bluuebunny/crossref_metadata_2025_split huggingface dataset:
0726 Impact Of Anesthetic Agents On Sleep Apnea Severity
Authors: Albrecht E , Hirotsu C , Bayon V , Heinzer R 
Published: May 2020

Abstract

Introduction
Sleep apnea is associated with negative outcomes after general anesthesia. Current recommendations suggest using short-acting over standard anesthetic agents to reduce this risk, but there is currently no evidence to support this. This randomized controlled triple-blind trial tested the hypothesis that a combination of short-acting agents (desflurane-remifentanil) would reduce the postoperative impact of general anesthesia on sleep apnea severity compared with standard agents (sevoflurane-fentanyl).

Methods
Sixty patients undergoing hip arthroplasty under general anesthesia were randomized to anesthesia with desflurane-remifentanil or sevoflurane-fentanyl. Respiratory polygraphy was performed before surgery and on the first and third postoperative nights. The primary outcome was the supine apnea-hypopnea index on the first postoperative night. Secondary outcomes were the supine apnea-hypopnea index on the third postoperative night, and the oxygen desaturation index on the first and third postoperative nights. Additional outcomes included intravenous morphine equivalent consumption and pain scores on postoperative days 1, 2 and 3.

Results
Preoperative sleep study data were similar between groups. Mean (95% confidence interval) values for the supine apnea-hypopnea index on the first postoperative night were 18.9 (12.7-25.0) and 21.4 (14.2-28.7) events/h, respectively, in the short-acting and standard anesthesia groups (p=0.64). Corresponding values on the third postoperative night were 28.1 (15.8-40.3) and 38.0 (18.3-57.6) events/h (p=0.34). Secondary sleep- and pain-related outcomes were generally similar in the two groups.

Conclusion
Short-acting anesthetic agents did not reduce the impact of general anesthesia on sleep apnea severity compared with standard agents. These data should prompt an update of current recommendations.

Support
SNSF
0755 Pitolisant (Wakix) is an Effective Anti-Cataplexy Agent in Narcolepsy Type 1
Authors: Meskill G J 
Published: May 2020

Abstract

Introduction
Harmony Biosciences initiated the Pitolisant Expanded Access Clinical Evaluation (PEACE) program to allow treatment with pitolisant in adult patients with narcolepsy while pitolisant was an investigational medication in the United States. Starting in March 2019, Comprehensive Sleep Medicine Associates (CSMA) offered enrollment to patients who met the inclusion/exclusion criteria and who were deemed appropriate based on clinical judgment. All patients who enrolled were taking at least one standard-of-care agent for narcolepsy at enrollment. Many of the enrolled patients had refractory/challenging cases of narcolepsy. On August 14, 2019, Wakix received FDA approval for the treatment of excessive daytime sleepiness in adult patients with narcolepsy, which contrasts with the European label that states that Wakix is indicated for the treatment of narcolepsy in adults with or without cataplexy.

Methods
CSMA enrolled 21 patients in the PEACE program. The charts for all 10 narcolepsy type 1 (NT1) patients were reviewed. The 2 patients who did not have follow up after starting pitolisant were excluded.

Results
Of the 8 NT1 patients who had at least one follow up visit after initiating pitolisant, 6 reported substantial improvement or complete resolution of cataplexy compared to baseline. For example, one patient’s wife stated, “I forgot my husband was funny because he would avoid telling jokes until he started pitolisant.” Another stated, “I have not had an episode of cataplexy since starting pitolisant.” 5 of these patients were taking an anti-cataplectic agent at the time of starting pitolisant (sodium oxybate 3, venlafaxine 2).

Conclusion
While a relatively small sample size, these results demonstrate that in a “real world” uncontrolled population of refractory/challenging NT1 patients, pitolisant is an effective anti-cataplectic agent. As there are relatively few treatment options for NT1, clinicians should consider use of pitolisant for patients with cataplexy, and further consideration for adding an indication for pitolisant to treat cataplexy is warranted.

Support
Harmony Biosciences (PEACE trial)
0756 A One Year Observational Early Access Pitolisant Study of Excessive Daytime Sleepiness in Narcolepsy
Authors: Stultz D J , Osburn S , Burns T , Stanley N , Walton R , Pawlowska-Wajswol S J , Moomaw S 
Published: May 2020

Abstract

Introduction
Pitolisant is a H3 receptor antagonist/inverse agonist that has been FDA approved for excessive daytime sleepiness in narcolepsy at doses of either 17.8 mg or 35.6 mg per day.

Methods
13 patients (3 males and 10 females) were studied having an average age of 46.8 years, with the majority receiving a dose of 35.6 mg Pitolisant. One patient received 17.8 mg throughout the year, and another advanced after 6 months to the 35.6 mg dose due to hepatic issues. 12 of the patients were Caucasian and one was Asian. 100% of the patients had co-existing sleep and psychiatric disorders. 46% had co-existing sleep apnea and were on CPAP/BIPAP. 38.5% had a history of a head injury. 84.6% of the patients had associated cataplexy, 38% had sleep paralysis, 92% had disrupted nocturnal sleep, and 46% had hypnogogic hallucinations. Throughout the year the patients were monitored using the Epworth Sleepiness Scale (ESS). Nine patients completed the 12-month ESS scales. 12/13 were on other medications to treat narcolepsy prior to starting Pitolisant. 6/13 were on sodium oxybate, 7/13 were on an antidepressant, and 11/13 were on either a stimulant, modafanil, or armodafanil. Only one patient was on Pitolisant alone.

Results
The patient’s average ESS score at onset was 16.2 Statistically significant findings using paired t-tests were documented. After one-month ESS scores decreased to an average of 13.2 (t=2.38, 9df, P=.04). At 3 months it was 12.4 (t=2.81, 10df, P=.02), at 6 months it was 12.75 (t=4.69, 11df, P&lt;.001) and at 12 months the average score was 13.11 (t=2.55, 8df, P=.03) documenting clinically meaningful decrease of ESS by &gt;/= 3 points. Three patients had ESS scores &lt;/=10 at 12 months.

Conclusion
Improvement on ESS was documented at one month and sustained for one year in patients diagnosed with having narcolepsy both with and without cataplexy.

Support
**No support was given for this study. Dr. Stultz is a speaker for Harmony Biosciences and has served on their advisory committee. She is also a speaker for Jazz Pharmaceuticals.
0758 Quantification of Late REM Periods in Patients With Prolonged Sleep Duration
Authors: Blattner M S , August J , Chopra S , Dalal L , Luthra S , Cunningham L , Dunham K , Thomas R J 
Published: May 2020

Abstract

Introduction
Evaluation of hypersomnia includes polysomnography followed by mean sleep latency testing (MSLT). As consistent with guidelines as applied in most centers, the overnight portion of the study will be terminated to begin sleep latency testing. For patients with prolonged sleep duration, this interruption could result in REM sleep on nap testing that reflects continuation of their biological night, rather than abnormalities in REM sleep pressure/regulation.

Methods
We reviewed 42 consecutive extended (unrestricted) sleep studies for patients with a total sleep time greater than 600 minutes. For studies with sleep onset before midnight, we evaluated for REM period onset after 6AM, the number of REM periods after 6AM and 8AM, and the time of the final REM period onset.

Results
42 hypnograms were reviewed for patients undergoing evaluation of hypersomnia, median age 32 years (range 19-92) with a median total sleep time of 663 minutes (range 602-832), of these 28/42 (67%) had sleep onset before midnight (12 AM) and were included in the analysis. 27/28 (96%) of hypnograms reviewed had REM sleep after 6 AM, 24/28 (86%) had REM sleep after 8 AM, with the onset of the final REM period ranging from 4:46 AM-12:30 PM for patients with sleep onset time before midnight (12 AM).

Conclusion
These data suggest that termination of overnight polysomnography to complete mean sleep latency testing, as is standard in most sleep labs, may influence the presence of REM sleep on MSLT for patients with prolonged total sleep duration. These results may have implications for the interpretation of MSLT for patients with long sleep duration, and may explain why a given individual may test as type II narcolepsy or idiopathic hypersomnia unpredictably on repeat testing.

Support
Sleep Medicine Fellowship at BIDMC
0761 Independent Components Analysis And Graph Theoretical Analysis In Patients With Narcolepsy
Authors: Xiao F , Zhao L , Han F 
Published: May 2020

Abstract

Introduction
To evaluate resting state functional connectivity and topological properties of brain network in narcolepsy compared with healthy controls.

Methods
Resting state fMRI was performed in 26 adult narcolepsy patients and 30 matched healthy controls. MRI data was first analyzed by group independent component analysis, then a graph theoretical method was applied to evaluate topological properties within whole brain. Small-world network parameters and nodal topological properties were measured. Altered topological properties in brain areas between groups were selected as ROI-seeds, then functional connectivity among these ROI-seeds were compared between groups. Partial correlation analysis was performed to evaluate the relationship between sleepiness severity and functional connectivity or topological properties in the narcolepsy.

Results
21 independent components out of 48 components were obtained. Compared with healthy controls, narcolepsy exhibited a significant decreased functional connectivity within the executive and salience network, while increased functional connectivity in bilateral frontal lobe within executive network can be detected in narcolepsy. There were no differences in small-world network properties between narcolepsy and healthy controls. The altered brain areas in nodal topological properties were mainly located in inferior frontal cortex, basal ganglia, anterior cingulate, sensory cortex, supplementary motor cortex and visual cortex between groups. In the partial correlation analysis, nodal topological properties in putamen, anterior cingulate and sensory cortex as well as functional connectivity between these brain regions were correlated with the severity of sleepiness (sleep latency, REM sleep latency and ESS) among narcolepsy.

Conclusion
Altered connectivity within executive network and salience network were found in narcolepsy. Functional connection changes between left frontal cortex and left caudate nucleus may be one of the parameters describing the severity of narcolepsy. Nodal topological properties alterations in left putamen and left posterior cingulate, changes in functional connectivity between left supplementary motor area and right occipital as well as changes in functional connectivity between left anterior cingulate gyrus and bilateral postcentral gyrus can be considered to be a specific indicator for evaluating the severity of narcolepsy.

Support
National Natural Science Foundation of China (81700088)National Program on Key Basic Research Project of China (973 Program, 2015CB856405)
0773 Why Did Pandemrix Trigger Narcolepsy? A Structural Approach
Authors: Peris Sempere V , Ambati A , Luo G , Lin L , Mignot E 
Published: May 2020

Abstract

Introduction
The 2009 Pandemrix influenza A pH1N1 vaccine has been linked to an increased number of Narcolepsy type I onsets in children across Europe whereas administration of a very similar adjuvanted vaccine, Arepanrix, had little effects in Canada. One possible explanation for the difference may be vaccine composition differences that could modify peptide binding to narcolepsy associated HLA-DQ0602 allele, as viral extracts for these two vaccines used distinct processes in different factories. Other explanations may involve differences in vaccination timing in relation to the pandemic H1N1 infection wave, or other environmental factors. We have previously compared the amino acid sequence of the Hemagglutinin (HA) component of the Pandemrix and the 2010 Arepanrix vaccine, finding possible contributors, but excluding most of these after DQ0602-tetramer analysis of T cell reactivity in narcolepsy versus controls.

Methods
Mass spectrometric characterization of multiple additional batches of Pandemrix and Arepanrix used during 2009 influenza pandemic vaccination campaign was performed.

Results
In addition to confirming previously published results such as increased deamidation of hemagglutinin (HA) (146N&gt;D) in Pandemrix (p=2.1e-9), we identified novel differences, including a significant 2-fold post-translation deamidation increase in 277N in Arepanrix versus Pandemrix (p=0.032), together with increased 2-fold glycosylation in the 286-323 positions in Arepanrix (p=0.00036). The 277 N to D/isoD substitution is located in pocket 1 of the binding core of a strong binder NAGSGIIIS, (&lt; 10% rank) for HLA-DQ0602 allele and abolishes epitope binding. The increased glycosylation in Arepanrix occurs in the immediate flanking area of the same 277N epitope and could also reduce DQ0602 presentation of the same epitope through differential binding and/or proteolysis of HA in this region of the molecules. As CD4 T cells recognizing this epitope have been reported to be significantly increased in narcolepsy versus DQ0602 controls, with possible mimicry with homologous hypocretin sequence.

Conclusion
These changes could explain why Arepanrix was less narcolepsy inducing. Confirmatory studies, as well as studies of all novel changes observed, are ongoing, but this is a promising result.

Support
Wake Up Narcolepsy
0790 The Clinical Significance of Hepcidin as a Predictive Value for Treatment Responses in Restless Legs Syndrome
Authors: Im H 
Published: May 2020

Abstract

Introduction
Restless legs syndrome (RLS) is a common sensory motor neurological disorder that is related to iron-dopamine dysregulation and immune system alteration. Hepcidin is the key regulatory hormone of systemic iron homeostasis and is related to inflammatory processes. We aimed to evaluate the clinical utility of hepcidin as a diagnostic biomarker and index of therapeutic responses in RLS patients after dopaminergic treatment.

Methods
Non-anemic and drug-naive RLS patients (n=18) and healthy controls (n=15) were enrolled. Hepcidin (pre-prohepcidin) and iron-related values in serum were measured upon the first visit in both groups and 12 weeks later after dopaminergic treatment in 12 RLS patients. Information about sociodemographic characteristics, sleep-related profiles, mood, and anxiety was obtained upon the first visit in all participants as well as after treatment in RLS patients.

Results
Hepcidin levels exhibited no significant differences between patients with drug-naïve RLS and healthy controls at a diagnosis (7.1 ± 2.4 vs. 7.0 ± 3.2 ng/ml, p = 0.978). Decreased hepcidin levels were significantly associated with decreased RLS severity (β = 0.002, 95% CI = 0.00−0.00, p = 0.005) and improved quality of life (β = 0.002, 95% CI = 0.00−7.01, p = 0.044) in a dose-dependent manner after 12 weeks of treatment with a dopamine agonist. This association was independent of age, sex, inflammatory markers, sleep quality, insomnia, daytime sleepiness, depression, and anxiety.

Conclusion
This study demonstrates a role of hepcidin as a predictor of therapeutic responses in RLS patients.

Support
This work was supported by the Korea Health technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, South Korea [grant number HI17C2072].
0803 Clinical and Polysomnographic Features of Trauma Associated Sleep Disorder (TASD)
Authors: Sanchez H O , Mysliwiec V , Froese R E , Creamer J L , Matsangas P , Foster S N , Hansen S L , Brock M S 
Published: May 2020

Abstract

Introduction
Trauma associated sleep disorder (TASD) is an emerging parasomnia that develops after trauma with clinical features of trauma related nightmares (TRN), disruptive nocturnal behaviors (DNB), and autonomic disturbances. The purpose of this study is to characterize the clinical and polysomnographic (PSG) features of TASD.

Methods
Clinical history and detailed video-PSG review, to include post-PSG nightmare reports, of a cohort of patients with TASD.

Results
Patients (n=40, 32 men, 8 women) were active duty service members with a median age of 38.9 yrs (range 24-57 yrs). Dream content typically related to combat (n=37, 92.5%), with 75% (n=30) reporting TRN and 60% (n=24) reporting dream enactment at least weekly. Self-reported DNB included vocalizations, violent limb movements, thrashing, defensive posturing, and jumping from bed. There was a high rate of comorbid insomnia (n=35, 87.5%), PTSD (n=23, 63.9%), anxiety (n=25, 62.5%), depression (n=20, 50%), OSA (n=19, 47.5%), chronic pain (n=12, 30%), and TBI (n=13, 32.5%). Most patients had REM sleep without atonia (RSWA) (n=33, 82.5%), though a minority had purposeful DNB (n=11, 27.5%). Vocalizations were present in seven (17.5%) patients. Patients with PTSD were more likely to have purposeful DNB (n=9, 100%) than those without PTSD (n=13, 50%; p=0.013), whereas patients with purposeful DNB had markedly less N3 sleep (1.0±11.4%) than those without purposeful DNB (13.8±16.2%; p=0.002). There was no significant difference in medications between DNB groups.

Conclusion
TASD is frequently comorbid with other sleep and behavioral health disorders. Characteristics of TASD are often captured on video-PSG during REM sleep, though DNB may be less pronounced than what patients report in their habitual sleeping environment. Clinical and video-PSG correlations are invaluable in assessing patients with TASD. This study, which is the largest cohort to date, provides a further basis for establishing TASD as a unique REM-related parasomnia.

Support
N/A
0804 Sleep Bruxism, Awake Bruxism and Sleep Related Breathing Disorders in Adults With Down Syndrome
Authors: Giannasi L , Meira e Cruz M , Rezende T , Dutra M , Nacif S , Oliveira E , Oliveira L , Oliveira W , Rode S , Nazário L , Silvestre P , Bacigalupo E , Amorim J , Salgado M , Gomes M 
Published: May 2020

Abstract

Introduction
To our knowledge, no studies have accessed theawake bruxism (AB) and stage by stage sleep bruxism (SB) in adults with Down syndrome. Recent works have shown that portable PSG systems are accurate for SB assessment even in the absence of audio-video recording. We aimed to evaluate the prevalence of awake bruxism, stage-by-stage sleep bruxism and Sleep Related Breathing Disorders (SRBD) in adults with Down syndrome.

Methods
Twenty-three adults with Down Syndrome (DS) were enrolled in this study. General health, dental status, parafunctional habits and temporomandibular symptoms were assessed. The history of SB/AB was taken from a questionnaire to the caregivers. A portable PSG type II system (Embla Embletta MPR+PG ST+Proxy, Natus, California-USA) was used to perform a full-sleep study at patients’ home. RMMA activity was defined as low (&gt;1 and &lt;2 episodes/h of sleep), moderate (&gt;2 and &lt;4 episodes/h of sleep), or high (&gt;4 episodes/h of sleep). PSG diagnose of SB was assumed if RMMA index was &gt;2 episodes/h of sleep.

Results
According to caregiver’s report, AB was present in all patients whereas only 13.1% had SB. PSG records showed a SB prevalence of 91.3%, with a mean RMMA index 40.0±30.0/h. Only 2 (8,7%) showed RMMA index of 0.0/h. SB episodes were predominant in N3 and REM sleep stage in 14 and 9 patients, respectively. All but one (95,7%) patient (isolated snoring) presented with OSA (AHI=32.8±28.6). A unique TMD symptom (pain on palpation) was present in 8,7% of the global sample.

Conclusion
The high prevalence of “definitive SB” together with the high prevalence of OSA and snoring point in favor to the recommendation of routine PSG in adults with DS. Furthermore, the low sensitivity of parent-oriented questionnaires reinforces the need of more accurate assessment tools in order to get a better standard of care in this particular group of patients.

Support
State of Sao Paulo Research Support Foundation - FAPESP grant number: 2017/06835-8
0805 Lack of Association Between Periodic Limb Movements of Sleep and Neuroimaging Signatures of Cerebral Small Vessel Disease in Stroke-Free Community-Dwelling Older Adults
Authors: Slota K A , Castillo P , Mera R M , Del Brutto V J , Del Brutto O H 
Published: May 2020

Abstract

Introduction
Evidence of the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease (cSVD) is limited and inconsistent. Here, we aimed to assess the independent association between PLMS and the different neuroimaging signatures of cSVD.

Methods
Community dwelling adults aged ≥60 years enrolled in the Atahualpa Project undergoing PSG and MRI with time intervals ≤6 months were included. MRI readings focused on white matter hyperintensities (WMH) of presumed vascular origin, deep cerebral microbleeds (CMB), silent lacunar infarcts (LI), and &gt;10 enlarged basal ganglia-perivascular spaces (BG-PVS). Data from single-night polysomnograms were interpreted according to recommendations of the American Academy of Sleep Medicine. Associations between the PLMS index and neuroimaging signatures of cSVD (as dependent variables) were assessed by means of logistic regression models, adjusted for relevant confounders.

Results
A total of 146 individuals (mean age: 71.4 ± 7.5 years; 64% women) were included. A PLMS index ≥15/hour were noted in 48 (33%) participants. Moderate-to-severe WMH were present in 33 individuals (23%), deep CMB in 9 (6%), silent LI in 16 (11%), and &gt;10 BG-PVS in 44 (30%). In univariate analyses, silent LI (p=0.035) and the presence of &gt;10 enlarged BG-PVS (p=0.034) were significantly higher among participants with a PLMS index ≥15/hour. However, fully-adjusted multivariate models showed no significant association between PLMS index ≥15/hour and any of the neuroimaging signatures of cSVD.

Conclusion
This study shows no independent association between the PLMS index and neuroimaging signatures of cSVD in stroke-free community-dwelling older adults.

Support
This study was supported by Universidad Espíritu Santo - Ecuador.