Narcolepsy and Cataplexy

What causes narcolepsy?

There have been major breakthroughs in understanding the cause of narcolepsy. We know that most cases of narcolepsy in humans are due to a lack of a chemical in the brain called hypocretin. This chemical was unknown before 1998, so this is very new research. Most patients with narcolepsy do not produce hypocretin in a deep part of the brain called the hypothalamus. If you don't produce hypocretin, it would appear that other chemicals that cause alertness cannot function properly.

Research studies have shown that most narcoleptic patients don't have hypocretin in their spinal fluid, and it is possible that this may become a diagnostic test for narcolepsy in the not-too-distant future. What we don't know is why patients with narcolepsy don't produce hypocretin. We think this is probably due to an attack of the body's immune system against the cells that produce it, but this is still speculative. But we are engaged in research projects to try to establish this.

What are the warning signs?

The most important symptom of narcolepsy is sleepiness. Of course, there are many causes of sleepiness, including sleep deprivation, the effect of medications or obstructive sleep apnea, and narcolepsy is not the most common cause. But in any young person who develops sleepiness, narcolepsy has to be considered. Sleepiness is not a specific symptom of narcolepsy.

The most specific symptom is cataplexy, a sudden weakness of the muscles of the body, especially the legs but also the face and neck, that is brought on by strong emotion, especially laughing. Patients with narcolepsy may also have strange dreamlike experiences before falling asleep or waking up in the morning, and they may also have temporary paralysis of the body at the same time. However, these two symptoms are common in the general population and by themselves do not make one a narcoleptic.

Who is affected by narcolepsy?

The frequency of narcolepsy in North America has been quite uncertain. It varies from country to country. It is most common in Japan, and rare in Israel. We embarked on a study to get good epidemiological data on the occurrence of narcolepsy in the US. What we found is that narcolepsy is not uncommon. In a million people, we would expect about 550 narcoleptics and approximately 14 new cases of narcolepsy a year. What we found was that the first symptoms start most frequently between the ages of 10 and 20.

The second most frequent time of onset was the decade between ages 20 and 30, and the third most frequent was before the age of 10 and between the ages of 30 and 40. So narcolepsy is a disorder that frequently starts in young people, and physicians who look after adolescents should be especially aware of it. We found that it is slightly more common in men than in women, a ratio of 1.5 to 1. We have no explanation for this phenomenon at present. We also found that one doesn't have to have cataplexy in order to have narcolepsy. About 1/3 of narcolepsy patients don't develop cataplexy.

How is it treated?

A sleep physician will take a careful history from the patient and his or her bed partner. A diagnosis is confirmed with an overnight sleep study and then a series of nap studies the following day, conducted every two hours. From this we will be able to see how quickly the patient falls asleep and whether they go quickly into rapid eye movement (REM) sleep. The propensity to go quickly into REM sleep is a marker for narcolepsy.

At present, we treat the symptoms; we don't treat the cause of the condition. We give medications that increase chemicals in the brain that are responsible for alertness.

There are a number of such medications available. Most narcoleptics are able to achieve 80% or more of their potential alertness with proper medication. We also have medications to treat cataplexy. Eventually we hope to have medications that act on the hypocretin system to treat the underlying cause, but that may be quite a while in the future.

--Michael H. Silber, MD, is a neurologist and sleep disorders specialist at the Mayo Clinic who recently conducted the first definitive epidemiologic study of narcolepsy in the United States. The study was published in the journal SLEEP.

This article originally appeared in the Fall 2002 issue of sleepmatters.