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than half of a large series of patients with narcolepsy-cataplexy (Guilleminault and Dement) Such patients are frequently involved in driving accidents, even more frequently than epileptics Nocturnal sleep is often disrupted and reduced in amount The number of hours in a 24-h day spent in sleep by the narcoleptic is no greater than that of a normal individual Narcoleptics have an increased incidence of sleep apnea and periodic leg and body movements, but not of somnambulism Approximately 70 percent of narcoleptics rst seeking professional help will report having some form of cataplexy, and about half of the remainder will develop cataplexy later in life Cataplexy refers to a sudden loss of muscle tone brought on by strong emotion that is, circumstances in which hearty laughter or, more rarely, excitement, surprise, anger, or intense athletic activity cause the patient s head to fall forward, the jaw to drop, the knees to buckle, even with sinking to the ground all with perfect preservation of consciousness Cataplectic attacks occur without provocation in perhaps 5 percent of cases The attacks last only a few seconds or a minute or two and are of variable frequency and intensity In most of our cases they have appeared at intervals of a few days or weeks Exceptionally there are many attacks daily and even status cataplexicus, in which the atonia lasts for hours This is more likely to happen at the beginning of the illness or upon discontinuing tricyclic medication Most attacks of cataplexy are partial (eg, only a dropping of the jaw) Wilson found that the tendon re exes were abolished during the attack Pupillary re exes are absent in some cases and preserved in others Rarely, cataplexy precedes the advent of sleep attacks, but usually it follows them, sometimes by many years Sleep paralysis and hypnagogic hallucinations together are stated to occur in about half the patients, but the incidence has been far less in our few personally observed cases It should also be noted that hypnagogic paralysis and hallucinations occur occasionally in otherwise normal persons and that normal children, especially when tickled, may laugh to the point of cataplexy About 10 percent of persons with sleep attacks indistinguishable from those of narcolepsy have none of the associated phenomena ( independent narcolepsy ), and in these cases REM periods are not found consistently at the onset of sleep (see further on) Once established, narcolepsy and cataplexy usually continue for the remainder of the patient s life The degree of sleepiness, once it has stabilized, rarely lessens, although cataplexy, sleep paralysis, and hallucinations improve or disappear with age in about one-third of patients who have those features (Billiard and Cadilhac) No other condition is consistently associated with narcolepsycataplexy and none develops later Cause and Pathogenesis Narcolepsy bears no relation to epilepsy or migraine That there is a familial component has been recognized for years The risk of narcolepsy in a rst-degree relative of an affected individual is 1 to 2 percent, more than 25 times that in the general population As reviewed by Chabas and colleagues, important insights into the pathogenesis have come from studies of recessively inherited narcolepsy in three species of dogs, in which mutations have been identi ed in a gene encoding a receptor for the protein hypocretin (Lin et al) These studies implicate the peptide hypocretin in the control of sleep (The hypocretins probably also regulate feeding behavior and energy metabolism in the lateral and posterior hypothalamus; indeed, they were also designated orexins, from the Greek word for appetite) In mice, in-.

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