bluuebunny/crossref_metadata_2025_split huggingface dataset:
1257 Low Nocturnal SpO2 and Daytime Sleepiness in a Child
Authors: Pi M Y , Han F 
Published: May 2020

Abstract

Introduction
Patients with nocturnal oximetry shows SpO2 during sleep of ≤ 90% in children for ≥ 5 minutes and sleep related hypoventilation is not documented could be diagnosed as sleep related hypoxemia (ICSD-3). However, known physiological causes should be indicated.

Report of Case
A 5-year-old Chinese boy was referred to sleep lab for daytime sleepiness for three months. Type I narcolepsy was confirmed.
Nocturnal PSG indicated a continuous low SpO2 baseline around 82%, with a nocturnal mean SpO2 of 83%, but no respiratory events. Voluntary hyperventilation made SpO2 increase from 83% to 95%, and hypoventilation syndrome was considered. PtcCO2 during PSG maintained 40mmHg, and no sleep related elevation observed. BPAP treatment had no effect on both SpO2. No dyspnea was complained. When he was 12 years old, follow-up PSG and MSLT indicated narcolepsy remained. During the past 7 years, no comorbidities occurred. Hb 104 g/L, RBC 3.53 × 1012/L, Hct 31%. ABG showed SaO2 of 97%, PaO2 98mmHg and PaCO2 40mmHg. Inconsistency between SpO2 and SaO2 reminds the existence of abnormal hemoglobin.
A positive isopropanol precipitation test and further hemoglobin electrophoresis showed abnormal Hb and HbA were 37.6% (normal 0%) and 58.4% (normal 94.3–98.5%), respectively, but HPLC did not identify. Spectrophotometric analysis indicated that the absorption spectra were significantly different at 450nm~540nm and 600nm~1000nm. Hemoglobin structure analysis found the abnormal site. Gene sequencing identified a novel HBB: c.212 C&gt;A mutation, resulting in amino acid 71 to change from alanine(Ala) to aspartic(Asp) acid as a de novo mutation. A diagnosis of Hemoglobin Seattle [β71:Ala→Asp；HBB:c.212C&gt;A] was confirmed.

Conclusion
Pediatric sleep medicine has a rapid development. Before a diagnosis of sleep related hypoxemia is made, in rare situation, abnormal hemoglobin should be considered.
1260 High Tidal Volume Non-invasive Ventilation Required to Treat Obesity Hypoventilation
Authors: Rezayat Talayeh , Beggs Abigail , Avidan Alon Y , Javaheri Shahrokh 
Published: May 2020

Abstract

Introduction
Current guidelines recommend CPAP or non-invasive ventilation with tidal volume (VT) &lt;10ml/kg of ideal body weight (IBW) for the treatment of obesity hypoventilation. However, in select patients with significant obesity hypoventilation, this recommendation may not be sufficient to resolve nocturnal hypoventilation.

Report of Case
A 35 y/o male with hypertension and class III obesity (BMI 58 kg/m2) was referred for evaluation of acute respiratory failure with hypoxia and hypercapnia. ABG demonstrated daytime PCO2 of 71 mmHg. Patient reported sleep fragmentation, snoring, choke awakenings, poor concentration, depression and sleep attacks. PSG demonstrated severe OSA, with an AHI of 154 events/hour, persistent hypoxia and hypercapnia with a SpO2 nadir of 50% and ET-CO2 of 83 mmHg during REM sleep. Respiratory events persisted with CPAP and bilevel, up to a setting of 25/16. Average volume assured pressure support (AVAPS) S/T titration study was performed and resolved sleep apnea at settings of IPAP 24-30, EPAP 4-15, VT 790 (10 mL/kg IBW), 0.5 LPM O2, rate 16. The patient reported having had the best sleep of his life at the end of this study and has since been started on treatment.

Conclusion
Treatment of OHS should be individualized and may require use of tidal volumes above 10ml/kg for effective treatment. We suggest that in super morbidly obese patients, with extremely noncompliant respiratory system, larger than recommended tidal volume is necessary to ventilate the patient and improve gas exchange. The sustained higher pressures achieved by AVAPS to impose the augmented tidal volume more effectively ameliorate OSA, by keeping the upper airway open. Higher pressures achieved also could elevate FRC, not only increasing oxygen stores, but also contributing to maintenance of open upper airway through its tethering effect. Further physiological studies are needed in super morbidly obese patients comparing low and high tidal volumes.
1261 The Long Term Exhaustion of a Viral Infection
Authors: Mulhern Kellen 
Published: May 2020

Abstract

Introduction
Narcolepsy is a rare condition affecting only 0.02% to 0.18% of United States and Euro-pean populations. Throughout the years, hypersomnolence in the form of narcolepsy or idiopathic hypersomnia has been identified as a post infectious syndrome in rare instances. In this case, we observe a child with excessive daytime sleepiness after an infectious rash.

Report of Case
A 4 year old male presented to clinic for evaluation of excessive daytime sleepiness for the past 10 months. At that time, he developed a full body rash that lasted for about 1 week, and was treated with diphenhydramine and prednisone. No imminent cause was identified. For the preced-ing weeks, he was taking frequent and longer naps, and complained of difficulty with keeping his head up and his eyes open.
He was evaluated for possible seizures via EEG with no seizure activity seen. Blood work was unremarkable, and a lumbar puncture showed highly elevated IgG for EBV, and low IgM for EBV, indicating a prior infection.
His excessive somnolence persistent, and he was referred to undergo actigraphy, poly-somnography (PSG), and a multiple sleep latency test (MSLT). Actigraphy demonstrated disrupt-ed nocturnal sleep, PSG showed an elevated periodic leg movement index of 8.6/hr, and MSLT showed reduced sleep onset latency and sleep onset REM on 2 of 4 naps.
During his physical exam, he had drooping eyelids and tongue protrusion, concerning for cataplectic facies, highly suspicious for Narcolepsy Type 1. Further confirmatory testing is pend-ing, including HLA subtype testing and hypocretin levels in CSF.

Conclusion
This case shows a strong association with a subacute EBV infection and the development of nar-colepsy. There are multiple cases involving the development of hypersomnolence conditions as a consequence of viral infections. Further cases would be beneficial to form additional associations.
1270 Wobbly Knees: Cataplexy Or Seizure? A Case Report
Authors: Nadhim A , Wong J , Gupta D 
Published: May 2020

Abstract

Introduction
Cataplexy (associated with narcolepsy) is difficult to differentiate from conditions such as seizure, syncope or TIA, but using validated clinical tools can help. We report a case that was mistakenly diagnosed as cataplexy, delaying diagnosis and treatment of his underlying seizures.

Report of Case
A 42 years old male presented with “freezing spells” described as spontaneous episodes of weakness in his knees. He may stagger and drop objects but had never fallen. He denies loss of consciousness. Post-ictally, he takes a moment to readjust his body and returns to baseline. There was no warning or aura before the episodes. These spells initially occurred 1-2 times/year in 2002, then progressed to 1/month by 2006 and then increased to 15 times/day in Jan 2019, lasting 5-10 seconds at a time. He became hesitant to drive. He was evaluated by a pulmonologist/sleep specialist. PSG showed Mild OSA but MSLT wasn’t suggestive of Narcolepsy. He was prescribed CPAP but stopped after 6 months since it didn’t improve his symptoms. He was prescribed Venlafaxine to treat presumptive Cataplexy, without any benefit. Eventually, he was referred to neurology/sleep clinic. Cataplexy questionnaire was administered and was negative: specifically, there were no emotional triggers of his episodes, such as hearing a joke, laughing or crying. Due to the stereotyped nature of his spells, he was referred to epilepsy specialist. He underwent 72 hours video EEG monitoring which showed that his clinical episodes were associated with EEG abnormality, suggestive of frontal lobe epilepsy. He was placed on Keppra and Oxcarbazepine. On follow up visit, he reported improvement in seizure frequency from 10-20/day to 1-2/day.

Conclusion
A validated1 clinical Tool such as Stanford Cataplexy questionnaire helps in differentiation of Cataplexy from other forms of transient muscle weakness. It can prevent 15 years delay in diagnosis and treatment of patients, or use of unnecessary medication.
0134 Self-Reported Sleep is Associated with Central, But Not Peripheral Blood Pressure Values in Healthy Children
Authors: Berube F R , Katulka E K , D’Agata M N , Patterson F , Ives S J , Farquhar W B , Witman M A 
Published: May 2020

Abstract

Introduction
Shortened and poor quality sleep have emerged as nontraditional risk factors for the development of high blood pressure (BP) in adults, but it is unclear if these relations exist in younger children. Self-report and objective sleep measurements are both clinically relevant and may inform interventions to improve sleep in this population, but do not always coincide with one another. The purpose of this study was to evaluate both self-reported and objective sleep metrics and their associations with central and peripheral BP values in younger children.

Methods
Participants included 21 healthy 7-12-year-old children (10±0.5 yrs, 10M/11F). Self-reported sleep was evaluated using the Children’s Sleep Health Questionnaire and a total sleep score was generated, where a higher score indicates worse sleep (a score &gt;41 indicates a pediatric sleep disorder). Objective sleep was recorded for 7 consecutive days and nights outside of the laboratory via wrist accelerometry and reported as sleep duration (SD) and sleep efficiency (SE). Following sleep monitoring, peripheral BP was measured and using pulse wave analysis (PWA) central BP was estimated, both of which were averaged over 3 trials. Pearson’s r correlations were used to assess relations between self-reported sleep score, objective sleep metrics, and BP values. Significance was set at p&lt;0.05.

Results
Self-reported sleep score averaged 40±1 points, objective SD averaged 7.9±0.1 hours/night, and SE averaged 82±2%. Sleep score was significantly associated with central systolic and diastolic BP (r = .485, p = 0.03, and r = .517, p = 0.02, respectively), but not peripheral BP values. Objective SD and SE were not significantly associated with central or peripheral BP values.

Conclusion
In this sample, self-reported sleep score, but not objective sleep metrics, was associated with higher central BP values in healthy children age 7–12.

Support
Provided in part by P20GM113125.
0136 Bright Light Could Be an Alternative to the Caffeine for Improving Driving Performance in Chronically Sleep-Deprived Young Drivers
Authors: Shekari Soleimanloo S , Garcia-Hansen V , White M , Smith S S 
Published: May 2020

Abstract

Introduction
Young drivers are over-involved in sleepiness-related crashes. Daytime and nighttime exposure to light might shift the human circadian phase and alertness. The alerting effects of bright light were compared with those of caffeine in young drivers.

Methods
In a within-subjects study, 30 chronically sleep-deprived non-professional drivers (aged 18–24 years) completed two simulated daytime driving sessions per day across three consecutive days. Participants completed the first drive under a Baseline condition (non-caffeinated gum, 555 nm light, 0.3 µW/cm²), and the second drive under the randomized conditions of Light (500 nm, 230 µW/cm²), Caffeine (100 mg caffeinated gum) or the combination of Light and Caffeine. Using mixed-effects models, the alerting effects of these conditions on objective sleepiness (ECG beat-to-beat intervals), driving performance (lateral lane variability) and subjective sleepiness (scores on the Karolinska sleepiness scale; KSS) were examined.

Results
Compared to the Baseline condition, lateral lane variability decreased under the Light (P=0.011), Caffeine (P=0.0001), and the combination of Light and Caffeine (P=0.046). Lateral lane variability was lower under Caffeine when compared with the Light (P=0.009) or the combination of Light and Caffeine (P= 0.0001). Average beat-to-beat intervals increased from the Baseline condition to the Light (P=0.017), Caffeine (P=0. 0.0001), and the combination of Light and Caffeine conditions (P=0.0001). All three conditions significantly reduced subjective sleepiness compared to the Baseline condition (KSS= 4–5 vs KSS=6, P= 0.0001).

Conclusion
Bright light, either alone or combined with caffeine, improves driving performance and subjective sleepiness during daytime drives. Light might better improve objective sleepiness and other sleepiness indicators during nighttime when drivers are sleepier and have an increased sensitivity to the light. Further research would clarify how the circadian effects are aligned with the alerting effects of the light. Bright light, as an alternative to or combined with caffeine, could reduce sleep-related crashes on the road.

Support
NA
0137 Self-Reported Sleep Quality is Associated with Central Hemodynamics in Healthy Individuals
Authors: Culver M N , Flatt A A , Grosicki G J 
Published: May 2020

Abstract

Introduction
Insufficient sleep is associated with arterial stiffness and elevated cardiovascular disease risk. Central hemodynamics are influenced by arterial stiffness, yet independently predict cardiovascular risk. Relationships between sleep characteristics and central hemodynamic parameters are largely unexplored. We aimed to characterize the relationship between self-reported sleep quality and central hemodynamics in healthy individuals. To explore the hypothesis that impairments in glucose metabolism, resulting from lack of sleep, may underlie relationships between sleep and central hemodynamic variables, we also examined associations between self-reported sleep quality and fasting blood glucose values.

Methods
Thirty-one healthy subjects (14 females /17 males; 20–69 years) that were free from metabolic or cardiovascular disease, and that did not take sleep medication were included in the study. Relationships between self-reported sleep quality, obtained using the Pittsburgh Sleep Quality Index (PSQI), with central hemodynamic profiles(systolic and diastolic blood pressures, pulse and augmentation pressures, augmentation index) estimated from oscillometric pulse wave analysis, and fasting blood glucose values were assessed.

Results
Central pulse pressure was significantly elevated (P&lt;0.05) in poor (PSQIscore &gt;5) compared to normal (PSQI score 0–5) self-reported sleepers. Linear regression models, adjusted for age, gender, and body mass index, demonstrated PSQI score to be an independent predictor (P&lt;0.05) of both central pulse (β=0.469) and augmentation (β=0.364) pressures. Global PSQI scores were not related to fasting blood glucose values (r=0.045; P&gt;0.05).

Conclusion
Significant relationships between central pulse and augmentationpressures and self-reported sleep quality highlight the importance of considering sleep when examining lifestyle contributors to central hemodynamics.

Support
No funding.
0143 Vigilance Declines Following Sleep Deprivation are Associated with Two Previously Identified Dynamic Connectivity States
Authors: Teng J , Ong J , Patanaik A , Zhou J , Chee M , Lim J 
Published: May 2020

Abstract

Introduction
Dynamic functional connectivity (DFC) analysis of resting-state fMRI data has been successfully used to track fluctuations in arousal in the human brain. Changes in DFC have also been reported with acute sleep deprivation. Here, we demonstrate that dynamic connectivity states (DCS) previously related to arousal are reproducible, and are associated with individual differences in sustained attention declines after one night of total sleep deprivation.

Methods
32 participants underwent two counterbalanced resting-state fMRI scans: during rested wakefulness (RW) and following total sleep deprivation (SD). They also completed the Psychomotor Vigilance Test (PVT), a sustained attention task that is highly sensitive to the effects of sleep loss. SD vulnerability was computed as the decrease in response speed (∆RS) and increase in lapses (∆lapse) in SD compared with RW.
Dynamic functional connectivity analysis was conducted on rs-fMRI data. Connectivity matrices were clustered to obtain 5 prototypical DCS. We calculated the proportion of time participants spent in each of these DCS, as well as how often participants transitioned between DCSs. Relationships between SD vulnerability and connectivity metrics were then correlated.

Results
We recovered two DCS that were highly similar (ρ = .89-.91) to arousal-related DCS observed in previous work (high arousal state (HAS); low arousal state (LAS)).
After sleep deprivation, the proportion of time spent in the LAS increased significantly (t29=3.16, p=.0039), while there was no significant change in HAS (t29=-1.43, p=.16). We observed significantly more state transitions in RW compared with SD. Change in LAS and HAS across sleep conditions correlated significantly with SD vulnerability (ΔLASxΔRS: r=-0.64, p&lt;.0001; ΔLASxΔlapse: r=0.43, p=.018; ΔHASxΔRS; r=0.43, p=.019; ΔHASxΔlapse; r=-0.39, p=.033). Finally, Δ%transitions was correlated with ΔRS but not Δlapse.

Conclusion
This study adds to the evidence that two specific reproducible DCS are robust markers of arousal and attention, and may be useful indicators of SD vulnerability.

Support
This work was supported by the National Medical Research Council, Singapore (STaR/0015/2013), and the National Research Foundation Science of Learning (NRF2016-SOL002-001).
0144 Relationship Between Sleep EEG K-Complex Slow Wave Coupling and Next-Day Thalamic Activity During Psychomotor Vigilance Test in Obstructive Sleep Apnea
Authors: Parekh A A , Kam K , Mullins A , Fakhoury A , Castillo B , Roberts Z , Hedden T , Varga A W , Rapoport D M , Ayappa I 
Published: May 2020

Abstract

Introduction
There is large inter-individual variability in the relationship between obstructive sleep apnea (OSA) severity and lapses in vigilance as measured using psychomotor vigilance test (PVT). We have previously shown that overnight sleep EEG K-complex slow wave coupling (∆SWAK) exhibits a dose-responsive relationship with next-day lapses in vigilance in OSA on and off treatment. We hypothesized that a variable thalamic dysfunction in OSA explains difference in lapses in vigilance and alterations in ∆SWAK across individuals.

Methods
Five newly diagnosed severe OSA subjects (mean apnea-hypopnea index [AHI4%=57.1±22.8/hr.]) with excessive daytime sleepiness (Epworth Sleepiness Scale=11±3.4) underwent nocturnal polysomnography followed by PVT testing within a 3T SKYRA MRI scanner. The PVT task inside the scanner (PVT-fMRI) was adapted to match the gold standard PVT-192 device. Each fMRI scanning session consisted of 2 10-min PVT runs interleaved with 2 control conditions wherein the subject pressed the response button at random intervals absent of a visual stimulus. fMRI data was analyzed in 2-step procedure (individual time-series followed by group analysis) using Analysis of Functional Neuroimages (AFNI) software package. To estimate thalamic activity during PVT-fMRI, parameter estimates of the %change in blood-oxygen-level-dependent (BOLD) signal using the contrast PVT-Control were used as the primary metric. The region of interest was limited to the bilateral thalamus using the Eickhoff-Zilles macro labels from the MNI N27 template.

Results
In a preliminary test, PVT performance for the subjects inside the scanner was not significantly different from that outside the scanner (PVTLapsesfMRI=7.3±2.1 vs. PVTLapsesPVT192=6.4±3.6 mean±std; PVTLapses=reaction time &gt; 500 ms.). Within subjects, a trend toward lower thalamic recruitment was observed during PVT-fMRI (-0.17±0.2%; p=0.1). Further, lower thalamic activity during PVT-fMRI also showed a trend to lower overnight ∆SWAK (mean -1.2±1.4) values (r = 0.61, p = 0.17).

Conclusion
In severe OSA subjects with excessive daytime sleepiness, we observed a trend to reduced thalamic activity during daytime PVT. Overnight EEG K-complex slow wave coupling showed a similar trend with next-day thalamic activity during PVT, however the small sample size may have limited our ability to detect this association with statistical significance.

Support
AASM Foundation 199-FP-18; NIH K24HL109156
0146 Efficacy and Safety of Single Dose of TS-142, a Novel and Potent Dual Orexin Receptor Antagonist, in Insomnia Patients
Authors: Uchiyama M , Kambe D , Imadera Y , Sunaga H , Hasegawa S , Nogi T , Kajiyama Y , Yoshida S , Ogo H , Uchimura N 
Published: May 2020

Abstract

Introduction
TS-142 is a novel dual orexin receptor antagonist (DORA) developed for the treatment of insomnia. Here we report its pharmacokinetic profile in the healthy subjects and its efficacy and safety in patients with insomnia.

Methods
A phase1 study was conducted to clarify pharmacokinetic profile, in which various doses of TS-142 (1–30 mg) were orally administered once to thirty two healthy subjects. Subsequently, a phase 2a study utilizing polysomnography (PSG) was carried out in patients with primary insomnia, in which 5, 10, or 30 mg of TS-142, or placebo was randomly administered in a double-blind manner. Karolinska Sleepiness Scale (KSS) and Digit Symbol Substitution Test (DSST) were also examined in the morning after PSG.

Results
Following single administration of TS-142, plasma concentration of unchanged compound reached maximum within 2.50 h (median), and then eliminated rapidly, giving mean elimination half-life between 1.32 and 3.25 h. Twenty-three patients with insomnia completed the Phase2a study. Both latency to persistent sleep (LPS) and wake after sleep onset (WASO) were significantly improved with TS-142 at all doses, in comparison with placebo (-42, -42 and -45 for LPS [min] and -28, -35 and -55 for WASO [min] in 5, 10, 30 mg, respectively). KSS and DSST administered in the morning indicated no serious hangover effects. No serious adverse events were observed in these trials.

Conclusion
The phase 1 trial showed favorable pharmacokinetic profiles. The phase 2a trial demonstrated that TS-142 was efficacious in objective sleep onset and maintenance with minimal next-day residual effects. TS-142 was generally well tolerated in both studies.

Support
Taisho Pharmaceutical. Co., Ltd.