This chapter discusses the neurochemistry of excessive daytime sleepiness (EDS) with various etiologies. It presents a brief discussion of basic sleep physiology and narcolepsy symptoms to explain the specific neurochemistry of hypersomnia. The significant roles hypocretin deficiency and postnatal cell death of hypocretin neurons as the major pathophysiological process underlying narcolepsy with cataplexy emerged from a decade of investigation, employing both animal and human models. The chapter talks about idiopathic hypersomnia and hypocretin non-deficient primary hypersomnia. It explains how hypocretin ligand deficiency may cause narcolepsy phenotype. Narcolepsy symptoms can also occur during the course of other neurological conditions, and discovery of hypocretin ligand deficiency in idiopathic narcolepsy has led to new insights into the pathophysiology of symptomatic narcolepsy and EDS. The metabolic data may support the hypothesis of a primary deficient arousal system in patients with idiopathic hypersomnia.

Fibromyalgia syndrome (FMS) is characterized by complaints of generalized musculoskeletal pain and the finding on physical examination of tenderness in characteristic regions. Approximately one-third of patients date the onset of their FMS to a traumatic experience such as a motor vehicle accident or to an event such as an illness. The prevalence of FMS has been studied in a number of settings including outpatients, private and hospital clinic populations, as well as community settings. The economic repercussions of FMS are enormous. One estimate suggests that long-term disability payments for FMS in Canada may cost the insurance industry as much as $200 million per year. An alteration in sleep physiology was hypothesized to be the underlying cause of FMS. There is a variable spectrum of complaints and findings in patients with FMS. Mild FMS is found in the community in patients who do not feel the need to seek medical attention.