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Perhaps because we all need sleep, we have an enduring interest in tales of people who sleep continuously or cannot stay awake 鈥� popular characters such as Sleeping Beauty and Rip Van Winkle are just two examples.

Totally somnolent characters in films, such as Rat Race (2001), Moulin Rouge! (2001) or Deuce Bigalow: Male Gigolo (1999) all highlight our fascination 鈥� and amusement 鈥� with such sleepy individuals. But funny as they may seem, the sad fact is that these characters are all almost certainly based on the medical condition known as narcolepsy.

It was first named by a French physician, Jean-Baptiste-脡douard G茅lineau, from the Greek terms for 鈥渟tupor鈥� and 鈥渟eizures鈥�. G茅lineau also observed cataplexy, which is the hallmark of classic narcolepsy.

Cataplexy entails loss of muscle activity in the face or body 鈥� resulting in sagging of the head to full body collapse to the ground 鈥� triggered by strong emotional responses, such as laughter. One of G茅lineau鈥檚 patients reported collapsing to the ground at the Paris Zoo watching monkeys making faces.

Disturbed slumber

Subsequent research based on better understanding of the sleeping brain showed cataplexy was the loss of postural muscle activity we all get during rapid-eye movement (REM, or dreaming) sleep, intruding on the waking state. This loss of muscle activity can be as subtle as a partial closure of the eyes due to loss of activity in the muscles encircling the eye, or as obvious as a total body collapse.

Other intrusive REM phenomena common in narcolepsy include the inability to move immediately before falling asleep or on waking (sleep paralysis), or visual hallucinations caused by awake dreaming.

Despite the profound sleepiness and drive to sleep exhibited by people with narcolepsy, most would describe their night-time sleep as disturbed. Essentially, it鈥檚 difficult for them to maintain wakefulness or sleep for consistent periods, so they have insomnia with constant micro-sleeps during the day.

Some people are also described as having 鈥減artial narcolepsy鈥�, when they have irrepressible sleepiness without any of these REM intrusive behaviours. But only a few people have true partial narcolepsy, while many others may have sleepiness due to other causes.

These days, it鈥檚 understood that people with classic narcolepsy have a faulty 鈥渟leep switch鈥�. Just as a faulty light switch results in a light flickering on and off, their sleep-wake transition is constantly going on and off.

The 鈥渟leep switch鈥� is actually a complex brain system acting as master controller for all aspects and behaviours associated with sleep. It鈥檚 located predominantly in the lateral hypothalamus and adjacent brain areas. A dominant part of the switch is a small cluster of brain cells containing the neurotransmitter hypocretin, which regulates appetite, wakefulness and arousal, and is also known as orexin.

In classic narcolepsy, there鈥檚 a degeneration or complete loss of hypocretin neurones, while adjacent neurones with other neurotransmitters are preserved. In effect, narcolepsy is a highly selective degeneration of hypocretin neurones, which makes it very different to other brain degenerative disorders with more widespread effects, such as Alzheimer鈥檚 or Parkinson鈥檚 diseases.

A hundred years of sleep

But why do some people get such a selective neurodegeneration? To answer that question, we need to go back to World War I, when Austro-Hungarian flying ace Constantin von Economo was dragged out his precarious profession by his wealthy parents and pushed into the safer pursuit of neuropathology.

He observed that victims of the mysterious encephalitis lethargica epidemic that followed the H1N1 Spanish flu had either severe sleepiness or insomnia. They also had lesions in the areas of the brain now known to contain the 鈥渟leep switch鈥�.

These historic findings have led researchers over the years to believe that narcolepsy has an environmental trigger in people susceptible to the condition. One vulnerability factor is a group of genes, called HLA genes, that determine immune responses.

In 1984, the late Yutaka Honda identified that 100% of his patients with classic narcolepsy had a particular type of HLA gene, in contrast to 25% of the general population. Other researchers in Europe and North America confirmed these findings.

Some years before his death, along with a number of others, I had dinner with a very jetlagged Honda, who exhibited frequent micro sleeps during the main course. The irony of this scene never left me 鈥� and it鈥檚 probably a very good way to understand how someone with narcolepsy feels.

Solving the mystery

Recently, 1,300 cases of classical narcolepsy were observed in people who were given GSK鈥檚 Pandemrix H1N1 flu vaccine (out of a total of 30 million Europeans given the vaccine). This led to a flurry of activity to try to identify diagnostic blood factors for narcolepsy, as well as proteins responsible for this side effect.

There were a number of dead ends, and one paper had to be retracted due to failure to replicate initial lab findings, but last month major progress was made. Scientists found a part of the H1N1 virus that resembled the hypocretin receptor. They used antibodies from Finnish patients who had developed narcolepsy following Pandemrix vaccination, and added them to cells that were engineered to have a human hypocretin receptor on its surface.

The antibodies bound to the hypocretin receptors, suggesting they may also latch onto these receptors in people and cause degeneration of the hypocretin system in the brain and, therefore, narcolepsy.

This insight, as well as some evidence that antibodies from some non-vaccinated patients with H1N1 infection binds to the hypocretin receptor, provides more data that viral agents act as a trigger for narcolepsy.

At present, treatment for narcolepsy involves using stimulant drugs such as dexamphetamine or modafinil to keep people awake, and certain types of antidepressants to prevent cataplexy.

The 鈥渄ate-rape鈥� drug gamma-hydroxybutyrate (GHB) is a powerful agent in people who have severe cataplexy and who don鈥檛 respond to antidepressants. GHB blocks the emotional triggering of loss of muscle tone and also improves sleep quality at night. It has just become available in Australia but is appropriate for only carefully selected patients.

Narcolepsy has devastating effects on quality of life; promising young students' careers are stopped in their tracks, and sufferers are often unemployable as they try to deal with intractable sleepiness and cataplexy attacks.

Often, it takes years to get diagnosed, with a further cost to their lives. But people treated with appropriate therapy combinations, quality specialist care and flexible employers can do well over time.

The mystery of narcolepsy is slowly being solved by painstaking research. There's hope that sufferers of this unusual condition will not indefinitely stay sleeping beauties.

听

听is a professor of sleep medicine at the University of Sydney鈥檚听. This article was first published in听.