Narcolepsy and hypersomnia can affect children, adolescents, adults, and older persons. In most cases these disorders begin in adolescence. The prevalence of narcolepsy with definite cataplexy has been documented in adults by numerous population-based studies and occurs in 0.02 to 0.05 percent of the population of Western Europe and North America (Mignot, 1998). In contrast, very little is known about the prevalence of narcolepsy without cataplexy. Recent studies using the MSLT indicate that approximately 3.9 percent of the general population has MSLT score abnormalities consistent with narcolepsy without cataplexy (Singh et al., 2005).
Secondary cases of narcolepsy or hypersomnia are also common, but the overall prevalence is not known (Table 3-3). These can occur in the context of psychiatric disorders, for example depression; central nervous system tumors, most notably in the hypothalamus; neurodegenerative disorders, such as Parkinson’s disease; inflammatory disorders, such as multiple sclerosis or paraneoplastic syndromes; traumatic disorders, such as head trauma; vascular disorders, such as those that are attributed to median thalamic stroke; and genetic disorders, including myotonic dystrophy or Prader-Willi syndrome (Billiard et al., 1994; Mignot et al., 2002a).
Similar to other sleep disorders, little is known about the pathophysiology and risk factors for narcolepsy and hypersomnia. Most of the knowledge in this area pertains to narcolepsy with cataplexy, which affects males and females equally. Symptoms usually arise during adolescence. Many contributing factors influence an individual’s susceptibility, including both genetic and environmental factors (Mignot, 1998, 2001).
Virtually all individuals who suffer narcolepsy with cataplexy carry the haplotype HLA-DQB1*0602 and have severe neuronal loss in regions of the brain that are responsible for regulating the sleep-wake cycle. Approximately 70,000 hypothalamic neurons that are responsible for producing the neuropeptide hypocretin (orexin) are lost in individuals with narcolepsy with cataplexy (Thannickal et al., 2000; Peyron et al., 2000). Hypocretin is an excitatory neuropeptide that regulates the activity of other sleep regulatory networks. Consequently, in some cases low levels of hypocretin-1 in the CSF, may be used to diagnose narcolepsy (Kanbayashi et al., 2002; Krahn et al., 2002; Mignot et al., 2002a) (Table 3-3). The cause of hypocretin cell loss is unknown but it may be autoimmune due to the association with the HLA-DQB1*0602 (Juji et al., 1984; Mignot, 2001).
Less is known regarding the pathophysiology of narcolepsy without cataplexy. The etiology is likely heterogeneous. An unknown portion may be caused by partial or complete hypocretin deficiency (Kanbayashi et al., 2002; Krahn et al., 2002; Mignot et al., 2002a). However, it has been