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Narcolepsy is mainly associated with excessive daytime sleepiness, but the characteristic feature is abnormal rapid eye movement (REM) sleep phenomena. REM sleep disturbances can manifest as cataplexy (in narcolepsy type 1), sleep paralysis, sleep-related hallucinations, REM sleep behavior disorder, abnormal dreams, polysomnographic evidence of REM sleep disruption with sleep-onset REM periods, and fragmented REM sleep. Characterization of REM sleep and related symptoms facilitates the differentiation of narcolepsy from other central hypersomnolence disorders and aids in distinguishing between narcolepsy types 1 and 2. A circuit comprising regions within the brainstem, forebrain, and hypothalamus is involved in generating and regulating REM sleep, which is influenced by changes in monoamines, acetylcholine, and neuropeptides. REM sleep is associated with brainstem functions, including autonomic control, and REM sleep disturbances may be associated with increased cardiovascular risk. Medications used to treat narcolepsy (and REM-related symptoms of narcolepsy) include stimulants/wake-promoting agents, pitolisant, oxybates, and antidepressants; hypocretin agonists are a potential new class of therapeutics. The role of REM sleep disturbances in narcolepsy remains an area of active research in pathophysiology, symptom management, and treatment. This review summarizes the current understanding of the role of REM sleep and its dysfunction in narcolepsy.

Disrupted sleep and rest-activity pattern are common clinical features in depressed individuals. This meta-analysis compared sleep and circadian rest-activity rhythms in people with major depressive disorder (MDD) or depressive symptoms and healthy controls. Eligible studies were identified in five databases up to December 2023. The search yielded 53 studies with a total of 11,115 participants, including 4000 depressed participants and 7115 healthy controls. Pooled meta-analyses demonstrated that depressed individuals have significantly longer sleep latency (SMD = 0.23, 95 % CI: 0.12 to 0.33) and wake time after sleep onset (SMD = 0.37, 95 % CI: 0.22 to 0.52), lower sleep efficiency (SMD = −0.41, 95 % CI: −0.56 to −0.25), more nocturnal awakenings (SMD = 0.58, 95 % CI: 0.29 to 0.88), lower MESOR (SMD = −0.54, 95 % CI: −0.81 to −0.28), amplitude (SMD = −0.33, 95 % CI: −0.57 to −0.09), and interdaily stability (SMD = −0.17, 95 % CI: −0.28 to −0.05), less daytime (SMD = −0.79, 95 % CI: −1.08 to −0.49) and total activities (SMD = −0.89, 95 % CI: −1.28 to −0.50) when compared with healthy controls. Most of the included studies reported separate sleep and activity parameters instead of 24-hour rest-activity rhythms. The variabilities among actigraphy devices and the types of participants recruited also impede precise comparisons. The findings emerging from this study offered a better understanding of sleep and rest-activity rhythm in individuals with MDD or depressive symptoms. Future studies could advocate for deriving objective, distinctive 24-hour rest-activity profiles contributing to the risk of depression. CRD42021259780. • The review included 53 new studies up to December 2023. • Depressed individuals reported significantly poorer sleep than healthy controls. • Depressed individuals had disrupted circadian rest-activity rhythms. • Actigraphy has wide reaching and cost-effective public mental health implication. • Future studies can identify objective, distinctive 24-h rest-activity profiles in depression. [ABSTRACT FROM AUTHOR]

Treatment adherence (TA) in narcolepsy is a complex phenomenon influenced by various factors beyond patient-related aspects. The management of narcolepsy involves non-pharmacological and symptomatic pharmacological treatment. Factors such as chronic daytime sleepiness, cognitive deficits, psychiatric comorbidities and adverse effects of pharmacological treatment are aspects of narcolepsy that could undermine TA, impacting patients' ability or willingness to consistently follow treatment plans. The aim of this study was to identify the factors influencing TA in narcolepsy and to determine the most significant barriers to adherence. An online survey was conducted during the pandemic, assessing demographic and clinical data, medication usage, and adverse effects of treatment. Various questionnaires, such as the Adherence Barriers Questionnaire (ABQ) and Epworth Sleepiness Scale (ESS), were utilized. The ABQ identified patient-specific barriers to medication adherence, while the Patient Health Questionnaire (PHQ-9) assessed depressive symptoms. We analyzed 243 narcolepsy patients (77 % female, mean age 35.7 ± 12.3 years) with 71 % having narcolepsy type 1 (NT1). The average ESS score was 16.4 (SD ± 3.7). Adherence barriers (AB) were identified in 89 % of patients (216/243) based on ABQ score. The most common barriers reported were "Forgetfulness" (77 %), "Depression" (57 %), and "Side effect-driven medication reduction/stopping behavior" (49 %). Approximately 72 % of patients reported side effects from their narcolepsy medication, leading to discontinuation in 78 % of cases. A moderate correlation was found between the severity of adherence barriers (ABQ score) and levels of depression (PHQ-9 score; rs = 0.412, p = 00.000), as well as ESS score (p =. 048). The results of this study may have been influenced by the pandemic situation. Adherence barriers are common (89 %) and diverse among people with narcolepsy. Many barriers are related to excessive daytime sleepiness (EDS), cognitive deficits or depressive symptoms, highlighting the importance of recognizing and addressing them for optimal TA. Medication side effects, especially occurring when polypharmacology is utilized, also significantly contribute to adherence challenges. Effective communication regarding therapy adherence and improved detection and management of EDS and depression are crucial for enhancing TA in narcolepsy patients. • Adherence barriers (AB) were identified in 89 % of patients (216/243) using the ABQ score. • Approximately 72 % of patients reported side effects from their narcolepsy medication. [ABSTRACT FROM AUTHOR]

Narcolepsy with cataplexy (NT1) is a rare hypothalamic disorder that presents with a dysregulation of the sleep–wake cycle (i.e., excessive daytime sleepiness and sleep and cataplectic attacks) and other motor, cognitive, psychiatric, metabolic, and autonomic disturbances, with putative autoimmune pathogenesis. Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinically heterogeneous disorder that presents with acute-onset obsessive–compulsive symptoms and/or a severe eating restriction, with concomitant cognitive, behavioral, or affective symptoms caused by infections and other environmental triggers provoking an inflammatory brain response, which evolves into a chronic or progressive neuroimmune disorder. In this study, we present the case of a 13-year-old boy with vocal tics and syncopal-like episodes, eventually diagnosed as NT1 and PANS, and from this we discuss the hypothesis that both NT1 and PANS might belong to the same immunological spectrum, resulting in comparable imbalances in key neurotransmitter axes (i.e., orexinergic and dopaminergic), with conceptual and operational implications, especially with regards to the pharmacological tretament • Highlights (3-5). • Pediatric acute-onset neuropsychiatric syndrome (PANS) and Narcolepsy type 1 (NT1) are two distinctive neurological diseases that begin during developmental age. • PANS and NT1 have a neuroimmune pathogenesis involving different neurotransmitter axes. • NT1 and PANS may belong to the same immunological spectrum, resulting in involvement of different neurotransmitter axes, respectively orexinergic and dopaminergic. [ABSTRACT FROM AUTHOR]

Narcolepsy is a chronic central disorder of hypersomnolence most frequently arising during childhood/adolescence. This review article examined the literature concerning the etiology, prevalence, clinical course, and treatment of children with type 1 narcolepsy (NT1). Core symptoms of pediatric NT1 include excessive daytime sleepiness (EDS) and cataplexy, together with disrupted night sleep, sleep paralysis, and hypnagogic and hypnopompic hallucinations that can also occur. This disease frequently presents several comorbidities, such as obesity and precocious puberty, conditions ranging from psychological distress to psychiatric disorders, and cognitive aspects that further worsen the clinical picture. NT1 impairs the quality of life of children, thus calling for an early diagnosis and adequate treatment. To date, pharmacological treatments have been registered for childhood NT1 and can improve symptoms. Non-pharmacological approaches are also essential to improve patients' well-being, ranging from behavioral treatments (e.g., planned napping) to psychosocial interventions (e.g., school programs). Multidisciplinary treatment management and early diagnosis are key factors in order to allow for adequate quality of life and development in children with NT1. [ABSTRACT FROM AUTHOR]

Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and long-term opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size, and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXBs mechanism of action on narcolepsy.

Ullanlinna Narcolepsy Scale (UNS) is the most widely used scale for primary screening for narcolepsy. It has a high sensitivity (83.5 %) and specificity (84.1 %). However, the length of the scale and the time taken by patients to complete it may limit its use. The shortest scale for primary detection of narcolepsy type 1 is the Swiss Narcolepsy Scale (SNS), which also has a high sensitivity (89 %) and specificity (88 %). Objective: to validate the SNS in Russian language and compare it with English and German versions as well as with some other scales. Material and methods. 53 patients with narcolepsy type 1 were included. Narcolepsy was diagnosed according to the ICSD-3 criteria. The control group consisted of patients with obstructive sleep apnea (n = 71) and chronic insomnia (n = 31). Sensitivity and specificity of the Russian version of the scale (RU-SNS) were compared with UNS and Epworth Sleepiness Scale (ESS) questionnaires. Results. The mean score of the RU-SNS for patients with narcolepsy was – 33.64 ± 5.14. In the control group, the mean score was 29.75 ± 16.68. The sensitivity and specificity were 84.9 % and 95.1 %, respectively. For UNS, the mean score was 32.79 ± 9.87 in the narcolepsy group and 8.35 ± 4.84 in the control group. Sensitivity was 96.2 % and specificity – 84.3 %. For ESS, the mean score in narcolepsy group was 17.75 ± 4.28 and 8.7 ± 5.7 for controls. The sensitivity was estimated at 94.3 % and specificity at 61.8 %. Conclusion. The RU-SNS demonstrated high sensitivity and specificity, while the UNS also has high sensitivity but low specificity. ESS has high sensitivity but low specificity as it is only designed to detect pathological daytime sleepiness. Based on these data, the SNS can be used as a valid tool for the early diagnosis of narcolepsy type 1.

Background: Pharmacologic treatments are available to treat insomnia, a common and burdensome sleep disorder, but may be contraindicated in older adults who are prone to side effects from sleep-promoting drugs. These analyses of sleep diary data from Study E2006-G000-303 (Study 303) investigated the benefits of lemborexant 5 mg (LEM5) and 10 mg (LEM10) in the subgroup age ≥ 65 years with insomnia. Method: Study 303, a 12-month, double-blind study of LEM5 and LEM10 in adults (age ≥ 18 years) with insomnia disorder (sleep onset and/or maintenance difficulties) assessed subject-reported (subjective) sleep-onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), and total sleep time (sTST). Morning sleepiness/alertness, insomnia severity (Insomnia Severity Index [ISI]), fatigue (Fatigue Severity Scale [FSS]), perceptions of sleep-related medication effects (Patient Global Impression–Insomnia [PGI-I] questionnaire), and safety were also evaluated. Results: In this subgroup of older adults (≥ 65 years; n = 262), there were significantly larger changes from baseline for sSOL, sSE, sTST, and sWASO with LEM5 and LEM10 versus placebo through month 6 (except sWASO month 1), indicating improvement; these improvements were sustained through month 12. Subject-reported increases in morning alertness were significantly greater with one or both LEM doses versus placebo through month 6 and sustained through month 12. There were significantly larger ISI total and daytime functioning score decreases (improvement) from baseline with LEM versus placebo at months 1, 3, and 6 (total score: both doses; daytime functioning: LEM5 month 1 and both doses months 3 and 6) and decreases from baseline FSS at months 1 and 3 (LEM5) and month 6 (both doses), sustained to month 12. Compared with placebo, more subjects reported that LEM (both doses) positively impacted ability to sleep, time to fall asleep, and TST through month 6, sustained to month 12, with no rebound after drug withdrawal. LEM was well tolerated to month 12; mild somnolence was the most common treatment-emergent adverse event. Conclusions: Improvements in subject-reported efficacy in LEM-treated adults age ≥ 65 years with insomnia were observed as early as the first week of treatment and sustained through end of month 12. LEM was well tolerated. Clinical trials registration: ClinicalTrials.gov identifier NCT02952820: E2006-G000-303; Study 303; SUNRISE-2 (First posted: October 2016); EudraCT 2015-001463-39 (First posted: November 2016). Plain Language Summary: Insomnia is a common sleep disorder associated with significant difficulties, particularly in older adults. Although there are many drug treatments available, some are associated with the important risk of side effects and may not adequately treat sleep maintenance (ability to stay asleep), which is a frequent sleep complaint in older people. Lemborexant has been approved in multiple countries for the treatment of adults with insomnia based on studies that show lemborexant improved adults' ability to fall asleep and stay asleep and is well tolerated. To examine the long-term benefit of lemborexant, we investigated subject-reported benefits and safety of lemborexant in older (≥ 65 years) adults who participated in a 1-year study. The results showed that within the first few days of taking lemborexant, and lasting through 12 months of treatment, nightly lemborexant improved nighttime sleep (that is, it reduced the time it took to fall asleep, reduced the time awake during the night, and increased total sleep time) more than placebo. Morning alertness improved more in older adults who took lemborexant compared with placebo. In addition, those who took lemborexant also reported that their insomnia symptoms were less severe and they had less fatigue compared with placebo. Lemborexant was well tolerated in older adults. These results suggest that lemborexant may be a good option for older adults with insomnia disorder. [ABSTRACT FROM AUTHOR]

Summary Since the first description of narcolepsy at the end of the 19th Century, great progress has been made. The disease is nowadays distinguished as narcolepsy type 1 and type 2. In the 1960s, the discovery of rapid eye movement sleep at sleep onset led to improved understanding of core sleep‐related disease symptoms of the disease (excessive daytime sleepiness with early occurrence of rapid eye movement sleep, sleep‐related hallucinations, sleep paralysis, rapid eye movement parasomnia), as possible dysregulation of rapid eye movement sleep, and cataplexy resembling an intrusion of rapid eye movement atonia during wake. The relevance of non‐sleep‐related symptoms, such as obesity, precocious puberty, psychiatric and cardiovascular morbidities, has subsequently been recognized. The diagnostic tools have been improved, but sleep‐onset rapid eye movement periods on polysomnography and Multiple Sleep Latency Test remain key criteria. The pathogenic mechanisms of narcolepsy type 1 have been partly elucidated after the discovery of strong HLA class II association and orexin/hypocretin deficiency, a neurotransmitter that is involved in altered rapid eye movement sleep regulation. Conversely, the causes of narcolepsy type 2, where cataplexy and orexin deficiency are absent, remain unknown. Symptomatic medications to treat patients with narcolepsy have been developed, and management has been codified with guidelines, until the recent promising orexin‐receptor agonists. The present review retraces the steps of the research on narcolepsy that linked the features of the disease with rapid eye movement sleep abnormality, and those that do not appear associated with rapid eye movement sleep. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic may have a significant impact on patients with narcolepsy, yet a long-term follow-up study is currently lacking. This study aims to investigate changes in symptom severity and the quality of life of patients with narcolepsy during and after the pandemic. Patients with type 1 or type 2 narcolepsy (NT1, NT2) were retrospectively recruited and prospectively followed from 2020 to 2023. They received evaluations including the Epworth Sleepiness Scale (ESS), the visual analog scale (VAS) for hypersomnolence, the VAS for cataplexy, the Short-form 36 Health Survey questionnaire (SF-36), and a sleep diary. We compared the differences between the pre-lockdown, the lockdown, the post-lockdown, and the post-pandemic periods by repeated measures ANOVA or the Friedman test, with the Bonferroni test for post hoc analysis. A total of 100 patients completed the 4-year study (mean age, 24.06 ± 7.00 years; 55% male). We observed significant differences in the ESS (p = 0.037), total nighttime sleep (p = 0.03), total sleep time (p = 0.035), and sleep efficiency (p = 0.035) during the study period. There was also significantly worse physical role functioning in the post-pandemic period (p = 0.014). In particular, the NT1 group had significantly decreased VAS-C scores (p < 0.001) but experienced worse physical role functioning in the post-pandemic period (p = 0.009). Patients with narcolepsy continue to face challenges after the pandemic. A more flexible lifestyle with an adequate sleep time may be beneficial, and medication adherence should be emphasized. [ABSTRACT FROM AUTHOR]

Nonconvulsive status epilepticus (NCSE) manifests as a change in mental status without a coma (NCSE proper) or comatose NCSE. Hypocretin-1/orexin-A (H/O) is involved in alertness and sleep maintenance. Sleep impairment and excessive daytime sleepiness (EDS) have a negative impact on cognitive functions and activities of daily living (ADL). Patients meeting the NCSE criteria underwent cerebrospinal fluid and brain magnetic resonance imaging examinations, polysomnographies (PSG), multiple latency sleep tests (MSLT), and completed Epworth Sleepiness Scale (ESS). Montreal Cognitive Assessment was used to evaluate cognitive functions, and the Barthel Index was used to assess ADL in the acute phase (V1) and three months follow-up (V2). From May 2020 to May 2023, we enrolled 15 patients, eight (53.3 %) women, with a median age of 69 (14) years. The median H/O CSF concentration was 250 (63.6) pg/ml; however, only three CSF samples (20 %) decreased below the borderline concentration of 200 pg/ml. Fourteen out of 15 patients (93.3 %) completed the PSG study. The median of wakefulness after sleep onset was 167 (173.5) min, sleep efficiency (SE) was 62.9 (63) %, sleep latency (SL) was 6 (32) min, REM sleep was 2.85 (7.2) %, and REM first episode latency was 210.5 (196.5) minutes. The medians of the stages N1 NREM were 4.65 (15) %, N2 NREM 68.4 (29.9) %, and N3 NREM 21.8 (35.5) %. MSLT mean latency was 7.7 (12.6) minutes. A significant negative correlation exists between H/O CSF concentrations and the stage N1 NREM (r s = −0.612, p = 0.02), and the proportion of cumulative sleep time with oxygen saturation below 90 % in total sleep time (TST) t90 (r s = −0.57, p = 0.03). MSLT had significant negative correlation with TST (r s = −0.5369, p = 0.0478), with SE (r s = −0.5897, p = 0.0265), with apnea-hypopnea index (r s = −0.7631, p = 0.0002) and with deoxygenation index (r s = −0.8009, p = 0.0006). A positive correlation exists between MSLT and SL (r s = 0.6284, p = 0.0161) and between ESS and t90 (r s = 0.9014, p = 0.0004). The correlation between H/O CSF concentrations and EDS, cognitive performance, and ADL was not proved. Patients after NCSE exhibited sleep impairment and excessive daytime sleepiness. Hypocretin-1/orexin-A concentrations decreased only in 20 % of these cases. • There is sleep impairment and excessive daytime sleepiness in elderly patients after NCSE. • Hypocretin-1/Orexin-A concentrations in cerebrospinal fluid decreased in 20 % of patients with NCSE. • Hypocretin-1/Orexin-A concentrations in cerebrospinal fluid have a significant correlation with stage N1 NREM. • Hypocretin-1/Orexin-A concentrations in cerebrospinal fluid have a significant correlation with deoxygenation. • Excessive daytime sleepiness has a significant association with OSA in elderly patients with NCSE. [ABSTRACT FROM AUTHOR]

Introduction: Low-sodium oxybate (LXB) is approved for treatment of narcolepsy in patients aged 7 years and older and treatment of idiopathic hypersomnia in adults. LXB contains the same active moiety with 92% less sodium than sodium oxybate (SXB). As the indication for oxybate treatment in patients with idiopathic hypersomnia is new and allows for individualized dosing optimization, guidance for beginning LXB treatment is needed. In particular, clinicians may benefit from guidance regarding treatment initiation, dosing/regimen options, potential challenges, and treatment expectations. Additionally, pharmacokinetic profiles differ slightly between both treatments, and further guidance on transitioning from SXB to LXB in patients with narcolepsy may aid clinicians. Methods: An expert panel of five sleep specialists was convened to obtain consensus on recommendations for these topics using a modified Delphi process. Results: Across two virtual meetings, the panel agreed on 31 recommendations with a high degree of consensus that fell into four overarching topics: (1) introducing LXB to patients; (2) initiating LXB for adult narcolepsy and idiopathic hypersomnia; (3) addressing challenges in using LXB; and (4) transitioning from SXB to LXB. The panel recommended that clinicians provide a clear overview of how LXB works for treating symptoms in narcolepsy or idiopathic hypersomnia, as appropriate for their patients, explain safety aspects, and set expectations prior to initiating LXB treatment. Strategies for initial dosing and regimen are provided. Strategies for adjusting the dose, regimen, timing, and consideration of individual factors were developed for specific instances in which patients may have trouble staying asleep or waking up, as well as guidance for addressing potential adverse events, such as nausea, dizziness, anxiety, and depression. Discussion points based on existing literature and clinical experience were included as relevant for each statement. Conclusion: Clinicians may use this resource to guide LXB dosing optimization with patients. [ABSTRACT FROM AUTHOR]

While the medical community continues to recognize the contributions of disordered sleep to the burden of Prader-Willi syndrome (PWS), the medical literature lacks characterization of the patient burden of sleep disorders by people living with PWS and their caregivers. We developed and fielded a 72-question survey to the online PWS community, to query caregivers about their experiences with sleep symptoms. Respondents for all age groups reported sleep-disordered breathing (40 %), cataplexy-like symptoms (28.4 %), and insomnia (43.5 %). The presentation of cataplexy-like symptoms tended to change as children aged, presenting initially (ages 0–4 years) as head bobbing while eating, then transitioning to knee buckling between the ages of 5–12 years. Finally, loss of generalized tone associated with extreme emotions became more common in the teenage years. Frequent screening for potentially treatable sleep disorders should be considered the standard of care for individuals with PWS.

Background: Once-nightly sodium oxybate (ON-SXB), an extended-release oxybate formulation, yielded significant (P

Background and objective: At present, the etiology of narcolepsy is not fully understood, and it is generally believed to be an autoimmune reaction caused by interactions between environmental and genetic factors. Human leukocyte antigen (HLA) class II genes are strongly associated with this gene, especially HLA-DQB1*0602/DQA1*0102. In this study, we mainly analyzed the correlation between different genotypes of HLA-DQB1*0602/DQA1*0102 and clinical manifestations in Chinese patients with narcolepsy. Experimental method: Narcolepsy patients who were treated at the Department of Neurology, The First Affiliated Hospital of Shandong First Medical University from January 2021 to September 2023 were selected. General information, sleep monitoring data, cerebrospinal fluid (CSF) orexin levels, and human leukocyte antigen gene typing data were collected. The statistical analysis was performed using SPSS 26.0, and the graphs were drawn using GraphPad Prism 9.5. Main results: A total of 78 patients were included in this study. The DQA1 and DQB1 gene loci were detected in 54 patients, and only the DQB1 gene locus was detected in 24 narcoleptic patients. The most common allele at the HLA-DQB1 locus was *0602 (89.7%), and the most common genotype at this locus was *0602*0301 (19.2%), followed by *0602*0602 (17.9%). The most common phenotype of the HLA-DQA1 locus is *0102 (92.6%), and the most common genotype of this locus is *0102*0102 (27.8%), followed by *0102*0505 (14.8%). There were significant differences (p < 0.05) between HLA-DQB1*0602-positive and HLA-DQB1*0602-negative patients in terms of orexin-A levels, presence or absence of cataplexy, UNS, PSG sleep latency, REM sleep latency, N1 sleep percentage, oxygen depletion index, and average REM latency on the MSLT. The HLA-DQA1*0102-positive and HLA-DQA1*0102-negative patients showed significant differences (p<0.05) in disease course, presence or absence of sudden onset, PSG REM sleep latency, N1 sleep percentage, and average REM latency on the MSLT. There were significant differences in the average REM latency of the MSLT between HLA-DQB1*0602/DQA1*0102 homozygous and heterozygous patients p<0.05, and no differences were found in the baseline data, orexin-A levels, scale scores, or other sleep parameters. Conclusion: Different genotypes of HLA-DQA1*0102/DQB1*0602 are associated with symptoms of cataplexy in Chinese narcoleptic patients. Homozygous individuals have a shorter mean REM latency in the MSLT, greater genetic susceptibility, and relatively more severe sleepiness. [ABSTRACT FROM AUTHOR]

This article discusses a case of a patient with anti-Ma encephalitis, a paraneoplastic neurological syndrome caused by the immune impact of cancer on the nervous system. The patient exhibited symptoms such as memory loss, narcolepsy, rapid eye movement behavior disorder, eye movement abnormalities, and parkinsonism. The case also highlights the presence of agrypnia excitata, a unique electroclinical syndrome that disrupts sleep structure. The article emphasizes the importance of investigating autoimmune origins in patients with sleep disorders and the emerging recognition of autoimmune disorders in rare electroclinical conditions. [Extracted from the article]

"The Orexinergic System: Neurobiology and Clinical Implications" is an article that provides an overview of the orexinergic system and its role in regulating sleep, energy balance, and arousal. It explains that orexins are neuropeptides produced in the hypothalamus and bind to specific receptors to exert their effects. The article discusses the neural connections of the orexinergic system and its involvement in sleep disorders, dementia, alcohol dependence, and eating disorders. It also highlights the potential therapeutic implications of targeting the orexin system, particularly in the treatment of insomnia and narcolepsy, but acknowledges the need for further research to fully understand the effectiveness and safety of these interventions for different patient populations. [Extracted from the article]

Physical activity (PA) is recommended as part of the management of narcolepsy type 1 (NT1). This study aimed at 1) characterizing PA in children and adolescents treated for NT1 using objective and subjective measurements, 2) evaluating how PA is associated with NT1 symptoms and comorbidities, and 3) evaluating the effects of an Adapted Physical Activity (APA) program on PA and clinical characteristics. Patients with NT1 from the National Reference Center of Narcolepsy (Lyon, France) were consecutively included in an APA intervention protocol. Narcolepsy symptoms and comorbidities were collected using standardized questionnaires and sustained attention was evaluated using the Bron-Lyon Attention Stability Test before and after the four-week APA intervention. PA was measured objectively using actigraphy throughout the study. Twenty-seven NT1 patients were included (median age 14.7 years [8.3–18.4], cataplexy 88.9%, obesity 37.0%). At baseline, 52.4% of the patients had satisfactory PA levels according to international recommendations. Patients with leisure-time PA (LTPA) showed higher quality of life than patients without. 45% of the patients increased PA during the intervention compared to baseline. These responsive patients had more depressive feelings and tended to have lower objective PA than non-responsive patients at baseline. No significant correlation was found between PA levels before and during the intervention and other clinical data. Most children with NT1 showed satisfying PA levels despite their daytime sleepiness. LTPA engagement was associated with higher quality of life. An APA intervention could be effective in children with narcolepsy, especially for those with depressive feelings. • More than half of the children with narcolepsy were physically active. • Those who engaged in leisure time physical activities showed higher quality of life. • Those with depression are particularly responsive to a physical activity program. [ABSTRACT FROM AUTHOR]

There was more than a 10-fold increase in the incidence of narcolepsy type 1 (NT1) after the H1N1 mass vaccination in 2009/2010 in several countries. NT1 is associated with loss and increase of cell groups in the hypothalamus which may be associated with secondary affected sub-cortical and cortical gray matter. We performed a case-control comparison of MRI-based global and sub-cortical volume and cortical thickness in post-H1N1 NT1 patients compared with controls. We included 54 post-H1N1 NT1 patients (51 with confirmed hypocretin-deficiency; 48 H1N1-vaccinated with Pandemrix®; 39 females, mean age 21.8 ± 11.0 years) and 114 healthy controls (77 females, mean age 23.2 ± 9.0 years). 3T MRI brain scans were obtained, and the T1-weighted MRI data were processed using FreeSurfer. Group differences among three global, 10 sub-cortical volume measures and 34 cortical thickness measures for bilateral brain regions were tested using general linear models with permutation testing. Patients had significantly thinner brain cortex bilaterally in the temporal poles (Cohen's d = 0.68, p = 0.00080), entorhinal cortex (d = 0.60, p = 0.0018) and superior temporal gyrus (d = 0.60, p = 0.0020) compared to healthy controls. The analysis revealed no significant group differences for sub-cortical volumes. Post-H1N1(largely Pandemrix®-vaccinated) NT1 patients have significantly thinner cortex in temporal brain regions compared to controls. We speculate that this effect can be partly attributed to the hypothalamic neuronal change in NT1, including loss of function of the widely projecting hypocretin-producing neurons and secondary effects of the abnormal sleep-wake pattern in NT1 or could be specific for post-H1N1 (largely Pandemrix®-vaccinated) NT1 patients. • Largest brain-wide T1-study of narcolepsy type 1 patients to date. • First brain-wide T1 study of largely Pandemrix®-vaccinated narcolepsy type 1. • Narcolepsy type 1 patients have thinner cortex in temporal brain regions. • Specific findings in superior temporal gyrus, temporal poles and entorhinal cortex. • Superior temporal gyrus has previously been implicated in hallucinations. [ABSTRACT FROM AUTHOR]

It is hypothesized that narcolepsy type 1 (NT1) develops in genetically susceptible people who encounter environmental triggers leading to immune-mediated hypocretin-1 deficiency. The pathophysiologies of narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) remain unknown. The main aim of this study was to collect all reported immunological events before onset of a central disorder of hypersomnolence. Medical records of 290 people with NT1, and 115 with NT2 or IH were retrospectively reviewed to extract infection and influenza vaccination history. Prevalence, distribution of immunological events, and time until hypersomnolence onset were compared between NT1 and the combined group of NT2 and IH. Immunological events were frequently reported before hypersomnolence disorder onset across groups. Flu and H1N1 influenza vaccination were more common in NT1, and Epstein–Barr virus and other respiratory and non-respiratory infections in NT2 and IH. Distributions of events were comparable between NT2 and IH. Rapid symptom onset within one month of infection was frequent across groups, especially after flu infection in NT1. Hypersomnolence disorder progression after an immunological event was reported in ten individuals. Our findings suggest a variety of immunological triggers potentially related to NT1, including H1N1 influenza infection or vaccination, infection with other flu types, and other respiratory and non-respiratory infections. Frequent reports of immunological events (other than those reported in NT1) immediately prior to the development of NT2 and IH support the specificity of triggers for NT1, and open important new research avenues into possible underlying immunological mechanisms in NT2 and IH. • We studied possible immunological triggers for central disorders of hypersomnolence. • Flu and H1N1 influenza vaccination were more common before narcolepsy type 1 onset. • Non-flu infections were common before narcolepsy type 2/idiopathic hypersomnia onset. • Rapid hypersomnolence onset within one month was frequent across groups. [ABSTRACT FROM AUTHOR]

Understanding how persons with narcolepsy conceptualize symptoms, daily impact and illness experience is key to facilitating dialogue between patients and healthcare professionals. These concepts are usually explored from the perspective of healthcare professionals/researchers and rarely from the perspective of those with narcolepsy. 127 self-reported persons with narcolepsy were recruited from an Australian patient support group. A short demographic survey was completed. All agreed to participate in a subsequent 1:1 semi-structured interview. Saturation was reached after 24 interviews (mean age = 33 years (SD 11) with 44% reporting cataplexy). A multidisciplinary team of researchers/clinicians analyzed interview transcripts using thematic analysis. Participants perceived physical fatigue, sleepiness, and two separate experiences of 'falling asleep/sleep attacks' as distinct symptoms rather than a multidimensional construct (i.e. excessive daytime sleepiness). We also identified two experiences of cataplexy, one triggered by acute emotion and another by a stressor. Participants determined their narcolepsy to be 'well-managed' by the level of functional impairment rather than the frequency of any symptom. Almost all participants described experiencing anticipated stigma and internalized or 'self-' stigma, likely stemming from societal devaluation of sleep and the conflation of sleepiness with laziness. Descriptions of common symptoms often differed between participants and the existing literature. These differences likely impact patient-physician communication, with both parties utilizing the same terminology to communicate different concepts. The characterization of stigma in narcolepsy presents opportunities for future research exploring the impact and possible development of interventions to reduce the substantial psychological comorbidity in persons with narcolepsy. • Study explores how narcolepsy symptoms and illness experience are conceptualized. • Misalignment in terminology used between medical establishment and patients. • Results have potential to reshape objectives associate with narcolepsy management. • Rethink needed around communication strategies employed with patients. • Almost every participant with narcolepsy experienced anticipated and self-stigma. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a rare neurodegenerative disorder with a distinct phenotype, including involuntary movements, cognitive decline, and behavioral disturbances. Sleep disorder include insomnia, increased sleep onset latency, decrease in total sleep time with frequent nocturnal awakenings and excessive daytime sleepiness. Increased sleep motor activities and abnormal nocturnal agitation have been increasingly recognized as an important component affecting negatively the sleep quality. Here, we report a case of an intensification of diurnal choreic movement during the night, notably during REM-sleep in a patient with manifest HD. This case highlights the diversity of nocturnal sleep motor disorders encountered in HD. [ABSTRACT FROM AUTHOR]

Narcolepsy with cataplexy is a complex disease with both genetic and environmental risk factors. To gain further insight into the homozygous HCRT-related narcolepsy, we present a case series of five patients from two consanguineous families, each harboring a novel homozygous variant of HCRT c.17_18del. All affected individuals exhibited severe cataplexy accompanied by narcolepsy symptoms during infancy. Additionally, cataplexy symptoms improved or disappeared in the majority of patients over time. Pathogenic variants in HCRT cause autosomal recessive narcolepsy with cataplexy. Genetic testing of the HCRT gene should be conducted in specific subgroups of narcolepsy, particularly those with early onset, familial cases, and a predominantly cataplexy phenotype. [ABSTRACT FROM AUTHOR]

Background and Aim: Migraine is a prevalent neurological disorder characterized by recurring episodes of debilitating headache accompanied by associated symptoms and sleep disorders. This study aims to investigate migraine‐associated symptoms in female migraineurs within the Syrian population and the relation between migraines and sleep issues. Methods: A questionnaire‐based cross‐sectional observational study was conducted among the Syrian population. A total of 1009 women were enrolled in this study, including women without a history of migraine (Control group) and migraineurs (Case group) who had received a diagnosis of migraine from a hospital or private clinic. Data about migraine‐related symptoms, including tingling, visual disturbances, Nausea/Vomiting, and epileptic seizures as well as sleep‐related symptoms such as interrupted sleep, frequent awakenings, insomnia, snoring, and narcolepsy were gathered. Chi‐square test was used to examine the relation between migraines and sleep issues. Results: A total of 1009 women were enrolled in this study including 531 migraineurs and 478 healthy women. The study revealed that the most commonly experienced symptoms during migraine attacks were nausea/vomiting and visual disturbances, followed by tingling. Total Unduplicated Reach and Frequency analysis showed that visual disturbances and nausea/vomiting were the two most frequent symptoms that co‐occurred during migraine attacks. The study also demonstrated a significant relationship between snoring, insomnia, and narcolepsy with migraine (p = 0.038), with these sleep disorders being more prevalent among migraineurs. Conclusion: The findings indicate a significant association between migraines and sleep disorders, with migraineurs being at a significantly higher risk of experiencing poor sleep quality compared to healthy women. Addressing sleep disorders is crucial in managing patients with migraines. This study is the first of its kind in the Syrian population, providing valuable insights into the symptoms and sleep disorders associated with migraines in this population. [ABSTRACT FROM AUTHOR]

Insomnia disorder is a common condition that is considered a risk factor for multiple physical and mental disorders, contributing to reduced quality of life and increased healthcare expenditures. Although cognitive behavioral therapy (CBT) is typically recommended as the primary intervention, its accessibility is hindered by limited resources, prompting the prevalent use of pharmacological interventions as the primary treatment in clinical settings. This study reviews the benefits and risks of current pharmacological treatments for insomnia, with special reference to the orexinergic system as a novel therapeutic target for treatment. The prescription of GABAergic mechanism enhancers (benzodiazepine (BZD) and "Z drugs") has shown efficacy in short-term insomnia treatment (less than 4 weeks), however, concerns arise regarding their longterm effectiveness, unfavorable tolerability and safety profiles, including the potential for dependency. Drugs with antihistamine properties, including certain antidepressants and antipsychotics, exhibit short-term efficacy but have documented tolerability limitations, especially in the elderly. The use of melatonin, available in various formulations, lacks comprehensive long-term data. Dual orexin receptor antagonists (DORAs) such as daridorexant, lemborexant, and suvorexant, represent a novel approach to insomnia treatment by inhibiting wakefulness rather than enhancing sedation. As the only DORA approved for insomnia treatment by the European Medicines Agency (EMA) and Food and Drug Administration (FDA), daridorexant has demonstrated sustained efficacy over a 12-month period, improving nocturnal sleep parameters and daytime functionality, with a favorable safety and tolerability profile. [ABSTRACT FROM AUTHOR]

To obtain insight in the spectrum of narcolepsy symptoms and associated burden in a large cohort of patients. We used the Narcolepsy Monitor, a mobile app, to easily rate the presence and burden of 20 narcolepsy symptoms. Baseline measures were obtained and analyzed from 746 users aged between 18 and 75 years with a reported diagnosis of narcolepsy. Median age was 33.0 years (IQR 25.0–43.0), median Ullanlinna Narcolepsy Scale 19 (IQR 14.0–26.0), 78% reported using narcolepsy pharmacotherapy. Excessive daytime sleepiness (97.2%) and lack of energy were most often present (95.0%) and most often caused a high burden (79.7% and 76.1% respectively). Cognitive symptoms (concentration 93.0%, memory 91.4%) and psychiatric symptoms (mood 76.8%, anxiety/panic 76.4%) were relatively often reported to be present and burdensome. Conversely, sleep paralysis and cataplexy were least often reported as highly bothersome. Females experienced a higher burden for anxiety/panic, memory, and lack of energy. This study supports the notion of an elaborate narcolepsy symptom spectrum. Each symptom's contribution to the experienced burden varied, but lesser-known symptoms did significantly add to this as well. This emphasizes the need to not only focus treatment on the classical core symptoms of narcolepsy. [ABSTRACT FROM AUTHOR]

Objective: X‐linked adrenoleukodystrophy is caused by mutations in the peroxisomal half‐transporter ABCD1. The most common manifestation is adrenomyeloneuropathy, a hereditary spastic paraplegia of adulthood. The present study set out to understand the role of neuronal ABCD1 in mice and humans with adrenomyeloneuropathy. Methods: Neuronal expression of ABCD1 during development was assessed in mice and humans. ABCD1‐deficient mice and human brain tissues were examined for corresponding pathology. Next, we silenced ABCD1 in cholinergic Sh‐sy5y neurons to investigate its impact on neuronal function. Finally, we tested adeno‐associated virus vector‐mediated ABCD1 delivery to the brain in mice with adrenomyeloneuropathy. Results: ABCD1 is highly expressed in neurons located in the periaqueductal gray matter, basal forebrain and hypothalamus. In ABCD1‐deficient mice (Abcd1−/y), these structures showed mild accumulations of α‐synuclein. Similarly, healthy human controls had high expression of ABCD1 in deep gray nuclei, whereas X‐ALD patients showed increased levels of phosphorylated tau, gliosis, and complement activation in those same regions, albeit not to the degree seen in neurodegenerative tauopathies. Silencing ABCD1 in Sh‐sy5y neurons impaired expression of functional proteins and decreased acetylcholine levels, similar to observations in plasma of Abcd1−/y mice. Notably, hind limb clasping in Abcd1−/y mice was corrected through transduction of ABCD1 in basal forebrain neurons following intracerebroventricular gene delivery. Interpretation: Our study suggests that the basal forebrain–cortical cholinergic pathway may contribute to dysfunction in adrenomyeloneuropathy. Rescuing peroxisomal transport activity in basal forebrain neurons and supporting glial cells might represent a viable therapeutic strategy. ANN NEUROL 2024;95:442–458 [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is a condition characterized by daytime sleepiness, with occurrence of ≥ 5 obstructive events per hour during sleep, associated with cyclic oxygen desaturation. The cumulative effect of intermittent hypoxia can lead to pulmonary hypertension (PH). The study aimed to assess the association of PH with recently diagnosed OSA. Methods: Fifty newly diagnosed OSA patients with PH were included. Their PH was diagnosed based on echocardiographic findings. They seemed to have PH, if mean pulmonary artery pressure (mPAP) ≥25 mmHg. Results: 42 patients (84%) reported daytime sleepiness, 41 (82%) were snorers, 37 patients (74%) experienced witnessed apnea, 36 patients (72%) reported tiredness or fatigue, 27 patients (54%) suffered from choking and 22 patients (44%) reported nocturia. Mean snoring index was 304.85 (±290.60) events/hour. On the other hand, 20% of moderate OSA patients had mild PH, 33.3% had moderate PH and 46.7% had severe PH. Finally, the percentages of mild, moderate, and severe PH in severe OSA patients were 12%, 28% and 60% respectively. There was a significant association between OSA severity and both approximated pulmonary artery systolic pressure (PASP) & approximated mPAP. Approximated PASP was significantly higher in severe OSA than mild and moderate OSA (75.3 vs 69.8 vs. 52.3 mmHg respectively, p =0.018). Approximated mPAP was significantly higher in patients with severe OSA than patients with mild and moderate OSA (47.93 vs. 44.6 vs. 33.9 mmHg respectively, p =0.016 Conclusions: PH and its degree are directly correlated to OSA and its severity. [ABSTRACT FROM AUTHOR]

The gold standard investigation for central disorders of hypersomnolence is the Multiple Sleep Latency Test (MSLT). As the clinical features of these disorders of hypersomnolence evolve with time in children, clinicians may consider repeating a previously non-diagnostic MSLT. Currently there are no guidelines available regards the utility and timing of repeating paediatric MSLTs. Retrospective review of children aged 3–18years with ≥2MSLTs between 2005 and 2022. Narcolepsy was defined as mean sleep latency (MSL) <8min with ≥2 sleep onset REM (SOREM); idiopathic hypersomnia (IH) was defined as MSL <8min with <2 SOREM. MSLTs not meeting these criteria were labelled non-diagnostic. 19 children (9 female) with initial non-diagnostic MSLT underwent repeat MSLT, with 6 proceeding to a 3rd MSLT following 2 non-diagnostic MSLTs. The 2nd MSLT resulted in diagnosis in 6/19 (32 %) (3 narcolepsy, 3 IH); and 2/6 (33 %) 3rd MSLT were diagnostic (2 IH). Median age at initial MSLT was 7.5y (range 3.4–17.8y), with repeat performed after median of 2.9y (range 0.9–8.2y), and 3rd after a further 1.9 years (range 1.2–4.2y). Mean change in MSL on repeat testing was -2min (range −15.5min to +4.9min, p = 0.18). Of the 8 diagnostic repeat MSLTs, in addition to the MSL falling below 8 min, 2 children also developed ≥2 SOREM that had not been previously present. A third of repeat MSLTs became diagnostic, suggesting repeat MSLT should be considered in childhood if clinical suspicion persists. Further work needs to address the ideal interval between MSLTs and diagnostic cut-points specific to the paediatric population. • Narcolepsy and idiopathic hypersomnia symptoms often begin in childhood • Diagnosis with the multiple sleep latency test (MSLT) is based on adult criteria • The utility or timing of repeating a non-diagnostic paediatric MSLT is unknown • A third of repeat MSLTs in children met diagnostic criteria • Repeat MSLT should be considered in childhood if clinical suspicion persists [ABSTRACT FROM AUTHOR]

Narcolepsy, a chronic neurologic sleep disorder, has sparked growing interest in the potential role of vitamin B12 in its pathogenic mechanism. However, research on this association has predominantly focused on adults. Our objective was to delineate the phenotypic and genetic connections between serum vitamin B12 levels and paediatric narcolepsy. To investigate the causal relationship between vitamin B12 and paediatric narcolepsy, we conducted a retrospective analysis involving 60 narcolepsy patients and a matched control group. Univariate and multivariate logistic regression models were employed to identify independent factors influencing paediatric narcolepsy. Furthermore, a bidirectional two-sample Mendelian randomization (MR) analysis was performed to assess the causal connection between serum vitamin B12 levels and narcolepsy. Paediatric narcolepsy patients showed significantly lower serum levels of vitamin B12 and folate compared to the control group (P < 0.05). Multivariate logistic regression analysis identified serum vitamin B12 as the exclusive independent factor influencing paediatric narcolepsy (P < 0.001; OR = 0.96; 95%CI: 0.94–0.98). Additionally, IVW model results provided compelling evidence supporting a potential causal association between serum vitamin B12 levels and paediatric narcolepsy (OR: 0.958, 95% CI = 0.946–0.969, P = 0.001). This study establishes connections at both phenotypic and genetic levels, associating vitamin B12 deficiency with an increased risk of paediatric narcolepsy. These findings provide innovative perspectives for clinical strategies in the prevention and treatment of narcolepsy. • Acknowledging the inherent limitations of observational studies, establishing a definitive causal or reverse causal association between vitamin B12 and narcolepsy proves challenging. • Serum vitamin B12 as the exclusive independent factor influencing paediatric narcolepsy. • Based on the MR findings, potential evidence was identified for the association between vitamin B12 deficiency and an increased risk of narcolepsy. [ABSTRACT FROM AUTHOR]

Introduction and aims: Narcolepsy type 1 (NT1) is a central disorder of hypersomnolence (CDH) characterized by excessive daytime sleepiness and cataplexy. The Swiss Narcolepsy Scale (SNS), which includes the updated and short (sSNS) versions, has recently been introduced as a reliable diagnostic tool for identifying NT1. This study aims to assess the validity of the SNS scales in a new cohort of patients with CDH, while also introducing the French and Italian versions of the SNS and providing a summary of the existing literature on SNS. Materials and methods: The current study is based on the international Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (iSPHYNCS) which aims to identify new biomarkers for CDH. Diagnostic accuracy of the SNS was assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value. Results: In our population, 108 participants with suspected CDH (including 28 NT1 patients) and 14 healthy controls completed the scale. Original SNS, updated SNS and sSNS scores showed a high sensitivity (86%, 89% and 79%, respectively) and high specificity (96%, 90% and 95%, respectively) for diagnosing NT1 compared to other CDH. The French version was completed by 5 participants, and the Italian version by 8 participants. Regarding previous studies, the SNS has now been assessed in six different populations, involving a total of 1247 subjects (including 326 with narcolepsy with cataplexy/NT1), suggesting high sensitivity (85–100%) and specificity (86–100%) of the SNS for the diagnosis of NT1. Conclusion: The SNS is a simple screening tool validated in seven languages (German, English, French, Italian, Dutch, Turkish and Japanese), demonstrating high sensitivity and specificity for the diagnosis of NT1. [ABSTRACT FROM AUTHOR]

What is this summary about? This is a plain language summary of a published article in the journal Sleep. Narcolepsy is a sleep condition that has 2 different subtypes: narcolepsy type 1 and narcolepsy type 2. These are called NT1 and NT2 for short. Sodium oxybate (SXB) is approved to treat excessive daytime sleepiness (EDS) and cataplexy. People with NT1 and NT2 both have EDS, but cataplexy is only present in people with NT1. Limited information is available about how SXB works in people with NT2. This is because previous trials have included only people with NT1 or people with unspecified narcolepsy. For more than 20 years, the only available formulation of this medicine had to be given twice during the night. Many people with narcolepsy find that chronically waking up in the middle of the night for a second dose of SXB is disruptive to themselves or others in their household. People have also reported sleeping through alarm clocks, missing their second dose, and feeling worse the next day. Some people have accidentally taken the second dose too early, putting them at risk for serious adverse effects. These adverse effects may include slow breathing, low blood pressure, or sedation. The US Food and Drug Administration (FDA) approved a medicine called LUMRYZ™ (sodium oxybate) for extended-release oral suspension in May 2023. LUMRYZ is a once-nightly formulation of SXB (ON-SXB for short) and is taken as a single dose before bedtime. This medicine treats EDS and muscle weakness (also known as cataplexy) in people with narcolepsy. A clinical trial called REST-ON studied ON-SXB to find out if it was better at treating narcolepsy symptoms than a medicine with no active ingredients (placebo). This summary describes a study that tested whether ON-SXB was better than placebo at treating narcolepsy symptoms in people with NT1 or NT2. What were the results? This study showed that compared to people who took placebo, people who took ON-SXB were able to stay awake longer during the day, felt less sleepy during the daytime, had less cataplexy, and had more improvements in their symptoms overall than people who took placebo. What do the results mean? ON-SXB has been proven effective for people with NT1 or NT2. Unlike prior formulations of SXB, ON-SXB is taken once at bedtime, without requiring waking up in the middle of the night for a second dose.

This letter to the editor responds to an article titled "Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary" by Rosenberg et al. The authors of the letter discuss the impact of different dosing regimens of sodium oxybate (SXB) on disrupted nighttime sleep (DNS) in patients with narcolepsy. They point out inaccuracies in the article's comparison of immediate-release (IR) SXB and extended-release SXB, and emphasize the importance of using accurate data when considering results from different trials. The authors also discuss the potential effects of concomitant stimulant use and the differences in slow-wave sleep (SWS) between the two dosing regimens. [Extracted from the article]