The nature and magnitude of cognitive impairment in narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia: a meta-analysis.

People with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) often report cognitive impairment which can be quite burdensome but is rarely evaluated in routine clinical practice. In this systematic review and meta-analysis, we assessed the nature and magnitude of cognitive impairment in NT1, NT2, and IH in studies conducted from January 2000 to October 2022. We classified cognitive tests assessing memory, executive function, and attention by cognitive domain. Between-group differences were analyzed as standardized mean differences (Cohen's d), and Cohen's d for individual tests were integrated according to cognitive domain and clinical disease group. Eighty-seven studies were screened for inclusion; 39 satisfied inclusion criteria, yielding 73 comparisons (k): NT1, k = 60; NT2, k = 8; IH, k = 5. Attention showed large impairment in people with NT1 (d = -0.90) and IH (d = -0.97), and moderate impairment in NT2 (d = -0.60). Executive function was moderately impaired in NT1 (d = -0.30) and NT2 (d = -0.38), and memory showed small impairments in NT1 (d = -0.33). A secondary meta-analysis identified sustained attention as the most impaired domain in NT1, NT2, and IH (d ≈ -0.5 to -1). These meta-analyses confirm that cognitive impairments are present in NT1, NT2, and IH, and provide quantitative confirmation of reports of cognitive difficulties made by patients and clinicians. These findings provide a basis for the future design of studies to determine whether cognitive impairments can improve with pharmacologic and nonpharmacologic treatments for narcolepsy and IH.

Narcolepsy and rapid eye movement sleep.

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.

Narcolepsy and pediatric acute-onset neuropsychiatric syndrome: A case report that suggests a putative link between the two disorders.

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.

Associations between obesity, a composite risk score for probable long COVID, and sleep problems in SARS-CoV-2 vaccinated individuals.

BACKGROUND: Preliminary data suggests that obesity might hasten the decline in mRNA vaccine-induced immunity against SARS-CoV-2. However, whether this renders individuals with obesity more susceptible to long COVID symptoms post-vaccination remains uncertain. Given sleep's critical role in immunity, exploring the associations between obesity, probable long COVID symptoms, and sleep disturbances is essential. METHODS: We analyzed data from a survey of 5919 adults aged 18 to 89, all of whom received two SARS-CoV-2 mRNA vaccinations. Participants were categorized into normal weight, overweight, and obesity groups based on ethnicity-specific BMI cutoffs. The probability of long COVID was evaluated using the Post-Acute Sequelae of SARS-CoV-2 (PASC) score, as our survey did not permit confirmation of acute SARS-CoV-2 infection through methods such as antibody testing. Additionally, sleep patterns were assessed through questionnaires. RESULTS: Participants with obesity exhibited a significantly higher adjusted odds ratio (OR) of having a PASC score of 12 or higher, indicative of probable long COVID in our study, compared to those with normal weight (OR: 1.55, 95% CI: 1.05, 2.28). No significant difference was observed for overweight individuals (OR: 0.92 [95% CI: 0.63, 1.33]). Both obesity and probable long COVID were associated with increased odds of experiencing a heightened sleep burden, such as the presence of obstructive sleep apnea or insomnia (P < 0.001). However, no significant interaction between BMI and probable long COVID status was found. CONCLUSIONS: Even post-vaccination, individuals with obesity may encounter a heightened risk of experiencing prolonged COVID-19 symptoms. However, confirming our observations necessitates comprehensive studies incorporating rigorous COVID infection testing, such as antibody assays - unavailable in our anonymous survey. Additionally, it is noteworthy that the correlation between probable long COVID and sleep disturbances appears to be independent of BMI.

Restless legs symptoms increased during COVID-19 pandemic. International ICOSS-survey.

BACKGROUND AND OBJECTIVES: Restless legs syndrome (RLS) has been associated with anxiety, depression, insomnia, lifestyle factors and infections. We aimed to study the prevalence of symptoms of RLS during the COVID-19 pandemic versus pre-pandemic. We hypothesized that pre-existing RLS symptoms worsened and pandemic-related factors may have triggered new symptoms of RLS. METHODS: Adults (≥18 years) from fifteen countries across four continents participated in an online survey between May and August 2020. The harmonized questionnaire included a validated single question on RLS with response alternatives from 1 to 5 on a scale from never to every/almost every evening or night. Other measures were the Insomnia Severity Index (ISI), measures of symptoms of anxiety (GAD-2) and depression (PHQ-2), and questions on different pandemic-related factors. RESULTS: Altogether, 17 846 subjects (63.8 % women) were included in the final analyses. The mean age was 41.4 years (SD 16.1). During the pandemic, symptoms of RLS (≥3 evenings/nights per week) were more common 9.1 % (95 % CI 8.7-10.1) compared to 5.4 % (95 % CI 4.9-6.0) before the pandemic (P < 0.0001). Alltogether 1.3 % (95 % CI 1.1-1.6) respondents had new-onset symptoms (≥3 evenings/nights per week). Moderate-severe insomnia was strongly associated with RLS symptoms. The occurrences of new-onset RLS symptoms were 5.6 % (95 % CI 0.9-13.0) for participants reporting COVID-19 and 1.1 % (95 % CI 0.7-1.5) for non-COVID-19 participants. In the fully adjusted logistic regression model, the occurrence of new-onset RLS symptoms was associated with younger age, social restrictions and insomnia severity. In a similar analysis, RLS symptoms (≥3 evenings/nights per week) were associated with lower education, financial hardship, sleep apnea symptoms, use of hypnotics, insomnia severity, symptoms of depression and possible post-traumatic stress disorder. DISCUSSION: Our findings indicate that RLS symptoms were more common during the pandemic than before. Usually, the prevalence of RLS increases with age. However, during the pandemic, new-onset symptoms of RLS were more common in younger age groups. This may be due to the pandemic-related factors being more pronounced in the younger compared to the older. The association between insomnia, psychiatric symptoms and RLS warrants clinical attention.

Sensory aspects of restless legs syndrome: Clinical, neurophysiological and neuroimaging prospectives.

Restless Legs Syndrome (RLS) is a complex sensorimotor disorder, classified among the sleep-related movement disorders. Although sensory symptoms appear as key features of the disorder, they are still poorly characterized from a clinical perspective and conceptualized from a pathophysiological point of view. In this review, we aim to describe the clinical and functional substrates of RLS, focusing mainly on its sensory symptoms and on their neurophysiological and anatomical correlates. Knowledge of both subjective sensory symptoms and objective sensory signs are still controversial. Current data also indicate that the sensory component of RLS seems to be subserved by anomalies of sensorimotor integration and by mechanism of central sensitization. Overall, electrophysiological findings highlight the involvement of multiple generators in the pathogenesis of RLS, eventually resulting in an increased nervous system excitability and/or alterations in inhibition within the somatosensory and nociceptive pathways. Structural and functional neuroimaging data show the involvement of several crucial areas and circuits, among which the thalamus appears to play a pivotal role. A holistic approach looking at brain connectivity, structural or functional abnormalities, and their interplay with molecular vulnerability and neurotransmitter alterations is warranted to disentangle the complex framework of RLS.

Navigating narcolepsy: exploring coping strategies and their association with quality of life in patients with narcolepsy type 1.

Narcolepsy type 1 (NT1) is a chronic neurological disorder characterized by symptoms such as excessive daytime sleepiness, sudden sleep episodes, disrupted nocturnal sleep, cataplexy, sleep paralysis, and hypnagogic hallucinations, which significantly impact the overall well-being and quality of life of individuals. While psychological factors have gained attention, there is limited research on the coping strategies employed by patients with NT1 and their association with quality of life. This study aimed to compare coping strategies in patients with NT1 and controls, as well as assess the relationship between coping strategies and quality of life in patients with NT1. A total of 122 individuals diagnosed with NT1 and 138 controls were enrolled in this cross-sectional study. Participants completed questionnaires assessing coping strategies and health-related quality of life. A Mann-Whitney U test was conducted to compare the use of different coping strategies by patients with NT1 and controls. Spearman's rho correlation was performed to examine the association between coping strategies and quality of life in the NT1 group. Results showed that patients with NT1 exhibited differences in the use of coping strategies compared to controls. They reported lower use of active coping, planning, instrumental, and emotional social support, and higher use of behavioral and mental disengagement. Denial and behavioral disengagement were significantly and negatively associated with quality of life. Identifying coping strategies and their association with quality of life may aid in the development of tailored interventions aimed at improving the adoption of effective coping strategies and reducing the use of maladaptive coping strategies.

A survey-based approach on restless legs syndrome: practices and perspectives among Italian neurologists.

INTRODUCTION: Restless Legs Syndrome (RLS) is a widely prevalent and complex neurological disorder. Despite notable advancements in managing RLS, the disorder continues to face challenges related to its recognition and management. OBJECTIVE: This study seeks to gain comprehensive insights into the knowledge and clinical practices among Italian neurologists regarding RLS diagnosis, management, and treatment, comparing approaches among general neurologists, movement disorder specialists, and sleep experts. METHODS: Members of the Italian Society of Neurology, the Italian Society of Parkinson and Movement Disorders, and the Italian Association of Sleep Medicine were invited to participate in a 19-question online survey. RESULTS: Among the 343 surveyed neurologists, 60% categorized RLS as a "sleep-related movement disorder." Forty% indicated managing 5-15 RLS patients annually, with sleep specialists handling the highest patient volume. Of note, only 34% adhered strictly to all five essential diagnostic criteria. The majority (69%) favored low-dosage dopamine agonists as their first-line treatment, with movement disorder specialists predominantly endorsing this approach, while sleep experts preferred iron supplementation. Regular screening for iron levels was widespread (91%), with supplementation typically guided by serum iron alterations. In cases of ineffective initial treatments, escalating dopamine agonist dosage was the preferred strategy (40%). CONCLUSIONS: These findings underscore a lack of a clear conceptualization of RLS, with a widespread misconception of the disorder as solely a movement disorder significantly influencing treatment approaches. Disparities in RLS understanding across neurology subspecialties underscore the necessity for improved diagnostic accuracy, targeted educational initiatives, and management guidelines to ensure consistent and effective RLS management.

Theory of Mind impairment in childhood narcolepsy type 1: a case-control study.

Narcolepsy type 1 is a central disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy and other rapid eye movement sleep-related manifestations. Neurophysiological studies suggest that narcolepsy type 1 patients may experience impairment in emotional processing due to structural and functional changes in limbic structures and associated areas. However, the only study exploring narcolepsy behavioural responses found no impairment in the ability to recognize emotions, possibly due to compensatory mechanisms. The present study was designed to fill this gap in the literature by investigating the behavioural impairment related to emotional processing focusing on an advanced socio-cognitive skill, namely Theory of Mind, in paediatric narcolepsy type 1 patients. Twenty-two narcolepsy type 1 children and adolescents (six female; age range: 8.0-13.5) and 22 healthy controls matched for age and sex (six female; age range: 8.9-13.0) underwent a neuropsychological evaluation to assess socio-economic status, verbal abilities, working memory, social anxiety and Theory of Mind via a verbal task (i.e. Strange Stories task) and a visual task (i.e. Silent Films). Narcolepsy type 1 patients were also evaluated for disease severity. Patients exhibited impairment in Theory of Mind skills, as assessed both through both verbal (controls median = 8; patients median = 5; P = 0.009) and visual tasks (controls median = 8; patients median = 6; P = 0.003), compared to healthy controls. Correlation analyses showed that verbal and visual Theory of Mind was negatively related to narcolepsy severity (ρ = -0.45, P = 0.035 and ρ = -0.52, P = 0.012), and daytime sleepiness (ρ = -0.48, P = 0.025 and ρ = -0.45, P = 0.038). Our study shows a selective impairment in the Theory of Mind domain in children and adolescents with narcolepsy type 1. In addition, our results highlight a link between symptom severity and Theory of Mind, suggesting that lower Theory of Mind levels are associated with higher symptom severity. Further, longitudinal studies are needed to disentangle the direction of this relation and to disambiguate if narcolepsy severity impaired children's Theory of Mind or if Theory of Mind skills modulate the severity of narcolepsy symptoms by providing a greater ability to avoid cataplexy.

Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy.

OBJECTIVE: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. RESULTS: Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters. INTERPRETATION: Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178-1192.

Biomarkers of neurodegeneration in isolated and antidepressant-related rapid eye movement sleep behavior disorder.

BACKGROUND AND PURPOSE: This study compared the features of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and antidepressant-related REM sleep behaviour disorder (RBD) with the aim of highlighting markers that might distinguish the two entities. METHODS: The observational cohort study included RBD patients with and without antidepressant use (antiD+ and antiD- patients, respectively), without cognitive impairment and parkinsonism. Clinical features of RBD, subtle motor and non-motor symptoms of parkinsonism, sleep architecture, REM atonia index, dopamine transporter-single photon emission computed tomography (DAT-SPECT) and skin biopsies for the intraneuronal alpha-synuclein (α-syn), were evaluated in the baseline work-up. RESULTS: Thirty-nine patients, 10 antiD+ and 29 antiD-, were included. AntiD+ patients (more frequently female) reported more psychiatric symptoms, less violent dream enactment, and less frequent hyposmia. Dermal α-syn was detected in 93.1% of antiD- versus 30% of antiD+ patients (p = 0.00024). No differences appeared in other motor and non-motor symptoms, Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III score, DAT-SPECT, or polysomnographic features. CONCLUSIONS: Patients with antidepressant-related RBD have clinical and neuropathological features suggesting a lower risk of evolution than those with iRBD.

Long sleep time and excessive need for sleep: State of the art and perspectives.

The mechanisms underlying the individual need for sleep are unclear. Sleep duration is indeed influenced by multiple factors, such as genetic background, circadian and homeostatic processes, environmental factors, and sometimes transient disturbances such as infections. In some cases, the need for sleep dramatically and chronically increases, inducing a daily-life disability. This "excessive need for sleep" (ENS) was recently proposed and defined in a European Position Paper as a dimension of the hypersomnolence spectrum, "hypersomnia" being the objectified complaint of ENS. The most severe form of ENS has been described in Idiopathic Hypersomnia, a rare neurological disorder, but this disabling symptom can be also found in other hypersomnolence conditions. Because ENS has been defined recently, it remains a symptom poorly investigated and understood. However, protocols of long-term polysomnography recordings have been reported by expert centers in the last decades and open the way to a better understanding of ENS through a neurophysiological approach. In this narrative review, we will 1) present data related to the physiological and pathological variability of sleep duration and their mechanisms, 2) describe the published long-term polysomnography recording protocols, and 3) describe current neurophysiological tools to study sleep microstructure and discuss perspectives for a better understanding of ENS.

Disclosing the Risk Associated with Isolated REM Behavior Disorder: The Sleep Experts' Perspective.

BACKGROUND: Isolated rapid-eye-movement sleep behavior disorder (iRBD) is associated with a high risk for phenoconversion to a neurodegenerative disorder, but the optimal approach for disclosure of this risk to patients is still debated. OBJECTIVES: The aim of this study was to explore views and experiences of iRBD experts regarding risk disclosure. METHODS: In this qualitative study, semi-structured interviews with sleep experts caring for patients with iRBD were analyzed through a conventional content analysis approach. RESULTS: We interviewed 22 iRBD experts (eight female, average age of 51.8 years) from 18 Italian sleep centers; 21/22 regularly disclosed the risks associated with iRBD, usually after the video-polysomnography, and 8/22 regularly mentioned phenoconversion rates. Content analysis allowed us to identify three main themes. First, sleep experts reported several points in favor of risk disclosure, especially related to the principle of beneficence, but some highlighted the need for specific learning on the topic. Second, experts favored a patient-tailored disclosure that should not upset the patient unnecessarily, since phenoconversion is uncertain. Third, risk disclosure was seen by participants as a relational task that should be carried out in person in the context of a trusting patient-physician relationship, while they had contrasting views regarding patients' previous knowledge. CONCLUSIONS: Sleep experts generally preferred a tailored and reassuring approach to risk disclosure within a framework of relational autonomy. The results of this study indicate the need for specific education, training, and recommendations concerning risk disclosure that should also include patients' and families' preferences.

Nightmare frequency is a risk factor for suicidal ideation during the COVID-19 pandemic.

The association between nightmare frequency (NMF) and suicidal ideation (SI) is well known, yet the impact of the COVID-19 pandemic on this relation is inconsistent. This study aimed to investigate changes in NMF, SI, and their association during the COVID-19 pandemic. Data were collected in 16 countries using a harmonised questionnaire. The sample included 9328 individuals (4848 women; age M[SD] = 46.85 [17.75] years), and 17.60% reported previous COVID-19. Overall, SI was significantly 2% lower during the pandemic vs. before, and this was consistent across genders and ages. Most countries/regions demonstrated decreases in SI during this pandemic, with Austria (-9.57%), Sweden (-6.18%), and Bulgaria (-5.14%) exhibiting significant declines in SI, but Italy (1.45%) and Portugal (2.45%) demonstrated non-significant increases. Suicidal ideation was more common in participants with long-COVID (21.10%) vs. short-COVID (12.40%), though SI did not vary by COVID-19 history. Nightmare frequency increased by 4.50% during the pandemic and was significantly higher in those with previous COVID-19 (14.50% vs. 10.70%), during infection (23.00% vs. 8.10%), and in those with long-COVID (18.00% vs. 8.50%). The relation between NMF and SI was not significantly stronger during the pandemic than prior (rs = 0.18 vs. 0.14; z = 2.80). Frequent nightmares during the pandemic increased the likelihood of reporting SI (OR = 1.57, 95% CI 1.20-2.05), while frequent dream recall during the pandemic served a protective effect (OR = 0.74, 95% CI 0.59-0.94). These findings have important implications for identifying those at risk of suicide and may offer a potential pathway for suicide prevention.

Eating disorders in narcolepsy type 1: Evidence from a cross-sectional Italian study.

Narcolepsy type 1 is a chronic central disorder of hypersomnolence, and it is frequently accompanied by overweight, but the association between narcolepsy type 1 and eating disorders is controversial. Our study aims to compare patients with narcolepsy type 1 and controls on the symptomatology of eating disorders and to evaluate the association between clinical factors. This is a cross-sectional study, with consecutive recruitment of patients with narcolepsy type 1 attending the Outpatient Clinic for Narcolepsy at the IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy) for routine follow-up visits. Healthy subjects from general populations were recruited as controls. Patients underwent a questionnaire-based assessment using the Eating Disorder Examination Questionnaire (EDE-Q), Binge Eating Scale (BES), Italian Night Eating Questionnaire (I-NEQ), Epworth Sleepiness Scale (ESS), and Narcolepsy Severity Scale (NSS). One hundred and thirty-eight patients with narcolepsy type 1 and 162 controls were enrolled. This study showed that individuals with narcolepsy type 1 reported higher scores on the EDE-Q, I-NEQ, and a higher body mass index (BMI) than the controls. The logistic regression analysis results, with EDE-Q positivity as a dependent variable, demonstrate a significant association with antidepressant drugs, female sex, and the use of sodium oxybate. We found an association between antidepressant drug consumption, the NSS total score, and female sex with BES positivity as the dependent variable. The logistic regression analysis for I-NEQ positivity found an association with antidepressant drug use. This study shows that patients with narcolepsy type 1 frequently present with comorbid eating disorder symptomatology, mainly night eating syndrome. Investigating the possible presence of eating disorders symptomatology through questionnaires is fundamental during the assessment of patients with narcolepsy type 1.

Estimation bias and agreement limits between two common self-report methods of habitual sleep duration in epidemiological surveys.

Accurate measurement of habitual sleep duration (HSD) is crucial for understanding the relationship between sleep and health. This study aimed to assess the bias and agreement limits between two commonly used short HSD self-report methods, considering sleep quality (SQ) and social jetlag (SJL) as potential predictors of bias. Data from 10,268 participants in the International COVID Sleep Study-II (ICOSS-II) were used. Method-Self and Method-MCTQ were compared. Method-Self involved a single question about average nightly sleep duration (HSDself), while Method-MCTQ estimated HSD from reported sleep times on workdays (HSDMCTQwork) and free days (HSDMCTQfree). Sleep quality was evaluated using a Likert scale and the Insomnia Severity Index (ISI) to explore its influence on estimation bias. HSDself was on average 42.41 ± 67.42 min lower than HSDMCTQweek, with an agreement range within ± 133 min. The bias and agreement range between methods increased with poorer SQ. HSDMCTQwork showed less bias and better agreement with HSDself compared to HSDMCTQfree. Sleep duration irregularity was - 43.35 ± 78.26 min on average. Subjective sleep quality predicted a significant proportion of variance in HSDself and estimation bias. The two methods showed very poor agreement and a significant systematic bias, both worsening with poorer SQ. Method-MCTQ considered sleep intervals without adjusting for SQ issues such as wakefulness after sleep onset but accounted for sleep irregularity and sleeping in on free days, while Method-Self reflected respondents' interpretation of their sleep, focusing on their sleep on workdays. Including an SQ-related question in surveys may help bidirectionally adjust the possible bias and enhance the accuracy of sleep-health studies.

Sex disparities in clinical features and burden of narcolepsy type 1.

To investigate potential sex-related differences in patients with narcolepsy type 1, we carried out an analysis of baseline data from 93 women and 89 men with narcolepsy type 1 who participated in the TElemedicine for NARcolepsy (TENAR) trial. The following data were considered: sociodemographics; diagnostic (disease history, polysomnography, orexin, human leukocyte antigen) and clinical features, including sleepiness (Epworth Sleepiness Scale), cataplexy and other narcolepsy symptoms; disease severity (Narcolepsy Severity Scale); pharmacological treatment; depressive symptoms (Beck Depression Inventory); and self-reported relevance of eight narcolepsy-related issues. We found that, compared with men, significantly more women reported automatic behaviours (55.4% versus 40%) and had higher Epworth Sleepiness Scale (median 10 versus 9) and Beck Depression Inventory scores (median 10.5 versus 5), and there was a trend for a higher Narcolepsy Severity Scale total score in women (median 19 versus 18, p = 0.057). More women than men were officially recognized as having a disability (38% versus 22.5%) and considered 5/8 narcolepsy-related issues investigated as a relevant problem. More severe sleepiness and a greater narcolepsy-related burden in women could mirror sex differences present in the general population, or may be related to suboptimal management of narcolepsy type 1 or to more severe depressive symptoms in women. Future studies and guidelines should address these aspects.

Role of Daytime Continuous Polysomnography in the Diagnosis of Pediatric Narcolepsy Type 1.

BACKGROUND AND OBJECTIVES: Narcolepsy type 1 (NT1) is still largely underdiagnosed or diagnosed too late in children. Difficulties in obtaining rapid and reliable diagnostic evaluations of the condition in clinical practice partially explain this problem. Predictors of NT1 include cataplexy and sleep-onset REM periods (SOREMPs), documented during nocturnal polysomnography (N-PSG) or through the multiple sleep latency test (MSLT), although low CSF hypocretin-1 (CSF hcrt-1) is the definitive biological disease marker. Obtaining reliable MSLT results is not always feasible in children; therefore, this study aimed to validate daytime continuous polysomnography (D-PSG) as an alternative diagnostic tool. METHODS: Two hundred consecutive patients aged younger than 18 years (112 with NT1; 25 with other hypersomnias, including narcolepsy type 2 and idiopathic hypersomnia; and 63 with subjective excessive daytime sleepiness) were randomly split into 2 groups: group 1 (n = 133) for the identification of diagnostic markers and group 2 (n = 67) for the validation of the detected markers. The D-PSG data collected included the number of spontaneous naps, total sleep time, and the number of daytime SOREMPs (d-SOREMP). D-PSG data were tested against CSF hcrt-1 deficiency (NT1 diagnosis) as the gold standard using receiver operating characteristic (ROC) curve analysis in group 1. ROC diagnostic performances of single and combined D-PSG parameters were tested in group 1 and validated in group 2. RESULTS: In group 1, the areas under the ROC curve (AUCs) were 0.91 (95% CI 0.86-0.96) for d-SOREMPs, 0.81 (95% CI 0.74-0.89) for the number of spontaneous naps, and 0.70 (95% CI 0.60-0.79) for total sleep time. A d-SOREMP count ≥1 (sensitivity of 95% and specificity of 72%), coupled with a diurnal total sleep time above 60 minutes (sensitivity of 89% and specificity of 91%), identified NT1 in group 1 with high reliability (area under the ROC curve of 0.93, 95% CI 0.88-0.97). These results were confirmed in the validation group with an AUC of 0.88 (95% CI 0.79-0.97). DISCUSSION: D-PSG recording is an easily performed, cost-effective, and reliable tool for identifying NT1 in children. Further studies should confirm its validity with home D-PSG monitoring. These alternative procedures could be used to confirm NT1 diagnosis and curtail diagnostic delay.

Effects of oxybate dose and regimen on disrupted nighttime sleep and sleep architecture.

Many components of sleep are disrupted in patients with narcolepsy, including sleep quality, sleep architecture, and sleep stability (ie, frequent awakenings/arousals and frequent shifts from deeper to lighter stages of sleep). Sodium oxybate, dosed twice nightly, has historically been used to improve sleep, and subsequent daytime symptoms, in patients with narcolepsy. Recently, new formulations have been developed to address the high sodium content and twice-nightly dosing regimen of sodium oxybate: low-sodium oxybate and once-nightly sodium oxybate. To date, no head-to-head trials have been conducted to compare the effects of each oxybate product. This review aims to give an overview of the existing scientific literature regarding the impact of oxybate dose and regimen on sleep architecture and disrupted nighttime sleep in patients with narcolepsy. Evidence from 5 key clinical trials, as well as supporting evidence from additional studies, suggests that sodium oxybate, dosed once- and twice-nightly, is effective in improving sleep, measures of sleep architecture, and disrupted nighttime sleep in patients with narcolepsy. Direct comparison of available efficacy and safety data between oxybate products is complicated by differences in trial designs, outcomes assessed, and statistical analyses; future head-to-head trials are needed to better understand the advantage and disadvantages of each agent.