Excessive Sleep Disorder
Excessive daytime sleepiness or Hypersomnolence
- Recurrent Hypersomnia
- Idiopathic Hypersomnia
- Posttraumatic Hypersomnia
Narcolepsy is a disabling neurological disorder of sleep regulation that affects the control of sleep and wakefulness. It may be described as an intrusion of the dreaming state of sleep (called REM or rapid eye movement sleep) into the waking state. Symptoms generally begin between the ages of 15 and 30. The four classic symptoms of the disorder are excessive daytime sleepiness; cataplexy (sudden, brief episodes of muscle weakness or paralysis brought on by strong emotions such as laughter, anger, surprise or anticipation); sleep paralysis (paralysis upon falling asleep or waking up); and hypnagogic hallucinations (vivid dream-like images that occur at sleep onset). Disturbed nighttime sleep, including tossing and turning in bed, leg jerks, nightmares, and frequent awakenings, may also occur. The development, number and severity of symptoms vary widely among individuals with the disorder. It is probable that there is an important genetic component to the disorder as well. Unrelenting excessive sleepiness is usually the first and most prominent symptom of narcolepsy. Patients with the disorder experience irresistible sleep attacks, throughout the day, which can last for 30 seconds to more than 30 minutes, regardless of the amount or quality of prior nighttime sleep. These attacks result in episodes of sleep at work and social events, while eating, talking and driving, and in other similarly inappropriate occasions. Although narcolepsy is not a rare disorder, it is often misdiagnosed or diagnosed only years after symptoms first appear. Early diagnosis and treatment, however, are important to the physical and mental well-being of the affected individual.
Scientists believe they may have identified the cause of the debilitating sleep disorder narcolepsy in humans. A new study shows a dramatic reduction – up to 95 percent – in the number of neurons containing a substance called hypocretins in the brains of people with narcolepsy compared to control brains. Hypocretin peptides are neurotransmitters that play an important role in regulating sleep and appetite. The researchers hypothesize that the pronounced loss of these neurons could be caused either by a neurodegenerative process or an autoimmune response.
Narcolepsy is a disabling sleep disorder that affects 135,000 Americans. Patients suffer from excessive daytime sleepiness; sudden brief episodes of muscle weakness or paralysis, also called cataplexy; paralysis while sleeping or upon waking up; and vivid dream-like images that occur at sleep onset. The disorder is often difficult to diagnose, and there is presently no cure.
The study, led by Jerome M. Siegel, Ph.D., Professor of Psychiatry and Biobehavioral Sciences at the University of California at Los Angeles, and Chief of Neurobiology Research at the Veterans Administration in Sepulveda, is being published in the September 2000 issue of Neuron. Dr. Siegel’s work is supported in part by the National Institute of Neurological Disorders and Stroke (NINDS).
Recent studies have shown that there is a genetic component to narcolepsy in dogs and mice involving mutations of the hypocretin precursor or receptor genes. However the authors point out that the genetics of human narcolepsy are well defined – most narcoleptics generally do not have first degree relatives with the disorder. When present in identical twins, in most cases only one twin is affected.
Because narcolepsy does not occur until later in life, after age 15 and into the 30’s, the researchers hypothesized that a loss of hypocretin neurons after birth could be responsible for narcolepsy. To test this theory they conducted a neuropathological study involving 16 human brains.
The researchers stained the hypothalamus region of four narcoleptic brains and 12 neurologically normal brains. The staining revealed the presence of hypocretin neurons and melanin concentrating hormone (MCH) neurons, which are intermixed with hypocretin neurons in the normal brain. The narcoleptic brains showed a dramatic loss of hypocretin cells, between 85 and 95 percent fewer than the normal brains. There was no marked difference in the number of MCH neurons, showing that it was the loss of hypocretin cells specifically that was significant in the narcoleptic group.
The narcoleptic brains also revealed signs of an inflammatory process called gliosis, which is linked to neuronal degeneration and may explain the loss of the hypocretin cells.
There has been other speculation that an autoimmune process might cause narcolepsy, although no clear evidence for this has been found in human studies. Dr. Siegel and his colleagues state that autoimmune attacks on the hypocretin neurons or cellular sensitivities to environmental or biological toxins are "reasonable possibilities" for the cause of the degeneration.
The findings suggest that replacement of the missing hypocretin cells may reverse the symptoms of narcolepsy, and this has been recently demonstrated by Dr. Siegel’s group in dogs. It is possible that administration of hypocretins to humans with narcolepsy may be an effective treatment.
A similar study led by NINDS grantee Emmanuel Mignot, MD, Ph.D. director of the Center for Narcolepsy at Stanford University Medical Center, will appear in the September 2000 issue of Nature Medicine. Dr. Mignot’s group looked at the role of hypocretins in six narcoleptic brains and also did genetic screening of 74 patients. In the neuropathology tests, the researchers found that concentrations of hypocretins were "undetectable" in the brain tissue of narcoleptic patients. In the genetic testing, the researchers found a genetic mutation in the hypocretin system of one very severe early onset case of narcolepsy. However, there was a very low frequency of genetic mutations in the other narcoleptic patients screened. The authors conclude that, "although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system."
"The results of both of these studies provide dramatic insight into the neurobiology of a very perplexing sleep disorder, and may lead directly to new therapeutic approaches for narcolepsy," said Cheryl Kitt, Ph.D, program director for NINDS.
The NINDS, part of the National Institutes of Health in Bethesda, Maryland, is the nation’s leading supporter of research on the brain and nervous system. The NINDS is now celebrating its 50th anniversary.
Individuals with this disorder have recurrent episodes of extreme sleepiness and significant sleep requirements. Hypersomnia may days or even weeks, and occur twice a year, on average (although they may occur multiple times a year). Individuals afflicted with this disorder have been known to sleep as much as 16 to 20 hours a day.
Idiopathic Hypersomnia is a disorder in which the individual may complain of excessive sleepiness and prolonged sleep at night. The difference between this disorder from normal long sleepers and narcoleptics is these individuals suffer numerous episodes of non-REM sleep that can last for up to two hours. Hence, this disorder is sometimes called non-REM narcolepsy.
Posttraumatic Hypersomnia is excessive sleepiness that develops as the result of physical injury or disease in the central nervous system. For example, a brain injury, neurosurgery, infection, or spinal cord injury. Typcially, hypersomnia usually goes away over weeks or months.
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