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Narcolepsy and Idiopathic Hypersomnia

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Orexin and Sleep

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Abstract

Recent progress for understanding the pathophysiology of excessive daytime sleepiness (EDS) particularly owes itself to the discovery of narcolepsy genes (i.e., hypocretin receptor and peptide genes) in animals in 1999 and the subsequent discovery in 2000, of hypocretin ligand deficiency (i.e., loss of hypocretin neurons in the brain) in idiopathic cases of human narcolepsy-cataplexy. The hypocretin deficiency can be clinically detected by cerebrospinal fluid (CSF) hypocretin-1 measures; low CSF hypocretin-1 levels are seen in over 90 % of narcolepsy-cataplexy patients (Type 1 narcolepsy by ICSD-3). Type 1 narcolepsy is tightly associated with human leukocyte antigen (HLA) DQB1*0602, suggesting an involvement of immune-mediated mechanisms in the loss of hypocretin neurons. Anatomical and functional studies demonstrate that the hypocretin systems integrate and coordinate the multiple wake-promoting systems, such as monoamine and acetylcholine systems to keep subjects  alert and prevent abnormal REM sleep manifestations. Hypocerin deficiency is not observed in Type 2 narcolepsy and  idiopathic hyperemia and pathophysiological mechanisms in these diseases are largely unknown. This review focuses on pathophysiological mechanisms and nosological aspects of Type 1 narcolepsy, Type 2 narcolepsy  and idiopathic hypersomnia. 

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Authors and Affiliations

  1. Stanford University Sleep and Circadian Neurobiology Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 3155 Porter Drive, Rm2106, Palo Alto, CA, 94304, USA

    Seiji Nishino

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  1. Seiji Nishino
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Correspondence to Seiji Nishino .

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Editors and Affiliations

  1. Dept. of Molecular Neurosci. & Integrati, Faculty of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan

    Takeshi Sakurai

  2. Somnogen Canada Inc, President and Chief Executive Officer, Toronto, Ontario, Canada

    S.R. Pandi-Perumal

  3. Dept. Pharmacology & Therapeutics, Clinics Hospital Montevideo School of Medicine, Montevideo, Uruguay

    Jaime M. Monti

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Nishino, S. (2015). Narcolepsy and Idiopathic Hypersomnia. In: Sakurai, T., Pandi-Perumal, S., Monti, J. (eds) Orexin and Sleep. Springer, Cham. https://doi.org/10.1007/978-3-319-23078-8_14

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