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Histamine (HA) is a biogenic amine, providing a number of functional roles throughout the body. HA release triggers inflammatory responses as a protective reaction against foreign pathogens. Released from basophils and mast cells in the periphery, HA causes increased vascular permeability and dilation of blood vessels to allow increased fluid infiltration into tissues which in turn induces swelling. Research designed to test the role of HA in mediating central nervous system (CNS) activity demonstrated that HA immunoreactive brain neurons actively fire action potentials and release HA during the wake phase but are essentially silent during sleep, supporting the hypothesis that increased HA tone is related to levels of wakefulness. Results of experiments investigating the effects of HA in the CNS, either through direct injection of HA or through pharmacological inhibition of its synthesis, show that increases in HA are positively correlated with amounts of wakefulness.
Narcolepsy is best characterized as a disorder of the regulation of sleep and wakefulness, resulting in a variety of symptoms such as excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations (HH), sleep paralysis, and disturbed nocturnal sleep. This chapter focuses on narcolepsy with cataplexy and narcolepsy without cataplexy. Cataplexy is characterized by a sudden bilateral loss of muscle tone, with preserved consciousness, elicited by emotions. Narcolepsy with cataplexy is diagnosed according to the criteria of the International Classification of Sleep Disorders (ICSD-2). The chapter summarizes the differential diagnoses of EDS and cataplexy. Cataplexy and sleep paralysis are both regarded as expressions of the atonia that physiologically occurs during REM sleep, occurring during wakefulness. Two treatment modalities have proven to be effective: behavioral modification and pharmacological therapy. Pharmacological treatment is supplementary to behavioral advice and should be tailored individually.