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Narcolepsy

Nature Reviews Disease Primers volume 3, Article number: 16100 (2017) Cite this article

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Abstract

Narcolepsy is a chronic sleep disorder that has a typical onset in adolescence and is characterized by excessive daytime sleepiness, which can have severe consequences for the patient. Problems faced by patients with narcolepsy include social stigma associated with this disease, difficulties in obtaining an education and keeping a job, a reduced quality of life and socioeconomic consequences. Two subtypes of narcolepsy have been described (narcolepsy type 1 and narcolepsy type 2), both of which have similar clinical profiles, except for the presence of cataplexy, which occurs only in patients with narcolepsy type 1. The pathogenesis of narcolepsy type 1 is hypothesized to be the autoimmune destruction of the hypocretin-producing neurons in the hypothalamus; this hypothesis is supported by immune-related genetic and environmental factors associated with the disease. However, direct evidence in support of the autoimmune hypothesis is currently unavailable. Diagnosis of narcolepsy encompasses clinical, electrophysiological and biological evaluations, but simpler and faster procedures are needed. Several medications are available for the symptomatic treatment of narcolepsy, all of which have quite good efficacy and safety profiles. However, to date, no treatment hinders or slows disease development. Improved diagnostic tools and increased understanding of the pathogenesis of narcolepsy type 1 are needed and might lead to therapeutic or even preventative interventions.

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Figure 1: Antigen presentation to T cells.
Figure 2: Autoimmune hypothesis of narcolepsy type 1.
Figure 3: Hypocretin excites the major neural networks controlling wakefulness.
Figure 4: Role of hypocretin neurons in wakefulness.
Figure 5: Electrophysiological hallmarks of narcolepsy type 1.
Figure 6: Treatment of narcolepsy.

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Acknowledgements

B.R.K. has received funding from the Lundbeck Foundation. S.K. has received funding from the Norwegian Ministry of Health and Care Services. H.M.O. has received funding from the Finnish Cultural Foundation, Jalmari and Rauha Ahokas Foundation, Sigrid Juselius Foundation, Emil Aaltonen Foundation, Päivikki and Sakari Sohlberg Foundation, Orion Farmos Research Foundation and Instrumentarium Science Foundation.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Molecular Sleep Laboratory, Rigshospitalet, Forskerparken, Nordre Ringvej 69, Glostrup, 2600, Denmark

    Birgitte R. Kornum

  2. Department of Clinical Neurophysiology, Danish Center for Sleep Medicine, Rigshospitalet, Glostrup, Denmark

    Birgitte R. Kornum & Poul J. Jennum

  3. Norwegian Centre of Expertise for Neurodevelopmental Disorders and Hypersomnias, Oslo University Hospital, Oslo, Norway

    Stine Knudsen

  4. Department of Psychiatry and Behavioral Sciences, Center for Sleep Sciences, Stanford University, Stanford, California, USA

    Hanna M. Ollila

  5. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy

    Fabio Pizza

  6. IRCCS Istituto delle Scienze Neurologiche di Bologna, Ospedale Bellaria, AUSL di Bologna, Bologna, Italy

    Fabio Pizza

  7. Department of Neurology, Sleep Unit, Narcolepsy Reference Center, Gui de Chauliac Hospital, Montpellier, INSERM 1061, France

    Yves Dauvilliers

  8. Sleep Medicine Center Kempenhaeghe, Heeze, The Netherlands

    Sebastiaan Overeem

  9. Department of Industrial Design, Eindhoven University of Technology, Eindhoven, The Netherlands

    Sebastiaan Overeem

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Contributions

Introduction (B.R.K.); Epidemiology (H.M.O.); Mechanisms/pathophysiology (S.O., Y.D. and B.R.K.); Diagnosis, screening and prevention (F.P.); Management (S.K., Y.D. and S.O.); Quality of life (S.K. and P.J.J.); Outlook (B.R.K., F.P. and Y.D.); Overview of Primer (B.R.K.).

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Correspondence to Birgitte R. Kornum.

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Competing interests

B.R.K. has received an unrestricted investigator-driven project grant from UCB Pharma. H.M.O. has acted as a consultant for Jazz Pharmaceuticals. P.J.J. has received funds from UCB Pharma. Y.D. has received funds for seminars, board engagements and travel to conferences by UCB Pharma, Jazz Pharmaceuticals, Theranexus, GlaxoSmithKline, Actelion and BioProject. S.O. has received an unrestricted investigator-driven project grant from UCB Pharma and conference travel support from UCB Pharma, Novartis and Boehringer Ingelheim. S.K. and F.P. declare no competing interests.

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Kornum, B., Knudsen, S., Ollila, H. et al. Narcolepsy. Nat Rev Dis Primers 3, 16100 (2017). https://doi.org/10.1038/nrdp.2016.100

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