PURPOSE: To report the efficacy and safety of lower-sodium oxybate (LXB; Xywav®) during the open-label titration and optimization period (OLT) and stable-dose period (SDP) in a clinical study for the treatment of idiopathic hypersomnia. PATIENTS AND METHODS: Data were collected during treatment titration and optimization in a phase 3 randomized withdrawal trial in adults (18-75 years of age) with idiopathic hypersomnia who took LXB treatment (once, twice, or thrice nightly, administered orally) in the OLT (10-14 weeks), followed by the 2-week, open-label SDP. Endpoints included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change, Clinical Global Impression of Change, Functional Outcomes of Sleep Questionnaire (FOSQ)-10, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). RESULTS: The safety population included 154 participants; the modified intent-to-treat population comprised 115 participants. During open-label treatment, mean (SD) ESS scores improved (decreased) from 15.7 (3.8) at baseline to 6.1 (4.0) at end of SDP, and IHSS scores improved (decreased) from 31.6 (8.3) to 15.3 (8.5). Improvements were also observed during OLT in each individual IHSS item and in FOSQ-10 and WPAI:SHP scores. Thirty-five (22.7%) participants discontinued during OLT and SDP, 22 (14.3%) due to treatment-emergent adverse events (TEAEs) during OLT and SDP. The most frequent TEAEs in the first 4 weeks were nausea, headache, dizziness, and dry mouth; TEAE incidence decreased throughout OLT and SDP (weeks 1-4, n = 87 [56.5%]; weeks 13-16, n = 39 [31.7%]). CONCLUSION: During open-label treatment with LXB, participants showed clinically meaningful improvements in idiopathic hypersomnia symptoms and in quality of life and functional measures. TEAE incidence declined over LXB titration and optimization.

• Klíčová slova
• excessive daytime sleepiness, hypersomnolence, pharmacotherapy, quality of life,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Previous research has demonstrated that paediatric cancer survivors (PCS) have lower sleep quality than their healthy peers. However, the research to date has focused mainly on self-reported data. Therefore, the aim of this cross-sectional study was to characterise selected sleep parameters in PCS using objective monitoring techniques and to compare them with a control group (CG) of their healthy peers during a structured recovery stay. A specific objective was to characterise sleep with respect to gender, age, and cancer type. METHODS: 26 PCS and 38 CG aged 7-15 years participated in the study. Selected sleep indicators (time in bed, total sleep time, sleep efficiency) were objectively assessed with an Actigraph wGT3X-BT accelerometer for 12 days during the recovery stay. RESULTS: No significant differences were found between the PCS and CG groups in terms of the selected sleep parameters. The total time in bed was 543.1 min/day in the PCS and 537.2 min/day in the CG (p=0.91). The total sleep time was 455.3 min/day in the PCS and 457.5 min/day in the CG (p=0.57). Sleep efficiency was 85.3% in the PCS and 86.3% in the CG (p=0.36). Sleep efficiency >85% was achieved by 62% of the PCS (n=16) and 68% of the CG (n=26). There were no significant differences in sleep parameters in terms of variables such as gender, age, or cancer type. CONCLUSION: The results of our study suggest that - under the same conditions - the PCS did not differ from their healthy peers in terms of the indicators of time in bed, total sleep time, and sleep efficiency. No significant differences according to age, gender, or cancer type were found.

• Klíčová slova
• accelerometry, cancer survivors, children, sleep,
• Publikační typ
• časopisecké články MeSH

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

• Klíčová slova
• cataplexy, diagnostic delay, machine learning, misdiagnosis, symptom onset,
• Publikační typ
• časopisecké články MeSH

Lower-sodium oxybate (LXB) is an oxybate medication approved to treat cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy 7 years of age and older in the United States. LXB was developed as an alternative to sodium oxybate (SXB), because the incidence of cardiovascular comorbidities is higher in patients with narcolepsy and there is an elevated cardiovascular risk associated with high sodium consumption. LXB has a unique formulation of calcium, magnesium, potassium, and sodium ions, containing 92% less sodium than SXB. Whereas the active oxybate moiety is the same for LXB and SXB, their pharmacokinetic profiles are not bioequivalent; therefore, a phase 3 trial in participants with narcolepsy was conducted for LXB. This review summarizes the background on oxybate as a therapeutic agent and its potential mechanism of action on the gamma-aminobutyric acid type B (GABAB) receptor at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons. The rationale leading to the development of LXB as a lower-sodium alternative to SXB and the key efficacy and safety data supporting its approval for both adult and pediatric patients with narcolepsy are also discussed. LXB was approved in August 2021 in the United States for the treatment of idiopathic hypersomnia in adults. Potential future developments in the field of oxybate medications may include novel formulations and expanded indications for other diseases.

• Klíčová slova
• cataplexy, drug development, excessive daytime sleepiness, idiopathic hypersomnia, narcolepsy, therapeutics,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Idiopathic hypersomnia was first described in 1976 under two forms: polysymptomatic, characterized by excessive daytime sleepiness, long and unrefreshing naps, nocturnal sleep of abnormally long duration and signs of sleep drunkenness upon awakening; monosymptomatic, manifested by excessive daytime sleepiness only. Yet, after 45 years, this sleep disorder is still poorly delineated and diagnostic criteria produced by successive International Classifications of Sleep Disorders are far from satisfactory. The first part of this review is a historical account of the successive names and descriptions of idiopathic hypersomnia: monosymptomatic and polysymptomatic idiopathic hypersomnia in 1976; central nervous system idiopathic hypersomnia in 1979; idiopathic hypersomnia in 1990; idiopathic hypersomnia with and without long sleep time in 2005; idiopathic hypersomnia again in 2014; and, within the last few years, the proposal of separating idiopathic hypersomnia into a well-defined subtype, idiopathic hypersomnia with long sleep duration, and a more heterogeneous subtype combining idiopathic hypersomnia without long sleep duration and narcolepsy type 2. The second part is a critical review of both current ICSD-3 diagnostic criteria and clinical features, scales and questionnaires, electrophysiological and circadian control tests, research techniques, currently used to diagnose idiopathic hypersomnia. The third part proposes a diagnostic evaluation of idiopathic hypersomnia, in the absence of biologic markers and of robust electrophysiological diagnostic criteria.

• Klíčová slova
• central disorders of hypersomnolence, idiopathic hypersomnia, idiopathic hypersomnia with long sleep duration, idiopathic hypersomnia with long sleep time, idiopathic hypersomnia without long sleep duration, idiopathic hypersomnia without long sleep time, narcolepsy, narcolepsy type 1 and narcolepsy type 2,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: To examine the associations between gait speed and sleep quality in first-year university students, according to gender. METHODS: In this cross-sectional study, we recruited 193 first-year university students [mean age±standard deviation (SD): 19.6±1.1 years; mean height: 178.0±10.5 cm; mean weight: 74.0±11.0 kg; 26.9% women). Sleep quality was assessed using the Pittsburgh Sleep Quality questionnaire, with a lower score indicating "better" sleep quality. Gait speed was measured using the Zebris pressure platform. The associations were examined with generalized linear models and multiple regression analysis. RESULTS: In the unadjusted model, faster participants had significantly "better" sleep quality (β=-3.15, 95% CI -3.82 to -2.47, p<0.001). When the model was adjusted for sex, age, body-mass index, self-rated health, smoking status, and psychological distress, faster participants remained having "better" sleep quality (β=-2.88, 95% CI -3.53 to -2.22, p<0.001). CONCLUSION: This study shows that sleep quality can be predicted by gait speed in the first-year university students.

• Klíčová slova
• biomechanics, relationship, sleep, youth,
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Both sleep disorders and BPD are prevalent in the population, and one is often a comorbidity of the other. This narrative review aims to assess contemporary literature and scientific databases to provide the current state of knowledge about sleep disorders in patients with borderline personality disorder (BPD) and clinical suggestions for managing sleep disorders in BPD patients and future research direction. METHODS: Articles were acquired via PubMed and Web of Science, and papers published between January 1980 and October 2020 were extracted. Authors made a series of literature searches using the keywords: Sleep problems, Insomnia, Nightmares, Obstructive sleep apnea, Borderline personality disorder. The inclusion criteria were: published in peer-reviewed journals; studies in humans; or reviews on the related topic; English language. The exclusion criteria were: abstracts from conferences; commentaries; subjects younger than 18 years. After an inspection of the full texts, 42 papers from 101 were selected. Secondary documents from the reference lists of the primary designated papers were searched, assessed for suitability, and included. In total, 71 papers were included in the review process. RESULTS: Sleep disturbance is common among patients with BPD. Nevertheless, the number of investigations is limited, and the prevalence differs between 5-45%. Studies assessing objective changes in sleep architecture in BPD show inconsistent results. Some of them identify REM sleep changes and a decrease in slow-wave sleep, while other studies found no objective sleep architecture changes. There is also a higher prevalence of nightmares in patients with BPD. Untreated insomnia can worsen BPD symptoms via interference with emotional regulation. BPD itself seems to influence the subjective quality of sleep significantly. Proper diagnosis and treatment of sleep disorders in patients with BPD could lead to better results in therapy. Psychotherapeutic approaches can improve both sleep disorders and BPD symptoms. CONCLUSION: Recognising and managing sleep disorders in patients with BPD may help alleviate the disorder's symptoms. Treatment of people with BPD may be more effective if the treatment plan explicitly addresses sleep problems. Further research is needed to reach reliable conclusions.

• Klíčová slova
• borderline personality disorder, cognitive behavioral therapy, dialectic behavioral therapy, insomnia, mentalization therapy, transference focus therapy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVE: Up to 20% of patients treated for epileptic seizures experience psychogenic nonepileptic paroxysms (PNES). These patients present a significant burden for the health care systems because of poor treatment outcomes. The presented review aims to summarize the current state of knowledge on sleep disturbances in patients with nonepileptic seizures. METHODS: Articles were acquired via PubMed and Web of Science, and papers between January 1990 and March 2020 were extracted. Inclusion criteria were (1) published in a peer-reviewed journal: (2) studies in humans only; or (3) reviews on a related topic; (4) English language. The exclusion criteria were: (1) abstracts from conferences; (2) commentaries; (3) subjects younger than 18 years. From primary assessment, 122 articles were extracted; after obtaining full texts and secondary articles from reference lists, 45 papers were used in this review. RESULTS: Limited data are available regarding sleep disorders in PNES patients, over the last 30 years only nine original research papers addressed sleep problems in patients with PNES with only six studies assessing objectively measured changes in sleep. Current literature supports the subjective perception of the sleep disturbances with mixed results in objective pathophysiological findings. Conflicting results regarding the REM phase can be found, and studies reported both shortening and prolonging of the REM phase with methodological limitations. Poor sleep quality and shortened duration have been consistently described in most of the studies. CONCLUSION: Further research on a broader spectrum of patients with PNES is needed, primarily focusing on objective neurophysiological findings. Quality of life in patients suffering from PNES can be increased by good sleep habits and treatment of comorbid sleep disorders.

• Klíčová slova
• emotional regulation, insomnia, mental disorders, psychogenic seizures, sleep disturbances,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The first night effect (FNE) is a polysomnography (PSG) habituation effect in the first of several consecutive in-laboratory PSGs (I-PSGs). The FNE is caused by the discomfort provoked by electrodes and cables and the exposure to an unfamiliar environment. A reverse FNE (RFNE) with an improved sleep in the first night is characteristic of insomnia, presumably because the video PSG in the sleep laboratory leads to a decrease in the negatively toned cognitive activity. Therefore, two or more I-PSGs are required for an accurate diagnosis. Although the FNE is well documented in I-PSG, little is known about the FNE and the RFNE in home-based PSGs (H-PSGs). METHODS: This is a retrospective analysis of a recently published cross-sectional study using H-PSG. Sixty-three consecutive patients suffering from multiple sclerosis (MS) were investigated by two consecutive H-PSGs without video. The differences between the first and second H-PSGs were analyzed. The patients were classified into four subgroups: no sleep disorder, insomnia, sleep-related breathing disorders (SRBDs), and periodic limb movement disorder or restless legs syndrome (PLMD/RLS). RESULTS: MS patients suffering from insomnia showed no RFNE. MS patients with SRBD or PLMD/RLS showed no reduced sleep efficiency but significantly less slow wave sleep. Furthermore, SRBD patients showed significantly less non-rapid eye movement (NREM) sleep, and PLMD/RLS patients were significantly awake longer in the first night after sleep onset (increased wake-after-sleep-onset time) and showed a higher rapid eye movement (REM) latency. CONCLUSION: SRBD and PLMD/RLS patients showed a significant FNE. Two consecutive H-PSGs are required in these patients to obtain a precise hypnogram even in the ambulatory field. In MS patients suffering from insomnia, no RFNE was found, and in insomnia patients one H-PSG seems to be sufficient.

• Klíčová slova
• insomnia, multiple sclerosis, outpatient sleep studies, polysomnography, sleep latency, wake after sleep onset,
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Many cases of obstructive sleep apnea (OSA) involve collapse of the tongue base and soft palate during sleep, causing occlusion of the upper airway and leading to oxygen desaturation. Existing therapies can be effective, but they are plagued by patient adherence issues and the invasiveness of surgical approaches. A new, minimally invasive implant for OSA has been developed, which is elastic and contracts a few weeks after deployment, stabilizing the surrounding soft tissue. The device has had good outcomes in preclinical testing; this report describes the preliminary feasibility and safety of its implementation in humans. PATIENTS AND METHODS: A prospective, multicenter, single-arm feasibility study was conducted. Subjects were adults with moderate-to-severe OSA who had previously failed or refused conventional continuous positive airway pressure treatment. Intraoperative feasibility data, postoperative pain, and safety information were collected for a 30-day postoperative period. RESULTS: Forty subjects participated (37 men, three women; average age of 46.1 years); each received two tongue-base implants and two soft-palate implants. Surgical procedure time averaged 43 minutes. Postsurgical pain resolved readily in most cases; at 30 days post implantation, <20% of subjects reported pain, which averaged less than two out of ten. Adverse events were generally the mild and expected sequelae of a surgical procedure with general anesthesia and intraoral manipulation. The device was well tolerated. Implant extrusions were reported with soft-palate implants (n=12), while tongue-base implants required few revisions (n=2). Quantitative and qualitative sleep effectiveness outcomes (including full-night polysomnographic and quality-of-life measures) will be presented in a subsequent report. CONCLUSION: Implantation of the device was feasible. Although a relatively high rate of extrusions occurred in the now-discontinued palate implants, tongue-base implants were largely stable and well tolerated. The minimally invasive and maintenance-free implant may provide a new alternative to higher morbidity surgical procedures.

• Klíčová slova
• breathing, implantable device, obstructive sleep apnea, sleep, surgical treatment, tongue base,
• Publikační typ
• časopisecké články MeSH