The Neuroanatomy and Neurochemistry of Sleep. The Neurophysiology of Sleep
More Sleep Notes
Narcolepsy is a life-long, currently incurable neurological disorder. It is not life-threatening (aside from increasing the chances of a person being in an accident), but it does seriously reduce a person's quality of life. Untreated narcolepsy can be psycho-socially devastating and career limiting. It is characterized by:
(not everyone with narcolepsy has all of these symptoms, only about 15% do)
-excessive daytime sleepiness
-disrupted sleep at night
-sleep paralysis
-sleep onset REM
-hallucinations at sleep onset (hypnogogic hallucinations)
-cataplexy (means "falling down seizure", from Greek roots).
Cataplexy tends to be brought on by strong emotions, especially positive ones. Laughter is a common trigger. The incidence of narcolepsy in the US is about 1 in 2,000 people, or about 300,000 people total, which is about the same incidence as MS. The symptom that often begins the process of medical diagnosis is excessive daytime sleepiness, which can be so overwhelming that the person is unable to resist falling asleep during activities such as working, eating, or driving. Because there are other causes of excessive daytime sleepiness, other signs of narcolepsy need to be present for a diagnosis to be made. A definitive diagnosis can be made if the person lacks a neurotransmitter called Hypocretin in their cerebro-spinal fluid. This is not a preferred method of diagnosis because a spinal tap is such an invasive procedure.
Sleep paralysis is experienced by about half of people with narcolepsy, and about 25% of the population at one time or another, so does not in itself mean that a person has narcolepsy. It is a temporary inability to move or speak, often accompanied bu strange visions. It occurs when part of REM sleep happens when the person is awake. The reason that sleep paralysis is more common upon waking is because people generally awaken from REM sleep, but generally fall asleep into non-REM sleep. Sleep onset REM is another sign of narcolepsy. Hypnogogic hallucinations are experienced by about one third of people with narcolepsy, and are vivid and often terrifying visions (or sounds). They are the nightmare component of REM sleep occurring during wakefulness.
About 75% of people with narcolepsy experience cataplexy, which is when the muscle atonia of REM sleep occurs during wakefulness. People can experience partial cataplexy, which can include slurred speech, lack of facial expression, drooping of the head and eyelids, buckling of the knees, and weakness in the arms. The episode can escalate into a collapse. People can often anticipate a cataplectic attack and can take measures such as sitting down to avoid injury. Attacks usually last only a few minutes. Longer attacks are more likely to be accompanied by hypnogogic hallucinations.
There is no clear genetic inheritance pattern for narcolepsy as there is in genetic disorders such as Cystic Fibrosis or Sickle Cell Anemia, but relatives of people with narcolepsy have a risk 10 to 40 times greater than the general population, so there is clearly some genetic element. When one identical twin has narcolepsy, there is only a 25-30% chance that the other twin also has it. This means that while there is a weak genetic aspect to the disorder, there must also be an environmental factor. A gene was found in humans that affects the hypothalamus, and because the product of this gene is similar to a hormone that occurs in the gut called secretin, this gene and it's product were named Hypocretin (also called orexin by another team of researchers). This other team of researchers found evidence that this hormone may also play a role in appetite and eating behavior. Mice who were genetically engineered to not produce hypocretin/orexin slept more during their usual awake period, ate less, and had what looked like cataplectic episodes.
So there is a peptide produced in the hypothalamus called hypocretin, for which there are receptors in various parts of the brain including the nucleii involved in promoting wakefulness. This hypocretinergic system (cells that respond to hypocretin) are well positioned to orchestrate rousing the animal from sleep and to keep it in an awake state. It was found in studies that healthy subjects had measurable levels of hypocretin in their cerbro-spinal fluid, but that in people with narcolepsy there was little or no measurable hypocretin. Post-mortem studies found that the hypothalami of normal subjects had plentiful numbers of hypocretin cells, but samples taken from narcoleptic people showed very few. They also found evidence of cell damage in areas where the hypocretin cells should have been.
Narcolepsy usually has an onset in the late teens to early adulthood, and people with narcolepsy usually share a particular immune system gene (an HLA gene). This strongly indicates that narcolepsy is an autoimmune disease. There is no cure for narcolepsy and treatment usually focuses on addressing the excessive daytime sleepiness. Sleep hygiene is the basis, such as following a regular sleep schedule, which includes winding down before bed, having a good sleep environment (such as no work items in the bedroom), and no heavy meals, caffeine or alcohol before bed. Scheduled naps can also help. Medical treatments include stimulant (often Ritalin), sleeping medications, medications to help with cataplexy, and antidepressants. People with narcolepsy often self-medicate with coffee and other sources of caffeine. The other commonly used stimulant is a drug called Provigil, which enhances dopamine neurotransmission. It is a selective dopamine reuptake inhibitor.
A number of drugs that are used as antidepressants are also effective against cataplexy. Two of these drugs (imipramine and clomipramine) are tricyclic antidepressants. These drugs block the reuptake of serotonin and norepinephrine. Prozac is also effective against cataplexy. All of these drugs enhance the effectiveness of neurotransmitters that promote wakefulness and vigilance. There is a newer drug called Xyrem, also known as gammahydroxybutyrate. It elevates the release of growth hormone. This research into treating narcolepsy has led to the concept of developing drugs that block hypocretin receptors as a way to treat insomnia.
More Sleep Notes
Narcolepsy is a life-long, currently incurable neurological disorder. It is not life-threatening (aside from increasing the chances of a person being in an accident), but it does seriously reduce a person's quality of life. Untreated narcolepsy can be psycho-socially devastating and career limiting. It is characterized by:
(not everyone with narcolepsy has all of these symptoms, only about 15% do)
-excessive daytime sleepiness
-disrupted sleep at night
-sleep paralysis
-sleep onset REM
-hallucinations at sleep onset (hypnogogic hallucinations)
-cataplexy (means "falling down seizure", from Greek roots).
Cataplexy tends to be brought on by strong emotions, especially positive ones. Laughter is a common trigger. The incidence of narcolepsy in the US is about 1 in 2,000 people, or about 300,000 people total, which is about the same incidence as MS. The symptom that often begins the process of medical diagnosis is excessive daytime sleepiness, which can be so overwhelming that the person is unable to resist falling asleep during activities such as working, eating, or driving. Because there are other causes of excessive daytime sleepiness, other signs of narcolepsy need to be present for a diagnosis to be made. A definitive diagnosis can be made if the person lacks a neurotransmitter called Hypocretin in their cerebro-spinal fluid. This is not a preferred method of diagnosis because a spinal tap is such an invasive procedure.
Sleep paralysis is experienced by about half of people with narcolepsy, and about 25% of the population at one time or another, so does not in itself mean that a person has narcolepsy. It is a temporary inability to move or speak, often accompanied bu strange visions. It occurs when part of REM sleep happens when the person is awake. The reason that sleep paralysis is more common upon waking is because people generally awaken from REM sleep, but generally fall asleep into non-REM sleep. Sleep onset REM is another sign of narcolepsy. Hypnogogic hallucinations are experienced by about one third of people with narcolepsy, and are vivid and often terrifying visions (or sounds). They are the nightmare component of REM sleep occurring during wakefulness.
About 75% of people with narcolepsy experience cataplexy, which is when the muscle atonia of REM sleep occurs during wakefulness. People can experience partial cataplexy, which can include slurred speech, lack of facial expression, drooping of the head and eyelids, buckling of the knees, and weakness in the arms. The episode can escalate into a collapse. People can often anticipate a cataplectic attack and can take measures such as sitting down to avoid injury. Attacks usually last only a few minutes. Longer attacks are more likely to be accompanied by hypnogogic hallucinations.
There is no clear genetic inheritance pattern for narcolepsy as there is in genetic disorders such as Cystic Fibrosis or Sickle Cell Anemia, but relatives of people with narcolepsy have a risk 10 to 40 times greater than the general population, so there is clearly some genetic element. When one identical twin has narcolepsy, there is only a 25-30% chance that the other twin also has it. This means that while there is a weak genetic aspect to the disorder, there must also be an environmental factor. A gene was found in humans that affects the hypothalamus, and because the product of this gene is similar to a hormone that occurs in the gut called secretin, this gene and it's product were named Hypocretin (also called orexin by another team of researchers). This other team of researchers found evidence that this hormone may also play a role in appetite and eating behavior. Mice who were genetically engineered to not produce hypocretin/orexin slept more during their usual awake period, ate less, and had what looked like cataplectic episodes.
So there is a peptide produced in the hypothalamus called hypocretin, for which there are receptors in various parts of the brain including the nucleii involved in promoting wakefulness. This hypocretinergic system (cells that respond to hypocretin) are well positioned to orchestrate rousing the animal from sleep and to keep it in an awake state. It was found in studies that healthy subjects had measurable levels of hypocretin in their cerbro-spinal fluid, but that in people with narcolepsy there was little or no measurable hypocretin. Post-mortem studies found that the hypothalami of normal subjects had plentiful numbers of hypocretin cells, but samples taken from narcoleptic people showed very few. They also found evidence of cell damage in areas where the hypocretin cells should have been.
Narcolepsy usually has an onset in the late teens to early adulthood, and people with narcolepsy usually share a particular immune system gene (an HLA gene). This strongly indicates that narcolepsy is an autoimmune disease. There is no cure for narcolepsy and treatment usually focuses on addressing the excessive daytime sleepiness. Sleep hygiene is the basis, such as following a regular sleep schedule, which includes winding down before bed, having a good sleep environment (such as no work items in the bedroom), and no heavy meals, caffeine or alcohol before bed. Scheduled naps can also help. Medical treatments include stimulant (often Ritalin), sleeping medications, medications to help with cataplexy, and antidepressants. People with narcolepsy often self-medicate with coffee and other sources of caffeine. The other commonly used stimulant is a drug called Provigil, which enhances dopamine neurotransmission. It is a selective dopamine reuptake inhibitor.
A number of drugs that are used as antidepressants are also effective against cataplexy. Two of these drugs (imipramine and clomipramine) are tricyclic antidepressants. These drugs block the reuptake of serotonin and norepinephrine. Prozac is also effective against cataplexy. All of these drugs enhance the effectiveness of neurotransmitters that promote wakefulness and vigilance. There is a newer drug called Xyrem, also known as gammahydroxybutyrate. It elevates the release of growth hormone. This research into treating narcolepsy has led to the concept of developing drugs that block hypocretin receptors as a way to treat insomnia.
