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Journal of Sleep Research
Article . 2025 . Peer-reviewed
License: CC BY
Data sources: Crossref
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PubMed Central
Article . 2025
License: CC BY
Data sources: PubMed Central
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Present and Future of Central Disorders of Hypersomnolence

Authors: Francesco Biscarini; Lucie Barateau; Fabio Pizza; Giuseppe Plazzi; Yves Dauvilliers;

Present and Future of Central Disorders of Hypersomnolence

Abstract

ABSTRACT Central disorders of hypersomnolence (CDH) are rare neurological conditions lumped by excessive daytime sleepiness (EDS) as primary complaint mostly arising at young age, including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and Kleine‐Levin syndrome (KLS). Advances in clinical and translational research have deepened our understanding of NT1, particularly the loss of hypothalamic hypocretin/orexin‐producing neurons, establishing hypocretin deficiency as a reliable disease specific biomarker, although the exact mechanisms of neuronal loss remain unknown. Conversely, the pathophysiological mechanisms underlying NT2, IH, and KLS are still poorly understood, as well as their natural course. Standard diagnostic evaluation primarily relies on clinical symptoms, polysomnography and the multiple sleep latency test, with alternative neurophysiological markers (long term polysomnographic recordings), quantitative signal analysis, and wearables technologies being explored as potential innovative tools. Management remains symptomatic, combining pharmacological treatments such as stimulants, sodium oxybate, and emerging hypocretin/orexin receptor agonists, with nonpharmacological strategies tailored to improve patient quality of life. Notably, new therapies targeting orexin signalling offer promising avenues for transforming treatment approaches, particularly in NT1. Looking ahead, advancing precision medicine approaches and addressing unmet needs in CDH are essential to improve patient outcomes. This review summarises current knowledge and highlights future research directions in CDH pathophysiology, diagnostic approaches and pharmacological management.

Country
Italy
Keywords

The Future of Sleep Medicine, Orexins, excessive daytime sleepiness; hypersomnia; Kleine-Levin syndrome; narcolepsy; orexin/hypocretin; perspectives, Polysomnography, Humans, Disorders of Excessive Somnolence, Idiopathic Hypersomnia, Kleine-Levin Syndrome, Narcolepsy

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    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
8
Top 10%
Average
Top 10%
Green
hybrid