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Narcolepsy is believed to result from a genetic predisposition and abnormal neurotransmitter (hypocretin, also known as orexin) functioning and sensitivity.
Understanding of narcolepsy stems primarily from research involving narcoleptic dogs (for example, special laboratory-bred Dobermans and Labradors). In these animal models, the disorder is transmitted in an autosomal recessive fashion and is characterized mainly by cataplexy. Only 1% of human cases are inherited and, unlike the canine form, are transmitted in an autosomal dominant manner.
NeurotransmitterThe neurotransmitter hypocretin was identified in the last few years and is strongly associated with narcolepsy in dogs with a genetic predisposition. Hypocretin levels in human subjects with narcolepsy have been found to be undetectable or low in several recent studies of patients with narcolepsy. Hypocretin appears to modulate activity in the hypothalamus (the part of the brain associated with sleep). The deficiency of hypocretin might produce sleep attacks. The drug modafinil (Provigil) is useful in the treatment of narcolepsy is believed to activate hypocretin-containing nerve cells.
Selim R Benbadis, MD
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