ther parts of Northern Europe. In the winter of 2010–2011, governments and the general public were very concerned about a severe form of influenza, known as H1N1, spreading around the globe. In many countries, most of the population received vaccination against this flu, and Finland and some other northern European countries chose to use a very potent brand of H1N1 vaccine known as Pandemrix. One to two months after receiving this brand of vaccine, dozens of children developed narcolepsy, and overall, the rate of new cases of narcolepsy in children increased 8- to 12-fold.6, 7 Importantly, all of these children who developed narcolepsy carried the gene HLA-DQB1*06:02. Only a few adults appeared to develop narcolepsy in connection with this vaccine.8 (Pandemrix, which is no longer in use anywhere, was never licensed for use in the United States.)
In the last few years, several research labs have found that adults and children with narcolepsy may have T cells, a type of immune system cell, that selectively target the orexin peptides.21-24 These T cells may directly kill the orexin neurons, or more likely, they trigger other immune cells to damage and kill the orexin neurons.
Thus, it appears that three factors are important for the development of narcolepsy:
Genes that influence the immune system, such as HLA-DQB1*06:02
A triggering factor that activates the immune system, such as infection with strep
A vulnerable age during which the immune response or some characteristics of the brain make an autoimmune attack on the orexin neurons more likely
By gaining a better understanding of this process, researchers hope to develop medications that can stop narcolepsy just as it begins and prevent further injury to the orexin neurons.
What are the practical implications of these discoveries? First, it is important to recognize that the hereditary aspects of narcolepsy are a relatively small concern. If a parent has narcolepsy, there is only about a 1% chance that her or his child will have the disorder. Up to 25% of the population carries the gene HLA-DQB1*06:02, but less than 1% of them will develop narcolepsy as additional factors are needed to trigger an attack on the orexin neurons. Secondly, though it seems very likely that Pandemrix triggered narcolepsy in certain children, this vaccine was unusually potent, and future vaccines most likely will be designed differently now that this risk is known. There is no compelling evidence that other vaccines cause or worsen narcolepsy, so it is fine for people with narcolepsy and their families to receive all routine vaccinations.
Narcolepsy was first described by doctors in the 1870s, but only in the past 15 years has the underlying cause become clear. Some of the greatest insights about narcolepsy have come from the laboratories of Dr. Emmanuel Mignot of Stanford University and Dr. Jerome Siegel of the University of California, Los Angeles. In 2000, each group independently discovered that narcolepsy with cataplexy is caused by a loss of orexins in the brain. These and other valuable insights have revealed much about how the brain normally functions, as well as what goes wrong in narcolepsy.
Current theories about the role of orexins in narcolepsy are based on research findings that include the following:
Research in animals was the first to shed light on the connection between narcolepsy and loss of orexins. Just like people with narcolepsy, dogs, rats, and mice with disrupted orexin signaling fall asleep frequently and often have episodes of cataplexy.9, 10, 11, 12 In addition, tasty food can trigger cataplexy in dogs and mice with narcolepsy, suggesting that their cataplexy is triggered by positive emotions.13, 14
Researchers then examined the brains of people with narcolepsy with cataplexy and consistently found a 90–95% decrease in the number of orexin-producing neurons.15, 16, 17 orexin-1 can also be measured in cerebrospinal fluid, the liquid that surrounds the brain, and about 90% of people with narcolepsy with cataplexy have very low or undetectable levels of orexin-1.18 Thus