Masashi Yanagisawa's group produced an orexin ligand knock-out mouse with sleepiness and cataplexy strikingly similar to human narcolepsy ( Chemelli et al., 1999). The following year, another pair of research teams found compelling evidence that narcolepsy can be caused by a loss of orexin signaling.
The orexins have since been demonstrated to play essential roles in maintaining wakefulness and regulating transitions between sleep and wake ( Chemelli et al., 1999 Mochizuki et al., 2004 Adamantidis et al., 2007 Diniz Behn et al., 2010 Sasaki et al., 2011). In 1998, two labs independently discovered a pair of hypothalamic neuropeptides termed orexin-A and -B (or hypocretin 1 and 2) and their receptors (OX1 and OX2) ( de Lecea et al., 1998 Sakurai et al., 1998). He went on to speculate that the sleepiness of narcolepsy might be caused by injury to this region, but for decades this hypothesis could not be tested as so little was understood about the cells and functions of the hypothalamus. In many patients, this caused crushing sleepiness, and the Austrian neurologist Constantin von Economo found that these patients usually had inflammation and injury to the posterior hypothalamus ( von Economo, 1930). Toward the end of World War I, an epidemic of encephalitis swept across Europe. The goals of this review are to describe briefly the symptoms, etiology, and management of narcolepsy, and then review the underlying neurobiology and important directions for future research. Excessive daytime sleepiness is usually the first symptom, with cataplexy and other phenomena developing over the next few months and persisting for life.įor over 100 years, clinicians have recognized narcolepsy ( Westphal, 1877 Gelineau, 1880 Schenck et al., 2007), but only in the last decade have neuroscientists been able to shed light on its true cause and underlying neurobiology. Typically beginning in adolescence, narcolepsy is common, affecting ∼1 in 2000 people. In addition, people with narcolepsy usually have a variety of other symptoms including sleep paralysis (paralysis for approximately a minute upon awakening), hypnagogic hallucinations (vivid and sometimes frightening hallucinations at the beginning or end of sleep), and cataplexy (sudden episodes of emotionally triggered muscle weakness). They may feel rested upon awakening, but most of their day is disrupted by moderate to severe sleepiness that causes them to doze off at inappropriate times and interferes with their ability to remain attentive in school, at work, and when driving. Her story is quite typical, and now, even with a variety of medications, her day-to-day life is much harder than it used to be.Īs in this young woman, all individuals with narcolepsy experience persistent daytime sleepiness. A few weeks later, while joking with a friend, she suddenly slumped face down on her desk she was fully conscious but unable to move for approximately a minute. One night when dozing off, she was certain that she heard someone breaking into her apartment, but after a few minutes, she realized it was a vivid, dream-like hallucination. No matter how much she slept at night, she struggled to stay awake while studying and her grades began to slip. A patient of ours is an intelligent and highly motivated young woman who developed unrelenting sleepiness during law school. Narcolepsy is a common cause of chronic sleepiness and is often accompanied by symptoms that include odd mixtures of sleep and wakefulness.
0 kommentar(er)
