MPR: Dreaming Awake

Dreaming Awake Part 2: Narcolepsy Rsearch
By Stephen Smith
September 2, 1997

Almost a quarter-million Americans suffer from narcolepsy, a chronic and often debilitating sleep disorder. In Part One, we heard about the difficulties of living with narcolepsy. Daytime symptoms include sudden sleep attacks, temporary muscle paralysis and terrifying hallucinations.

Man: I am so tired I almost wanna cry. It's like, let me just sleep.
Woman: The dreams and hallucinations and things like that are always scary things - somebody attacking me, that's the worst for me.
Man: We see many people with narcolepsy who are fired from their jobs because they fall asleep in the workplace. We don't fire people for having angina, asthma, or seizures, but we fire people for falling asleep inappropriately.
Man: It'd almost be nice if it was something very obvious. If I were a paraplegic, people wouldn't expect me to be able to run. But I have this sleep disorder, and people just think you're lazy or something.

Doctors say the peculiar features of narcolepsy are actually quite normal - if you're asleep. But in narcoleptics, the brain's sleep machinery somehow confuses day for night. In the second of two reports on narcolepsy, Minnesota Public Radio's Stephen Smith explains that scientists are closing in on the potential genetic causes of narcolepsy. Their findings may help explain why - and how - all of us sleep.

On a typical night we snooze through about six dream phases known as Rapid Eye Movement - or REM sleep. During REM, the brain is remarkably active and we tend to experience our most vivid dreams. But at the same time, our muscles go limp - perhaps to prevent us from acting out the really violent dreams. According to researcher Emmanuel Mignot, the daytime paralysis and hallucinations common to narcolepsy are actually the misfiring of dream sleep.

Mignot: In REM sleep, normally you are paralyzed and you are actively dreaming. But REM sleep occurs in the middle of your night. In patients with narcolepsy it can occur on the spot very quickly, in the middle of the day.
Audio: dog kennel

Mignot directs the Stanford University Center for Narcolepsy in Palo Alto, California. It's one of the leading research programs in the world. At the heart of Mignot's work is a kennel of 20 narcoleptic dogs - mostly Doberman pinschers, but with the odd Labrador and Dachshund also sniffing about.

Mignot in lab: Come here, come here. Good food?

A 5-year-old Dachshund named Beau is Stanford's star narcoleptic dog. It is hard to tell whether Beau feels excessively sleepy, the way human narcoleptics do. But his attacks of muscular paralysis are obvious enough. That symptom is called "cataplexy." Mignot points out that, in humans, cataplexy is usually triggered by strong emotion like laughter and elation.

Mignot: But in dogs, what is a positive emotion? Good food? (Beau barks.) I can't hear you, Beau. (Barks again.)

Yes! Beau votes for good, tasty canned food over the dry stuff he usually gets. Mignot plops a scoopful in front of the expectant Dachshund.

Mignot: Here it is! (clattering of food scoop.)

Within seconds, Beau's legs go rubbery and he tumbles over.

Mignot: Hup! Beau totally crashed in front of your eyes. You see he is totally paralyzed. Basically Beau had an attack of REM sleep, triggered by the emotion of seeing this good food.

Mignot cradles Beau against his white lab coat, flapping a dangling paw to demonstrate how flaccid the dog is. Beau's eyes are open and he looks mesmerized.

Mignot: He can see you. He can hear. He would like to say "Hi." But he cannot do it. He's just totally floppy. This kind of paralysis it the kind of paralysis that you experience in the middle of your REM sleep, except that here it has been triggered by emotion.

Narcoleptic humans rarely go cataplectic on demand like this. The mix of human emotions necessary to fire an episode are too subtle to reproduce in a medical lab. So Stanford's colony of narcoleptic dogs is considered an extraordinary research model for human narcolepsy. In addition to genetic studies, the dogs are used in testing new drugs to treat the disease. Doctors commonly prescribe two medications: the stimulant Ritalin battles daytime sleepiness, while anti-depressants can suppress cataplexy and hallucinations. These drugs are certainly more effective than no treatment at all, but Stanford sleep expert Dale Edgar says better, more accurate medications are needed.

Edgar: It's analogous to basically using a sledgehammer to drive a pin into a board. These are very powerful drugs that are hitting all of the arousal systems in the brain. That kind of approach often leads to unwanted side effects.

...which can include higher blood pressure and heart rates, and sometimes even more sleepiness than without the medication. Scientists at Stanford and other labs are studying a stimulant called Modafinil, which appears to generate fewer side-effects. The FDA is considering approval of Modafinil for narcolepsy. The search for better medications may depend on tracking down the genetic culprits for the disease. Japanese scientists discovered in 1983 that narcolepsy is linked to a specific gene which helps control the immune system. While that and more recently detected genes are good markers for narcolepsy, Michael Thorpy of Montefiore Medical Center in the Bronx points out that many people can have the gene and never develop the disease.

Thorpy: There are sets of twins where both twin members have narcolepsy but there are sets of twins where one member does not have narcolepsy, even though they have exactly the same genetic material. So it's not just genetics, it's genetic plus something else.

At the moment, scientists can only speculate on what that "something else" might be. Some suspect it's a brand of immune system disorder. Others say it might be triggered by life stresses or by a critically timed viral illness. To find out more, American researchers are creating a national narcolepsy registry. Michael Thorpy directs the project, which aims to catalog 100 families featuring at least two siblings diagnosed with narcolepsy. The families will contribute genealogical data and blood samples for research. Thorpy says determining who to include on the list is a task itself.

Thorpy: It's not an easy disease to diagnose, narcolepsy. There's not an easy test that one can perform to show if somebody has it. The symptoms can vary enormously from being severe to being very mild. There are many people that may have narcolepsy that don't even realize that they have it. They just think they're a little bit more tired than they should be.

Some scientists believe that narcolepsy may be more than one condition, and that some forms of it will resemble more familiar sleep disorders. In addition to the genetic aspects of narcolepsy, researchers are studying how the disease affects the machinery of sleep. Merrill Mitler is a professor of neuro-pharmacology at the Scripps Research Institute in La Jolla, California. Mitler says the biological clock dictates a relatively consistent sleep schedule in most humans: a long period of daytime activity, followed by about eight hours of sleep.

Mitler: With narcoleptics you see a very different situation where you'll see sleep and wake alternating through the 24-hour period. It's as if the narcoleptics need the same amount of sleep but can't get it all in one or two consolidated episodes.

Mitler says that if scientists can isolate the brain chemicals that regulate the onset of sleep in narcoleptics, it might explain the on-going puzzle of how all of us slumber. Is it to repay some kind of sleep-debt incurred during the hours we're awake? Does the brain need time to perform other neuro-chemical chores? Researcher say they have much more to learn. But perhaps the odd and debilitating disease of narcolepsy - and Stanford's pack of narcoleptic dogs - may help them identify the mysterious ebb-and-flow of human sleep.

Dreaming Awake Index - Part One: Living with Narcolepsy

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