P034 Inter-scorer concordance impacts MSLT results

Introduction A retrospective study on the effect of inter-scorer concordance and impact of analysing polysomnography (PSG) data prior to the Multiple Sleep Latency Test (MSLT) on clinical interpretation of Narcolepsy (N) and Idiopathic Hypersomnolence (IH). Methods Data of four individuals was randomly selected from a cohort of patients that participated in MSLT studies. De-identified MSLT fragments from four nap periods (n=16) were scored in two groups: analysis of PSG conducted prior to the respective MSLT fragments, and analysis without access to prior PSG. Individual scorers were compared to a master score set, by consensus from two experienced sleep scientists. Spearman correlation and percentage agreement statistics were applied to calculate the inter-scorer concordance in sleep latency and REM latency. Mann-Whitney test was utilised to assess differences between the two groups. A positive result was assigned as: mean (n=4) sleep latency of <10min (IH), and mean (n=4) sleep latency of <8min including (n=2) SOREMs (N). Results From 16 sets of data, four false positive results were identified when PSG was not analysed prior to scoring the MSLT fragments. Additionally, statistically significant differences were present when PSG analysis was conducted prior to scoring MSLT sleep latency and REM latency data. Discussion These results support a recommendation that PSG analysis (sleep and REM latency) should be encouraged prior to MSLT studies and performed by the same sleep scientist. Furthermore, including MSLT data in intra-lab concordance activities is important, particularly in relation to medical interpretation and practice.

Chronic antidepressant treatment rescues abnormally reduced REM sleep theta power in socially defeated rats

The effects of chronic antidepressant (AD) treatment on sleep disturbances in rodent chronic stress models have not been thoroughly investigated. Here, we show that chronic social defeat stress (SDS) in rats induces prolonged social avoidance, alterations in sleep architecture (increased total rapid eye movement [REM] sleep duration, bout, and shortened REM latency), and contextual but not cued fear memory deficits, even 1 month after the last SDS. These abnormalities were associated with changes in electroencephalography (EEG) spectral powers, including reduced REM sleep theta power during the light phase. Chronic treatment with two different classes of antidepressants (ADs), imipramine and fluoxetine, significantly ameliorated these behavioral, sleep, and EEG abnormalities. Interestingly, REM theta power was normalized by chronic (1 month) but not 1 week AD administration and solely correlated with the ratio (an objective indicator) of social interaction 1 month after the last SDS. These data suggest that reductions in REM sleep theta power, an EEG parameter that has never been directly investigated in humans, is a core sleep symptom in socially defeated rats, and, potentially, also in patients with stress-related psychiatric disorders, including major depressive and posttraumatic stress disorders.

Sex differences in sleep and influence of the menstrual cycle on women’s sleep in junior endurance athletes

Previous research shows that female athletes sleep better according to objective parameters but report worse subjective sleep quality than male athletes. However, existing sleep studies did not investigate variations in sleep and sleep stages over longer periods and have, so far, not elucidated the role of the menstrual cycle in female athletes’ sleep. To address these methodological shortcomings, we investigated sex differences in sleep and sleep stages over 61 continuous days in 37 men and 19 women and examined the role of the menstrual cycle and its phases in 15 women. Sleep was measured by a non-contact radar, and menstrual bleeding was self-reported. Associations were investigated with multilevel modeling. Overall, women tended to report poorer subjective sleep quality (p = .057), but objective measurements showed that women obtained longer sleep duration (p < .001), more light (p = .013) and rapid eye movement sleep (REM; hours (h): p < .001, %: p = .007), shorter REM latency (p < .001), and higher sleep efficiency (p = .003) than men. R2 values showed that sleep duration, REM and REM latency were especially affected by sex. Among women, we found longer time in bed (p = .027) and deep sleep (h: p = .036), and shorter light sleep (%: p = .021) during menstrual bleeding vs. non-bleeding days; less light sleep (h: p = .040), deep sleep (%: p = .013) and shorter REM latency (p = .011) during the menstrual than pre-menstrual phase; and lower sleep efficiency (p = .042) and more deep sleep (%: p = .026) during the follicular than luteal phase. These findings indicate that the menstrual cycle may impact the need for physiological recovery, as evidenced by the sleep stage variations. Altogether, the observed sex differences in subjective and objective sleep parameters may be related to the female athletes’ menstrual cycle. The paper provides unique data of sex differences in sleep stages and novel insights into the role of the menstrual cycle in sleep among female athletes.

336 Effect of Lemborexant Versus Placebo and Zolpidem on REM Sleep by Quarter Night Intervals in Older Adults with Insomnia Disorder

Introduction Effects of the dual orexin receptor antagonist lemborexant (LEM) on sleep architecture in adults ≥55y with insomnia disorder were assessed in Study E2006-G000-304 (Study 304; SUNRISE-1; NCT02783729). These post hoc analyses of Study 304 examined the acute effect of LEM on REM pressure (REM latency [REM-L] and REM by quarter of the night [QoN]). Methods This study was a 1mo, randomized, double-blind, placebo- and active-controlled (zolpidem tartrate extended-release 6.25mg [ZOL]) study of LEM (5mg, LEM5; 10mg, LEM10). Subjects received placebo (n=208), ZOL (n=263), LEM5 (n=266), or LEM10 (n=269). Two nights of PSGs were recorded at baseline, first 2 (N1/2), and last 2 (N29/30) treatment nights. Results Baseline REM-L (minutes) was similar across treatments (98.4–101.4). Significant decreases from baseline in REM-L were observed for LEM5 (−42.6 [53.9]) and LEM10 (−49.6[52.9]) vs placebo (−6.9[54.5]) and ZOL (0.2[54.2]) on N1/2 (all P&lt;0.0001). No difference was observed for ZOL vs placebo. Baseline REM (minutes) for each QoN was similar across treatments. In Q1, mean(SD) REM (minutes) on N1/2 was 16.5(9.7), 19.7(10.5), 10.3(8.2), and 8.5(7.6) for LEM5, LEM10, placebo, and ZOL, respectively. The difference was significant for LEM5 and LEM10 vs placebo and ZOL (all P&lt;0.0001), and ZOL vs placebo (P&lt;0.05). In Q2, mean(SD) REM on N1/2 was 19.2(9.4), 21.6(10.0), 17.9(8.9), and 17.2(9.3) for LEM5, LEM10, placebo, and ZOL, respectively. The difference was significant for LEM10 vs placebo (P&lt;0.0001) and for LEM5 and LEM10 vs ZOL (P&lt;0.01, P&lt;0.0001, respectively). No difference was observed for ZOL vs placebo. In Q3, mean(SD) REM on N1/2 was 23.3(10.3), 25.9(9.7), 20.8(9.4), and 22.8(9.9) for LEM5, LEM10, placebo, and ZOL, respectively. The difference was significant for LEM5, LEM10, and ZOL vs placebo (P&lt;0.01, P&lt;0.0001, P&lt;0.05, respectively) and LEM10 vs ZOL (P&lt;0.001). In Q4, mean (SD) REM on N1/2 was 23.8(9.4), 26.1(11.0), 21.6(10.9), and 22.5(10.1) for LEM5, LEM10, placebo, and ZOL, respectively. The differences were significant for LEM5 and LEM10 vs placebo (P&lt;0.05, P&lt;0.0001, respectively), and for LEM10 vs ZOL (P&lt;0.0001). Generally, similar findings were noted at N29/30; these data will be reported. Conclusion LEM, but not ZOL, acutely increases REM pressure as evidenced by REM latency and REM duration per quarter. Support (if any) Eisai Inc.

100 Effect of 3 consecutive nights of alcohol on sleep variables: Preliminary report

Introduction The effects of a moderate dose of alcohol one hour before bedtime on sleep have not often been studied nor is the effect across nights well known. We therefore sought to test whether such effects as sleep disruption, increased early-night slow wave sleep (SWS), and reduced early-night REM sleep would be sustained across nights. Methods Twenty-five healthy participants (13 male; ages 22–69 yr, mean = 35) reporting moderate drinking kept a fixed sleep schedule (8–9 h TIB, confirmed by actigraphy) for about one week before two 3-night sleep studies in the lab separated by ≥ 3 days. Participants drank either mixer alone or a beverage containing alcohol targeting a breath alcohol content (BrAC) of 0.08% in a counter-balanced order over 45 min ending 1 hr before lights out. Sleep was scored using Rechtschaffen & Kales (1968) rules in 30-sec epochs. Mixed-effects models examined beverage type, study night, and the interaction of beverage and night for 13 variables: sleep efficiency, sleep latency, REM latency, and full-night percent of Stage 1, Stage 2, SWS, and REM sleep; and percent of SWS and REM sleep by thirds of night. Results A significant effect of Night was seen for sleep efficiency (F(2,120)=3.79; p=.025) and sleep latency (F(2,120)=5.19;p=.007), both lower on N1, as well as for REM latency, longer on N1 (F(2,120)=6.52;p=.002). REM latency was longer with alcohol (F(1,120)=14.16; p&lt;.000) and no interaction was apparent. St2% was higher (F(1,120)=4.47; p=.037) and REM% lower (F(1,120)=4.41; p=.038) with alcohol, whereas overnight SWS% was unaffected; none showed an effect of night or an interaction. SWS% in the first (F(1,120)=10.51; p=.002) and second thirds (F(1,120)=8.27; p=.005) of the night was higher with alcohol and unaffected in the last third. REM% in the first third alone was higher with alcohol (F(1,120)=10.71; p=.01). Conclusion These findings show only modest effects of pre-sleep alcohol consumption (targeting 0.08% BrAC) on subsequent sleep in healthy drinkers, with no evidence of a cumulative impact across three nights. We aim to increase the sample size and examine effects on next-day cognitive function in subsequent analyses. Support (if any) R01AA025593

ASSOCIATION BETWEEN QUALITY OF SLEEPAND OTHER PARAMETERS IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE.

Background: Night time reux has been shown to be associated with fragmented sleep. However, few studies have assessed the quality of sleep on gastroesophageal reux and the impact of gastroesophageal reux on reported quality of sleep and quality of sleep on gastroesophageal reux. The aims of this study were to evaluate the quality of sleep and other parameters in patients with gastroesophageal reux disease.50 Subjects with typical GERD symptoms ≥3 times a week and All subjects were administered 3 questionnaires: PSQI , ESS, GERD-HRQL . All the subjects underwent nocturnal polysomnography and completed a all 3 questionnaire before NPSG. Results: Overall ,the mean percentage of N1 was 9.10±9.74 ,N2 was 83.97±13.81 , N3 was 3.44±4.16 , N4 was 0.60±2.04 , REM was 2.14±3.79 , PSQI was 12.48±1.23 , ESS was 11.80±0.76 , TST (hr) was 5.19±0.74 , SPT(hr) was 6.58±0.77 , sleep efciency(%) was 52.50±27.16 , Latency (mint) was 22.79±30.85 , REM Latency (mints) was 96.99±151.86 ,and Microarousal index was 36.05±25.93 . To assess the potential impact of sleep quality via nocturnal polysomnography on severity of gastroesophageal reux , we performed correlations between the GERD questionnaire and nocturnal polysomnography reports . We observed that PSQI(r= -0.285, p<0.045) , ESS(r=0.206, p=0.05) , N1(r=0.202 , p>0.160) , N2(r=- 0.045 ,p>0.758) , N3(r=-0.079, p>0.583) , N4(r-0.209 ,p>0.145),REM(r=0.045 ,p>0.756) , TST(r=0.036 ,p>0.803), SPT(r=0.015,p>0.917) , Sleep Efciency (r=-0.113,p>0.435) , Sleep Latency (r=-0.045 ,p>0.756), REM Latency (r=0.165, p >0.253), Microarousal index (r=0.058 , p>0.683). Conclusions: Gastroesophageal reux disease and sleep disorders are extremely prevalent conditions, and it seems intuitive that there must be some overlap between the two. Sleep disorders may in fact be one of the most prevalent of the extraesophageal complications of GERD and often goes unrecognized.

Sleep Abnormalities in the Synaptopathies: SYNGAP1-related Intellectual Disability and Phelan-McDermid syndrome

Neurodevelopmental disorders are frequently associated with sleep disturbances. One class of neurodevelopmental disorders, the genetic synaptopathies, is caused by mutations in genes encoding proteins found at the synapse. Mutations in these genes cause derangement of synapse development and function. We utilized a validated sleep instrument, Childrens Sleep Habits Questionnaire (CSHQ) to discover what sleep abnormalities occur in individuals with two synaptopathies Phelan-McDermid syndrome (PMD) and SYNGAP1-related Intellectual Disability (SYNGAP1-ID) when compared with healthy controls. We found both PMD and SYNGAP1-ID have significant sleep abnormalities with SYNGAP1-ID having greater severity of sleep disturbance than PMD. We found that sleep disturbances were more severe for both disorders in individuals 10 years and older compared with those less than 10 years old. Individuals with either disorder were more likely to use sleep aids than healthy controls. Furthermore, review of polysomnography studies for individuals with SYNGAP1-ID revealed significant reduction in rapid eye movement (REM) sleep content and delayed REM latency demonstrating abnormalities in sleep architecture. In conclusion, sleep disturbances are a significant phenotype in the synaptopathies PMD and SYNGAP1-ID. Improved sleep is a viable clinical endpoint for future clinical trials for these neurodevelopmental disorders.

0304 Greater Slow-Wave Activity is Associated with Deteriorating Mood Across Sleep Restriction

Introduction Mood progressively deteriorates over consecutive days of sleep restriction. The neurobiological processes active during sleep that influence the risk of mood disturbance are unknown. This study investigated the relationships between physiological sleep parameters (i.e., slow-wave activity (SWA), slow-wave energy (SWE), rapid eye-movement (REM) sleep duration and latency), and self-reported measures of mood across sleep restriction. Methods N=181 healthy participants (48.1% female; 30±6.8 yrs) had valid polysomnography (PSG) and mood data. The study design included two baseline nights (8h time in bed [TIB]) followed by five nights of 4h TIB. PSG (EEG derivations C3-A2, Fz-A1, O2-A1) was collected on the second baseline night (B2), first night of 4h TIB (SR1), and the fifth night of 4h TIB (SR5). The Profile of Mood States was assayed on days following PSG. Power spectral analysis for SWE and SWA was conducted (delta power; band: 0.5-4.5 Hz). General linear regression models were used to independently assess the slope of SWE, SWA, percent REM of total sleep time (TST), and REM latency on mood disturbance across sleep restriction. Results At baseline, higher SWE (unadjusted; r=0.21; P=0.004) and SWA (unadjusted; r=0.19; P=0.007) were associated with greater mood disturbance; these relations were attenuated when adjusted for age and sex. No relation was found between mood and REM latency or REM percent of TST. The slope of mood disturbance from B2 to SR5 was associated with greater percentage increases in C3 SWA on SR5 relative to B2 (β=0.039; P=0.008); this association was not observed for SWE (β=-0.016; P=0.48). The slope of REM latency and REM percent of TST were not associated with the slope of mood disturbance. Conclusion Our results indicate that greater SWA due to sleep restriction was associated with greater mood disturbance, suggesting that less SWA may confer resilience to mood disturbances resulting from sleep restriction. Support This work was supported by National Institute of Health NIH R01NR004281 and National Space and Biomedical Research Institute NSRBI NCC 5-98.

1256 Narcolepsy Type 2 in a Pediatric Patient with Auto-Immune Disease

Introduction We present a case of Narcolepsy Type 2 in the setting of concomitant auto-immune disease. Report of Case At 9 years of age, an African-American female was referred to a sleep center for fatigue, excessive daytime sleepiness (EDS), and snoring. Polysomnogram (PSG) at an outside facility recorded a total sleep time (TST) of 408 minutes, 92% sleep efficiency (SE), sleep onset latency (SOL) 22 minutes, REM latency 70 minutes, and apnea-hypopnea index (AHI) of 0.3. Multiple Sleep Latency Test (MSLT) was not done at that time. Due to her daytime sleepiness, methylphenidate was initiated empirically twice daily with improvement in daytime sleepiness and sleep maintenance. Over time, methylphenidate was steadily increased due to increasing daytime sleepiness. Between 14 to 15 years of age, she developed increased fatigue, skin changes, arthralgias, myalgias, and presented to our hospital in respiratory distress secondary to severe pulmonary hypertension. Clinical exam and workup indicated scleroderma. Methylphenidate was discontinued due to pulmonary hypertension. At 17 years of age (after receiving treatment for scleroderma and pulmonary hypertension), she had an overnight PSG followed by MSLT. PSG recorded TST 309 minutes, 67% SE, SOL 1.5 minutes, REM latency 48 minutes, AHI 0.2. The MSLT recorded a mean SOL of 2.4 minutes with 2 out of 4 sleep onset REM periods - diagnostic of narcolepsy. She does not endorse cataplexy, hallucinations or sleep paralysis. Conclusion While the link between Narcolepsy Type 1 and an auto-mediated process is more supported given consistent human leukocyte antigen findings, the link between Narcolepsy Type 2 and auto-immune mediated process is less clear. Patients with autoimmune disease may have symptoms of narcolepsy; therefore, they may benefit from screening for EDS.