When sleep goes awry

In a previous entry (“Zzzz….”), I talked about sleep – why we need it, what happens when we don’t get it, and how the sleeping habits of animals across the world compare to our own. Having delved into what constitutes normal patterns of sleep, I wanted to know about what happens when sleep goes awry. If sleep is such an important part of our biology, why do some people have so much difficulty with it?

The term “sleep disorder” encompasses a wide variety of sleeping problems. Sleep disorders can be grouped into 4 main categories: dyssomnias, parasomnias, proposed disorders, and medical/psychiatric disorders. Of these, dyssomnias and parasomnias are the most prevalent. Dyssomnias are disturbances in the timing, amount or quality of sleep. Common dyssomnias include: insomnia, narcolepsy, restless leg syndrome, sleep apnea, jet lag and shift-work sleep disorder. Parasomnias interfere with the transitions between sleep stages, and include: sleepwalking, sleep talking, sleep terrors, bedwetting and teeth grinding. While much work is being done on many of these different sleep disorders, one in particular has been extensively studied in terms of its biological cause. This condition is called narcolepsy.

Narcolepsy is a sleep disorder that affects almost 150,000 people in the US (about 1 in 2,000 people). It is a neurological condition characterized by excessive daytime sleepiness and abnormal REM sleep. (Remember, REM sleep is that stage in our sleep cycles when our brains are active but our bodies are inactive.) A narcoleptic often becomes so drowsy that they will fall asleep wherever they are, irresistibly and without warning. There are additional manifestations of narcolepsy, including sleep paralysis (inability to talk or move upon waking), hypnagogic hallucinations (auditory or visual hallucinations while falling asleep or waking up) and cataplexy (a sudden episode of muscle weakness that is triggered by strong emotions). While symptoms of excessive daytime sleepiness, sleep paralysis and hypnagogic hallucinations are sometimes seen in people who are not narcoleptic (usually people who are extremely sleep deprived), cataplexy appears to be exclusive to narcolepsy.

Narcoleptics who are having an attack of cataplexy is a truly unusual thing to watch. There are several fairly well known videos of narcoleptic dogs, including Rusty the narcoleptic daschund and several from the Stanford Center for Narcolepsy. Typically, the dogs in the videos are playing and seemingly having a great time, then suddenly their knees buckle and give way and their necks and jaws go slack. The dogs fall down and become paralyzed for a period of time, during which all of their reflexes are lost. After some time, they recover with no ill effects, and resume their previous activities.

So why does this happen? I’ve said it before, and I’ll say it again – it’s not fully understood. Sleep researchers have shown that over 90% of narcolepsy with cataplexy is caused by defective signaling from 2 related chemicals in the brain. These chemicals – hypocretin-1 and hypocretin-2 – regulate activity in the hypothalamus, the part of the brain that regulates sleep and appetite. Scientists have shown that the inherited form of narcolepsy in dogs is caused by genetic mutations that make their brains unable to respond to hypocretin-1 and hypocretin-2. In humans, it appears that the chemicals are physically absent, because the cells that make the hypocretins are mysteriously missing. The current thinking is that those cells have been killed off by the body’s own immune system. But why that happens is still unknown, as is what causes narcolepsy without cataplexy.

I guess I shouldn’t be surprised that there are so many ways that sleep can go awry, as well as the fact that we don’t really understand why yet. After all, sleep is an enormously complicated part of the brain, and it integrates a huge number of different factors of genetics and environment. It’s amazing that our brains and our bodies handle it as well as they do.