hypothesized that some individuals with partial cell loss may have normal CSF hypocretin-1 (Mignot et al., 2002a; Scammell, 2003).
The pathophysiology of idiopathic hypersomnia is unknown. When the disorder is associated with prolonged sleep time, it typically starts during adolescence and is lifelong. It is essential to exclude secondary causes, such as head trauma or hypersomnia owing to depression (Roth, 1976; Billiard and Dauvilliers, 2001). Some cases with prolonged sleep times have been reported to be familial, suggesting a genetic origin. Even less is known about idiopathic hypersomnia with normal sleep time. This condition is more variable and symptomatically defined. The cause of Kleine-Levin syndrome is unknown (Arnulf et al., 2005b).
Treatment for these conditions is symptomatically based. Even in the case of narcolepsy in which the disorder is caused by hypocretin deficiency, current treatment does not aim at improving the defective neurotransmission (Mignot et al., 1993; Nishino and Mignot, 1997; Wisor et al., 2001). Behavioral measures, such as napping, support groups, and work arrangements are helpful but rarely sufficient. In most cases, pharmacological treatment is needed (Nishino and Mignot, 1997; Lammers and Overeem, 2003). However, as with other pharmaceuticals designed to treat sleep problems, large-scale clinical trails have not examined the efficacy and safety of drugs to treat narcolepsy in children and adolescents.
In narcolepsy with cataplexy, pharmacological treatment for daytime sleepiness involves modafinil or amphetamine-like stimulants, which likely act through increasing dopamine transmission. Cataplexy and abnormal REM sleep symptoms, sleep paralysis and hallucinations, are typically treated with tricyclic antidepressants or serotonin and norepinephrine reuptake inhibitors. Adrenergic reuptake inhibition is believed to be the primary mode of action. Sodium oxybate, or gamma hydroxybutyric acid, is also used at night to consolidate disturbed nocturnal sleep. This treatment is also effective on cataplexy and other symptoms.
The treatment of narcolepsy without cataplexy and idiopathic hypersomnia uses similar compounds, most notably modafinil and amphetamine-like stimulants (Billiard and Dauvilliers, 2001). Treatments, with the possible exception of lithium, of periodic hypersomnia and Kleine-Levin syndrome type are typically ineffective (Arnulf et al., 2005a).