THE MYSTERY. How is it possible for people to dream while awake? How can a sleep problem affect muscle tone? The devastating disorder narcolepsy is often not diagnosed until years, sometimes decades, after the symptoms start.
The Case of the First-Year Med Student
At the end of a lecture I gave to a first-year medical school class, seven or eight students rushed down to speak to me about their personal sleep problems. I was not surprised: medical students often think they have whatever illness they’ve just learned about. All but one had a problem with daytime sleepiness caused by not getting enough sleep because of their demanding schedule. After listening to lectures most of the day and studying long hours each night, most students come to class toting a large cup of coffee, and several nod off during the class. One sleepy young student had another symptom that I had mentioned during the lecture. Unfortunately, she had ignored this symptom for several years, assuming—incorrectly—that everyone had it.
She told me that about twice a week she would awaken from sleep in the middle of a dream and discover that she was absolutely paralyzed. She could breathe, but she could not move her arms, legs, or head, nor could she speak. The problem had started about five or six years earlier, and it had terrified her, especially when she dreamt that a devil-like creature was staring at her. The paralysis was not her only symptom. She also experienced an onrush of dream imagery as she was falling asleep and at times even before she started to fall asleep. Sometimes she had a vivid dream but could not tell whether she was awake or asleep. Because she had experienced these symptoms for so long, and because her sister had identical symptoms, she assumed that everyone had them. But everyone doesn’t.
What Is Narcolepsy, and Who Gets It?
Narcolepsy is a chronic neurological disorder caused by abnormal brain chemistry, which leads to a perplexing constellation of symptoms that may include one or more of the following: severe sleepiness, vivid dream imagery upon falling asleep (known as hypnagogic hallucinations) or waking up (hypnopompic hallucinations), waking up paralyzed (sleep paralysis), and sudden-onset temporary muscle weakness (cataplexy). The most common symptom is falling asleep at inappropriate times and places. Narcoleptic patients frequently have difficulty falling asleep and sleeping through the night. Narcolepsy most often comes on in the mid-teenage years, and it affects women and men equally.
Scientists around the world have been trying to determine how common narcolepsy is, and the answer seems to vary from country to country. Narcolepsy appears to be very common in Japan, whereas in North America it is estimated that it affects approximately 1 out of every 2,000 people. Based on research studies, it is estimated that in the United States there are between 100,000 and 150,000 people with the disorder. Most of them have not been diagnosed.
One study of a large group of patients (63 percent women, 37 percent men) in 1997 reported that most had had symptoms for roughly fifteen years before their narcolepsy was correctly diagnosed. People with narcolepsy are often treated for some other condition, often depression, which they might not have. Children might be misdiagnosed with attention deficit disorder or attention deficit hyperactivity disorder (ADD or ADHD) when they are simply too tired to pay attention. Some doctors assume that a woman who is sleepy probably has depression. Not only does the incorrect diagnosis delay the correct treatment, some of the drugs used to treat these disorders can make the narcoleptic’s sleepiness worse. Because the disorder comes on often during the middle teenage years, people with narcolepsy are left untreated at precisely the time when they are going to school and developing the skills that will carry them through the rest of their lives. Teenagers with undiagnosed narcolepsy might feel that they cannot cope with school and drop out. Narcoleptic patients are also at much greater risk of having automobile accidents. Narcolepsy can be especially devastating for caregivers who also work outside the home. Keeping a job is difficult when a person cannot stay awake. Maintaining a relationship is a challenge. Raising children and keeping up with their busy schedules is even more exhausting. Simply put, narcolepsy can ruin lives. It is essential that sufferers get a correct diagnosis as soon as possible.
Narcolepsy seems to be due to the brain’s abnormal regulation of rapid eye movement sleep. As we have seen, during REM sleep (dreaming sleep), humans are paralyzed. (This phenomenon has also been observed in virtually all higher life forms including other mammals and birds.) During REM sleep, the muscles of the body are paralyzed except the ones necessary to sustain life, such as the breathing muscles (diaphragm), the heart and other muscles that are controlled within themselves, and some of the muscles at the top and bottom of the gastrointestinal system.
Scientists have made great strides in the understanding of the brain circuits and chemicals that are involved in REM sleep. But they still cannot explain why we dream and why we are paralyzed during REM sleep, though one hypothesis is that our bodies are paralyzed so that we cannot physically react to our dreams. Normally, adults do not experience the first episode of REM sleep until they have been asleep for about ninety minutes. Thereafter, they will have an episode of REM sleep at roughly ninety-minute intervals. Most people will dream three to five times a night, and while they are dreaming, they are paralyzed. This is normal sleep.
Patients with narcolepsy fall into REM sleep at the wrong time and in the wrong place. The dreamlike imagery that they see at the onset of sleep or even while they are still awake is called a hypnagogic hallucination. Sometimes when a patient with narcolepsy awakens from a dream, the paralysis of REM persists. One eighteen-year-old narcoleptic described his dreams: “I have seen a man at the window with a pointed face, and when he sees that I have seen him he turns around to leave and the entire back of his head is a metal plate that is actually screwed into his head. This is one dream that I had when I was very young and still have recurring dreams with him in them. At the time of this dream I had difficulty believing that this man was not real because I thought I was awake.”
Although we do not know for certain what causes narcolepsy, many clues are coming in from unexpected sources, such as research on Doberman pinschers and mice. (Narcolepsy has been found in several breeds of dogs, including not only Doberman pinschers but Labrador retrievers, poodles, dachshunds, and some mixed breeds.) Science made a huge leap forward recently when a new chemical culprit was discovered that might play a major role in causing narcolepsy. This chemical is known by two names, orexin and hypocretin. Research suggests that patients with narcolepsy do not produce sufficient quantities of this chemical, or that receptors in the nervous system might have stopped responding to it adequately. Experiments have been done in which the genes responsible for the production of this chemical are knocked out in experimental animals; the animals developed the features of narcolepsy, sleep attacks, and cataplexy. The discovery of this chemical and its function will help scientists and doctors better understand and treat this debilitating sleep disorder.
It is believed that narcolepsy has both a genetic component and an auto-immune component. People are not born with the disorder. The symptoms usually appear unexpectedly, although they sometimes show up after a mild infection, a traumatic brain injury, or a concussion. Specific gene variations have been reported recently that show a strong association with the age when some of the symptoms appear.
Narcolepsy can apparently also be triggered by chemicals. In the winter of 2009–10 the world was trying to contain an epidemic of the H1N1 virus (swine flu). A vaccine containing an “enhancer,” a chemical called ASO3, was widely used in Finland, Sweden, and the United Kingdom. Some children and young adults with genetic susceptibility who were vaccinated with this product developed narcolepsy. (This vaccine was never approved for use in the United States.)
One other symptom of narcolepsy, which can be very upsetting to the sufferer, is the experience of a sudden loss of muscle control. This sometimes happens when patients are awake and they become excited. After hearing a joke, for example, a narcoleptic person might feel some of the manifestations of REM sleep come on. These lead to a form of temporary paralysis called cataplexy that can cause the individual to collapse in a heap. One patient said that she felt like a puppet with all the strings cut off whenever she heard a joke. Yet the person is awake and conscious, even though he or she cannot move. Women with cataplexy might not have orgasms during sexual intercourse because they try to avoid arousal that might lead to a cataplexy attack. At other times, the loss of muscle tone is more limited and might involve only the muscles of the face or the neck. These episodes are sometimes misinterpreted as an epileptic seizure.
Depending on the symptoms and with recent understanding of the brain mechanisms, doctors have defined two types of narcolepsy: narcolepsy with cataplexy (now called type 1 narcolepsy) and narcolepsy without cataplexy (now called type 2 narcolepsy). Scientists believe that type 1 narcolepsy is caused by low levels of the chemical orexin or hypocretin, and one way to test for the disorder is to measure the level of this chemical in the fluid that bathes the nervous system.
RECOGNIZING NARCOLEPSY IN OTHERS
In addition to recognizing their own symptoms of narcolepsy, parents and care givers should be alert to symptoms in their children.
Young children. Recognizing narcolepsy in young children is difficult, but there are clues parents can watch out for. A child over the age of five who starts to take naps again might have narcolepsy. Children who fall asleep at the wrong time and in the wrong place—for example, at school, when watching television, or in the car—probably have an abnormal sleep condition. Teachers might tell parents that their child is very sleepy or daydreaming in the classroom. Some children complain of frightening nightmares, which could be hypnagogic hallucinations; parents should pay attention to how frightened the child seems to be and whether specific nightmares recur. One mother described her daughter’s experience: “When she was much younger, she used to come into our bedroom afraid after a dream; we would make her a bed beside ours to sleep there the rest of the night. One particular dream was of a pointed-face man looking into her bedroom window. She was so scared that we actually investigated the window and outside to make sure someone hadn’t been there. We found that it was not physically possible for anyone to be looking in. This was still not enough for her, and we never completely convinced her it wasn’t real. She had many more dreams that unsettled her over the years and some she just could not bring herself to relate to us.”
The child’s sleepiness might appear or be diagnosed as an attention deficit hyperactivity disorder. Children diagnosed with ADD and ADHD are often treated with methylphenidate (Ritalin), a central nervous system stimulant. Thus children with narcolepsy misdiagnosed with ADHD or ADD will have improvement of their sleepiness. Parents should be alert to all the other symptoms, and if they suspect narcolepsy, take the child to a sleep clinic.
Adolescents and teenagers. As we have seen, the onset of narcolepsy frequently comes during the teenage years. The teenager may start to sleep in and have to be dragged out of bed, even though he or she has gone to sleep at a normal time. He or she might fall asleep in school and experience a drop in school performance and grades. People with narcolepsy are almost always sleepy. They differ from normal sleep-deprived teenagers, who become alert as soon as they have a few good nights of sleep. They also differ from teenagers with circadian clock problems (see Chapter 8), who might fall asleep late and wake up late, but who have no trouble staying awake in the afternoon.
The symptoms of these young patients are often interpreted as depression, and their narcolepsy goes undiagnosed and therefore untreated for years. Sometimes children might become so discouraged by the constellation of problems facing them that they start to avoid school. This can also be a warning sign for parents. When children do not want to go to school because they fall asleep in class and their friends make fun of them, it is not a sign of laziness. At this time in an adolescent’s life, when so many hormonal and growth changes are occurring, the addition of the symptoms of narcolepsy can be extremely difficult to deal with. It is essential that teenagers with narcolepsy be diagnosed correctly as soon as possible.
As my colleagues and I reported in a medical article in 2002, family doctors diagnose only about 20 percent of narcolepsy cases even when patients have classic symptoms. One reason why narcolepsy is underdiagnosed is that most doctors do not question patients about how they sleep. And many doctors know little if anything about narcolepsy. In most medical schools, students receive just two to four hours of sleep medicine training during their entire educational process. Most of the patients with narcolepsy that I have seen have a classical clinical history.
For teenagers, often the first symptoms are a drop in grades at school. As a member of the Yale University faculty, I have seen a number of students for whom this was the first symptom. The students have difficulty staying awake in class, trouble concentrating, and difficulty completing their work. Sometimes parents blame their schedules, sometimes they assume the problem is depression. Doctors might even start the student on antidepressants, which could make matters worse.
Yet narcolepsy can be diagnosed in a few minutes if the doctor asks three or four specific questions.
Clinical interview and examination. When was the last time a doctor asked you whether you dream while falling asleep? This and a few other questions can help the doctor make a diagnosis of narcolepsy. The questions might include: Do you fall asleep at the wrong time and place? Do your knees buckle or feel weak if you hear a joke or become angry? Do you sometimes wake up and find that you cannot move? Do you dream during naps?
Because narcolepsy is a lifelong illness that will require lifelong treatment and because narcolepsy patients sometimes suffer from other sleep disorders as well, most sleep specialists will order a sleep test to confirm the diagnosis.
Sleep test. At the sleep lab, doctors perform two types of sleep studies, a nighttime and a daytime study.
The nighttime study (called a polysomnogram) can show the early onset of REM when the patient falls asleep, and the patient’s sleep might be disrupted with many awakenings. Ironically, people with narcolepsy, who fall asleep too easily during the day, often have trouble falling or staying asleep at night. The personnel conducting the study should also look for other disorders that might cause sleepiness such as sleep apnea.
In the daytime study, called a multiple sleep latency test (MSLT), the patient is given four or five twenty-minute opportunities to fall asleep every two hours. If it takes the patient eight minutes or less to fall asleep on average, sleep scientists or technologists can diagnose severe sleepiness; if the person has REM sleep during two or more of the naps, it supports a diagnosis of narcolepsy.
Some patients experience profound sleepiness, but the clinical history does not include the REM-related symptoms that are the hallmarks of narcolepsy (cataplexy, hallucinations, sleep paralysis). When these patients are tested by MSLT, it confirms that they have a form of pathological sleepiness in spite of their sleeping eight hours or more a night. But if they do not have REM sleep during the opportunities to nap the test does not document narcolepsy.
In most cases the cause of the sleep disorder is unknown (hence the name idiopathic, which means “unknown cause”). Some patients may have had a concussion or traumatic brain injury. In most cases we do not know what brought on the condition.
Medical science cannot cure narcolepsy at this time. Instead, doctors must treat the symptoms, recognizing that this is a disease that is not going to resolve on its own. (This is also true of people with idiopathic hypersomnia, for which doctors treat the symptoms—with, in fact, the same medications.) Though the individuals will probably have to use medication for the rest of their lives, their lives can be dramatically improved. They will be able to live a fairly normal life on treatment, and can be successful in their careers and other endeavors.
Sleepiness, which is the most common and debilitating symptom of people with narcolepsy, can be treated with medications that make the patient more alert and help prevent the irresistible urge to fall asleep. There have been exciting developments in new medications, and research is ongoing.
Wake-promoting medications. Armodafinil (Nuvigil) and modafinil (Alertec in Canada, Provigil in the United States, the United Kingdom, and Australia), two related compounds, are the most commonly prescribed treatments to promote wakefulness. Both work on the specific parts of the brain that help maintain alertness. In contrast to stimulant medications, they have little effect on the body’s other functions. These compounds might reduce the levels of estrogen (even those in birth control pills) in the blood, so females are warned to stop taking them when they are trying to become pregnant, and to use an additional form of birth control when they are trying not to become pregnant. Since patients with narcolepsy experience different degrees of daytime sleepiness in response to medications, the dosage needs to be customized to the individual. At this time, these two compounds, along with sodium oxybate, are the only medications approved in the United States for excessive daytime sleepiness associated with narcolepsy.
A reformulation in the past two decades of an old medication (gamma hydroxybutyrate) has been approved for narcolepsy under the name sodium oxybate (Xyrem). This medication, when taken at night, reduces cataplexy the following day. In addition, the medication improves daytime alertness. It is very short acting and thus is usually taken at bedtime and again four hours later. A newer formulation is being developed; this will allow the patient to take a single dose at night. There are tight controls on the use of sodium oxybate. Some antidepressants have also been given at bedtime to reduce REM-related symptoms.
Methylphenidate (Ritalin). Methylphenidate is widely known as the medication prescribed to children with attention deficit hyperactivity disorder. Paradoxically, the drug, used to wake up people with narcolepsy, is also used to calm down people with ADHD; it allows them to focus on their tasks. Besides having an effect on the central nervous system that makes individuals more alert, this medication also affects the sympathetic nervous system, which controls how some of our organ systems work. Stimulation of this part of the nervous system can result in an increased heart rate, rise in blood pressure, and a jittery feeling in some people. Although these symptoms may decrease with time, there is some concern that long-term use by people with narcolepsy could lead to adverse effects on the cardiovascular system. Thus, most sleep experts no longer consider methylphenidate the first drug of choice for increasing alertness in narcolepsy patients.
Amphetamines. For many people, amphetamines are “speed,” illegal street drugs. But amphetamines have been prescribed by doctors for decades for a variety of conditions, and they have been used to treat narcolepsy since the 1930s. Many patients are still treated with them. Amphetamine molecules exist in two forms, which are chemically mirror images of each other. The brand names of preparations in the United States include Adderall (made up of both forms), Dexedrine (made up of one of the forms), and Vyvanse (a chemical that the body turns into one of the forms).
Amphetamines have a powerful stimulant effect on the brain and the sympathetic nervous system. They can also cause increases in heart rate and blood pressure, and they may cause sweating and jitteriness as well. Although amphetamines present the potential for abuse, I have seen this only rarely in my clinical practice. But the potential for abuse has led many countries (though not the United States and Canada) to remove them from the market, which can make crossing borders with them difficult. In some places, the prescription regulations for amphetamines (and other drugs that tend to be abused) are so strict that doctors do not prescribe them. (In some countries, doctors are required to fill out a triple-copy prescription form: one copy of the prescription stays in the doctor’s file, one goes to the pharmacy, and a third goes to the medical licensing authorities, who monitor the usage of such medications. Prescriptions cannot be refilled over the telephone, and only short-term prescriptions are allowed.) In spite of these difficulties, some doctors—perhaps because they are not familiar with modafinil, described above—still prescribe amphetamines as soon as narcolepsy is diagnosed. I rarely prescribe an amphetamine preparation as the first treatment for narcolepsy.
NAPPING AND SCHEDULE ADJUSTMENT
Imagine patients’ surprise when I prescribe naps. Naps can be extremely therapeutic for people with narcolepsy. A short nap of fifteen to thirty minutes can sometimes result in several hours of markedly improved alertness. (Long naps can leave a person feeling drugged or dopey and are not recommended.) Often a nap around lunchtime is sufficient to keep narcoleptic patients alert for several hours; some people may require a second nap later in the afternoon around 4:00 or 5:00. Children with narcolepsy can benefit from a short nap during lunch period at school.
An important aspect in the life of a patient with narcolepsy is finding ways to adjust his or her daytime schedule. Patients might need to take a nap during the day. Schoolchildren might need the school nurse to administer medications or to be allowed extra time to complete an examination. Patients seeking such accommodations find that a letter from the doctor can be helpful.
Living with Narcolepsy
DEALING WITH OTHERS
Hollywood has not been kind to people with narcolepsy. In the movie Deuce Bigalow: Male Gigolo (1999) one of the characters is a woman with narcolepsy who is shown falling face first into a bowl of soup. In Bandits (2001) a bank manager collapses from the excitement of being taken hostage and forced to open a vault.
Whether it is because of the jokes about narcolepsy in popular culture or because the condition is so misunderstood and stereotyped, people with narcolepsy often feel ashamed of their condition or worry that they won’t be taken seriously by co-workers, supervisors, and others. An important aspect of living with narcolepsy is explaining the disease to family and friends. They need to be very direct: “No, I am not stupid. No, I am not lazy. No, I am not bored by what you are saying.” Parents of children with narcolepsy should notify school administrators and teachers and others with whom the child interacts about their child’s problem and its symptoms, explaining that if the child falls asleep it is not a sign of lack of respect or laziness but the result of a neurological disorder. In my experience, when someone with narcolepsy educates the members of his or her community about the disease, people will try to make proper accommodations. For one of my child patients, for example, the school set up a room where she could nap after lunch, which resulted in improvement in her academic performance.
A crucial aspect of daily life that is affected by narcolepsy is driving a car. Driving regulations vary substantially from place to place; in some states people with narcolepsy cannot drive unless they are undergoing treatment. When a child with narcolepsy is about fourteen or fifteen years old, parents need to have a conversation with him or her about the implications of the disorder as it relates to operating a motor vehicle. Even while on treatment, the narcoleptic must be taught about the importance of napping and not driving late at night when the medications might have worn off.
Government regulations in most developed countries do not allow people with narcolepsy to have commercial motor vehicle licenses: for example, they may not drive tractor trailers or buses.
PREGNANCY AND PARENTING
Because narcolepsy usually comes on during the teenage years, it is likely that women with the disease will have to face the problem of what to do about it during pregnancy. In my experience, narcolepsy does not affect fertility. The issue is how to treat symptoms during pregnancy. The safest approach is for the pregnant woman to stop using medications during pregnancy, just as she would stop taking most prescription and over-the-counter drugs. If the alternative treatments such as daytime naps and other accommodations are not possible, the pregnant woman may have to take a medical or other leave from employment. Further, it is dangerous and in many places illegal for her to drive while she is off the medication. Pregnant women must also make sure they do not become deficient in iron and folic acid as that may cause them to develop restless legs syndrome, which would worsen their already severe sleep problem.
After the baby is born, the mother or caregiver must be alert when taking care of both the newborn and any other children. Mothers who have stopped taking medications during pregnancy should probably resume them after the baby is born; however, because the long-term effects of these medications on breastfed babies are not known, pregnant women should discuss the problem with their doctor before giving birth. A narcoleptic mother might decide that bottle-feeding is the best option. Additionally, narcoleptic mothers might find that extra help at home is necessary to help them cope. Fathers could take over the bottle-feeding chores at night, for example. New motherhood can be a trying and tiring time for any woman, but it becomes significantly more so when the new mother is narcoleptic.
Back to the First-Year Med Student
The medical student with narcolepsy had legitimate concerns about how the disorder was going to affect her life, and whether she would be able to complete her studies. Although sleeping had been a problem for her for years, she now knew that her sleep disorder was a medical condition that could be treated, though not cured. I encouraged her to go to her doctor for diagnosis and treatment. I also told her about another medical student I had diagnosed with narcolepsy a few years earlier. This student was referred to me when he was in his last year of medical school. He had been falling asleep at rounds and was functioning at a low level. His instructors believed he was lazy; they wanted me to confirm that there was nothing medically wrong with him so they could fail him. Deciding to fail a student who has already spent more than three years in medical school is not a decision taken lightly, and it is considered only when there are severe performance issues. I found that the student was not lazy; he had instead a classic case of narcolepsy, which had been missed by his professors and doctors—who could have caught it by asking him a few simple questions. He was started on treatment, graduated from medical school and finished his postgraduate specialty training, and is now a successful doctor. After hearing this, the medical student was reassured that there was hope for her. The lecture she might have dozed off in had probably saved her career.
Like people with restless legs syndrome and sleep apnea, narcolepsy sufferers can go undiagnosed for years. Even medical professors can miss the implications of its symptoms; the average overworked family practitioner is even less likely to notice them. But while the quality of life may decrease for RLS sufferers, life itself is at risk for people with sleep apnea or narcolepsy. They need to get an accurate diagnosis as soon as possible.