed up all night? Or did he sleep another five hours at night and just slept a lot? No. So that's one of the key reasons that there is such a thing as excessive daytime sleepiness as part of narcolepsy.

11:18It's that your sleep is so disrupted that it's basically spread out over 24 hours rather than concentrated over, you know, eight hours at night. So they're up and awake in the middle of the night for very long periods, just like they fall asleep suddenly during the day. But if you put all those bouts of sleep together, even when they're trying at night and then when they can't help it during the day, it adds up to about the same that a person without narcolepsy will sleep. That's my understanding.

11:48No, that's pretty remarkable. It is. Like the brain's like, I'm getting sleep whether you like it or not. We're making this happen. At least by 24 hours, we're going to have had enough. And of course, you know, since this has been, you know, we're talking about the 1880s, there have been a lot of explanations over the years. Everyone from Freud to, you know, I was about to say legitimate doctors that probably would offend certain people. I like Freud. I like Freud too, but I meant like, you know, never mind.

12:19Sure. But Freud, of course, said that sleep is an escape. And he said, you know, narcolepsy is a lot of times triggered by really intense emotions. So here's what I think. It's just an extreme defense mechanism that lets you escape from those emotions. I love it. Why not? It's pretty Freudian. It's about as Freudian an explanation for anything as I've heard. It's just classic, right? Of course, it's just utterly wrong. But I love, I just think Freud's attempts at explaining the world were great and valuable in the way that like preserving classic art is.

12:57Yeah, I've been to his house. What? Where? In Texas? Yeah, the Sigmund Freud house in Tyler, Texas. There are a lot of Germans in Texas, although I know he was Austrian. Yeah, I mean, I believe I saw it in Vienna, if I'm not mistaken. That's neat. That is very neat. Was this when you were backpacking? Yeah, of course. Chuck, you need to do a memoir of that time in your life and call it Backpacking to Freud's House.

13:25Okay? Okay. Okay. And the book could just be shaped like a penis.

13:31Sometimes a book is just a book, Chuck. That's right. So Freud missed the mark a little bit, but still, again, it's worth mentioning just like appreciating art. It wasn't until the 60s where they're like, okay, I think we're starting to get some real clues here. And that was when they first established that people with narcolepsy enter REM sleep during these bouts of narcolepsy, which you are not supposed to do. Under normal sleep patterns, which we talked about many, many times before, like you said, when you fall asleep, it should take you a little while to enter REM sleep.

14:07That's a deeper phase of your sleep pattern, right? With narcolepsy, they're out and into REM sleep so quickly that a different way to characterize it, that narcolepsy researchers put it, is that REM activity, it intrudes into wakefulness. The line between being awake and being in deep REM sleep is that blurred for people with narcolepsy. Yeah. And I feel like I've occasionally, in a really intense power nap, had a dream, but that's only when it's, and I don't get to nap anymore, but that's when I've just been so tired that I just nap and fall asleep like immediately.

14:50That's neat. I'll bet you, do you feel refreshed when you wake up? I tend to nap longer when I would nap, so I wouldn't do the, when I say power nap, I don't mean the 20-minute disco nap. I mean, you really power through for a couple of hours. Right. I thought you were recounting some of your cocaine-using days. No, no, no. I gotcha. So, that was in the 60s. So, they say, okay, REM and narcolepsy, they go together like chocolate and peanut butter, right? We're on to something here. But finally, in the 90s, they're like, really have started to figure it out.

15:24And they've zeroed in on the hypothalamus and specifically a small cluster of cells in the rear of the hypothalamus that we'll talk about later. And if you learn about that, as far as narcolepsy goes, you can find it pretty convincing that we have begun at least to finally truly understand the cause of narcolepsy. Yeah, I totally agree. They make a great case. Yeah. So, if you want to talk just some initial stats, it occurs in all ethnic groups. It has equal incidence on the gender spectrum, evidently.

15:58Yeah, that's interesting. And, yeah, because usually you would see it tilted one way or the other. Yeah, for sure. And then, as far as how often you're going to see this, it's in about 0.03 to 0.16% of gen pop, or about 1 in 2,000 people. Yeah, which makes it, which classifies it as a rare disease. Which, by the way, shout out to, among several others, rarediseases.org for their take on narcolepsy.

16:30It was very instructive. Is it a disease or a disorder? Or is it a fine line? Jeez. I think because there's a brain dysfunction that it would be characterized as a disease, wouldn't you? I don't know. I still don't know the difference after all these years. So, it was, I mean, when it was considered an REM sleep disorder, and maybe it still is, it was considered a parasomnia, like sleepwalking or whatever. So, it would have been considered a disorder then. But I think it's a disease now.

17:00Okay. Okay. Do you want to take a break and come back and talk about what narcolepsy is? Yes. Okay. Well, we'll be right back, everybody.

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20:31Okay, we're back.

The two types of narcolepsy

20:41And it turns out, Chuck, that there are two types of narcolepsy. And just from all of the research that we've done over the years on interesting health stuff, this smells a lot to me like something that's going to be broken out into its own thing over time. Yeah, I agree, because we've seen that happen time and time again. We have narcolepsy type 2, which is what we were talking about, sort of the more, like when you think of narcolepsy, this is probably what you're thinking of, Aunt Laura falling asleep during the middle of a sentence.

21:13Right. And it's type 2 because it's by far less prevalent than type 1. And type 1 is narcolepsy like you'd think of with the daytime, excessive daytime sleepiness. But on top of that, there's something called cataplexy too. And cataplexy can exist on its own. It's the just sudden loss of voluntary muscle function. Like you can't keep your head up because your neck muscles just went limp or your arms go limp or something like that.

21:44And cataplexy can exist on its own. It can exist in conjunction with other diseases too or disorders. But it very frequently coexists with narcolepsy. Yeah. And one of the hallmarks of it from what I understand, because it gets kind of confusing. And I couldn't fully find this out, Chuck. But I think that it can exist in a person with narcolepsy in conjunction with a sleep attack or separately to where you just suddenly like can't hold your head up anymore.

22:19The key is you're still conscious. Conscious. Oh, my God. I just turned into an illiterate seventh grader. You're still conscious. You might look like you have just fainted or something like that depending on the severity of the cataplexic attack. Yeah. It's almost like a fainting goat, right? Yes. Very much like that. Almost exactly like that because, remember, with the fainting goats, they would basically just fall over because they were startled. Yeah. I think pretty much the same thing with cataplexy in humans, although it seems to be more associated with positive emotions.

22:53Yeah. It's so interesting. Yeah. We're going to get into that. There are four symptoms of narcolepsy, which we're going to break down in a second. But they are excessive daytime sleepiness, like we've talked about. There is the cataplexy. There's sleep paralysis. And then hypnagogic hallucinations. And if you have narcolepsy, well, there's about a 20% to 25% chance that you have all four. And I don't think there's any rhyme or reason which ones you do have.

23:28But like we said, everybody has the excessive daytime sleepiness. And they're also talking about a fifth beetle. I was going to say that, too. Clarence? Was that his name? Yeah. Or Pooh said he was, too. The fifth symptom, which is disturbed nocturnal sleep, which about 50% of the patients have. But they haven't. I think that will end up in there at some point. And technically, there may be a sixth one, too, which is called automatic behavior. Where have you ever been like driving and you're suddenly like five exits further than you thought you were?

24:04And you realize you just zoned out and were just driving just fine. But you were basically on autopilot. I don't know. I mean, is that like the same as just daydreaming or? Maybe. I think so. But there's like no recollection of anything. You didn't note any landmarks that you just passed. Or let's say you're gardening or something like that. You don't remember finishing digging the hole with a trowel. Well, it's you've just completed a task that you have no memory of undertaking.

24:34I don't think that happens. Okay. So that's happened to me before. But that's a symptom of it's an additional symptom. It's not a classic symptom. But they're starting to figure out that it is a symptom of narcolepsy. Yes. So you're like, I just I went in my garage one day and I had built a penny farthing. Right. No memory of how it got there.

Breakdown of the main symptoms

24:54So it usually starts out in adolescence, which surprised me. I did not know that just maybe because my Aunt Laura characterized it as something you got later in life. But they do worsen with age. So maybe that does make sense after all. And sometimes your symptoms can be very steady. Sometimes it can be months or years in between changes. And sometimes the symptoms change a lot very quickly. Right. But the symptom that, again, 100% of people with narcolepsy have is excessive daytime sleepiness.

25:29And in almost every case of narcolepsy, that is the first symptom that starts. You almost never start with the other ones. It's that one first. And that's exactly what you think of where somebody just falls asleep and they're out for a few seconds to a few minutes, depending. And it's not going to be the same amount of time every time. They're not going to have the same number of sleep attacks every time. Yeah. A lot of it has to do with just how tired they are, like how poorly they slept the night before. Yeah.

25:59That's going to make them more susceptible to sleep attacks during the day. And this is not the same as hitting the wall at 3 o'clock because you ate lunch and all of your coffee from the morning wore off. I mean, it bears some resemblance to it, but it is irresistible, this urge to sleep or just sleep. It just comes on. So that's the main characteristic of narcolepsy. But anybody who's kind of dozed off like sitting in a comfortable chair when it was, you know, a little warmer than normal at work or something like that, right?

26:33Like that is a – it bears a resemblance to that specific symptom of narcolepsy. It's the other ones that you have in conjunction with that that really make narcolepsy like its own disorder. Have you ever slept at any job you've ever had? It doesn't sound like me, but probably. I'm sure I have, you know, here or there. Why you? Well, I mean, when I worked the midnight to 7 a.m. shift at the Golden Pantry in Athens, I had a regular routine of sleeping.

27:08Oh, really? Yeah, because you were allowed to close up the store and mop and do things for like an hour. So I would close up the store, go back in the back, and lay down on a little pallet I made on top of a freezer. Nice. Did you get some good sleep? I would. It was pretty hard sleep. And I will admit that when I had a baby, I took a nap or two right here in our own office. Oh, nice. Can you tell me where?

27:39Is it still a secret? In one of the private telephone rooms. Oh, that would be a good place to take a nap. If you've ever gone in there and seen a pillow, then. In the camp stove? Yeah.

27:53Sleep machine? Yeah, there's like an open bag of marshmallows and a stick. No, I took a couple of cat naps here at work and such that I was like, you know what? Some countries and companies embrace this, and there's a lot of value to knocking out for 20 or 30 minutes during a work day. Is that what that one HR email they sent out was all about? Maybe. Did you try to convince them of that? Did you go to them and say, you know, some countries really embrace this? Why don't you guys be more continental?

28:25At least don't fire me. Right. Yeah. So, yeah. So, this is akin to that, you know, falling asleep. But the key here is that it's unplanned. And with narcolepsy, it is straight up irresistible. You know how like when you sit up and you like open your eyes a little bit, you're like, well, I can't fall asleep. I got to stay awake because I'm being paid right now. Yeah. Like if you have narcolepsy, you can't do that. You just fall asleep and you're out. And the other key is you feel really good and refreshed right after one of those sleep attacks.

28:58Yeah. Which is, it's weird to think that 10 seconds of that can refresh you. I know. It is very weird, but that's part of it for sure. So, cataplexy, which we've talked about, the fainting goat-like thing, you mentioned positive emotions can trigger it. Being surprised, laughter, elation, sometimes anger, which is not positive. But intense emotions like that can trigger this. And it can be everything from, like you said, your head just sort of nodding down to full-on just collapsing.

29:32Yeah, which is called a drop attack, which are kind of dangerous. You can get banged up pretty bad because this is not necessarily you falling asleep or fainting. Or as a matter of fact, it's not that. Yeah, you're up. You're awake at least. You're still totally conscious. You are, you just can't control your muscles all of a sudden for a very short period of time. Yeah, and interestingly, which is good news, is that as you get older, cataplexy might actually improve. Yeah, that is good news.

30:03Because taking a fall in the hallway at, you know, 80 years old is much different than at 18. For sure.

30:11Let's see. Oh, there's also sleep paralysis, which we did an entire episode on. Yeah. It's not fun. It frequently is accompanied by hallucinations, which is another symptom we'll talk about next. But sleep paralysis was first described by a physician who had a patient that presented with narcolepsy. And this guy figured out there was such a thing as sleep paralysis. But it's basically when you're falling asleep or waking up, there's a few fleeting moments where you can't move at all.

30:42You're paralyzed and it's not pleasant one bit. So if you are having a sleep attack and you're coming in and out of sleep, you know, a bunch of times a day and you feel paralyzed as you're coming in and out of sleep and you don't know what's going on, it can make the whole narcoleptic experience a lot more terrifying. Yeah, as will hallucinations. These can come at the onset of sleep or at the end of sleep. They can be really scary.

31:13Sometimes it could just be hearing a noise. What was the one thing we talked about at the time where you hear a loud noise? Exploding head. That's right. Exploding head. Somehow all this seems to be related somehow. Oh, yeah. Right? Yeah. I think so, yeah. I think a lot of it has to do with the neurons that we'll talk about in a little bit. So the hallucinations, when they happen when you're waking up, they're called hypnopompic. And when you're falling asleep, those are the hypnagogic that we mentioned earlier.

31:46Yeah. And again, they very frequently accompany sleep paralysis in that, like, you can't move and you're hallucinating a demon standing on your chest. Right. And that's why you can't move. And again, this is happening to you many, many times a day against your will. And it makes it unpleasant. And then there's also something called disrupted nighttime sleep, which is basically the exact polar opposite of excessive daytime sleepiness. Where during the night when everybody else is asleep and when you wish you were sleeping, you might be wide awake.

32:19So that, again, your sleep pattern is not concentrated into eight hours at night. It's spread out in about eight hours throughout a 24-hour period. That's right. So we talked a lot about the various sort of explanations for this over the years, what they thought was going on, and that it wasn't until the 1990s that they kind of zeroed in on what they think is going on now, which to me and you holds a lot of promise.

Discovering hypocretin and neurons

32:46But 1998 was the year that they finally discovered and isolated the chemical in the brain that seems to be the cause of all this, and it's called hypocretin. Hypocretin? I want to say hypocretin. I do, too. So let's do. Okay. Let's. Hypocretin. Yeah, so they isolated that, and we have our cousins, the rats, to thank for this because they did a lot of rats tests and figured out from those tests just how this whole thing works.

33:20But what they figured out is that hypocretin has a few different functions, but its main function is maintaining wakefulness in us humans, and it's a peptide. It also has another name, Chuck, called orexin, and it's the exact same neurochemical, but it just happened to be discovered independently by two different groups at about the same time. So it has two names still. They haven't settled on one. But it basically goes around and says, hey, serotonin, you're looking good.

33:52Here's a little boost. Hey, norepinephrine, you're looking great yourself. Here's another little boost. And so all of these neurochemicals that keep us awake and alert get a boost from hypocretin so that they can do their job better. And what they found is that people with type 1 narcolepsy have about 90 to 95 percent fewer of this very specialized cluster of neurons in the brain that are responsible for producing all of the hypocretin in our bodies.

34:25Yeah, that's case closed, right? Basically, yeah. I think the only thing left to explain is twofold. One, exactly why the hypocretin is—the neurons that produce hypocretin are so diminished, and it seems like they basically explain that one. And then two, what to do about it. That's the big one. Yeah, and we should mention, too, that there are about 86 million—I'm sorry, billion neurons in the brain, and only about between 100 and 200,000 neurons produce hypocretin.

34:58So it is a very specialized cluster of neural cells. Yeah, but it also makes it really vulnerable, too, and they're all in one space in the rear of the hypothalamus. So it's really weird that evolution was like, oh, it's fine. This is a really, really, really important chemical, but we're just going to localize it right here in this one spot to just 100,000 neurons. Yeah, and it's also really weird that if you only have type 2 narcolepsy, you don't show any decrease in hypocretin.

35:30Right, right. That's just the one where you have sleep attacks and not cataplexy. And it is really weird, and that's why I was saying, like, I wonder if that's going to be broken out eventually in the future into its own disorder or disease. But the current thinking for that is that that is a less pronounced or less advanced case of type 1 narcolepsy to where you're probably going to eventually get cataplexy, or you may never get cataplexy, but your case of narcolepsy just stopped progressing at some point.

36:06That's what they think currently. A lot of the sleepiness of narcolepsy, it's a theory at least from researchers, is that it's a consequence of sleep state instability. And that's something I know we've talked about before, that threshold between being awake and being asleep and those lines getting blurred and crossing over. And I guess that must have been sleep paralysis that we talked about that. I think so, because that is like an example of, like, that is like wakefulness intruding on REM sleep.

36:41It's almost like the opposite of narcolepsy, people experiencing sleep paralysis without narcolepsy. It's kind of like that. But it's ultimately that. It's a consequence of your brain no longer able to, being able to hold the switch down between the on-off switch between sleep and wakefulness, right? So it's like hypocritin is the thumb that holds the on-off switch in place.

37:12And without it, that switch is kind of hair trigger so that it just kind of can shift back and forth between on and off really easily and really quickly. And so without that hypocritin, that's that you can just kind of go in between wakefulness and REM sleep with no transition and just at the drop of the hat, basically. So they think that that's it, that it is a lack of hypocritin that is responsible at least for type 1 narcolepsy, which is narcolepsy with cataplexy.

37:45Should we take the break now? Sure. All right. Let's take a break because we're going to get into our third act here with a very, what I think is the most interesting part of all this, which is what it has to do with your genes and your immune system right after this. For most students, math class moves at the wrong pace.

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41:09All right.

Genetics and the immune system

41:11So, I promised talk of genes in your immune system. This is super interesting to me because I feel like they're really zeroing in on what's going on here with this research. Dude, how many episodes have we done on stuff like this where we're like, they think maybe this or studies are starting to come in. We have caught this at like peak ripeness. Yeah. Right before, everybody knows that it's just so plain and obvious and it's been talked about so much. But right after, all of these important advancements in the study of it have really kind of come together and gelled.

41:49I mean, it is perfectly fresh. Yeah. It is a very rare, satisfying feeling. I feel satisfied myself. So, they think there's a genetic basis for narcolepsy, but the genes that are involved in narcolepsy really aren't involved with sleep. It's about your immune system. So, how it goes is a little something like this. All right, man. There are genes that code for these T cell receptors and the HLA gene, human leukocyte antigen.

42:25And not everyone has this variant, but if you do, you're going to have about a 25% greater chance of having narcolepsy. Yeah, that variant of the HLA gene. Very important. That's a big increase. Yeah, 25% is for real. Because a lot of those, they'll show like the relative increase. It increases your risk, you know, 80%. But if you look at the absolute increase, it's like, well, that, you know, you have, you know, 1.5 times the chance or something like that.

42:5525 times likelier is definitely a huge increase for sure. My hat is off to that one. Yeah, but so what they're thinking is that it's actually the basis of narcolepsy is an autoimmune disease, and that is what's killing off. Your immune system is killing off those hypocretin-producing neurons. Yes, yes. Just like Crohn's or irritable bowel syndrome or rheumatoid arthritis, it's your body turning on itself. It's mistaken, so it attacks itself.

43:26Your immune system attacks your own body. And in this case, in the case of narcolepsy, they think that something about those hypocritin-producing neurons, I guess, are producing something that seems like an antigen to your body. If you have that specific variant of that HLA gene and it attacks them, kills off those neurons, you don't have any hypocretin any longer, and so you can't maintain wakefulness. And so sleep and wakefulness just toggle back and forth throughout your day.

43:59Are you going to drop the streptococcus bomb? I think you should. I think I understand it, but just after the onset of narcolepsy, it looks like you have an increased level of antibodies against streptococcus, and that's like strep throat and there are other infections involved. And so they've also tied that to the time of year. Narcolepsy usually begins in late spring and early summer, which would kind of make sense that there's an autoimmune attack going on against those neurons triggered by strep throat or some other kind of infection you get during the winter.

44:34Yeah, like your immune system just goes bonkers because of strep, and it's like, what else? What else can I go after? I'm really primed and pumped, and for some reason, it goes after your hypocretin-producing neurons in your hypothalamus. That's nuts. So your immune response is triggered by an actual infection, they think, and the reason why they think this, and it greatly pains me to reveal this. I know. But there is a vaccine called Pandemrix that is no longer available anywhere in the world, but it was hot and heavy as a vaccine against H1N1 swine flu, and it was a really potent vaccine against H1N1 swine flu.

45:13And some European, northern European countries during the 2009 to 2011 swine flu pandemic chose to use this to inoculate their population with, right? Yeah. Well, there were reports that have been backed up by studies, not just in Finland, which is a big place where this happened, but in other places like the UK did studies, too, that found the same results, that there was a link between Pandemrix and narcolepsy, that the Pandemrix triggered that immune response that ultimately led to the immune system attacking the hypocretin-producing neurons.

45:54So that H1N1 vaccine brought on a lifelong chronic case of narcolepsy. Yeah.

Vaccine links and future tests

46:03I thought that was hard to say, wasn't it? Yeah. It really was. I really, really hate saying stuff like that. I know. But you know what? You got to—we got to preach the science, and the science appears valid here. Agreed. Yeah. For sure. Tons of kids in Finland developed narcolepsy, and I think the new rate of cases of narcolepsy in kids increased 8 to 12-fold. And, you know, I think out of the 54 kids who were diagnosed with narcolepsy, 50 of them had had the vaccine.

46:34So 50 out of 54. Yeah, and I mean, these numbers are really, really small, but if you think about it, so four kids apparently in 2010 would have been diagnosed with narcolepsy. Right. Had that pandemic not happened or that particular vaccine not been administered. But because it was, the number was 54, not 4. So even though the numbers, again, absolutely are rather small, percentage-wise, that's an enormous, a mind-boggling increase in the number of narcolepsy diagnoses.

47:10Yeah. And it was linked directly to that vaccine. Yeah, and they caught it. I'm so sorry I keep saying that. And they caught it, and it is no longer being given anywhere. It was never available in the United States. Yeah. So Finland just sort of got the brunt of it, it seems like. Yeah, Finland, the U.K. had a bunch, their rate was one case of diagnosed narcolepsy for every 55,000 inoculations in children, I think, six months to 18.

47:41Oh, wow. But that washed out to like 16 people, which still, I mean, if you're one of those people, you're like, well, son of a gun. Yeah. That really sucks. But here's the key, and this is really, really important, and this is how we will be able to still use a vaccine that is viable and potent and works against swine flu without giving somebody narcolepsy, and that is personalized drugs based on gene tests. Yes. DNA tests.

48:12Because of those 50 kids in Finland that received the vaccine in 2010 that developed narcolepsy, every single one of them carried that specific variant of the HLA gene that is tied to narcolepsy. So if you just did a simple DNA test, which hopefully will be widespread in just a few years, you'd say, oh, no, I'm glad we did this, you can't have pandemrics, you might get narcolepsy, or basically there's a 100% chance you're going to get narcolepsy. We'll give you this other vaccine instead that has been shown not to produce narcolepsy in people like you.

48:46That's right. And you can refer to our episode on personalized medicine? Yes. Right? We should do a follow-up on that one. Yeah, I agree. We'll put that on the list for six years from now. So basically, you've got these genes that predispose you to your immune system mistakenly attacking that part of your hypothalamus. There has to be some sort of trigger, either an infection or pandemrics, something like that, typically an infection with strep. And then there seem to be two age windows where you're particularly vulnerable, around 15 and around 36.

49:22They have no idea about any of that. They just have, they're starting to put this data together. Yeah. I bet you they'll figure that out, too. Agreed. I really feel like narcolepsy is going to be, like, totally and completely figured out in the next decade, and I cannot be more jazzed about it. Really? Yeah. I love science just figuring things out. You know, just doggedly, you know, working and building on, you know, somebody else's work. It's just, it's a beautiful thing when it's done right.

49:52Agreed.

Diagnostic tests and treatments

49:53So if you are going to be diagnosed with narcolepsy, there are a couple of tests that they're going to give you. One is called an overnight polysomnogram. That's right, a PSG. And that is a test when you, it's one of those tests, it's like a sleep study, is when you go in and sleep for them, basically. Sleep for me, baby. Yeah. And they measure a lot of things. They measure your brain waves. They measure your heart rate, eye movements, limb movements, muscle tone, respiration.

50:24Get a lot of info there, and then they'll say, now you're going to, this is going to be followed by the multiple sleep latency test, which also sounds kind of fun, because that measures how quickly you fall asleep for a nap every couple of hours during the day. I know. When you have to go in for one, you're like, I got to go to a doctor's appointment. Somebody goes, oh, sorry. And go, no, no. It's great. It's going to be the greatest day of my life. Yeah, those rooms make me sleepy. I could see some people being like, oh, I can't go sleep in a room. But I was well known as a child for falling asleep in like a dentist chair, waiting for the dentist to come in, or in a waiting room for, or not a waiting room, but in the exam room for a doctor.

51:05I still get sleepy in those just super clean, super cool, quiet rooms with fluorescent lighting. It just, it zaps me. Yeah. That's very odd. Yeah. Very odd indeed. So, four or five nap opportunities during the day. They're going to see how fast you fall asleep. And if you have narcolepsy, you're going to fall asleep super easy compared to someone without narcolepsy. Right. So, that's a pretty big giveaway. If they're still like, I don't know, this is all this, you know, this patient history that we've taken in these tests are inconclusive, they might test your cerebrospinal fluid,

51:43because hypocretin levels are very easily tested through that. Not as fun. No, not nearly as fun, because they're going to go through the base of your skull, that hole in your skull where your spinal cord is. Oh, yeah. I know. I know. I hope that that never befalls either one of us and anyone who's ever had to go through that. We are very, very sorry. Yeah. But that also is looking like a place where they're trying to figure out how to cure narcolepsy. Because as it stands right now, if you were diagnosed with narcolepsy, you had just been given a lifelong chronic diagnosis.

52:18Yep. There's no cure for narcolepsy as it stands right now. But there are treatments, and from everything I read, if you are actively treating your narcolepsy through a doctor, usually with prescriptions and also, like, behavioral modification, not like, you know, hooking you up to a car battery and changing your behavior like that, more like making sure you stick to, like, a good sleep pattern. Right. You can very much keep your symptoms in check, for sure. It doesn't have to ruin your life.

52:50The trouble is, is that it's very frequently misdiagnosed and it's underdiagnosed. And they think it's because it occurs with so many comorbidities like depression, where the doctor's like, well, sure, you're falling asleep all day because you're just sitting around on the couch because you don't have any low energy because you're depressed. Really, it's possible that you have developed depression because of the narcolepsy. Yeah. They haven't figured out if they're comorbid or if one causes the other, but they're pretty sure that the narcolepsy causes the depression.

53:25Yeah. You're probably going to get a prescription for something. It may be, or it's probably likely to be modafinil these days. And we talked about that in our Is Science Phasing Out Sleep episode. Yeah. We've done a bunch of sleep ones. I forgot about that one. Ritalin you might get, you know, it says in the old days, methamphetamines, but they still prescribe a variation of speed for, I'm not sure if it's narcolepsy, but I know an individual that was diagnosed with, I guess, just extreme daytime sleepiness.

54:01Not doing chores fast enough? No. No, for falling or just feeling really, really sleepy during the day and did the sleep study and all that. And they were prescribed kind of whatever the version of speed is these days. When was that? When were they prescribed that? Was that back in the 90s? Like last year. Oh, really? I'm surprised because from what I saw, modafinil is like, no, don't need anything else. Just take modafinil. You don't get addicted to it. There are very few side effects. It's supposed to just be like a wonder drug, basically.

54:35Anytime I hear that, I get dubious. Right. I think that's pretty smart, actually. They might also prescribe you antidepressant, like an SSRI, which inhibits reuptake of serotonin, which means you have more serotonin in your brain, which would make sense because what hypocretin does is boost your levels of serotonin in other neurochemicals. So this is kind of going around that problem and just making you have more serotonin than before, which apparently helps maintain REM sleep, the barrier between that and wakefulness, a lot better.

55:13Yeah. And then the final thing, which is really interesting and promising, is they did the sort of logical thing, which is, hey, maybe we can just get some more hypocretin in your body because if that's the problem, why don't we just do that? So they cut out fat hog legs of it for you at the doctor's office? There are different methods. Cell transplantation, which is just implanting cells, maybe implantation of the gene, like gene therapy, maybe just giving it through your nose or injecting it into your body.

55:47That's what I'm saying. Or intrasisternally, Chuck, which is, again, through the base of the skull in the back of your head. Yeah. Where your spinal cord goes up to your brain. They can inject it into your cerebrospinal fluid like that, too. Yeah. It's probably the least fun of all of them, but they're on the case, basically, is what that means.

Quality of life and safety risks

56:11Yeah.

Quality of life and safety risks

56:12And, you know, we've talked sort of off and on throughout this thing about your quality of life with narcolepsy. It's obviously a serious thing. Besides just, like, holding a job and socially and not being depressed because you don't want to hang out with people because you may be embarrassed by it. Mm-hmm. There's also, like, the very real chance of accidents. Some people are not allowed to drive. Some people are allowed to drive. It kind of depends on, I guess, your diagnosis.

56:44School is tricky. Work can be tricky, although they do. They do with the Americans with Disabilities Act. They provide for letting people take naps and stuff like that, which is kind of cool. It is. Yeah. If you have narcolepsy and you're at work, you can say, hey, employer, I need a place to take a nap. And they'll say, okay, that's great. They'll say, right in here. And they're like, oh, my God, Chuck's in there. Right. Chuck. Sorry. I mean, it gets even sadder, though. Like, there are people who die by suicide from narcolepsy.

57:19There was a girl named Katie Clack who got Pandemrix and developed narcolepsy as a result. And she ended up taking her life because it just completely derailed things for her. She was in no way, shape, or form prepared for it, although I don't know that anybody's prepared for it. And then also, like you were saying, an accident can happen. And from what I read, the risk of death and injury among people with narcolepsy is almost twice that of the general population.

57:50Man. Through things like car accidents or, you know, cooking or going up a ladder or something like that. Wow. If you suddenly develop cataplexy or a sleep attack or something, that's a bad time to fall asleep or lose control of your muscles, you know? Well, and at the very least, you're going to have to really arrange your life to accommodate for this stuff. Right. You know? But again, if you are managing your symptoms, you can lead a pretty normal life. I think it's just a question of, like, getting diagnosed correctly.

58:21Yeah. Yeah. Well, that's it for narcolepsy. Hopefully, we'll have it all figured out. And when we revisit it in five or ten years, we'll be like, it was all right. Everything was correct. It was all right. And since I said it was all right, it's time for Listener Mail.

Soul train listener feedback

58:41I'm going to call this Soul Train Feedback. Nice. That was a fun show. And this is from Julia. Hello, guys. We really enjoyed your Soul Train episode. You did a great job capturing the feeling and cultural significance of the show. You depicted a brilliant, flawed Don Cornelius without negating his profound contribution. There was a monthly black teenage magazine named Right On. This publication gave names to the dances and dancers. We would read the ink off of the pages.

59:12Being black in America then and now, we watch mainstream America love the culture while devaluing the people and criminalizing the young. Thank you for this episode. And that is from Julia Pierce, the president of the Tybee MLK Human Rights Committee. Nice. Tybee Island, I guess, down in Georgia? I don't know. I guess so. I hope so. That's great. Thanks a lot, Julia. Much appreciated. Agreed. If you want to get in touch with us like Julia did, give us props, or just say, hey, you guys are doing this too much, or be quiet.

59:47We never will, but you can still say it. You can send us an email to stuffpodcasts at iheartradio.com.

59:57Stuff You Should Know is a production of iHeart Radio. For more podcasts from iHeart Radio, visit the iHeart Radio app. Apple Podcasts are wherever you listen to your favorite shows.

Final sponsor messages and outro

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