Pp. 182-192 (11)
Narcolepsy with and without cataplexy has two different nosological entities. Narcolepsy-cataplexy is strongly associated with HLA-DQB1*0602 and usually caused by a selective deficiency in the hypothalamic neuropeptide hypocretin (orexin). The cause of hypocretin deficiency is most likely an autoimmune attack directed against hypocretin cells. Diagnosis is performed clinically, with the additional sleep tests such as the Multiple Sleep Latency Test, or in some cases, by measuring hypocretin-1 levels in the Cerebrospinal fluid (CSF).< /p> < p>To date, therapy is mostly pharmacological and does not act directly on the hypocretin system. Stimulant compounds seem to increase alertness by activating dopaminergic transmission in the brain, while antidepressant therapy reduces cataplexy by increasing adrenergic and serotoninergic transmission. The mode of action of gamma-hydroxybutyrate (sodium oxybate), a treatment for cataplexy and disturbed nocturnal sleep is uncertain, but may involve GABA-B receptors. Narcolepsy without cataplexy is primarily diagnosed using MSLT, with a finding of a short mean sleep latency (≤ 8 min) and at least 2 Sleep Onset REM Periods (SOREMPs). The population-based prevalence of narcolepsy without cataplexy is unknown. It is likely that many cases of narcolepsy without cataplexy have very different pathogenesis, and/or result from false-positive MSLT. A minority of cases without cataplexy have hypocretin deficiency. For cases without cataplexy or hypocretin deficiency, research is needed to better understand the pathophysiology. Therapy is similar to that used for cases with cataplexy, although amphetamine stimulants should be used with more caution.
Professor of Medicine, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford University Center for Narcolepsy, 701b Welch Rd Room 145, Palo Alto, CA, USA.