Narcolepsy

Narcolepsy

Narcolepsy is a disorder involving a chemical imbalance in the brain cells that control wakefulness and sleep. The disorder can run in families or appear as an isolated problem affecting only one individual in a family. Narcolepsy, after sleep apnea, is the second most common cause of the symptom of disabling daytime sleepiness. Narcolepsy is not rare in humans. Afflicting about 1 of every 2000 people throughout the world, narcolepsy is about as common as Multiple Sclerosis. Several symptoms are characteristic of narcolepsy:
The patient suffers from excessive daytime sleepiness, with the possibility of a "sleep attack" -- at mealtime, at the theater -- really anywhere. The patient can often fight this sleepiness for awhile but eventually the sleepiness is overwhelming. A short nap may restore wakefulness temporarily.

Narcolepsy involves the abnormal intrusion of part or all of rapid eye movement or dream sleep (REM sleep) into wakefulness. Narcoleptic paralysis is involuntary and can come under two circumstances:

(a) cataplexy -- sudden muscle weakness leading to partial or complete collapse precipitated by excitement or an emotional response, most frequently laughter.

(b) sleep paralysis -- an often frightening inability to move just before falling asleep or upon awakening.

The hallucinations of narcolepsy are known as hypnagogic hallucinations. These hallucinations also depend on REM sleep mechanisms and come as sometimes benign, sometimes terrifying apparitions just as the narcoleptic falls asleep or just as they are awakening.

Animal forms of narcolepsy exist and can be passed genetically from parents to offspring, complete with abnormal sleepiness and cataplexy. Narcolepsy has been described in species such as dogs and horses. There are also reports of people getting narcolepsy after a disease or an injury to the brain. But the few carefully-studied cases of this 'acquired narcolepsy', indicate that there is no single disease of 'acquired narcolepsy', just various medical conditions with few real and sustained similarities to narcolepsy.
Exciting genetic discoveries have recently been made involving animal models of narcolepsy. Stanford University scientists identified a mutant gene that causes narcolepsy in dogs. The normal gene is called the hypocretin receptor 2 gene. The abnormal gene disrupts communications between neurons that use the neurotransmitter, hypocretin 2.
Working independently, a group in Dallas, TX and Boston, MA created a mouse strain that cannot produce hypocretin. This knock-out mouse has the symptoms of narcolepsy. It is expected that, because of the high degree of conservation across species in the hypocretin system, genetic defects affect hypocretin communication will be found to cause narcolepsy in some humans. However, it is not likely that defects in the hypocretin system will explain all narcolepsy because there are familial forms, non-familial forms and post traumatic forms.

The new anti-narcolepsy drug, modafinil, is chemically different from other drugs used to treat the sleepiness of narcolepsy. Modafinil, as well as older stimulant drugs activate hypocretin-containing neurons. These drug effects support the idea that hypocretin is somehow involved in the control of sleep.

Recent genetic studies have linked narcolepsy to certain genes at a particular location, called the Major Histocompatibility Complex, on chromosome number 6. The two genes most often studied because of their linkage with narcolepsy are those that produce the HLA-DR15 and HLA-DQ6 antigens found on the surface of white blood cells. Exhaustive research indicates that the gene which produces the specific HLA-DQ antigen called, HLA-DQB*0602, seems to be a true narcolepsy susceptibility gene. However, about 20 - 30 percent of the population have this gene and only about 0.05 percent of the population have narcolepsy. This means that other genes or environmental factors are necessary for narcolepsy to develop in people with the HLA-BQB*0602 gene. Since several genes in the Major Histocompatibility Complex have been linked to diseases of the immune system, there is currently much research on the genetic and the immunological make-up of narcoleptics and their families. To date, family studies of patients with narcolepsy have shown that in families where multiple members have narcolepsy, the HLA-DQB*0602 gene tends not to be present, indicating that familial forms of narcolepsy are caused by another gene or genes.

There is no cure, as yet, for narcolepsy. The symptoms of narcolepsy are controlled with a 'double barreled' approach: (a) Several daytime naps and stimulants, such as amphetamines, control the abnormal tendency to fall asleep at inappropriate times; (b) Other drugs that suppress REM sleep such as antidepressants, help control the symptoms of cataplexy, sleep paralysis and hypnagogic hallucinations.