2001 WINNER

When sleep becomes a nightmare

By Meera Ladwa

ARE you feeling tired today? With our busy lifestyles and commitments, the answer is probably yes. But imagine for one moment that you felt so exhausted, you fell asleep in the middle of a conversation, or while you were eating.

Imagine that every time you felt angry, afraid, or overjoyed, your body could be paralysed for up to several minutes. Imaging having visions so disturbing and lifelike that you didn't know if you were dreaming or awake.

One in 2,000 people do not have to imagine-they have narcolepsy, a disabling sleep disorder that can prevent them from working, driving and leading normal lives.

Sufferers feel as if they have been awake for days even if they have just had a night's sleep. Over half also have cataplexy, a symptom that often occurs during extreme emotions, when they lose control of their muscles and may be unable to move or talk even though they remain conscious.

Many also suffer from vivid, frightening dreams known as "hypnagogic" hallucinations. There is no cure for narcolepsy, and until recently scientists had very little idea of what causes terrifying conditions.

How and why we sleep and dream is still unknown to scientists. What we do know is that normal sleep is a cycle: we first fall into deep sleep, when our breathing is slow and our brainwaves are regular. Deep sleep is punctuated, however, by short periods of REM, or "rapid eye movement", sleep when our brainwaves become irregular, we have dreams, we lose muscle tone and our closed eyes flicker.

Scientists have believed since the 1960s that narcolepsy is an unusual form of this part of the sleep cycle. Narcoleptics may go into a state that is like a conscious version of REM sleep because their brain's way of controlling sleep has failed.

This could explain the weakening of muscles and the dream-like hallucinations they experience. What causes the fault in the brain's method of sleep control is the subject of a recent and exciting discovery that could not only offer narcoleptics hope of a cure, but also give scientists insights into what happens in our brains when we sleep.

The Stanford Centre for Narcolepsy in the US studied the disease in both animals and humans, and found that narcolepsy is almost certainly caused by an abnormality of brain chemicals. In August 1999, a team led by Drs Emmanuel Mignot and Seiji Nishino found that narcoleptic dogs possessed a mutated gene that meant that they lacked a receptor in their brains for a chemical called hypocretin. Further investigations found that most human narcoloptics had abnormally low levels of the same chemical hypocretin in their cerebrospinal fluid, the liquid that surrounds the brain and spine. Studies by the Stanford group and by Prof Jerome Siegel of the University of California, Los Angeles, found that all human narcoleptic brains could show a loss of over 85 per cent of brain cells containing hypocretin.

Hypocretin is a neurotransmitter, a chemical messenger carrying information from one brain cell to another, made in a part of the brain called the hypothalamus. Without it, the hypothalamus cannot communicate with the other areas of the brain it is linked to, such as those involved in wakefulness and muscle tone, meaning that these vital features are no longer under control.

The fact that the loss of hypocretin is involved in both animal and human narcolepsy, and that two separate studies showed that most narcoleptics have very low levels of hypocretin in their bodies suggests that this new research holds a compelling key to the cause of the disorder.

However, unlike the narcoleptic dogs, none of the human narcoleptics showed any sign of a gene mutation apart from a young child who, unusually, had developed narcolepsy at an early age. If a genetic abnormality does not cause humans to lose hypocretin, what does?

The answer may be that narcolepsy is an auto-immune disease, when the immune system mistakenly begins to destroy healthy body tissues, in this case a narcoleptic's own hypocretin producing brain cells. Prof Siegel's team found evidence of this destruction: scar tissue in parts of the brain where the hypocretin cells should have been.

If the theories are true, new drugs could be developed which replace the missing chemical in narcoleptics. Research could be done into how cells containing hypocretin might be transplanted into the brain.

Not only have these new discoveries provided hope for sufferers of narcolepsy, but as scientists probe the causes of this strange disorder, they discover more and more about the complex brain chemistry which controls the way each of us rests and wakes. And considering that none of us think of going to bed as a chore, it comes as a surprise to find out how much effort the brain puts into falling asleep.