Nocturnal Arousals Research Articles

Heart rate response to cortical arousals in patients with isolated obstructive sleep apnea and with comorbid insomnia (COMISA).

Comorbid insomnia often occurs in patients with obstructive sleep apnea (OSA), referred to as COMISA. Cortical arousals manifest as a common feature in both OSA and insomnia, often accompanied by elevated heart rate (HR). Our objective was to evaluate the heart rate response to nocturnal cortical arousals in patients with COMISA and patients with OSA alone. We analyzed data from patients with COMISA and frompatients with OSAmatched for apnea-hypopnea index. Sleep staging and analysis of respiratory events and cortical arousals were performed using the Philips Somnolyzer automatic scoring system. Beat-by-beat HR was analyzed from the onset of the cortical arousal to 30 heartbeats afterwards. HR responses were divided into peak and recovery phases. Cortical arousals were separately evaluated according to subtype (related to respiratory events and spontaneous) and duration (3-6s, 6-10s, 10-15s). A total of 72 patients with COMISA and 72 patients with OSA were included in this study. There were no overall group differences in the number of cortical arousals with and without autonomic activation. No significant differences were found for spontaneous cortical arousals. The OSA group had more cortical arousals related to respiratory events (21.0 [14.8-30.0] vs 16.0 [9.0-27.0], p = 0.016). However, the COMISA group had longer cortical arousals (7.2 [6.4-7.8] vs 6.7 [6.2-7.7] s, p = 0.024) and the HR recovery phase was prolonged (52.5 [30.8-82.5] vs 40.0 [21.8-55.5] beats/min, p = 0.017). Both the peak and the recovery phase for longer cortical arousals with a duration of 10-15s were significantly higher in patients with COMISA compared to patients with OSA (47.0 [27.0-97.5] vs 34.0 [21.0-71.0] beats/min, p = 0.032 and 87.0 [47.0-132.0] vs 71.0 [43.0-103.5] beats/min, p = 0.049, respectively). The HR recovery phase after cortical arousals related to respiratory events is prolonged in patients with COMISA compared to patients with OSAalone. This response could be indicative of the insomnia component in COMISA.

Cortical hyperarousal in individuals with frequent nightmares.

Nightmares are common among the general population and psychiatric patients and have been associated with signs of nocturnal arousal such as increased heart rate or increased high-frequency electroencephalographic (EEG) activity. However, it is still unclear, whether these characteristics are more of a trait occurring in people with frequent nightmares or rather indicators of the nightmare state. We compared participants with frequent nightmares (NM group; n = 30) and healthy controls (controls; n = 27) who spent 4 nights in the sleep laboratory over the course of 8 weeks. The NM group received six sessions of imagery rehearsal therapy (IRT), the 'gold standard' of cognitive-behavioural therapy for nightmares, between the second and the third night. Sleep architecture and spectral power were compared between groups, and between nights of nightmare occurrence and nights without nightmare occurrence in the NM group. Additionally, changes before and after therapy were recorded. The NM group showed increased beta (16.25-31 Hz) and low gamma (31.25-35 Hz) power during the entire night compared to the controls, but not when comparing nights of nightmare occurrence to those without. Moreover, low gamma activity in rapid eye movement sleep was reduced after therapy in the NM group. Our findings indicate, cortical hyperarousal is more of a trait in people with frequent nightmares within a network of other symptoms, but also malleable by therapy. This is not only a new finding for IRT but could also lead to improved treatment options in the future that directly target high-frequency EEG activity.

Accuracy of cuff-less, continuous, and non-invasive blood pressure measurement in 24-h ABPM in children aged 5–17

Purpose Ambulatory, cuff-less blood pressure (BP) measurement devices are a promising trend to alleviate the strains of conventional, cuff-based BP determination. Cuff-less devices circumvent discomfort and nocturnal arousal reactions which can be triggered by cuff inflation from conventional, cuff-based ambulatory blood pressure measurement devices. Mitigating these discomforts is especially desirable when performing measurement in children. In this study we want to assess the clinical validity of a cuff-less BP measurement device for 24-h measurements in children and adolescents. Materials and methods We compared the simultaneously retrieved BP data of the cuff-less SOMNOtouch NIBP and the cuff-based Mobil-O-Graph in 24-h use in 90 children in the range from 5 to 17 years old. Results A total of 1218 valid measurement pairs showed a mean deviation of 0.99 mmHg (limits of agreement: 21.44/-19.46) for systolic and 3.03 mmHg (limits of agreement: 24.37/−18.31) for diastolic BP values. Patient-specific difference of means was within 15 mmHg in 97.7% (systolic BP) and 93.2% (diastolic BP) patients. 25.6% of nocturnal cuff inflations led to determinable, BP-relevant arousal reactions. Conclusions The SOMNOtouch NIBP demonstrated little measurement deviation of mean BP compared to the cuff-based technique over a broad spectrum of 24-h, ambulatory BP measurements in children and adolescents. Cuff-less blood pressure measurement relieves the issue of nocturnal arousal reactions which are shown to be frequently induced by cuff-based measurements. Driven by these promising results, we encourage ongoing efforts to create enough evidence on cuff-less BP measurement to promote it into broad clinical application.

Single-night continuous positive airway pressure treatment improves blood fluid properties in individuals recently diagnosed with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a prevalent disorder that causes repetitive, temporary collapses of the upper airways during sleep, resulting in intermittent hypoxaemia and sleep fragmentation. Given those with OSA also exhibit decreased blood fluidity, this clinical population is at heightened risk for cardiovascular disease (CVD) development. Continuous positive airway pressure (CPAP) remains a primary therapy in OSA, which improves sleep quality and limits sleep fragmentation. While CPAP effectively ameliorates nocturnal hypoxic events and associated arousals, it remains unclear whether CVD risk factors are positively impacted. The aim of the present study was thus to assess the effects of an acute CPAP therapy on sleep quality and the physical properties of blood that determine blood fluidity. Sixteen participants with suspected OSA were recruited into the current study. Participants attended the sleep laboratory for two visits: an initial diagnostic visit that included confirmation of OSA severity and comprehensive assessments of blood parameters, followed by a subsequent visit where participants were administered an individualised, acute CPAP therapy session and had their blood assessments repeated. Holistic appraisal of blood rheological properties included assessment of blood and plasma viscosity, red blood cell (RBC) aggregation, deformability, and osmotic gradient ektacytometry. Acute CPAP treatment significantly improved sleep quality parameters, which were associated with decreased nocturnal arousals and improved blood oxygen saturation. Whole blood viscosity was significantly decreased following acute CPAP treatment, which might be explained by the improved RBC aggregation during this visit. Although an acute increase in plasma viscosity was observed, it appears that the alterations in RBC properties that mediate cell-cell aggregation, and thus blood viscosity, overcame the increased plasma viscosity. While deformability of RBC was unaltered, CPAP therapy had mild effects on the osmotic tolerance of RBC. Collectively, novel observations demonstrate that a single CPAP treatment session acutely improved sleep quality, which was accompanied by improved rheological properties.

Perinatal Understanding of Mindful Awareness for Sleep (PUMAS): A single-arm proof-of-concept clinical trial of a mindfulness-based intervention for DSM-5 insomnia disorder during pregnancy

ObjectivesCognitive-behavioral therapy is effective for prenatal insomnia, but unresolved cognitive arousal limits patient outcomes. Therapies aimed at reducing cognitive arousal may benefit pregnant women with insomnia. This proof-of-concept trial evaluated Perinatal Understanding of Mindful Awareness for Sleep (PUMAS, which combines mindfulness with behavioral sleep strategies) on insomnia, depression, and cognitive arousal. MethodsA single-arm trial of 12 pregnant women with DSM-5 insomnia disorder (n = 5/12 with comorbid depression) who received six sessions of PUMAS delivered individually via telemedicine. Pretreatment and posttreatment outcomes included the insomnia severity index (ISI), Edinburgh postnatal depression scale (EPDS), pre-sleep arousal scale's cognitive factor (PSASC; nocturnal cognitive arousal), perinatal-focused rumination (appended to PSASC), and Glasgow sleep effort scale. ResultsEleven of 12 patients completed all sessions. Intent-to-treat analyses revealed a 10.83-point reduction in ISI (Cohen's dz = 3.05), resulting in 83.3% insomnia remission. PUMAS produced large reductions in EPDS (Cohen's dz = 2.76 in depressed group), resulting in all five baseline depressed patients remitting from depression. PUMAS produced large reductions in nocturnal cognitive arousal, perinatal-focused rumination, and sleep effort (all Cohen's dzs>2.00). Patients were highly satisfied with PUMAS and identified the telemedicine format and meditation app as positive features of its delivery. Patients rated sleep restriction and guided meditations as the most helpful treatment components. ConclusionPrenatal insomnia patients were highly engaged in PUMAS, which produced large acute reductions in insomnia, depression, and cognitive arousal. These findings support the concept and feasibility of PUMAS for pregnant women with insomnia who present with or without comorbid depression. Clinicaltrials.gov idNCT04443959.

0325 Reducing nocturnal cognitive arousal and rumination mediate treatment effects of digital cognitive behavioral therapy for insomnia

Abstract Introduction High cognitive arousal—i.e., heightened cognitive activity often in the form of perseverative thinking—is a central feature insomnia. Emerging evidence from randomized controlled trials (RCTs) support alleviating cognitive arousal as a mechanism by which cognitive behavioral therapy for insomnia (CBTI) reduces symptoms of insomnia and depression. However, few RCTs have published CBTI data on cognitive arousal outcomes. The present study tested whether CBTI alleviates cognitive arousal symptoms, and whether reducing cognitive arousal symptoms mediate CBTI effects on insomnia and depression. Methods 434 patients with clinical insomnia symptoms (Insomnia Severity Index [ISI] ≥ 15) were randomized to digital CBTI or digital sleep education control. Study outcomes included insomnia (ISI), depression (quick inventory of depressive symptomatology self-report 16-item survey, QIDS-SR16), and two indices of cognitive arousal (pre-sleep arousal scale’s cognitive factor [PSASC] and daytime insomnia symptoms response scale [DISRS]). Treatment effects and mediation analyses were conducted using multivariate linear regression. Results While controlling for baseline symptoms, CBTI patients, relative to controls, reported lower levels of insomnia (b=-2.45, p<.001), depression (b=-1.13, p<.001), nocturnal cognitive arousal (b=-2.37, p<.001) and insomnia-focused rumination (b=-3.43, p<.001) after treatment. Posthoc independent samples t-tests showed that CBTI produced small-medium effects on nocturnal cognitive arousal (Cohen’s d=.40) and insomnia-focused rumination (Cohen’s d=.31). Mediation analyses showed that reducing nocturnal cognitive arousal (PSASCT2-T1) mediated 29.0% of CBTI effects on insomnia (αβ=-.709, 95%CI=-1.09, -0.38), and 35.1% of CBTI effects on depression (αβ=-.397, 95%CI=-0.65, -0.19). Mediation analyses showed that reducing insomnia-focused rumination (DISRST2-T1) mediated 10.6% of CBTI on insomnia (αβ=-.261, 95%CI=-0.50, -0.08), but did not mediate antidepressant effects (αβ=-.300, 95%CI=-1.46, 0.72). Conclusion Digital CBTI effectively alleviated nocturnal cognitive arousal and insomnia-focused rumination. Moreover, alleviating nocturnal cognitive arousal was a mechanism by which CBTI reduced symptoms of insomnia and depression. By comparison, reducing insomnia-focused rumination mediated a small proportion of CBTI effects on insomnia and was uninvolved in depression effects. Although reducing cognitive arousal facilitated insomnia and depression outcomes, CBTI is likely limited by its modest effects on cognitive arousal symptoms. Improving insomnia therapy benefits for cognitive arousal may enhance patient outcomes. Support (if any) This RCT (NCT03322774) was supported by NIMH R01-MH122636.

Efficacy of Once-Nightly Sodium Oxybate (FT218) in Narcolepsy Type 1 and Type 2: Post Hoc Analysis From the Phase 3 REST-ON Trial.

Post hoc analyses from the phase 3 REST-ON trial evaluated efficacy of extended-release once-nightly sodium oxybate (ON-SXB; FT218) vs placebo for daytime sleepiness and disrupted nighttime sleep in narcolepsy type 1 (NT1) and 2 (NT2). Participants were stratified by narcolepsy type and randomized 1:1 to ON-SXB (4.5g, week 1; 6g, weeks 2-3; 7.5g, weeks 4-8; and 9g, weeks 9-13) or placebo. Assessments included mean sleep latency on Maintenance of Wakefulness Test (MWT) and Clinical Global Impression-Improvement (CGI-I) rating (coprimary endpoints) and sleep stage shifts, nocturnal arousals, and patient-reported sleep quality, refreshing nature of sleep, and Epworth Sleepiness Scale (ESS) score (secondary endpoints) separately in NT1 and NT2 subgroups. The modified intent-to-treat population comprised 190 participants (NT1, n=145; NT2, n=45). Significant improvements were demonstrated with ON-SXB vs placebo in sleep latency for NT1 (all doses, P<0.001) and NT2 (6 and 9g, P<0.05) subgroups. Greater proportions of participants in both subgroups had CGI-I ratings of much/very much improved with ON-SXB vs placebo. Sleep stage shifts and sleep quality significantly improved in both subgroups (all doses vs placebo, P<0.001). Significant improvements with all ON-SXB doses vs placebo in refreshing nature of sleep (P<0.001), nocturnal arousals (P<0.05), and ESS scores (P≤0.001) were reported for NT1 with directional improvements for NT2. Clinically meaningful improvements of a single ON-SXB bedtime dose were shown for daytime sleepiness and DNS in NT1 and NT2, with less power for the limited NT2 subgroup.

0370 A three-arm randomized controlled trial examining mindfulness-based and cognitive-behavioral therapies for prenatal insomnia

Abstract Introduction Cognitive behavioral therapy for insomnia (CBTI) improves sleep in pregnancy, but its therapeutic benefits may be diminished in pregnancy due to undertreatment of cognitive arousal (i.e., heightened cognitive activity, especially at night). A recent proof-of-concept, single-arm trial suggested that combining behavioral sleep strategies with mindfulness components produced large reductions in prenatal insomnia, depression, and cognitive arousal. The present study was a randomized controlled trial evaluating the effectiveness of this mindfulness-based intervention and CBTI relative to a control condition. Methods Sixty-four pregnant women with clinically significant insomnia symptoms were randomized to a mindfulness-based intervention, CBTI, or control. The mindfulness intervention was Perinatal Understanding of Mindful Awareness for Sleep (PUMAS), which places behavioral sleep strategies within a mindfulness framework and tailors all components to pregnancy. PUMAS and CBTI were delivered via six telemedicine sessions, whereas control patients electronically received six weekly information sheets on perinatal sleep health. Treatment outcomes were assessed before and after treatment, which included the insomnia severity index (ISI), Edinburgh postnatal depression scale (EPDS), and pre-sleep arousal scale’s cognitive factor (PSASC; nocturnal cognitive arousal). Treatment outcomes were analyzed via general linear models, and the PRODCLIN method tested mediation models in evaluation of treatment mechanisms. Results Intent-to-treat analyses revealed significant ISI reductions in the PUMAS (-11.05±3.84) and CBTI (-11.20±6.87) conditions relative to control (-4.27±1.96). Insomnia remission rates were highest among PUMAS patients (81.8%), whereas 65.0% of CBTI patients and 13.6% of controls remitted. PUMAS significantly alleviated depression relative to control (EPDS: -3.77±3.88 vs -0.59±2.84, p=.017), whereas CBTI did not differ from either group (EPDS: -2.55±4.25, p-values ≥ .271). Similarly, PUMAS alleviated cognitive arousal relative to control (PSASC: -8.82±4.99 vs -3.45±4.53, p=.009), whereas CBTI did not differ from either group (PSASC: -7.30±7.49, p-values ≥ .104). Mediation analyses estimated that reductions in cognitive arousal mediated 26.6% and 40.6% of PUMAS effects on insomnia and depression. Conclusion PUMAS alleviated insomnia, depression, and cognitive arousal relative to control. Reducing cognitive arousal was a significant treatment mechanism by which PUMAS alleviated insomnia and depression. By comparison, CBTI significantly alleviated insomnia relative to control, but yielded no significant effects on depression or cognitive arousal. Support (if any)

Monitoring Faciobrachial Dystonic Seizures with Wearable Devices (P5-5.015)

<h3>Objective:</h3> This study sought to assess whether faciobrachial dystonic seizures (FBDS) can be reliably identified and differentiated from normal nocturnal arousals using a wrist-worn device. <h3>Background:</h3> Detection of FBDS in patients with Leucine-rich glioma inactivated-1 (LGI1-IgG) associated autoimmune encephalitis is challenging due to high event frequency and lack of a robust EEG correlate. Wearable devices may provide a convenient, noninvasive means to measure these events and provide an objective seizure diary. <h3>Design/Methods:</h3> Two LGI1-IgG seropositive patients (P1 and P2) and four control subjects, wearing Empatica E4 devices, were recruited for this study. Two eight-hour sleep periods of each patient: pre- and post-treatment, were analyzed. An algorithm was developed based on accelerometry (ACC) signals to detect events of interest. After event identification, we calculated the ACC magnitude, duration, and electrodermal activity (EDA) characteristics of detected events. Presently, we are actively expanding the patient cohort and are investigating machine learning methods to improve the accuracy of event detection. <h3>Results:</h3> Statistically significant differences were found in device signals pre- and post-treatment, and between FBDS events in LGI1-IgG and nocturnal arousals in control subjects. The frequency of actigraphy events was higher in both patients (P1: pre-treatment 13.93±3.82 ev/h, post-treatment 9.66±3.37 ev/h; P2: pre-treatment 26.21±13.16 ev/h, post-treatment 29.06±9.79 ev/h), than controls (3.47±2.77 ev/h). For ACC magnitude and event duration, the medians were lower post-treatment and significantly lower for ACC magnitude in P2. Post-treatment, significant differences were only observed between controls and P1. For EDA activity, tonic and phasic components for controls were significantly lower than for patients pre-treatment. Additionally, means and medians decreased post-treatment in both patients. <h3>Conclusions:</h3> Robust characteristics were identified in actigraphy and EDA signals from a wrist-worn device during FBDS events. This evidence suggests an accurate monitor can be developed to automatically detect FBDS, providing objective measurements for treatment guidance and clinical decisions. <b>Disclosure:</b> Dr. Cui has nothing to disclose. Dr. Faust has nothing to disclose. Boney Joseph has nothing to disclose. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. The institution of Dr. Dubey has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for AGRIMS. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Advances in Neurology . Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Moffit Cancer Center . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Brinkmann has received personal compensation in the range of $0-$499 for serving as a Consultant for Otsuka Pharmaceuticals. Dr. Brinkmann has stock in Cadence Neuroscience. The institution of Dr. Brinkmann has received research support from Epilepsy Foundation of America. The institution of Dr. Brinkmann has received research support from National Institutes of Health. The institution of Dr. Brinkmann has received research support from National Institutes of Health. The institution of Dr. Brinkmann has received research support from UNEEG A/S. The institution of Dr. Brinkmann has received research support from Seer Medical Pty. Dr. Brinkmann has received intellectual property interests from a discovery or technology relating to health care. Dr. Brinkmann has a non-compensated relationship as a Co-Investigator with Medtronic Inc. that is relevant to AAN interests or activities.

Understanding daily rhythms in weakly electric fish: the role of melatonin on the electric behavior of Brachyhypopomus gauderio.

Living organisms display molecular, physiological and behavioral rhythms synchronized with natural environmental cycles. Understanding the interaction between environment, physiology and behavior requires taking into account the complexity of natural habitats and the diversity of behavioral and physiological adaptations. Brachyhypopomus gauderio is characterized by the emission of electric organ discharges (EOD), with a very stable rate modulated by social and environmental cues. The nocturnal arousal in B. gauderio coincides with a melatonin-dependent EOD rate increase. Here, we first show a daily cycle in both the EOD basal rate (EOD-BR) and EOD-BR variability of B. gauderio in nature. We approached the understanding of the role of melatonin in this natural behavior through both behavioral pharmacology and in vitro assays. We report, for the first time in gymnotiformes, a direct effect of melatonin on the pacemaker nucleus (PN) inin vitro preparation. Melatonin treatment lowered EOD-BR in freely moving fish and PN basal rate, while increasing the variability of both. These results show that melatonin plays a key role in modulating the electric behavior of B. gauderio through its effect on rate and variability, both of which must be under a tight temporal regulation to prepare the animal for the challenging nocturnal environment.

Association between poor sleep quality and locomotive syndrome in middle-aged and older women: A community-based, cross-sectional study.

Poor sleep quality, such as nocturnal arousal and sleep inefficiency, is associated with frailty and sarcopenia. Herein, we evaluated the relationship between poor sleep quality and locomotive syndrome (LS), a motor organ dysfunction common among community-dwelling middle-aged and older women. Participants comprised 2246 Japanese middle-aged and older women. LS was classified into stages LS-1, LS-2, and LS-3 (from least to most severe) according to the results of the stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale. Sleep quality was assessed using the Pittsburgh Sleep Quality Index. The Pittsburgh Sleep Quality Index scores were significantly higher in the LS group than that in the non-LS group (P < .001). Multivariate logistic regression analyses adjusted for potential confounders identified poor sleep quality as an independent factor of LS (odds ratio 1.59 [95% confidence interval 1.30-1.93], P < .001). Similar results were observed in the sensitivity analysis in postmenopausal women. LS and trouble sleeping because of pain showed stepwise association in all LS stages. Poor sleep quality was independently associated with LS among community-dwelling middle-aged and older women. As the stage of LS progressed, the proportion of women with poor sleep quality increased significantly.

A two-night polysomnography preliminary study in pregnant women with insomnia: suicidal ideation and nocturnal cognitive arousal prospectively predict objective nocturnal wakefulness.

Sleep disruption is common in pregnancy, manifesting as insomnia in half of pregnant women as well as increasing objective nocturnal wakefulness across gestation. Despite potential overlap between insomnia and objective sleep disturbances in pregnancy, objective nocturnal wakefulness and its potential contributing factors remain uncharacterized in prenatal insomnia. The present study described objective sleep disturbances in pregnant women with insomnia and identified insomnia-related predictors of objective nocturnal wakefulness. Eighteen pregnant women with clinically significant insomnia symptoms (n = 12/18 with DSM-5 insomnia disorder) underwent two overnight polysomnography (PSG) studies. Insomnia symptoms (Insomnia Severity Index), depression and suicidal ideation (Edinburgh Postnatal Depression Scale), and nocturnal cognitive arousal (Pre-Sleep Arousal Scale, Cognitive factor) were assessed before bedtime on each PSG night. Unique to Night 2, participants were awakened after 2 minutes of N2 sleep and reported their in-lab nocturnal (i.e. pre-sleep) cognitive arousal. Difficulty maintaining sleep was the most common objective sleep disturbance affecting 65%-67% of women across both nights, which contributed to short and inefficient sleep. Nocturnal cognitive arousal and suicidal ideation were the most robust predictors of objective nocturnal wakefulness. Preliminary evidence suggested nocturnal cognitive arousal mediates the effects of suicidal ideation and insomnia symptoms on objective nocturnal wakefulness. Nocturnal cognitive arousal may facilitate upstream effects of suicidal ideation and insomnia symptoms on objective nocturnal wakefulness. Insomnia therapeutics reducing nocturnal cognitive arousal may benefit objective sleep in pregnant women presenting with these symptoms.

Reducing cognitive arousal and sleep effort alleviates insomnia and depression in pregnant women with DSM-5 insomnia disorder treated with a mindfulness sleep program.

Combining mindfulness with behavioral sleep strategies has been found to alleviate symptoms of insomnia and depression during pregnancy, but mechanisms for this treatment approach remain unclear. The present study examined nocturnal cognitive arousal and sleep effort as potential treatment mechanisms for alleviating insomnia and depression via a mindfulness sleep program for pregnant women. Secondary analysis from a proof-of-concept trial of 12 pregnant women with DSM-5 insomnia disorder who were treated with Perinatal Understanding of Mindful Awareness for Sleep (PUMAS), which places behavioral sleep strategies within a mindfulness framework. Data were collected across eight weekly assessments: pretreatment, six sessions, and posttreatment. Measures included the insomnia severity index (ISI), Edinburgh postnatal depression scale (EPDS), pre-sleep arousal scale's cognitive factor (PSASC), and the Glasgow sleep effort scale (GSES). We used linear mixed modeling to test cognitive arousal and sleep effort as concurrent and prospective predictors of insomnia and depression. Most patients reported high cognitive arousal before PUMAS (75.0%), which decreased to 8.3% after treatment. All insomnia remitters reported low cognitive arousal after treatment, whereas half of nonremitters continued reporting high cognitive arousal. Both nocturnal cognitive arousal and sleep effort were associated with same-week changes in insomnia throughout treatment, and sleep effort yielded a prospective effect on insomnia. Lower levels of nocturnal cognitive arousal and sleep effort prospectively predicted reductions in depression. The present study offers preliminary evidence that reducing sleep effort and nocturnal cognitive arousal may serve as key mechanisms for alleviating insomnia and depression via mindfulness-based insomnia therapy. ClinicalTrials.gov ID: NCT04443959.

Adulthood Urge Incontinence: Is Childhood Nocturnal Enuresis A Risk Factor?

Urge incontinence and childhood nocturnal enuresis are two related urinary conditions that significantly affect individuals and their quality of life, varying prevalence between age and obesity. This systematic review examines the literature on the relationship between childhood nocturnal enuresis and urge incontinence in adulthood, including the potential mechanisms linking these conditions. Ten studies met the inclusion criteria and were included in the review. The results showed a consistent association between childhood nocturnal enuresis and urge incontinence in adulthood. The pooled analysis demonstrated that childhood nocturnal enuresis was a risk factor for adult urge incontinence, with odds ratios ranging from 1.75 to 2.7. This relationship’s potential mechanisms include nocturnal polyuria, detrusor overactivity, and arousal thresholds. However, the exact mechanisms still need to be fully understood and further investigated. Clinical implications of these findings suggest the importance of early identification and intervention for childhood nocturnal enuresis to potentially reduce the risk of developing urge incontinence in adulthood. Future research should focus on longitudinal studies to better understand the association between these conditions and explore potential risk factors and preventive strategies. Overall, this review highlights the need for increased awareness and management of childhood nocturnal enuresis to minimize the socioeconomic burden and improve the outcomes for individuals with urge incontinence.

Periodic limb movements among dialysis and non-dialysis chronic kidney disease patients: a comparative study

BackgroundPeriodic leg movement disorder is defined as periodic episodes of repetitive limb movements during sleep that mainly occurs in the lower limb, including the hips, knees, and toes, and sometimes affects the upper limb. It may be accompanied by frequent nocturnal arousals, and if so, this sleep disturbance may cause excessive daytime sleepiness. Chronic kidney disease patients are at risk of periodic leg movements and common causes are iron deficiency, anemia, raised serum calcium, and central and peripheral nervous system disorders. This study aimed to screen the prevalence of periodic limb movements among chronic kidney disease patients using full-night attended polysomnography, compare dialysis with non-dialysis CKD patients, and correlate PLM prevalence with the HGB level and degree of renal impairment.ResultsThis cross-sectional study was carried out on one hundred chronic kidney disease patients during the period between May 2017 and March 2020. The patients were subdivided into two groups: group I included patients on regular hemodialysis (n = 50), and group II included patients not on dialysis. All patients were screened for periodic limb movement using full-night attended polysomnography. Our study revealed a high prevalence of periodic limb movements in both groups of chronic kidney disease patients (60% in dialysis and 66% in non-dialysis patients) with mean PLM indices insignificantly higher in group I than group II (29.90 ± 19.19/h vs. 17.54 ± 13.56/h, P-value = 0.748). Moreover, there was a significant positive correlation between periodic leg movements and serum urea level (r-value = 0.38 and 0.33 and P-value = 0.04 and 0.030 in group I and group II consequently). Also, we reported a significant negative correlation between periodic leg movements and hemoglobin level (r = −0.251 and −0.291 and P-value = 0.037 and 0.010 in group I and group II consequently).ConclusionPeriodic leg movement disorder is highly prevalent among CKD patients either on dialysis or not, and good management of renal dysfunction and anemia in those patients can help in the management of PLM.

OR14-4 Acute sleep disruption does not diminish pulsatile growth hormone secretion in pubertal children

Abstract Context: Growth hormone (GH) plays a critical role in glucose homeostasis and linear growth during childhood. GH secretion is controlled by multiple neurotransmitters and hormones. Sleep is also a powerful stimulus for GH secretion. In children, GH pulses occur after sleep onset in association with slow-wave sleep (SWS), but it is unclear if undisrupted sleep is required for normal GH secretion. Given the rising incidence of pediatric sleep disorders such as obstructive sleep apnea (OSA) that cause sleep fragmentation, it is critical to determine whether sleep fragmentation during childhood may dysregulate the somatotropic axis. Objective To quantify how undisrupted vs fragmented sleep affects GH secretion in children. Methods Pubertal subjects (10 M, 9 F; 9.1-14.4 yrs) were randomized to two overnight polysomnographic studies with frequent blood sampling (q10min) to measure GH: fourteen were healthy subjects studied with or without SWS disruption via auditory stimuli (3 sec, 1500 Hz tones, 40-100 dB followed by 18 sec of a 75 dB noise simulating a knock on the door) and five were subjects with OSA studied with or without prescribed continuous positive airway pressure (CPAP); the latter condition was expected to have sleep fragmentation due to untreated OSA. GH pulses were identified using sparse deconvolution. Studies without auditory stimuli or when using CPAP were combined and analyzed as 'undisrupted sleep'. The relationship between GH pulse rate per hour and sleep stage was evaluated using Poisson generalized estimating equations. Results In SWS disruption studies, an average of 77.51 ± 13.61 (range 23-190) auditory stimuli were delivered, causing a 40.02 ± 7.78% decrease in SWS in favor of lighter sleep stages. In subjects with OSA, CPAP withdrawal caused a slight increase in the apnea hypopnea index (1.08 ± 0.10 vs. 2.20 ± 1.70 events/hour of sleep, p=0.07) with no change in sleep stage durations. During undisrupted sleep, subjects had an average of 0.91 ± 0.067 GH pulses/hour with a mean pulse amplitude of 10.03 ± 1.00 ng/mL and mean basal secretion rate of 0.26 ± 0.10 ng/ml per min. GH pulses occurred more frequently during SWS (2.3 pulses/hour SWS, amplitude 9.92 ± 2.59 ng/mL) than during any other sleep stage (P &amp;lt; 0.001). Neither form of sleep disruption affected the distribution of GH pulses across sleep stages, GH pulse amplitude and frequency, nor basal GH secretion. Conclusion In children, nocturnal GH pulses are temporally associated with SWS. However, neither acute fragmentation of SWS nor nocturnal arousals from OSA altered basal or pulsatile GH secretion, indicating that somatotrophic axis activity is preserved in the face of acute sleep disruption in children. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

A WEARABLE DEVICE USING CLOTH BASED NANOSENSOR TECHNOLOGY DEMONSTRATES MORE PROLONGED CHANGES IN CARDIAC AND RESPIRATORY PHYSIOLOGY FOLLOWING NOCTURNAL AROUSALS IN HEART FAILURE PATIENTS WITH HOSPITALIZATION EVENTS

Nocturnal symptoms such as Paroxysmal Nocturnal Dyspnea (PND) events are common in Heart Failure (HF) patients. However, the changes in cardiac and respiratory physiology leading up to and in recovery after a waking event (WE) has not been presented thus far with fine granularity in HF patients. A wearable device was used to collect multi-parametric data for 12 hrs—per day over 90 days following discharge from a HF-related hospitalization (HFE). With a WE defined as a postural transition from lateral or supine to sitting between 12 AM and 4 AM, a total of 370 WE were detected across three patients, including 238 WE in a patient (Age 58, M, ischemic, NYHA 4, LVEF 65%) who had a HFE on day 65 and 132 control WE in 2 patients (Age 74 & 61, M, ischemic, NYHA 3, LVEF <25% 30%) with no HFE within 90 days. For each WE, respiration rate, heart rate, and relative tidal volume were extracted for a 2-hour window centered on the time of the WE. Ensemble averages were computed for the normalized data windows across 238 events (HFE) and 132 events (no HFE) (Figure). Recovery time was defined as time to recover to within 10% of the baseline following a WE. The recovery times for heart rate, respiratory rate, and relative tidal volume were 33%, 44%, and 100% longer, respectively, for the patient with a HFE compared to patients with no HFE. Nocturnal arousals in a HF patient with a HFE are associated with more prolonged changes in cardiac and respiratory physiology as compared to more stable HF patients. This early observation provides justification for further study to confirm its utility in monitoring HF patients.

A WEARABLE DEVICE USING CLOTH-BASED NANOSENSOR TECHNOLOGY, SIMPLESENSE, CAPTURES MULTI-PARAMETRIC CHANGES IN NOCTURNAL PHYSIOLOGY IN A HEART FAILURE PATIENT LEADING UP TO A HOSPITALIZATION EVENT

Nocturnal symptoms such as Paroxysmal nocturnal dyspnea (PND) are common among Heart Failure (HF) patients. Current HF management does not include a method to continuously monitor and risk-stratify patients based on physiological changes surrounding nocturnal arousals.

0401 Efficacy of Once-Nightly Sodium Oxybate (ON-SXB; FT218) By Narcolepsy Type: Post-hoc Analyses From the REST-ON Trial

Abstract Introduction Once-nightly sodium oxybate (ON-SXB; FT218) was evaluated for treatment of narcolepsy in the phase 3 REST-ON trial (NCT02720744). Significant improvement was shown for the three coprimary endpoints mean sleep latency on the Maintenance of Wakefulness test (MWT), Clinical Global Impression of Improvement (CGI-I) rating, and weekly number of cataplexy attacks overall (all P&amp;lt;0.001 vs placebo) and in post-hoc analyses by narcolepsy type (NT1/NT2) for MWT and CGI-I (all P&amp;lt;0.05). Post-hoc efficacy analyses of objective and subjective measures of disrupted nighttime sleep and daytime sleepiness by narcolepsy type were conducted. Methods Participants aged ≥16 years were randomized 1:1 to receive ON-SXB (1 week, 4.5 g; 2 weeks, 6 g; 5 weeks, 7.5 g; 5 weeks, 9 g) or placebo. Mixed-effects models for repeated measures were used to calculate P values for change from baseline vs placebo at weeks 3 (6 g), 8 (7.5 g), and 13 (9 g) for secondary REST-ON endpoints of Epworth sleepiness scale (ESS) score, sleep shifts (ie, the number of shifts from stages N1, N2, N3 and rapid eye movement [REM] sleep to Wake and from N2, N3 and REM sleep to N1), nocturnal arousals (NA), and patient-reported sleep quality and refreshing nature of sleep (100-point visual analog scale). Results Of 190 participants, 145 had NT1 (ON-SXB, n=73; placebo, n=72) and 45 had NT2 (ON-SXB, n=24; placebo, n=21). Improvements with ON-SXB vs placebo were reported for shifts to a lighter stage of sleep (NT1: 6, 7.5, 9 g, all P&amp;lt;0.001; NT2: 6 and 7.5 g, P&amp;lt;0.05; 9 g, P&amp;lt;0.001), NA (NT1: 6 g, P&amp;lt;0.05; 7.5 and 9 g, P&amp;lt;0.01; NT2: 6 g, directional improvement; 7.5 and 9 g, P&amp;lt;0.05), and sleep quality (NT1: 6, 7.5, 9 g, all P&amp;lt;0.001; NT2: 6, 7.5, 9 g, all P&amp;lt;0.05). Significant improvements in ESS and refreshing nature of sleep for ON-SXB vs placebo were reported for NT1 (6, 7.5, 9 g, P≤0.001) with directional improvements observed for the NT2 subgroup. Conclusion Results of these subgroup efficacy analyses are generally consistent with previously reported REST-ON endpoints and support ON-SXB treatment efficacy in adults with NT1 or NT2. Support (If Any) Avadel Pharmaceuticals

0406 Efficacy of Once-Nightly Sodium Oxybate (ON-SXB; FT218) Across Stimulant Use Subgroups: Post-hoc Analyses From the REST-ON Trial

Abstract Introduction In the REST-ON trial (NCT02720744), once-nightly sodium oxybate (ON-SXB; FT218) was associated with significant improvement vs placebo for mean sleep latency on the Maintenance of Wakefulness test (MWT) and Clinical Global Impression of Improvement (CGI-I) rating in the overall population (both P&amp;lt;0.001) and in subgroups of participants taking concomitant stimulants (both P&amp;lt;0.05). Post-hoc analyses of ON-SXB efficacy on disturbed nocturnal sleep (DNS) and Epworth Sleepiness Scale (ESS) score were conducted. Methods Participants (≥16 years of age) with narcolepsy type 1 or 2 were randomized 1:1 to ON-SXB (1 week, 4.5 g; 2 weeks, 6 g; 5 weeks, 7.5 g; 5 weeks, 9 g) or placebo. Mixed-effects models for repeated measures calculated P values for change from baseline vs placebo at weeks 3 (6 g), 8 (7.5 g), and 13 (9 g) in ESS score, sleep shifts (ie, number of shifts from N1, N2, N3, and rapid eye movement [REM] sleep to Wake and from N2, N3, and REM sleep to N1), nocturnal arousals (NA), and patient-reported outcomes of sleep quality and refreshing nature of sleep on a 100-point visual analog scale. Results In the modified intent-to-treat population (n=190), 119 participants took concomitant stimulants (ON-SXB, n=66; placebo, n=53); 71 did not take stimulants (ON-SXB, n=31; placebo, n=40). Improvements with ON-SXB vs placebo were reported: ESS (stimulants: all doses, P≤0.01; no stimulants: 6 g, directional improvement; 7.5 g, P&amp;lt;0.01; 9 g, P&amp;lt;0.001), sleep shifts (stimulants: 6 g, P&amp;lt;0.01; 7.5 and 9 g, P&amp;lt;0.001; no stimulants: all doses P&amp;lt;0.001), NA (stimulants: 6 g, directional improvement; 7.5 g, P&amp;lt;0.01; 9 g, P=0.001; no stimulants: 6 and 7.5 g, P&amp;lt;0.05; 9 g, P=0.01), sleep quality (stimulants: 6 and 7.5 g, P&amp;lt;0.01; 9 g, P&amp;lt;0.05; no stimulants: all doses P&amp;lt;0.001), refreshing nature of sleep (stimulants: 6 and 9 g, P&amp;lt;0.05; 7.5 g, P&amp;lt;0.001; no stimulants: 6 and 7.5 g, P&amp;lt;0.01; 9 g, P=0.001). Conclusion Data from these post-hoc analyses were consistent with the previously reported results from REST-ON and support the efficacy of ON-SXB for EDS and DNS, as measured by objective and subjective endpoints whether or not stimulants were concurrently used. Support (If Any) Avadel Pharmaceuticals