European guideline and expert statements on the management of narcolepsy in adults and children

Bassetti, Claudio; Kallweit, Ulf; Vignatelli, Luca; Plazzi, Giuseppe; Lecendreux, Michel; Baldin, Elisa; Dolenc‐Grošelj, Leja; Jennum, Poul; Khatami, Ramin; Manconi, Mauro; Mayer, Geert; Partinen, Markku; Pollmächer, Thomas; Reading, Paul; Santamaría, Joan; Šonka, Karel; Dauvilliers, Yves; Lammers, Gert Jan

doi:10.1111/ene.14888

Cited by 79 publications

(98 citation statements)

References 163 publications

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“…efficacy and safety profiles, abuse potential, convenience of administration and costs) characteristics [ 1 – 5 ]. American Academy of Sleep Medicine (AASM) practice guideline and European narcolepsy guideline recommend several wake-promoting agents with varying mechanisms of actions, and stimulants for the management of central hypersomnolence disorders, including narcolepsy and idiopathic hypersomnia [ 4 , 5 ]. Of note, pharmacological agents currently recommended for idiopathic hypersomnia by AASM guideline are not specifically approved for this indication [ 4 ].…”

Section: What Is the Rationale For Developing Lower-sodium Oxybate?mentioning

confidence: 99%

“…In AASM practice guideline, based on available evidence, sodium oxybate is given a strong recommendation for treating narcolepsy in adults and a conditional recommendation for treating narcolepsy in children and idiopathic hypersomnia in adults [ 4 ]. Sodium oxybate is also given a strong recommendation for the treatment of cataplexy and EDS in children and adults with narcolepsy in European narcolepsy guideline [ 5 ]. At the recommended dosages, sodium oxybate can increase daily sodium intake by 1100–1640 mg [ 6 ], which is > 70% of recommended maximum sodium daily intake [ 9 , 10 ].…”

Section: What Is the Rationale For Developing Lower-sodium Oxybate?mentioning

confidence: 99%

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Calcium, Magnesium, Potassium and Sodium Oxybates (Xywav®) in Sleep Disorders: A Profile of Its Use

Heo

2022

CNS Drugs

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Calcium, magnesium, potassium and sodium oxybates (Xywav ® ; hereafter referred to as lower-sodium oxybate), a new oxybate formulation with a greatly reduced sodium burden compared with previously approved sodium oxybate (Xyrem ® ), is approved for the treatment of cataplexy and excessive daytime sleepiness (EDS) in adults and children aged ≥ 7 years with narcolepsy, and is the first drug approved for the treatment of idiopathic hypersomnia in adults in the USA. In two pivotal, double-blind, placebo-controlled, phase 3 trials of randomized-withdrawal design, lower-sodium oxybate effectively improved cataplexy and EDS in adults with narcolepsy, and EDS and overall idiopathic hypersomnia symptoms in adults with idiopathic hypersomnia during open-label titration and optimization periods. At the end of the double-blind, randomized withdrawal period, participants randomized to switch to placebo experienced significant worsening in these symptoms compared with those randomized to continue lower-sodium oxybate. Furthermore, worsening in patient- and clinical-rated global scales, as well as measures of health-related quality of life were also seen with placebo versus lower-sodium oxybate. Lower-sodium oxybate is generally well tolerated, with the tolerability profile being largely consistent to that seen with sodium oxybate. Supplementary Information The online version contains supplementary material available at 10.1007/s40263-022-00912-6.

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Section: What Is the Rationale For Developing Lower-sodium Oxybate?mentioning

confidence: 99%

Section: What Is the Rationale For Developing Lower-sodium Oxybate?mentioning

confidence: 99%

Calcium, Magnesium, Potassium and Sodium Oxybates (Xywav®) in Sleep Disorders: A Profile of Its Use

Heo

2022

CNS Drugs

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“… 53 In fact, currently most narcolepsy medications (except for Sodium Oxybate) cannot consolidate the patient’s nocturnal sleep, in spite of the improvement of EDS and cataplexy. 54 We reported here the association between diagnostic delay and poor nighttime sleep. We recently found that disturbed nocturnal sleep is associated with aging, 52 disease severity, and objective daytime sleepiness in NT1.…”

Section: Discussionmentioning

confidence: 75%

Idling for Decades: A European Study on Risk Factors Associated with the Delay Before a Narcolepsy Diagnosis

Zhang¹,

Dauvilliers²,

Plazzi³

et al. 2022

NSS

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Purpose Narcolepsy type-1 (NT1) is a rare chronic neurological sleep disorder with excessive daytime sleepiness (EDS) as usual first and cataplexy as pathognomonic symptom. Shortening the NT1 diagnostic delay is the key to reduce disease burden and related low quality of life. Here we investigated the changes of diagnostic delay over the diagnostic years (1990–2018) and the factors associated with the delay in Europe. Patients and Methods We analyzed 580 NT1 patients (male: 325, female: 255) from 12 European countries using the European Narcolepsy Network database. We combined machine learning and linear mixed-effect regression to identify factors associated with the delay. Results The mean age at EDS onset and diagnosis of our patients was 20.9±11.8 (mean ± standard deviation) and 30.5±14.9 years old, respectively. Their mean and median diagnostic delay was 9.7±11.5 and 5.3 (interquartile range: 1.7−13.2 years) years, respectively. We did not find significant differences in the diagnostic delay over years in either the whole dataset or in individual countries, although the delay showed significant differences in various countries. The number of patients with short (≤2-year) and long (≥13-year) diagnostic delay equally increased over decades, suggesting that subgroups of NT1 patients with variable disease progression may co-exist. Younger age at cataplexy onset, longer interval between EDS and cataplexy onsets, lower cataplexy frequency, shorter duration of irresistible daytime sleep, lower daytime REM sleep propensity, and being female are associated with longer diagnostic delay. Conclusion Our findings contrast the results of previous studies reporting shorter delay over time which is confounded by calendar year, because they characterized the changes in diagnostic delay over the symptom onset year. Our study indicates that new strategies such as increasing media attention/awareness and developing new biomarkers are needed to better detect EDS, cataplexy, and changes of nocturnal sleep in narcolepsy, in order to shorten the diagnostic interval.

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“…First, literature data demonstrate that secondary narcolepsy in patients with EDS after treatment for CP occurs at high rates (14–35%) ( 36 , 40 , 45 ), whereas the worldwide prevalence of narcolepsy in the general population is 25–50 persons per 100.000 ( 57 ). However, this rate may be underestimated, considering that not all patients with EDS undergo targeted diagnostic investigations.…”

Section: Discussionmentioning

confidence: 99%

“…Narcolepsy is linked to the dysfunction of the hypocretin system in the dorsolateral hypothalamus, which projects rostrally to the forebrain and caudally to the tuberomammillary nucleus, nucleus accumbens, and raphe system, and regulates arousal, REM sleep, general sleep-wake balance, and stability of sleep stages ( 58 ). Notably, a low CSF level of hypocretin, the neuropeptide that promotes wakefulness and is typically reduced in patients with type 1 narcolepsy ( 57 ), has been detected in some CP patients with symptomatic narcolepsy ( 40 , 48 ), suggesting the possibility that surgical removal of the hypothalamic tumor could cause defective orexin production and consequently induce narcolepsy and excessive daytime sleepiness. Low levels of hypocretin have also been observed in other disorders with hypothalamic dysfunction other than type 1 narcolepsy, such as ROHHAD ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

Sleep Disturbances in Pediatric Craniopharyngioma: A Systematic Review

et al. 2022

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Craniopharyngiomas are rare brain tumors of the sellar region and are the most common non-neuroepithelial intracerebral neoplasm in children. Despite a low-grade histologic classification, craniopharyngiomas can have a severe clinical course due to hypothalamic involvement. The hypothalamus plays a crucial role in regulating vital functions, and it is a critical component of the sleep-wake regulatory system. This systematic review aims to provide an overview of the current knowledge on sleep disorders in patients with craniopharyngioma to unravel their underlying mechanisms and identify possible therapeutic strategies. A comprehensive electronic literature search of the PubMed/MEDLINE and Scopus databases was conducted in accordance with the PRISMA® statement. Extensively published, peer-reviewed articles involving patients with childhood craniopharyngioma and focused on this specific topic were considered eligible for inclusion. Thirty-two articles were included; a high prevalence of excessive daytime sleepiness was reported in CP patients, with wide variability (25–100%) depending on the diagnostic method of detection (25–43% by subjective measures, 50–100% by objective investigations). In particular, secondary narcolepsy was reported in 14–35%, sleep-disordered breathing in 4–46%. Moreover, sleep-wake rhythm dysregulation has been notified, although no prevalence data are available. Possible mechanisms underlying these disorders are discussed, including hypothalamic injury, damage to the suprachiasmatic nucleus, low melatonin levels, hypocretin deficiency, and hypothalamic obesity. The diagnosis and management of sleep disorders and associated comorbidities are challenging. This review summarizes the pathophysiology of sleep disorders in childhood-onset CP and the main treatment options. Finally, a possible diagnostic algorithm in order to accurately identify and treat sleep disorders in these patients is proposed.

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European guideline and expert statements on the management of narcolepsy in adults and children

Abstract: Bassetti and Kallweit shared first authorship. Dauvilliers and Lammers shared last authorship. Bassetti, Kallweit, Dauvilliers and Lammers contributed equally.

Cited by 79 publications

References 163 publications

Calcium, Magnesium, Potassium and Sodium Oxybates (Xywav®) in Sleep Disorders: A Profile of Its Use

Calcium, Magnesium, Potassium and Sodium Oxybates (Xywav®) in Sleep Disorders: A Profile of Its Use

Idling for Decades: A European Study on Risk Factors Associated with the Delay Before a Narcolepsy Diagnosis

Sleep Disturbances in Pediatric Craniopharyngioma: A Systematic Review

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