Recent advances in narcolepsy

Abstract

Narcolepsy is thought to affect 0.05% of Caucasian populations and frequently causes severe symptoms across the 24-hour period. It is best viewed as a disorder of sleep-wake regulation with particular abnormalities of the rapid eye movement (REM). Typical cases are due to specific loss of a subset of hypothalamic neurons containing the neuropeptide, hypocretin (orexin). Several lines of evidence, including a causal link to the swine ‘flu vaccination, suggest autoimmune destruction of these neurons as an initial event. Narcolepsy is now classed as either type 1 or type 2, depending on sleep investigation results and whether cataplexy and/or hypocretin deficiency is present. However, it is likely the classification system will be further refined. Treatment options remain symptomatic and are often only partially effective. A new wake-promoting agent that increases brain histamine levels (pitolisant) has recently become available and will probably be used alongside modafinil and more traditional psychostimulants such as dexamphetamine. Powerful hypnotic agents, notably, sodium oxybate, consolidate the fragmented sleep frequently seen in narcolepsy and improve many of the daytime symptoms as a likely consequence.