Purpose of Review: This article focuses on the clinical presentation, pathophysiology, diagnosis, differential diagnosis, and management of narcolepsy type 1 and narcolepsy type 2, idiopathic hypersomnia, Kleine-Levin syndrome, and other central disorders of hypersomnolence, as defined in the International Classification of Sleep Disorders, Third Edition (ICSD-3).
Recent Findings: In ICSD-3, the names of some central disorders of hypersomnolence have been changed: narcolepsy with cataplexy and narcolepsy without cataplexy have been renamed narcolepsy type 1 and narcolepsy type 2, respectively. A low level of hypocretin-1/orexin-A in the CSF is now theoretically sufficient to diagnose narcolepsy type 1, as it is a highly specific and sensitive biomarker. Conversely, other central hypersomnias are less well-defined disorders with variability in the phenotype, and few reliable biomarkers have been discovered so far. The epidemiologic observation that influenza A (H1N1) infection and vaccination are potential triggering factors of narcolepsy type 1 (discovered during the 2009 H1N1 pandemic) has increased interest in this rare disease, and progress is being made to better understand the process (highly suspected to be autoimmune) responsible for the destruction of hypocretin neurons. Treatment of narcolepsy remains largely symptomatic, usually initially with modafinil or armodafinil or with higher-potency stimulants such as methylphenidate or amphetamines. Several newer wake-promoting agents and psychostimulants have also been developed, including sodium oxybate, which has a role in the treatment of cataplexy and as an adjunctive wake-promoting agent, and pitolisant, a selective histamine H3 receptor inverse agonist that is currently only available in Europe.
Summary: Although far less common than many other sleep disorders, central hypersomnias are among the most severe and disabling diseases in the field of sleep medicine, and their early recognition is of major importance for patients, especially children, to maximize their quality of life and functioning in activities of daily living.
Address correspondence to Dr Yves Dauvilliers, Centre National de Référence Narcolepsie Hypersomnies, INSERM U1061, Département de Neurologie, CHRU Gui de Chauliac, 80 avenue Augustin Fliche, 34295 Montpellier Cedex 5, France, firstname.lastname@example.org.
Relationship Disclosure: Dr Dauvilliers has received personal compensation for speaking engagements and travel expenses, served as consultant for, and received research/grant support from Bioprojet Pharma, Flamel Technologies, Jazz Pharmaceuticals, Theranexus, and UCB SA. Dr Dauvilliers serves as specialty chief editor of the Sleep and Chronobiology section of Frontiers in Neurology. Dr Barateau has received reimbursement for travel expenses from Laidet Médical and has received personal compensation as a speaker for UCB SA.
Unlabeled Use of Products/Investigational Use Disclosure: Drs Dauvilliers and Barateau report no disclosures.