Sleep inertia impairs performance upon awakening and may be assessed using the psychomotor vigilance task (PVT). This study aimed to determine optimal PVT lapse cut-offs at awakening to objectively measure sleep inertia by comparing patients with idiopathic hypersomnia (IH) and severe sleep inertia to patients with other sleep disorders (OSD) without sleep inertia, to assess the discriminative performance of these thresholds in OSD patients with sleep inertia; and to explore factors associated with PVT lapses. 350 drug-free consecutive patients (227 females, 30.7 ± 11.0 y.o.) were included: 131 IH and 219 OSD (75 non-specified hypersomnolence, 54 narcolepsy, 50 obstructive sleep apnea, 40 others). All patients performed two 5-min PVTs at 07:00 pm and 07:00 am upon awakening. Sleep inertia was self-reported with the Idiopathic Hypersomnia Severity Scale. Receiver operating characteristic analyses were used to determine optimal cut-offs for 7:00 am PVT lapses and the change between 07:00 am and 07:00 pm in IH patients with severe sleep inertia (n = 73) and OSD patients without sleep inertia (n = 84). Optimal PVT cut-offs were ≥ 4 for 7 am-Lapses (sensitivity 72.6%, specificity 69.1%) and ≥ 4 for Delta 7 am-7 pm-Lapses (sensitivity 50.9%, specificity 83.3%). Across all 350 participants, 56.9% exhibited 7 am-Lapses ≥ 4, while 39.7% had Delta 7 am-7 pm Lapses ≥ 4. In conclusion, a threshold of ≥ 4 PVT lapses at 07:00 am, along with an increase of ≥ 4 lapses from 07:00 pm to 07:00 am best capture sleep inertia-related performance impairment in IH, supporting their use as objective markers in clinical practice and research settings.

Slow waves during non-rapid eye movement (NREM) sleep are associated with the restorative aspects of sleep. Previous research has suggested reduced normalized slow wave activity (SWA), particularly in the first cycle of NREM sleep, as a feature of hypersomnolence disorder (HD); however, the scarcity of existing research highlights the need for replication studies. Thus, the aim of this investigation was to evaluate normalized SWA in patients with HD, relative to healthy sleeper controls (HSC). Nocturnal polysomnography from 37 unmedicated HD clinical patients were compared against 29 HSC. Six-channel electroencephalographic data from polysomnography was processed according to consensus standards. Normalized SWA (0.5-4.5hz) was calculated from artefact-free NREM epochs for all-night data, as well as sleep cycle 1, 2, and 3. Normalized SWA was compared across groups, with adjusted analyses accounting for age, sex, body mass index, and depressive symptomatology. Post hoc analyses compared HD who met objective criteria for idiopathic hypersomnia (HD/IH+), those who did not (HD/IH-), and HSC. HD demonstrated significantly reduced all-night, normalized SWA in unadjusted analyses across all channels, without significant differences observed in fully adjusted analyses. In cycle 1, HD displayed significantly reduced normalized SWA across all channels in both unadjusted and adjusted analyses. HD/IH+ and HD/IH- were statistically comparable in normalized SWA across all analyses. This study provides further evidence of reduced SWA, particularly during cycle 1 of NREM sleep, as a core feature of HD. Future studies that investigate the causal role of slow waves in the pathophysiology of HD are warranted.

Over 37% of pregnant women report excessive daytime sleepiness or hypersomnia during the first trimester, and commonly throughout the remaining trimesters of pregnancy and the postpartum period. The clinical presentation and symptoms of central disorders of hypersomnolence (CDH) such as narcolepsy, idiopathic hypersomnia, or excessive daytime sleepiness secondary to shift work or obstructive sleep apnea may be confounded by physiological changes in sleep architecture and hormonal fluctuations occurring during pregnancy. These overlapping features may cause delays in diagnosis and treatment, impacting quality of life, maternal functioning, and overall health. Management of CDH during pregnancy and lactation requires careful consideration of maternal benefits, potential side effects of medications and fetal and neonatal safety. Here, we present a case of idiopathic hypersomnia and detail management and outcomes during pregnancy and lactation. We briefly review the existing literature on prevalence, pathophysiological mechanisms, diagnostic challenges, objective findings, and risks posed by CDH in pregnancy and lactation. In this narrative review for primary care clinicians, we also summarize currently available evidence regarding the efficacy, teratogenic and other risks of pharmacologic agents used in the treatment of CDH in pregnancy and lactation. Lastly, we provide a clinical algorithm for management of CDH during pregnancy and lactation.

Narcolepsy is a chronic neurological disorder of sleep-wake regulation whose cardinal features include pathological daytime somnolence and dysregulation of rapid eye movement (REM) sleep. It is frequently underdiagnosed in adolescents owing to symptom overlap with psychiatric, behavioral, and prior sleep disorders, including childhood obstructive sleep apnea (OSA). Narcolepsy type 2 (NT2), defined by excessive daytime sleepiness (EDS) without cataplexy, poses particular diagnostic challenges due to the absence of a single pathognomonic feature. We report an 18-year-old female who presented with a four-year history of persistent EDS, hypnopompic hallucinations, sleep paralysis, and automatic behaviors during microsleeps, including episodes of irrelevant writing during examinations. Subjective daytime somnolence was severe, with an Epworth Sleepiness Scale (ESS) score of 19/24. Past history was notable for childhood OSA managed with adenoidectomy, with residual mild snoring. Physical and neurological examinations were unremarkable. Polysomnography (PSG) demonstrated markedly short sleep latency, multiple sleep-onset REM periods (SOREMPs), and periodic limb movements without apneic episodes or nocturnal desaturation. The Multiple Sleep Latency Test (MSLT) confirmed severe objective hypersomnolence with a mean sleep latency of 1.25 minutes and SOREMPs in three out of four naps. Electroencephalography (EEG) revealed findings consistent with absence seizures, an uncommonly encountered comorbidity in narcolepsy, raising a rare dual diagnosis of NT2 and absence epilepsy. The prior history of childhood OSA and residual snoring initially confounded the clinical picture, underscoring the necessity of objective sleep testing in adolescents with EDS. PSG and MSLT confirmed the diagnosis while excluding insufficient sleep syndrome and untreated OSA. Periodic limb movements observed on PSG may represent a comorbid disorder or an associated feature of narcolepsy. The coexistence of absence epilepsy with NT2 is a rarely reported clinical phenomenon, and its presence in this case further underscores the diagnostic complexity and the critical need for comprehensive neurological evaluation in adolescents presenting with EDS. NT2 in adolescents can be diagnostically challenging due to symptom overlap with prior sleep disorders, psychiatric conditions, and epilepsy. Early recognition, supported by PSG and MSLT, is essential to guide pharmacologic and behavioral interventions, improve daytime function, and reduce psychosocial burden, particularly in rare presentations where narcolepsy coexists with absence epilepsy, demanding heightened clinical vigilance and a broad neurological workup.

In-ear electroencephalography (EEG) has emerged as a promising alternative to traditional in-laboratory sleep studies, offering greater comfort and practicality. Here we present a novel in-ear EEG system, comparing in-ear recordings against scalp EEG channels acquired concurrently as part of polysomnography (PSG). The study enrolled 16 healthy control participants in a single-visit overnight-plus-daytime design, and 8 participants with central disorders of hypersomnolence (CDH) in a randomized crossover daytime design (medication vs. medication-holiday). For overnight sleep recordings, ear-EEG and scalp EEG sleep staging showed substantial agreement (Cohen's [Formula: see text]). For daytime MWT trials, agreement was moderate (Cohen's [Formula: see text]), reflecting the predominance of wake epochs in this paradigm. For the primary Maintenance of Wakefulness Test (MWT) endpoint of sleep onset latency (SOL), at the per-subject level ([Formula: see text])-averaging across trials as in standard clinical practice-agreement was good (ICC = 0.71, [Formula: see text], MAD = 5.1 min). Among the 37 of 126 trials where both devices detected sleep (approximately 30% of trials), agreement was strong (ICC = 0.82, MAD = 1.9 min), with excellent agreement in healthy controls (ICC = 0.95, MAD = 1.2 min). Overall trial-level agreement across all 126 trials was moderate (ICC = 0.55), reflecting 22 discordant trials in which scalp EEG detected sleep but in-ear EEG did not-predominantly brief, subtle N1 transitions, concentrated in a subset of CDH participants. For overnight sleep architecture ([Formula: see text] healthy controls), total sleep time ([Formula: see text], ICC = 0.85), sleep efficiency ([Formula: see text]), and wake after sleep onset ([Formula: see text]) showed strong agreement, with small systematic biases consistent with reduced N1 detection sensitivity. These findings support the feasibility of in-ear EEG for sleep staging and daytime sleepiness assessment in laboratory settings, and motivate larger confirmatory studies-including home-based longitudinal monitoring-to establish clinical utility, particularly in populations with altered sleep architecture.

Isolated/idiopathic rapid-eye movement (REM) sleep behavior disorder (iRBD) is, in most cases, an early form of α -synuclein-related neurodegenerative diseases, including Parkinson's disease and dementia with Lewy bodies. Clinical reports suggest that iRBD is more common in individuals with Post-Traumatic Stress Disorder (PTSD) compared to those without PTSD. We conducted polygenic risk score (PRS), genetic correlation, and Mendelian randomization analyses to explore potential genetic and/or causal associations between PTSD and iRBD. Dopamine transporter imaging binding status was also examined in iRBD patients with (N = 6) and without PTSD (N = 32). While not supporting a causal relationship, genetic analyses revealed a significant association between PTSD and iRBD, consistent with the exploratory imaging substudy. These findings suggest that individuals genetically at risk for PTSD may also be at higher risk for iRBD. Further investigation of iRBD in individuals with PTSD may help inform potential neurodegenerative risk.

Provided herein are novel 3-heteroaryl pyrrolidine and piperidine compounds as orexin receptor agonists, pharmaceutical compositions, use of such compounds in treating sleep disorders, namely, narcolepsy and hypersomnia, and processes for preparing such compounds.

This study aims to analyze excessive daytime sleepiness in relation to health risk behaviors among adolescents. Epidemiological and cross-sectional study carried out with 1st-year high school students from 20 state public schools in the city of Montes Claros, Minas Gerais, Brazil. Data were collected in 2022/2023. The dependent variable was analyzed using the Pediatric Daytime Sleepiness Scale, validated for Brazil. Descriptive, bivariate and multiple analyses were performed using Poisson Regression. 1,616 adolescents participated in the study, among them, 72% had excessive daytime sleepiness, with higher prevalence among girls (PR=1.22), those who studied in the morning (PR=1.35) and full-time (PR=1.35) shifts, those who were in the pre-contemplation stage of behavior change (PR=1.15), those who consumed ultra-processed foods daily (PR=1.09), with severe depressive symptoms (PR=1.16) and with smartphone addiction (PR=1.36). The high prevalence of daytime sleepiness was associated with health risk behaviors among adolescents. Thus, actions that encourage the adoption of healthy lifestyles are necessary to minimize health damage in the short, medium and long term.