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      Current Understanding of Narcolepsy 1 and its Comorbidities: What Clinicians Need to Know

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          Abstract

          Narcolepsy is a chronic neurologic disorder associated with the dysregulation of the sleep–wake cycle that often leads to a decreased quality of life and results in a considerable health burden. There is often a delay to diagnosis of narcolepsy, mainly due to the lack of recognition of this disorder. One of the main factors hindering the diagnosis of narcolepsy is the association of comorbidities, which include other sleep disorders, psychiatric disorders, cardiovascular disorders, and metabolic disorders. The signs and symptoms of these comorbidities often overlap with those of narcolepsy, and some of the medications used for their treatment may obscure the symptoms of narcolepsy, leading to a delay in diagnosis. This review is targeted to clinicians unaccustomed to working with sleep disorders and aims to increase recognition and improve the management of narcolepsy.

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          International classification of sleep disorders-third edition: highlights and modifications.

          The recently released third edition of the International Classification of Sleep Disorders (ICSD) is a fully revised version of the American Academy of Sleep Medicine's manual of sleep disorders nosology, published in cooperation with international sleep societies. It is the key reference work for the diagnosis of sleep disorders. The ICSD-3 is built on the same basic outline as the ICSD-2, identifying seven major categories that include insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, and other sleep disorders. Significant modifications have been made to the nosology of insomnia, narcolepsy, and parasomnias. Major features and changes of the manual are reviewed in this article. The rationales for these changes are also discussed.
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            International Classification of Sleep Disorders

            "The International Classification of Sleep Disorders - Third Edition (ICSD-3) is the authoritative clinical text for the diagnosis of sleep disorders. This is an essential reference for all clinicians with sleep disorders patients. Updated in 2014, the third revision to the ICSD features significant content changes, including new nomenclature, classifications and diagnoses. The book also features accurate diagnostic codes for the corresponding ICD-9 and ICD-10 diagnoses at the beginning of each diagnosis section of the ICSD-3. Disorders are grouped into six major categories: Insomnia ; Sleep Related Breathing Disorders ; Central Disorders of Hypersomnolence ; Circadian Rhythm Sleep-Wake Disorders ; Parasomnias ; Sleep Related Movement Disorders." --
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              Narcolepsy — clinical spectrum, aetiopathophysiology, diagnosis and treatment

              Narcolepsy is a rare brain disorder that reflects a selective loss or dysfunction of orexin (also known as hypocretin) neurons of the lateral hypothalamus. Narcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy, accompanied by sleep-wake symptoms, such as hallucinations, sleep paralysis and disturbed sleep. Diagnosis is based on these clinical features and supported by biomarkers: evidence of rapid eye movement sleep periods soon after sleep onset; cerebrospinal fluid orexin deficiency; and positivity for HLA-DQB1*06:02. Symptomatic treatment with stimulant and anticataplectic drugs is usually efficacious. This Review focuses on our current understanding of how genetic, environmental and immune-related factors contribute to a prominent (but not isolated) orexin signalling deficiency in patients with NT1. Data supporting the view of NT1 as a hypothalamic disorder affecting not only sleep-wake but also motor, psychiatric, emotional, cognitive, metabolic and autonomic functions are presented, along with uncertainties concerning the 'narcoleptic borderland', including narcolepsy type 2 (NT2). The limitations of current diagnostic criteria for narcolepsy are discussed, and a possible new classification system incorporating the borderland conditions is presented. Finally, advances and obstacles in the symptomatic and causal treatment of narcolepsy are reviewed.
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                Author and article information

                Contributors
                michael.thorpy@einsteinmed.org
                Journal
                Adv Ther
                Adv Ther
                Advances in Therapy
                Springer Healthcare (Cheshire )
                0741-238X
                1865-8652
                11 December 2021
                11 December 2021
                2022
                : 39
                : 1
                : 221-243
                Affiliations
                [1 ]GRID grid.417468.8, ISNI 0000 0000 8875 6339, Department of Psychiatry and Psychology, , Mayo Clinic College of Medicine, ; Phoenix, AZ USA
                [2 ]GRID grid.417468.8, ISNI 0000 0000 8875 6339, Division of Pulmonary Medicine, , Mayo Clinic College of Medicine, ; Phoenix, AZ USA
                [3 ]GRID grid.417468.8, ISNI 0000 0000 8875 6339, Center of the Science of Healthcare Delivery, , Mayo Clinic College of Medicine, ; Phoenix, AZ USA
                [4 ]GRID grid.16753.36, ISNI 0000 0001 2299 3507, Center for Circadian and Sleep Medicine, , Northwestern University, ; Chicago, IL USA
                [5 ]GRID grid.16753.36, ISNI 0000 0001 2299 3507, Department of Neurology, Sleep Medicine, , Northwestern University, ; Chicago, IL USA
                [6 ]GRID grid.251993.5, ISNI 0000000121791997, Montefiore Medical Center, , Albert Einstein College of Medicine, ; 111 East 210th Street, Bronx, NY 10467 USA
                Article
                1992
                10.1007/s12325-021-01992-4
                8799537
                34894325
                070acfa8-2716-49f3-b4e6-291c249fb79b
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 1 September 2021
                : 9 November 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100011096, Jazz Pharmaceuticals;
                Categories
                Review
                Custom metadata
                © Springer Healthcare Ltd., part of Springer Nature 2022

                cataplexy,comorbidities,diagnostic delay,excessive daytime sleepiness,hypersomnolence,narcolepsy,orexin,rapid eye movement,sleep disorders

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