Epilepsy & Seizures
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Mar. 01, 2021
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What is narcolepsy?
Narcolepsy is a chronic neurological disorder that affects the brain’s ability to control sleep-wake cycles. People with narcolepsy usually feel rested after waking, but then feel very sleepy throughout much of the day. Many individuals with narcolepsy also experience uneven and interrupted sleep that can involve waking up frequently during the night.
Narcolepsy can greatly affect daily activities. People may unwillingly fall asleep even if they are in the middle of an activity like driving, eating, or talking. Other symptoms may include sudden muscle weakness while awake that makes a person go limp or unable to move (cataplexy), vivid dream-like images or hallucinations, and total paralysis just before falling asleep or just after waking up (sleep paralysis).
In a normal sleep cycle, a person enters rapid eye movement (REM) sleep after about 60 to 90 minutes. Dreams occur during REM sleep, and the brain keeps muscles limp during this sleep stage, which prevents people from acting out their dreams. People with narcolepsy frequently enter REM sleep rapidly, within 15 minutes of falling asleep. Also, the muscle weakness or dream activity of REM sleep can occur during wakefulness or be absent during sleep. This helps explain some symptoms of narcolepsy.
If left undiagnosed or untreated, narcolepsy can interfere with psychological, social, and cognitive function and development and can inhibit academic, work, and social activities.
Who gets narcolepsy?
Narcolepsy affects both males and females equally. Symptoms often start in childhood, adolescence, or young adulthood (ages 7 to 25), but can occur at any time in life. It is estimated that anywhere from 135,000 to 200,000 people in the United States have narcolepsy. However, since this condition often goes undiagnosed, the number may be higher. Since people with narcolepsy are often misdiagnosed with other conditions, such as psychiatric disorders or emotional problems, it can take years for someone to get the proper diagnosis.
What are the symptoms?
Narcolepsy is a lifelong problem, but it does not usually worsen as the person ages. Symptoms can partially improve over time, but they will never disappear completely. The most typical symptoms are excessive daytime sleepiness, cataplexy, sleep paralysis, and hallucinations. Though all have excessive daytime sleepiness, only 10 to 25 percent of affected individuals will experience all of the other symptoms during the course of their illness.
Additional symptoms of narcolepsy include:
What are the types of narcolepsy?
There are two major types of narcolepsy:
What causes narcolepsy?
Narcolepsy may have several causes. Nearly all people with narcolepsy who have cataplexy have extremely low levels of the naturally occurring chemical hypocretin, which promotes wakefulness and regulates REM sleep. Hypocretin levels are usually normal in people who have narcolepsy without cataplexy.
Although the cause of narcolepsy is not completely understood, current research suggests that narcolepsy may be the result of a combination of factors working together to cause a lack of hypocretin. These factors include:
How is narcolepsy diagnosed?
A clinical examination and detailed medical history are essential for diagnosis and treatment of narcolepsy. Individuals may be asked by their doctor to keep a sleep journal noting the times of sleep and symptoms over a one- to two-week period. Although none of the major symptoms are exclusive to narcolepsy, cataplexy is the most specific symptom and occurs in almost no other diseases.
A physical exam can rule out or identify other neurological conditions that may be causing the symptoms. Two specialized tests, which can be performed in a sleep disorders clinic, are required to establish a diagnosis of narcolepsy:
What treatments are available?
Although there is no cure for narcolepsy, some of the symptoms can be treated with medicines and lifestyle changes. When cataplexy is present, the loss of hypocretin is believed to be irreversible and lifelong. Excessive daytime sleepiness and cataplexy can be controlled in most individuals with medications.
Lifestyle changes. Not everyone with narcolepsy can consistently maintain a fully normal state of alertness using currently available medications. Drug therapy should accompany various lifestyle changes. The following strategies may be helpful:
Safety precautions, particularly when driving, are important for everyone with narcolepsy. People with untreated symptoms are more likely to be involved in automobile accidents although the risk is lower among individuals who are taking appropriate medication. EDS and cataplexy can lead to serious injury or death if left uncontrolled. Suddenly falling asleep or losing muscle control can transform actions that are ordinarily safe, such as walking down a long flight of stairs, into hazards.
The Americans with Disabilities Act requires employers to provide reasonable accommodations for all employees with disabilities. Adults with narcolepsy can often negotiate with employers to modify their work schedules so they can take naps when necessary and perform their most demanding tasks when they are most alert. Similarly, children and adolescents with narcolepsy may be able to work with school administrators to accommodate special needs, like taking medications during the school day, modifying class schedules to fit in a nap, and other strategies.
Additionally, support groups can be extremely beneficial for people with narcolepsy who want to develop better coping strategies or feel socially isolated due to embarrassment about their symptoms. Support groups also provide individuals with a network of social contacts who can offer practical help and emotional support.
What is the state of the science involving narcolepsy?
In the past few decades, scientists have made considerable progress in understanding narcolepsy and identifying genes strongly associated with the disorder.
Groups of neurons in several parts of the brain interact to control sleep, and the activity of these neurons is controlled by a large number of genes. The loss of hypocretin-producing neurons in the hypothalamus is the primary cause of type 1 narcolepsy. These neurons are important for stabilizing sleep and wake states. When these neurons are gone, changes between wake, REM sleep, and non-REM sleep can happen spontaneously. This results in the sleep fragmentation and daytime symptoms that people with narcolepsy experience.
It remains unclear exactly why hypocretin neurons die. However, research increasingly points to immune system abnormalities. HLA—human leukocyte antigen—genes play an important role in regulating the immune system. This gene family provides instructions for making a group of related proteins called the HLA complex, which helps the immune system distinguish between good proteins from an individual’s own body and bad ones made by foreign invaders like viruses and bacteria. One of the genes in this family is HLA-DQB1. A variation in this gene, called HLA-DQB1*06:02, increases the chance of developing narcolepsy, particularly the type of narcolepsy with cataplexy and a loss of hypocretins (also known as orexins). HLA-DQB1*06:02 and other HLA gene variations may increase susceptibility to an immune attack on hypocretin neurons, causing these cells to die. Most people with narcolepsy have this gene variation and may also have specific versions of closely related HLA genes.
However, it is important to note that these gene variations are common in the general population and only a small portion of the people with the HLA-DQB1*06:02 variation will develop narcolepsy. This indicates that other genetic and environmental factors are important in determining if an individual will develop the disorder.
Narcolepsy follows a seasonal pattern and is more likely to develop in the spring and early summer after the winter season, a time when people are more likely to get sick. By studying people soon after they develop the disorder, scientists have discovered that individuals with narcolepsy have high levels of anti-streptolysin O antibodies, indicating an immune response to a recent bacterial infection such as strep throat. Also, the H1N1 influenza epidemic in 2009 resulted in a large increase in the number of new cases of narcolepsy. Together, this suggests that individuals with the HLA-DQB1*06:02 variation are at risk for developing narcolepsy after they are exposed to a specific trigger, like certain infections that trick the immune system to attack the body.
What research is being done?
The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The NINDS is a component of the National Institutes of Health (NIH), the leading supporter of biomedical research in the world.
The NINDS, along with several other NIH Institutes and Centers, supports research on narcolepsy and other sleep disorders through grants to medical institutions across the country. Additionally, the NIH’s National Heart, Lung, and Blood Institute manages the National Center on Sleep Disorders Research (NCSDR), which coordinates Federal government sleep research activities, promotes doctoral and postdoctoral training programs, and educates the public and health care professionals about sleep disorders. For more information, visit the NCSDR website at www.nhlbi.nih.gov/about/ncsdr.
Genetics and biochemicals. NINDS-sponsored researchers are conducting studies devoted to further clarifying the wide range of genetic —both HLA genes and non-HLA genes—and environmental factors that may cause narcolepsy. Other investigators are using animal models to better understand hypocretin and other chemicals such as glutamate that may play a key role in regulating sleep and wakefulness. Researchers are also investigating wake-promoting compounds to widen the range of available therapeutic options and create treatment options that reduce undesired side effects and decrease the potential for abuse. A greater understanding of the complex genetic and biochemical bases of narcolepsy will eventually lead to new therapies to control symptoms and may lead to a cure.
Immune system. Abnormalities in the immune system may play an important role in the development of narcolepsy. NINDS-sponsored scientists have demonstrated the presence of unusual immune system activity in people with narcolepsy. Further, strep throat and certain varieties of influenza are now thought to be triggers in some at-risk individuals. Other NINDS researchers are also working to understand why the immune system destroys hypocretin neurons in narcolepsy in the hopes of finding a way to prevent or cure the disorder.
Sleep biology. The NINDS continues to support investigations into the basic biology of sleep, such as examining the brain mechanisms involved in generating and regulating REM sleep and other sleep behaviors. Since sleep and circadian rhythms are controlled by networks of neurons in the brain, NINDS researchers are also examining how neuronal circuits function in the body and contribute to sleep disorders like narcolepsy. A more comprehensive understanding of the complex biology of sleep will give scientists a better understanding of the processes that underlie narcolepsy and other sleep disorders.
How can I help research?
The NINDS supports the NIH NeuroBioBank, a national resource for investigators using human post-mortem brain tissue and related biospecimens for their research to understand conditions of the nervous system. The NeuroBioBank serves as a central point of access to collections that span neurological, neuropsychiatric, and neurodevelopmental diseases and disorders. Tissue from individuals with narcolepsy is needed to enable scientists to study this disorder more intensely. Participating groups include brain and tissue repositories, researchers, NIH program staff, information technology experts, disease advocacy groups, and, most importantly, individuals seeking information about opportunities to donate. More information about NeuroBioBank and opportunities to donate tissue is available at https://neurobiobank.nih.gov/.
Additionally, the NINDS supports genetic and immunological research in narcolepsy at Stanford University. Blood samples from individuals with narcolepsy can be sent by mail and are needed to enable scientists to study this disorder more intensely. Prospective donors may contact:
Stanford University Center for Narcolepsy
450 Broadway Street
Redwood City, CA 94063
Where can I get more information?
For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:
P.O. Box 5801
Bethesda, MD 20824
Information is also available from the following organizations:
46 Union Drive #A212
North Kingstown, RI 02852
National Sleep Foundation
1010 N. Glebe Road, Suite 420
Arlington, VA 22201
Wake Up Narcolepsy
P.O. Box 60293
Worcester, MA 01606
National Heart, Lung, and Blood Institute (NHLBI) Health Information Center
National Institutes of Health/DHHS
P.O. Box 30105
Bethesda, MD 20824-0105
U.S. National Library of Medicine
National Institutes of Health/DHHS
8600 Rockville Pike
Bethesda, MD 20894
"Narcolepsy Fact Sheet", NINDS. NIH Publication No. 17-1637.
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892
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