Narcolepsy is a REM sleep hypersomnia of unknown etiology that is attributed to dysfunction of brain-stem mechanisms associated with sleep-wake regulation (Broughton 1990). Epidemiological studies have reported the prevalence of narcolepsy at 0.04%-0.07%, making narcolepsy twice as common as multiple sclerosis and half as common as Parkinson’s disease. The peak age at onset is in adolescence and young adulthood, although cases of childhood onset have been reported (Guilleminault and Pelayo 1998; Wise 1998). Genetic factors are important. First-degree probands of narcoleptic patients are at eight times greater risk of having some disorder of excessive sleepiness than are individuals in the general population. Speculation regarding pathophysiology has recently focused on genetically mediated dysfunction in cholinergic-dopaminergic interactions (Guilleminault et al. 1998). Human leukocyte antigen (HLA) testing is essentially 85% positive for the HLA-DQB1*0602 and HLA-DR2 alleles for patients with narcolepsy compared with 12%-38% of the general population. Genetic factors other than HLA are also likely to be involved. In narcoleptic dogs, a specific narcolepsy gene has been identified, and the human gene(s) will likely be discovered soon (Takahashi 1999). Nevertheless, the importance of environmental factors is evidenced by the reported 25%-30% of monozygotic twins who are concordant for narcolepsy (Honda and Matsuki 1990; Mignot 1998).
The narcoleptic tetrad of symptoms includes 1) excessive daytime sleepiness with sleep attacks, 2) cataplexy, 3) sleep paralysis, and 4) vivid hypnagogic and hypnopompic hallucinations. The excessive sleepiness of narcolepsy leads to irresistible sleep attacks in situations in which sleep normally never occurs. The narcoleptic patient naps repeatedly for 20- to 40-minute periods, awakening refreshed. He or she then becomes sleepy again within 2-3 hours. Cataplexy is characterized by sudden loss of bilateral peripheral muscle tone, often provoked by strong affect. This condition reflects the peripheral muscle inhibition of REM sleep. Consciousness and memory remain intact. Cataplectic attacks are brief, rarely more than several minutes, with immediate and complete recovery. Attacks may occur only several times a year or as frequently as many times in one day. Both sleep paralysis and hypnagogic hallucinations similarly represent REM sleep concomitants, occurring during sleep onset, when REM sleep normally is not prominent. Although cataplexy, sleep paralysis, and hypnagogic hallucinations diminish in frequency over time, narcolepsy, once present, is a lifelong, chronic condition.
The treatment of narcolepsy is symptomatic and must be individualized depending on the severity of specific symptoms (Thorpy and Goswami 1990). Stimulant medications are used most commonly for the treatment of excessive daytime sleepiness, and tricyclic antidepressant medications are used for the treatment of cataplexy. Because psychostimulants are often used in the treatment of ADHD, children who combat sleep attacks with fidgetiness and motor restlessness often receive the proper treatment for the wrong reason. In a retrospective study of adult patients with narcolepsy, a significant number had been misdiagnosed as having ADHD in adolescence but had been treated appropriately with amphetamines or methylphenidate, with good symptom improvement (Navelet et al. 1976). Clomipramine, 10-20 mg/day in divided doses, has been used successfully to manage cataplexy. Monoamine oxidase inhibitors may be used to manage both cataplexy and the REM sleep-onset symptoms of sleep paralysis and hypnagogic hallucinations. A new wake-promoting drug, modafinil, which activates orexin-containing neurons, is reported to be more effective and to have fewer side effects than the traditional stimulants (Chemelli et al. 1999; Fry 1998).
Patients with narcolepsy usually adjust poorly to their disorder. They have problems in school, at work, and in social relationships. Associated psychiatric disorders include major depression, generalized anxiety, and substance abuse. Behavioral management with psychosocial support and counseling is an essential component of treatment. Patients must be encouraged to follow regular bedtimes and rise times. Regularly scheduled naps for 20-30 minutes, two to three times daily, should be encouraged. School and work schedules need to be designed to accommodate the sleep needs of the patient. Patients are advised to attend self-help support groups. The American Narcolepsy Association publishes a newsletter that keeps members informed of recent advances.
Revision date: June 21, 2011
Last revised: by Jorge P. Ribeiro, MD