Stanford Center for Narcolepsy studies disorder’s causes, symptoms February 25, 2013 0 Comments Share tweet Nithya Vijayakumar By: Nithya Vijayakumar Imagine waking up one morning to the sounds of a burglar rustling at your doorknob. As the door creaks open, however, you are unable to move — confined to your bed. Moments later, you realize the burglar was just a hallucination and your movement is restored. It was only a dream. These two conditions — hypnagogic hallucinations, which occur when waking up or falling asleep, and cataplexy, a sudden loss of muscle tone often accompanying strong emotion — are characteristics of the sleep disorder narcolepsy, a disease that affects nearly one in 2000 Americans. “Some people have one attack a month, one cataplexy, a little bit of nightmares, but they’re okay,” said Emmanuel Mignot, director of the Stanford Center for Narcolepsy, part of the School of Medicine. “Others have it really bad.” Mignot is widely recognized as the international expert on the disorder, having discovered its genetic cause. In addition to hallucinations and cataplexy, victims of narcolepsy can also suffer from excessive daytime sleepiness, fatigue and sleep paralysis. Much of Mignot’s research is dedicated to finding both effective treatment for these symptoms and, eventually, a cure for the condition itself. “[Narcolepsy is] little bits of REM sleep mixed with the waking world, which isn’t supposed to be possible…It’s a normal thing happening at an abnormal time,” said Mali Einen, a research coordinator at the center. With his team of researchers, Mignot conducts tests on individuals who think they might have narcolepsy, which he said often goes undiagnosed. “The worst thing is not knowing [if you have it], because the treatment can be really very effective,” he said. According to Mignot, the disorder’s symptoms most often manifest themselves immediately before falling asleep or soon after waking. The daytime sleepiness can often persist throughout the day, and passive activities such as watching a movie or listening to lecture can cause one to doze off. Einen said that such chronic symptoms can seriously impede a sufferer’s day-to-day life. “In humans, cataplexy is most commonly triggered by humor, finding something amusing or doing well at something,” Einen said. “That part of it is kind of sad. Every time you say something funny or hear something funny, you have this sudden loss of muscle tone. It prevents you from being the person you were meant to be.” During a narcolepsy diagnosis, Mignot and his team use a variety of tests to determine how intense the symptoms are and thus how severe the condition is. One such diagnostic measurement is the Epworth Sleepiness Scale, a survey in which people rate how likely they are to fall asleep during specific situations. “Some things on the Epworth sleepiness scale are sitting and reading, watching T.V., sitting inactive in a public place — say a theater or a meeting,” Einen said. “Those things are all super hard for a person with narcolepsy to stay awake in. “ Research to understand narcolepsy was first conducted at the Stanford Narcolepsy Center with help from a breed of genetically narcoleptic dogs. Studying the dogs helped researchers understand the symptoms of the disorder and led to the center’s major breakthrough in 1999. By analyzing the spinal cord fluid of the dogs, it was found that narcoleptic individuals lack hypocretin, a chemical produced by specialized cells in the hypothalamus of the brain. As a result, they are unable to regulate REM sleep. Mignot said that while many in the scientific community remain skeptical about narcolepsy, his research proved there was a biological cause for the disorder. Furthermore, the center also discovered that 25 percent of the population carries a genetic marker for narcolepsy, signifying genetic susceptibility. However, only 0.02 percent of that population experiences narcoleptic symptoms. “The [genetic] marker doesn’t mean you’re going to get narcolepsy, but it makes it possible,” Einen said. “It is one piece of the puzzle, and they are trying to figure out what are the other pieces.” Current research has focused on understanding what factors trigger narcolepsy among the susceptible population. Mignot recently found that the T-cells in narcoleptic individuals’ immune systems may play a part in killing these depleted hypocretin cells. After the global swine flu epidemic of 2009, Mignot noted that there has been a global increase in the incidence of narcolepsy among young people. The H1N1 vaccine Pandemrix, distributed in some parts of Europe, has recently received significant media attention after studies demonstrated that it increased the risk for developing narcolepsy. However, this increased incidence of narcolepsy has also affected populations in both China and the United States, where this vaccine was not administered. “We think it may be the T-cells, which have the dirty job of fighting the H1N1, and then [make] the mistake of killing hypocretin cells,” Mignot said. “Even with this Pandemrix, it should be noted that only one person for 16,000 developed narcolepsy. So…the risk of developing narcolepsy is still very low. So it’s a rare complication. It doesn’t mean that you should not get vaccinated. ” The center conducts research using blood samples and brain donations from around the world. Most of the narcoleptic dogs used in earlier studies have passed on from old age, but Mignot adopted the last surviving dog, Bear. “I’m sure a lot of people have seen us on campus,” he said. Researchers at the center collaborate with other scientists internationally to study the blood samples of those with narcolepsy and identify which immune responses may lead to the disorder. Although treatments exist, they often only address symptoms. “It is a bit like taking aspirin for a fever,” Mignot said. “They either really wake you up or make you go to sleep more deeply. It doesn’t feel very natural.” Mignot plans to continue studying T-cells in order to determine exactly what triggers the autoimmune response against hypocretin cells. “I think what’s most exciting about this work is that we may one day be able to prevent narcolepsy,” he said. cataplexy Emmanuel Mignot Epworth Sleepiness Scale hypnagogic hallucinations hypocretin Mali Einen narcolepsy School of Medicine Stanford Center for Narcolepsy 2013-02-25 Nithya Vijayakumar February 25, 2013 0 Comments Share tweet Subscribe Click here to subscribe to our daily newsletter of top headlines.