Sleep Disorders

Narcolepsy affects an estimated 25 in every 100,000 people in the United States . This sleep disorder is primarily characterized by intermittent, uncontrollable episodes of falling asleep during the daytime. Three additional symptoms are typically associated with narcolepsy: cataplexy (short-lived intermittent muscle weakness), hypnogogic and hypnopompic hallucinations (hallucinations while falling asleep or waking), and sleep paralysis (paralysis while falling asleep or waking). Narcolepsy usually begins when a person is in their teens or early twenties. Stimulants and antidepressants are used to treat narcolepsy and subsequent cataplexy. Although it has been linked with blood pressure management and depression, the genesis of narcolepsy is unknown. However, recent advances in narcolepsy study suggest the possibility of a cure.

INCIDENCE

Narcolepsy usually begins in the teens or early twenties (10 to 20 years old), but this varies; both young children and the elderly experience sleep attacks as well. Approximately 125,000 people in the United States alone suffer from this disorder, with an equal incidence among both women and men. Excessive daytime sleepiness and sudden sleep onset are the hallmarks of narcolepsy. Whether narcolepsy is a life-long disorder or not is controversial. Some evidence suggests that it is, while other studies have shown that symptoms fade in older age.

CAUSES

Narcolepsy is a syndrome of unknown cause; therefore, it is helpful to look at related problems. Narcoleptic dysfunction may be associated with genetic links, rapid eye movement (REM) sleep disorder, and blood pressure issues.

Although poorly defined, there is some hereditary component to the occurrence of narcolepsy. People with narcolepsy have a slightly increased incidence of it in the family. In fact, narcolepsy fits the paradigm established by most sleep disorders, in which there exists a family history of a specifically nonhereditary disorder. However, there is a genetic linkage between narcolepsy and a certain human leukocyte antigen (HLA) type, HLA DQB1 0602. Approximately 90% to 100% of patients with narcolepsy have this HLA type, as opposed to less than 50 percent of nonnarcoleptic patients. Despite the fact that these findings are currently inconclusive, they suggest that immune system studies are the future of genetic narcolepsy investigation. It may be that all sleep disorder patients share a genetic predisposition to their symptoms.

Physiologically, several interrelated functions seem to precede and accompany the various symptoms of narcolepsy. Narcolepsy patients have shown REM sleep control dysfunction in some studies. Specifically, immediate REM sleep characterizes narcoleptic sleep attacks. In patients with normal sleep-wake patterns, REM sleep usually occurs 90 minutes after sleep onset. In some studies, 50% of patients with narcolepsy experienced REM sleep within the first 10 minutes of sleep. The result is a disruption of the natural sleep cycle, replete with myoclonic movements and less time spent in deep sleep. The cause may be a general change in biorhythm associated with narcolepsy.

There has also been some speculation about the function of blood pressure regulation in narcolepsy. Blood pressure fluctuation has been linked to the atony (loss of muscle tone) patients experience while in a cataplexic state. Furthermore, a similar loss of muscle tone is characteristic of REM sleep.

SYMPTOMS

Narcolepsy is technically defined by excessive daytime sleepiness and sleep attacks, in conjunction with one or more auxiliary symptoms, which can include cataplexy, hallucination, and sleep paralysis. The entire tetrad of symptoms, as it is often called, occurs only in about 10 percent of cases. Cataplexy is the most common auxiliary symptom of narcolepsy, afflicting roughly 70 percent of patients. Sleep paralysis and hypnogogic and hypnopompic hallucinations are less common. Sleep paralysis occurs in 30 percent of cases, and hallucination in approximately 25 percent. In narcoleptic patients, these symptoms usually accompany cataplexy; they rarely occur on their own. When they occur as a set, the symptoms are intensified.

Excessive Daytime Sleepiness and “Sleep Attacks”

The most prevalent symptom of narcolepsy is suddenly and unexpectedly falling asleep during the day. In fact, narcoleptic attacks often occur at inappropriate times with significant consequences for those who experience them. For example, patients with narcolepsy may fall asleep while driving, during a meeting, and even during sex.

A typical bout of sleep may last 15 minutes to an hour, rarely longer. Sleep can reoccur within one to several hours. Usually, a patient wakes up refreshed, tires slowly within an hour or two, and then falls asleep again. The cycle then repeats. Some people may not actually fall asleep but struggle with extreme sleepiness throughout the day. Excessive daytime sleepiness has been documented in studies using EEGs that show the occurrence of abnormal daytime biorhythms. Many people with narcolepsy try to combat the overwhelming urge to sleep with stimulants like caffeine or other drugs. Uncontrollable sleepiness, combined with continual efforts to resist it, often leads to significant disruption in the lives of people with narcolepsy. Usually, a day’s worth of compounded sleepiness results in deep, brief sleep episodes.

It may seem that narcolepsy patients would have normal nocturnal sleep habits. Ironically, this is not the case. When measured with polysomnography, narcolepsy patients demonstrate nonspecific changes in their sleep pattern, which include an increased number of arousals, sleep maintenance insomnia, and less time spent in stage 1 sleep.

Cataplexy

Cataplexy, the most prevalent secondary symptom of narcolepsy, is almost exclusive to narcolepsy. It is the sudden, temporary loss of muscle tone in the body. When loss of muscle strength is severe, all the voluntary muscles in the body are affected, leading to complete collapse. In mild cases, the loss in muscle strength can be quite subtle, partially involving only a few muscle groups. For example, partial neck muscle weakness may cause a person to struggle to keep their head from drooping. Interestingly, the muscles of the eyes are not affected during cataplexy; individuals can move their eyes during a cataplectic episode. The effects of cataplexy are all- consuming, which makes it nearly impossible for a bystander to guide an individual out of an episode. Furthermore, loss of muscle function may not be evident, and the patient may experience only a vague feeling of weakness. Cataplectic episodes usually last from a few seconds to 30 minutes; rarely does an attack last longer.

Cataplexy is thought to occur during times of intense emotional states. For example, the shock of winning the lottery or extreme anger may trigger an episode. This distinguishes cataplexy from its host condition, narcolepsy, whose onset does not discriminate with regard to the patient’s emotional state.

During a cataplectic attack, the person is completely awake and later will have total recall of the entire event. If episodes last longer than a few minutes, the patient may begin to hallucinate (distinguishable in occurrence from those described below). It is extremely rare for cataplexy to occur independently of narcolepsy. Indeed, excessive daytime sleepiness and cataplexy are sufficient for a diagnosis of narcolepsy.

Hypnogogic and Hypnopompic Hallucinations

Hypnogogic and hypnopompic hallucinations are not peculiar to narcolepsy, though they occur at a very high rate of frequency in most cases of narcolepsy. However, they are the predominant subsymptom in only an estimated 5 percent of narcolepsy patients and appear in other disorders as well. Hypnogogic hallucinations occur while falling asleep and hypnopompic hallucinations upon awakening. Both last a few minutes. The hallucinations can be visual, auditory, or tactile and often frighten or disconcert the patient with terrifying shapes and noises. It is possible to wake up a patient during hypnogogic and hypnopompic hallucinations without further distressing them.

These hallucinations are similar to nightmares, in that they are typically more intense, and their effects last longer than mild dreams or daydreams. In the past, patients who suffered from hallucinations were sometimes misdiagnosed as schizophrenic.

Sleep Paralysis

Sleep paralysis, the inability to move immediately before falling asleep or upon awakening, has been described and documented since the early 19th century. People who experience sleep paralysis have described feeling afraid, as if some person or creature were sitting on their chest, holding them down.

Like hypnogogic and hypnopompic hallucinations, sleep paralysis is a nonexclusive secondary symptom of narcolepsy. Sleep paralysis usually lasts from a few seconds to 30 minutes and is usually accompanied by hypnogogic and hypnopompic hallucinations. Like hallucinations, sleep paralysis can be alleviated temporarily if an observer intervenes and wakes up the patient.

DIAGNOSIS

Diagnosis of narcolepsy is based on the clinical recognition of excessive daytime sleepiness, uncontrollable sleep, observed cataplexy, and the exclusion of other causes of excessive daytime sleepiness. The occurrence of hypnogogic and hypnopompic hallucinations or sleep paralysis suggests narcolepsy, but because they are not exclusive to the condition, they are not essential components of a diagnosis.

It is important to review the entire sleep history. A patient is often asked to keep a two-week sleep diary so that his or her doctor can evaluate the quality of recent sleep and exclude the possible influence of other sleep disorders.

Peripheral Concerns with Narcolepsy

Although the symptoms of narcolepsy seem distinct to the disorder, they warrant differential diagnosis. Symptoms like excessive daytime sleepiness are also indicative of serious physiological diseases and disorders, ranging from brain tumors to heart disease to anemia. Uncontrollable sleep related to these conditions is often more extensive; it lasts longer and does not usually allow the patient to feel refreshed.

In addition, affective disorders, including various types of depression, share symptoms with narcolepsy. The extent to which depression is found in cases of narcolepsy has not been thoroughly examined. Complaints of tiredness and disrupted sleep are often the product of depression or stress. Both conditions respond to REM sleep manipulation. Distinguishing the presence of narcolepsy from these conditions may require comprehensive lifestyle assessment.

Diagnostic Tests

It usually is difficult to confirm true cataplexy or to rule out other causes of excessive daytime sleepiness, so overnight polysomnography and a multiple sleep latency test (MSLT) are performed. Before polysomnographic testing is performed, a minimum two-week withdrawal period from any drugs with side effects that disrupt sleep is usually required; these include alcohol, antidepressants, narcotics, and other medications.

On rare occasions, blood testing for HLA type may support the clinical theory that a distinct HLA type exists in narcolepsy patients.

Multiple Sleep Latency Test

Once a "normal" night's sleep has been confirmed and other causes of excessive daytime sleepiness, such as obstructive sleep apnea (OSA) and periodic limb movement disorder (PLMD) have been excluded, a multiple sleep latency test (MSLT) is performed, usually the morning after polysomnography. The MSLT is a similar test, but it measures fewer parameters. The MSLT measures EEG, EOG, chin EMG, and usually heart rate. The patient attempts to take four to five 20-minute naps (depending on the protocol) every 2 hours throughout the day. After these naps, the time it takes the patient to fall asleep (sleep latency) is averaged. Sleep latency usually fluctuates in narcolepsy patients, where it may lengthen, but will most often remain shorter than normal latency.

In addition to measuring sleep latency, sleep technicians also assess the patient's REM sleep patterns. Rapid eye movement sleep during the first 15 minutes of sleep is called sleep onset REM (SOREM). The occurrence of SOREM is indicative of severe sleep deprivation or narcolepsy and is almost exclusive to these conditions. A positive MSLT for narcolepsy is generally indicated by two factors, sleep latency of less than 8 minutes and two or more occurrences of SOREM.

Fewer than 10% of patients demonstrate narcoleptic sleep latencies that are longer than 8 minutes. It is fairly common for patients to exhibit SOREM twice during an MSLT; this happens in approximately 16% of cases.

Narcoleptic sleep patterns obtained from the MSLT create a strikingly objective picture that provides an understanding of narcolepsy as an imposing and disturbing condition.

The maintenance of wakefulness test (MWT) and the repeated test of sustained wakefulness (RTSW), also used to measure daytime sleepiness, are similar to the MSLT. However, unlike the MSLT, patients participating in the MWT or RTSW try to stay awake. Pupillometry, the study of pupil diameter, also can be pertinent in narcolepsy cases, because the pupil diameters of narcoleptic patients may vary rhythmically in the dark.

TREATMENT

There is no cure for narcolepsy, so excessive daytime sleepiness, sudden sleep onset, and cataplexy is treated symptomatically. Therapies for narcolepsy involve the practice of getting sufficient nocturnal sleep, proper sleep hygiene practice, and drug therapy. Proper sleep hygiene, which includes a consistent sleep schedule and the avoidance of shift work and alcohol, is especially important.

Patients with narcolepsy often feel refreshed after a short nap; therefore, taking short scheduled naps may greatly benefit patients combating excessive daytime sleepiness. For example, a 15-minute nap after lunch and another at 5:30 p.m. may help diminish the intensity of daytime sleepiness and provide temporary alertness.

DRUG THERAPY

Stimulants are the mainstay of drug therapy for excessive daytime sleepiness and sleep attacks in narcolepsy patients. These include methylphenidate (Ritalin®), modafinil, dextroamphetamine, and pemoline. Dosages of these medications are determined on a case-by-case basis, and they are generally taken in the morning and at noon . Other drugs, such as certain antidepressants and drugs that are still being tested in the United States are also used to treat the predominant symptoms of narcolepsy.

The major side effects of these stimulants are irritability, anxiety, quickened heart rate, hypertension, substance abuse, and disturbances of nocturnal sleep. Methylphenidate and dextroamphetamine are known to cause hypertension. A common side effect of modafinil is headache, usually related to dose size, which occurs in up to 5 percent of patients. Pemoline poses a very low but noticeable risk for liver complication. None of these stimulants influences the occurrence of narcolepsy’s auxiliary symptoms and usually are not used to treat them.

Modafinil does not carry the addiction potential that methylphenidate and dextroamphetamine do. In fact, the latest development in treatment is a new modafinil drug called Provigil®, which does not act as a stimulant and so does not produce side effects like anxiety and irritability. Provigil®’s therapeutic effects have been observed in maintenance of wakefulness test research, where patients have tripled their wakefulness.

Treatment of Auxiliary Symptoms

Pharmacological control of narcolepsy’s auxiliary symptoms - cataplexy, hypnogogic and hypnopompic hallucinations, and sleep paralysis - is achieved with antidepressants and selective serotonin reuptake inhibitors (SSRIs).

Tricyclic antidepressants, such as imipramine or chlorimimipramine, are the most widely prescribed medications for the three subsymptoms of narcolepsy. In some cases, they have improved symptoms within two days. Side effects include dry mouth, blurred vision, and sweating, among others.

Selective serotonin reuptake inhibitors, such as fluoxetine (Prozac®), work especially well in treating cataplexy. These medications have even affected the frequency of sleep attacks in some cases. Cataplexy is often much worse in sleep-deprived patients with poor sleep hygiene; therefore, establishing good sleep practices may be the most important aspect of controlling cataplexy.

Recent Developments in Treatment and a Possible Cure

The study of narcolepsy in other animals has illuminated continuities between human narcolepsy and that found in dogs and mice. This information is being used to try to find the cause of the condition and to improve treatment for human narcolepsy. The inheritance of narcolepsy in dogs is distinct from human patterns and is much better defined. These studies have focused on the biochemical dissimilarities that exist between humans and other animals, dissimilarities that may lead to new treatment.

Currently, researchers are working with a gene they believe is responsible for narcolepsy. Comparison between the human gene map and the genes of dogs who suffer from narcolepsy has led to the discovery of a mutual deficiency in hypocretin, a chemical in the brain whose absence seems to correspond to narcolepsy. Narcoleptic dogs are being injected with this chemical in an attempt to affect the symptoms of narcolepsy and cataplexy. At this point, researchers expect that a version of this substance will be administered to human narcolepsy patients in the future. Treatment with hypocretin would not only treat the symptoms of narcolepsy but the underlying deficiency that may cause it; a cure for narcolepsy may exist in the future.