- December 31, 2015
- Posted by: emobile
- Category: Trending Issues
Narcolepsy, one of the most common causes of chronic sleepiness, affects about 1 in 2000 people. Despite the frequency of narcolepsy, the average time from the onset of symptoms to diagnosis is 5 to 15 years, and narcolepsy may remain undiagnosed in as many as half of all affected people with narcolepsy, since many clinicians are unfamiliar with this disorder.
Fortunately, awareness of narcolepsy and other sleep disorders is increasing, and over the past several years researchers have made great progress in understanding narcolepsy. Clinicians now recognize two types of narcolepsy namely Type 1, which is caused by extensive loss of hypothalamic neurons that produce the neuropeptides orexin-A and -B (also referred to as hypocretin-1 and -2) and type 2 includes most of the same symptoms, but its cause is unknown.
Narcolepsy usually begins between the ages of 10 and 20 years with the sudden onset of persistent daytime sleepiness although it can also develop gradually. In many persons with narcolepsy, the sleepiness is severe, resulting in difficulty focusing and staying awake at school, at work, and during periods of inactivity (e.g when watching a movie). Quite often, the diagnosis is made only after serious problems have arisen, such as declining grades at school, poor performance at work, or a motor vehicle accident. Although it may appear to be challenging to distinguish daytime sleepiness due to narcolepsy from that caused by insufficient sleep, especially in teenagers. People with narcolepsy are sleepy every day, even with adequate nighttime sleep. In contrast to people with disorders such as obstructive sleep apnea who have poor-quality sleep, those with narcolepsy usually feel refreshed after a full night’s sleep or a brief nap, but their sleepiness returns 1 to 2 hours later, especially when they are sedentary.
Narcolepsy is also characterized by disordered regulation of rapid-eye-movement (REM) sleep. REM sleep normally occurs only during the usual sleep period and includes vivid, story like dreams, rapid (saccadic) eye movements, and paralysis of nearly all skeletal muscles, except the muscle of respiration. REM sleep can occur in persons with narcolepsy at any time of day, and the classic elements of REM sleep often intrude into wakefulness, creating peculiar intermediate states.
The most dramatic of these REM sleep–like states is cataplexy — sudden episodes of partial or complete paralysis of voluntary muscles. These episodes are triggered by strong emotions , most often by positive emotions such as those associated with laughing at a joke or unexpectedly encountering a friend. In some people, however, cataplexy can be triggered by intense negative emotions, such as frustration or anger. The paralysis usually evolves over many seconds, first affecting the face and neck and then causing weakness in the trunk and limbs, although the muscles associated with breathing are spared. With partial cataplexy, slurred speech and a sagging face are common; with complete episodes, the person may slump to the ground, fully conscious but immobile for as long as 1 or 2 minutes. Children with cataplexy can have long-lasting periods of low muscle tone, with a wobbly gait and perioral movements such as grimacing and tongue protrusion. A patient’s report of a history of cataplexy is diagnostically very helpful to the physician, since cataplexy occurs almost exclusively in type 1 narcolepsy.
The paralysis and dreams typical of REM sleep can also occur at the borders of sleep. Sleep paralysis is much like cataplexy, but it can occur spontaneously on awakening from sleep and occasionally as the person is falling asleep. Dreamlike and often disturbing hallucinations are common in narcolepsy. Those that occur at the onset of sleep are referred to as hypnagogic hallucinations, and those that occur on awakening as hypnopompic hallucinations. Typical hallucinations might include the sense that a threatening stranger is in the bedroom or that one is being attacked by animals. In contrast to people with psychotic disorders, those with narcolepsy rarely have complex auditory hallucinations or fixed delusions, although hypnopompic hallucinations can occasionally be so vivid that the person acts on them (e.g calling the police to report that there is a burglar in the house). Like cataplexy, sleep paralysis and hypnagogic hallucinations rarely last more than 1 or 2 minutes. Because hypnagogic hallucinations and sleep paralysis occur occasionally in about 20% of the general population, they are less informative diagnostically than a history of cataplexy.
Narcolepsy often includes additional problems that may require independent treatment. Although people with narcolepsy are sleepy much the day, they often have fragmented sleep at night and sometimes require treatment with a sleep-promoting medication. They also have a tendency to gain excess weight; at the onset of narcolepsy, children can gain 20 to 40 lb (9 to 18 kg), and the body-mass index in adults is approximately 15% above average, possibly because of a low metabolic rate. Other sleep disorders that are more prevalent among persons with narcolepsy than in the general population include obstructive sleep apnea, periodic limb movement disorder (nocturnal myoclonus), sleepwalking, and REM sleep behavior disorder. In addition, depression is common in persons with narcolepsy, although it remains unclear whether this is due to the effect of narcolepsy on the person’s life or the underlying neuropathologic state.
The diagnosis of narcolepsy is often apparent from the clinical history, but it is essential to confirm the diagnosis with overnight polysomnography followed by a multiple sleep latency test the next day. The overnight sleep study helps rule out other potential causes of daytime sleepiness; in people with narcolepsy, it may show fragmented, light sleep and an early transition into REM sleep (<15 minutes after the onset of sleep). During the multiple sleep latency test, the patient is encouraged every 2 hours to fall asleep for 20 minutes; the test usually begins at 8 a.m. and ends at approximately 5 to 6 p.m. Given the opportunity to nap, people with narcolepsy usually fall asleep in less than 8 minutes, whereas healthy people generally fall asleep in 15 minutes or more. In addition, people with narcolepsy usually have REM sleep during at least two of these daytime naps (known as sleep-onset REM sleep periods), whereas people without narcolepsy rarely have any daytime REM sleep. A positive multiple sleep latency test (defined as a short time to fall asleep plus REM sleep in at least two of the naps) provides strong, objective evidence of excessive sleepiness and poorly regulated REM sleep.
Because the diagnosis of narcolepsy relies heavily on the multiple sleep latency test, it is essential that the test be performed under the correct conditions. Medications that suppress REM sleep should be discontinued well in advance of the test (e.g 3 weeks for antidepressants with a long half-life), and any other psychoactive medications, especially stimulants, should be discontinued 1 week in advance. The patient should obtain and document with a sleep log an adequate amount of sleep each night in the week before the multiple sleep latency test, since inadequate nighttime sleep may result in short daytime sleep latencies. During the overnight sleep study preceding the test, adults should get at least hours of sleep, and children should get more. Adherence to these conditions is important, because people with sleep deprivation or shift-work schedules and those who receive psychoactive medications can have test results that are similar to those seen in people with narcolepsy.
Narcolepsy is treated with a combination of behavioral and pharmacologic approaches. Daytime sleepiness often partially decreases with sufficient good-quality sleep at night and a 15-to-20-minute nap in the afternoon. Any additional sleep disorders in the patient, such as sleep apnea, should also be addressed. The Epworth Sleepiness Scale is a helpful tool for assessing subjective sleepiness and the response to medications. The multiple sleep latency test and the maintenance of wakefulness test, which measures alertness during the day, can provide complementary, objective measures of the degree of sleepiness.
Even with good nighttime sleep, daytime naps, and appropriate medications, many people with narcolepsy still have some lingering daytime sleepiness and in attentiveness. Thus, it is important for people with narcolepsy to have honest discussions with their family members and medical providers about lifestyle choices. For example, the risk of motor vehicle accidents among people with narcolepsy is increased by a factor of three to five; some people may therefore choose to take a stimulant before driving, drive only for short periods, or not drive at all. With regard to work, persons with narcolepsy can thrive in stimulating environments such as teaching, but sedentary jobs that require sustained attention may be a poor fit.
Article of Thomas E. Scammell, M.D.
The New England Journal of Medicine