Figure. Another test monitors a patient through several naps over the day.
With the advantage of hindsight, Mary Ann B. realizes her illness began to affect her when she was a teenager. In high school, she failed written tests she'd studied for, yet did well when they were given as oral tests. If she laughed hard, she lost control of her body. My head would go down on the table, she recalls. I could not lift my head until I was done laughing.
As a young wife and mother, Mary Ann routinely fell asleep after dinner. At the grocery store, she would find strange items in her shopping cart.
And then, while Mary Ann was driving one day, her mind drifted. Her young son, who was about 4 at the time, hit the back of her head. Mary Ann awakened to see they were careening toward a gas station. I knew then something was wrong, she says.
Mary Ann was in her late 30s at the time, three decades ago. Her personal physician referred her to a neurologist, who performed a battery of tests and diagnosed her malady: narcolepsy. The word was new to her.
To doctors in the burgeoning field of sleep medicine, however, her tale - its onset in adolescence and its loss of muscle control brought on by laughter - is a classic presentation of what can be a baffling and frustrating condition. At least, as Mary Ann learned, it's a condition that is manageable, though still not cured.
The defining symptom of narcolepsy is excessive daytime sleepiness, ranging from sleep attacks to persistent drowsiness.
Most people with narcolepsy feel all day, every day, the way the rest of us feel after staying up all night, explains neurologist Mark Mahowald, M.D., director of the Minnesota Regional Sleep Disorders Center in Minneapolis, not far from Mary Ann's Hennepin County home. Thus a person with narcolepsy often stays awake when active but falls asleep when doing something quiet, such as reading, studying or, most ominously, driving.
The root of the problem is a brain abnormality that disrupts the body's normal sleep cycles. A healthy person sleeps in cycles that typically last 100 to 110 minutes, with REM (rapid eye movement) sleep - the phase in which we dream - occurring for relatively brief periods of 10 to 30 minutes at the end of each cycle. Both REM and non-REM sleep, properly coordinated, are essential to the feeling of restfulness that follows a good night's sleep.
In contrast, people with narcolepsy fall quickly into REM sleep - at times, within just a few minutes. They enter REM sleep far too early, says neurologist Michael Silber, M.D., co-director of the Mayo Clinic Sleep Disorders Center in Rochester, Minn. As a result, people with narcolepsy sleep in snatches that can last for mere seconds.
Its second major symptom is cataplexy - a sudden loss of muscle control. Since excessive daytime sleepiness is also present in other conditions, the addition of cataplexy allows for a textbook diagnosis of narcolepsy. Cataplexy is usually triggered by a strong emotion. Laughter is most common: When Mary Ann B.'s head collapsed onto the table, she was unwittingly experiencing a cataplectic attack.
Other major symptoms include: sleep paralysis, which is the inability to move while falling asleep or waking up; and hallucinations, which are in essence waking dreams that typically occur when a person is either falling asleep or waking up.
DR. MAHOWALD WORKS on the sixth floor of Hennepin County Medical Center, a sprawling public complex on the edge of downtown Minneapolis. He drinks coffee from a huge ceramic mug on which the sun and moon have been fashioned into a sleep specialist's version of the Chinese yin-yang symbol.
Day and night are intertwined.
Dr. Mahowald explains narcolepsy in similar terms - as a boundary control problem. At night, sleep is fragmented; people with narcolepsy awaken frequently. During the day, at least one narcolepsy symptom intrudes on a person's waking life.
The brain is not a light bulb that can only be turned on or off. Most people have this idea that the brain is either completely in REM sleep or completely awake, says Dr. Mahowald. We can have parts of the brain that are awake and parts that are dreaming.
Cataplexy is an episode which has features of REM sleep as well as wakefulness, says neurologist Clete Kushida, M.D., Ph.D., director of the Stanford University Center for Human Sleep Research.
Narcolepsy explains even what happened to Mary Ann B. at the grocery store when unwanted items would mysteriously wind up in her cart: She was shopping while partially asleep. Sleep is a state of amnesia, Dr. Mahowald says. During sleep, we have no waking memory. That's why we only remember our dreams if we wake up while we are dreaming.
People with narcolepsy live on a double-edged sword, Dr. Kushida says. In situations where there is very little stimulation, or if they're doing boring, repetitive tasks, they can have a sleep attack. If they get too stimulated, they can have cataplexy. It's hard to perform activities of daily living. And they have to keep a tight rein on their emotions.
In the past decade, researchers have made substantial progress in understanding what causes narcolepsy. Psychiatrist Emmanuel Mignot, M.D., Ph.D., director of the Center for Narcolepsy Research at Stanford School of Medicine, found that dogs with narcolepsy - they experienced episodes of cataplexy when playing - had very low levels of hypocretin, a brain protein involved in the regulation of the sleep/wake cycle. Human studies have likewise identified hypocretin deficiency as a primary cause of narcolepsy. It's pretty clear that does cause most cases of narcolepsy, at least in patients who also experience cataplexy, Dr. Mignot says.
NARCOLEPSY MAY AFFECT as many as 200,000 Americans (1 in 1,500), according to the National Institutes of Health, with only a quarter having been diagnosed correctly. Most individuals with narcolepsy begin to experience symptoms in late adolescence, but are not diagnosed for a decade or more.
There are a lot of people out there with narcolepsy who are untreated, says Dr. Mahowald. Their complaints of sleepiness are not taken seriously because it's seen as a defect of character. Our society equates sleepiness with laziness, with depression. Often, by the time people are diagnosed, they have been badly maligned - told they're lazy, depressed, or not interested.
Two tests are essential for diagnosing narcolepsy: An overnight polysomnogram, tracking electrical activity in the brain, determines if REM sleep occurs at normal intervals. And an multiple sleep latency test, tracking a patient through several naps in one day, measures how long it takes to fall asleep and to enter REM sleep.
For those properly diagnosed by a specialist, the goal of treatment plans is to decrease excessive daytime sleepiness and control cataplexy using minimal medication.
A variety of drugs are used to manage the symptoms of narcolepsy:
Amphetamines and other central nervous system stimulants, such as methylphenidate (Ritalin), traditionally have been used to help people with narcolepsy remain awake during the day. In 1999, modafinil (Provigil), became the first stimulant approved by the Food and Drug Administration for treatment of excessive daytime sleepiness associated with narcolepsy. It is longer-lasting and acts in a somewhat different fashion than older stimulants, affording a milder and more-targeted effect on the central nervous system as the only wake-promoting medication that's not a controlled substance.
* Antidepressants are sometimes used to manage cataplexy. Traditionally, tricyclic antidepressants and serotonin reuptake inhibitors have been used; most recently, norepinephrine reuptake inhibitors have shown excellent results. In 2002, sodium oxybate (Xyrem), a highly controlled central nervous system depressant, became the first drug specifically approved by the FDA for the treatment of cataplexy.
* With the majority of narcoleptics, we can get them to the point where they are alert enough, and their cataplexy is controlled enough, that they can lead normal lives, says Dr. Silber, who was recently elected president of the American Academy of Sleep Medicine.
Many patients learn also to manage their condition. Mary Ann B., for example, takes extra methylphenidate when she drives. A retail appliance salesperson, she has also told coworkers about her ailment, and asks them to watch for the glassy-eyed stare that signals a sleep attack. When that happens, she takes medicine and goes to the lounge for a short nap. I'll wake up 10 or 15 minutes later, and be totally fine, she says. I'll go out and sell up a storm.