bluuebunny/crossref_metadata_2025_split huggingface dataset:
0586 An observational retrospective study of the prevalence of comorbid postural orthostatic tachycardia syndrome (POTS) in narcolepsy
Authors: Meskill Gerard , Rege Riddhi , Meskill Sarah 
Published: May 2023

Abstract

Introduction
Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of dysautonomia associated with an excessive increase in heart rate following a shift to standing posture. As of 2019, POTS has a prevalence of 1-3 million (0.3-0.9%) in the United States. Narcolepsy is a chronic neurologic condition of persistent hypersomnolence irrespective of total sleep time that also is associated with REM-sleep dissociative features (i.e., cataplexy, sleep paralysis, sleep-related hallucinations). In recent years, viral infections have been established as a trigger for both neurologic conditions.

Methods
A manual chart review was performed for records from 11/1/2020 to 12/20/2022. The overall clinic population of narcolepsy was identified by searching the electronic medical record for the ICD-10 codes G47.411 (narcolepsy type 1 [NT1]), and G47.419 (narcolepsy type 2 [NT2]). The past medical history of these charts then was searched for a history of POTS to identify patients with both conditions. A separate chart review was performed to identify all patients with POTS in the clinic.

Results
Of the 1,433 total patients in the clinic population, 207 narcolepsy patients (NT1=73, 35.3%; NT2=134, 64.7%) and 24 POTS patients were identified. The co-morbid prevalence of narcolepsy with POTS was 8.7% (18, 95% CI 5.2-13.4%); of those patients with POTS, 75% had narcolepsy (95% CI 53.3-90.2%). Co-morbid prevalence was higher in NT1 (13, 17.8% with 95% CI 9.8-28.5%) than NT2 (5, 3.7% with 95% CI 1.2-8.5%). The overall co-morbid prevalence and the NT1 co-morbid prevalence was significantly higher than the overall clinic POTS population (1.26% with 95% CI 0.75-1.98%) and the general population.

Conclusion
The prevalence of POTS is significantly higher in narcolepsy patients than the overall general population, especially in the NT1 subgroup. Clinicians should consider screening POTS patients for narcolepsy, and vice versa. Further studies are warranted to explore the etiology of co-morbid narcolepsy and POTS.

Support (if any)
N/A
0588 DNS and Sleep-Dependent Memory Consolidation in Pediatric Narcolepsy Type 1
Authors: Maski Kiran , Boduch Madeline , Heckler Gillian , Worhach Jennifer , Scammell Thomas , Behn Cecilia Diniz , Mylonas Dimitrios , Stickgold Robert 
Published: May 2023

Abstract

Introduction
Disrupted nighttime sleep (DNS) is common in narcolepsy type 1 (NT1), yet its impact on cognitive function is unknown. Given known associations between sleep-dependent memory consolidation and N2 sleep spindles, we hypothesized that NT1 impairs memory consolidation, due to fragmented N2 sleep and altered N2 sleep spindles in the NT1 group.

Methods
In this case-control study, we trained n=23 NT1 participants [mean age 15.8 years (3.2)] and n=28 healthy control (HC) patients [13.6 years (3.7)] to criterion on a spatial declarative memory task before a nocturnal in-lab polysomnogram and then gave them a cued recall test upon awakening in the morning. NT1 participants could take SSRI/SNRI medication for cataplexy but were weaned off wake-promoting medications and excluded if on an oxybate. We extracted wake and sleep stage bout numbers from sleep and N2 spindle characteristics from the polysomnogram and conducted linear regression with memory consolidation results across groups.

Results
Adjusting for age, NT1 participants had longer sleep duration than HC, more N1%, lower N3%, higher Wake/N1 Index, as well as more bouts per hour of Wake, N1, N2, REM than controls (p’s &lt; 0.04). Compared to HC, NT1 subjects had similar N2 spindle density, amplitude, and sigma power, but shorter duration of N2 spindles (p=0.009). More NT1 participants could not meet performance criterion on the initial learning task and required an easier memory task vs. HC (p=0.02) despite being older than HC. NT1 participants showed a trend for impaired memory consolidation vs. HC across a night of sleep after adjusting for age, gender, and total sleep time (p=0.07). Across groups, shorter N2 spindle duration (p=0.02) but not increased N2 bout number was associated with worse sleep-dependent memory consolidation.

Conclusion
Compared to controls, NT1 participants showed encoding difficulties but only a trend difference in memory consolidation despite greater sleep fragmentation. NT1 participants had briefer N2 sleep spindles and overall, these shorter N2 spindles were associated with greater memory consolidation deficits. Future sleep therapeutic studies are needed to determine if sleep-dependent memory consolidation can be improved to address daytime cognitive problems in NT1 patients.

Support (if any)
Jazz Pharmaceuticals and National Institutes of Health grant 5K23NS104267-2
0590 Effect of a whole-food plant-based diet on daytime sleepiness in patients with obstructive sleep apnea
Authors: Cheung Joseph , Patel Kripa , Lawson Melanie 
Published: May 2023

Abstract

Introduction
Consumption of diet rich in high saturated fats has been associated with a higher degree of daytime sleepiness. A whole-food, plant-based (WFPB) dietary pattern, which is low in saturated fat, has been shown to be beneficial in weight loss and other health conditions. Patients with obstructive sleep apnea (OSA) frequently experience excessive daytime sleepiness despite treatment. This study aims to assess the effect of a short term (21 days) WFPB diet on daytime sleepiness in patients with obstructive sleep apnea.

Methods
Patients were recruited from the Mayo Clinic Jacksonville sleep clinic who have a diagnosis of OSA who are on PAP therapy but have daytime sleepiness with Epworth Sleepiness Scale (ESS) score of 5 or above. Participants were asked to follow a strict WFPB diet for 21 days using the Fork Over Knives handbook as a guide. They were also asked to complete ESS before switching to and after completing a WFPB diet for 21 days.

Results
A total of 10 participants completed the 21-day WFPB diet. Eight out of ten participants had reported a reduction in daytime sleepiness. Overall, we found a mean decrease in ESS score of 3.8 in all participants, with 3 patients had a significant decrease in ESS score of ≥ 7. All participants completed the study with ≥ 90% adherence to a WFPB diet. In addition, participants also reported a mean weight loss of 4.2 kg. Two participants noted headaches during this 21-day period.

Conclusion
Significant improvement with daytime sleepiness was found in patients who switched to a WFPB diet for 21 days. No significant correlation between improvement in ESS and weight loss was found.

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0592 Efficacy of Lower-Sodium Oxybate by Baseline Sleep Inertia in a Phase 3 Clinical Study in Patients With Idiopathic Hypersomnia
Authors: Dauvilliers Yves , Chen Abby , Whalen Marisa , Macfadden Wayne , Thorpy Michael 
Published: May 2023

Abstract

Introduction
Idiopathic hypersomnia is a debilitating neurologic sleep disorder. Sleep inertia (difficulty awakening) is a common symptom that can significantly impair functioning and quality of life. This post hoc analysis evaluated response to lower-sodium oxybate (LXB; Xywav®) by baseline sleep inertia in a phase 3 trial (NCT03533114).

Methods
Eligible participants began LXB treatment with an open-label treatment titration and optimization period (10–14 weeks), followed by a 2-week stable-dose period (SDP). Participants were randomized to placebo or continued LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). Using the visual analog scale for sleep inertia (VAS-SI), participants rated their difficulty awakening during baseline, SDP, and DBRWP on a 100-mm line with anchors at 0 (very easy) and 100 (very difficult). VAS-SI terciles comprised score segments of &lt; 44 (group A), ≥44 to &lt; 70 (group B), and ≥70 (group C). Efficacy assessments included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Clinical Global Impression of Severity (CGIs), and Patient Global Impression of Change (PGIc).

Results
Participants (A, n=34; B, n=33; C, n=32) were a mean (SD) 40.7 (13.5) years of age and primarily female (74%). At baseline, participants with the highest VAS-SI scores had numerically higher mean (SD) ESS (A=16.0 [3.1], B=15.6 [2.6], C=17.1 [2.4]) and IHSS (A=26.7 [7.7], B=34.5 [5.9], C=36.3 [5.5]) scores. Participants with the highest baseline sleep inertia were more frequently rated severely ill on the CGIs (A=17.6%, B=12.1%, C=34.4%). Baseline total sleep time trended higher with increasing VAS-SI scores. From baseline to end of SDP, mean (SD) scores decreased (improved) on the ESS (A=−9.9 [5.1], B=−9.8 [3.5], C=−10.0 [5.1]) and IHSS (A=−14.1 [9.9], B=−19.0 [9.0], C=−18.1 [9.9]), regardless of baseline sleep inertia; nearly all (99%) participants reported improvement on the PGIc. Mean (SD) VAS-SI scores decreased by 9.3 (11.9), 31.5 (14.8), and 42.8 (22.9) in groups A, B, and C, respectively, at end of SDP. Spearman correlation coefficients for VAS-SI and IHSS items assessing sleep inertia were moderate (≥0.3) to strong (≥0.6).

Conclusion
Participants with higher baseline sleep inertia generally had greater baseline disease burden. LXB treatment was efficacious across subgroups regardless of baseline sleep inertia.

Support (if any)
Jazz Pharmaceuticals.
0604 Diagnostic Delay and Its Causes in Narcolepsy Type 1 in Japan : with special emphasis on cataplexy
Authors: Tachibana Naoko , Mihara Takenao , Sugita Naoko , Egawa Naohiro , Hamano Toshiaki 
Published: May 2023

Abstract

Introduction
Although narcolepsy type 1 is characterized by the pathognomonic symptom of cataplexy, it has been reported that there is long diagnostic delay in various countries. However, the causes of this delay have not been studied enough except for European counties. Japan is in a unique position in that all the people have public medical insurance coverage that allows them to have unlimited direct access to any medical specialists, therefore, once the patients experienced cataplexy, theoretically they could consult their symptom to sleep specialists with no financial burden. Under this condition, this study aims at characterizing the diagnostic delay and its causes in patients with narcolepsy type 1, and investigating whether cataplexy contributes to the accelerating the diagnostic process.

Methods
This retrospective study dealt with consecutive 45 patients (20 men/ 25 women) with narcolepsy type 1, whose diagnosis was made from April 2006 to September 2022 based on the PSG/MSLT criteria of the International Classification of Sleep Disorders, 3rd edition. We performed the chart review to retrieve demographic and clinical information, and the diagnostic process including the stage before coming to our sleep clinic.

Results
The diagnostic delay was 13.7±11.9 years (range 0.5-47 years, median 9.0 years). Cataplexy was the first manifestation in 9 out of 45 (20.0%), and excessive daytime sleepiness (EDS) and cataplexy occurred almost at the same time in 11(24.4%) patients. 24 (53.3%) patients considered cataplexy disturbing and/or of pathological nature, but for the remaining 21 patients, cataplexy was a kind of habit until EDS became problematic for their daily life. Seven (15.6%) patients had been diagnosed as having epilepsy, and the first medical contact of 4 patients was emergency room visit due to cataplexy leading to the diagnoses of hyperventilation syndrome, transient ischemic attack, and consciousness loss attack of unknown origin.

Conclusion
There was substantial diagnostic delay in patients with narcolepsy type 1, and cataplexy did not seem to be properly evaluated in Japan.

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0605 Effect of a Mindfulness-Based Intervention on Hypersomnia Symptom Severity in Participants with Narcolepsy: A Preliminary Report
Authors: Schuiling Matthew , Ong Jason , Zee Phyllis , Hakenjos Alec , Victorson David , Fox Rina , Rogers Ann , Mundt Jennifer 
Published: May 2023

Abstract

Introduction
Narcolepsy is a chronic sleep disorder that can greatly inhibit sleep quality, daytime functioning, and health-related quality of life. Although medication is the first-line treatment to manage narcolepsy symptoms, behavioral interventions may provide additional benefits. We examined the impact of varying lengths of a group mindfulness-based intervention on symptoms of hypersomnia among participants diagnosed with narcolepsy.

Methods
We randomized 60 participants to 3 versions of a mindfulness-based intervention: brief (4 weeks), standard (8 weeks), or extended (12 weeks). Groups of four participants met weekly or biweekly with a trained instructor via videoconference. Participants completed the Hypersomnia Severity Index (HSI) at baseline, 4 weeks, 8 weeks, and 12 weeks to assess hypersomnolence severity and related impairment. Paired samples t-tests were conducted to examine differences from baseline to post-treatment for the HSI total score, symptoms subfactor, and impairment subfactor. Linear mixed models (LMM) were conducted on the HSI total score to examine changes in the three groups across each assessment time point. Analyses were conducted using an intent-to-treat approach with the last observation carried forward for participants who had missing data after the baseline assessment (brief, n = 1; standard, n = 5; extended, n = 3).

Results
There were no significant group differences on the HSI total score or subfactor scores at baseline. Analyses revealed a significant decrease in HSI total scores from baseline to post-treatment (d=.533, p&lt;.001), a significant decrease in hypersomnia symptoms (d=.373, p&lt;.01) and a significant decrease in hypersomnia impairment (d=.549, p&lt;.001). LMM revealed a main effect over time, indicating that hypersomnia severity improved from baseline to the study endpoint, across all treatment arms (t=-3.58, p&lt;.001) but no significant time x treatment interaction effects emerged.

Conclusion
This preliminary report suggest that mindfulness programs can reduce hypersomnia symptoms for individuals with narcolepsy over a 12-week period, regardless of the duration of treatment. Additional analyses are being examined to determine ideal treatment duration to maximize benefits and minimize costs.

Support (if any)
This research was supported by a grant from NCCIH (R34AT009551)
0608 PAX8/PAX8-AS1 DNA methylation levels are not associated with sleep duration in medicated patients with unexplained hypersomnolence
Authors: Madrid Andy , Papale Ligia , Cook Jesse , Tran Kieulinh , Prairie Michael , Vascan Ana Maria , Alisch Reid , Plante David 
Published: May 2023

Abstract

Introduction
The biological basis of daytime sleepiness and excessive sleep duration in patients with unexplained hypersomnolence is unknown. However, a growing body of evidence suggests modulations in the epigenome coincide with objective measures of sleep, suggesting epigenetic mechanisms may be related to hypersomnolence. Previously, we identified significant correlations between saliva DNA methylation abundance at nine CpG sites located in the PAX8/PAX8-AS1 genes and total sleep time measured using polysomnography in unmedicated, clinical patients with unexplained hypersomnolence. Since psychotropic medications frequently affect clinical sleep testing and may also affect DNA methylation, here we attempted to replicate prior findings in a separate, medicated sample.

Methods
Forty-three medicated clinical patients with unexplained hypersomnolence were drawn from a larger study of a multimodal sleep assessment that included ad libitum overnight polysomnography. Pyrosequencing quantified DNA methylation at the previously identified CpG sites in PAX8/PAX8-AS1. Multivariate linear models, adjusting for age, sex, and body mass index (BMI), assessed relationships between total sleep time and DNA methylation at these prespecified CpG sites.

Results
Participants were young -to middle-aged (Mean Age = 32.2±10 years) and predominantly female (Percent Female = 95.3%), with a mean BMI of 27.8±5.4kg/m2. Epworth Sleepiness Scale (ESS) score was consistent with complaints of daytime sleepiness (Mean ESS =15.1±-4.3). Total sleep time on ad libitum polysomnography was 9.2±1.7 hours (range 5.6-12.8 hours). No significant associations between DNA methylation at the PAX8/PAX8-AS1 CpG sites and sleep duration were identified in adjusted models.

Conclusion
We were unable to replicate findings of an association between sleep duration and DNA methylation levels at specific PAX8/PAX8-AS1 CpG sites in medicated patients with unexplained hypersomnolence. Further research to clarify whether this is a result of medications affecting the DNA methylation levels at these CpG sites or previously identified associations between DNA methylation of PAX8/PAX8-AS1 and sleep length are spurious will require replication of prior findings in a novel unmedicated cohort and quantification of within-subjects effects of psychotropic medications on DNA methylation levels in genes of interest.

Support (if any)
AASM Foundation (229 SR-20 - Diversity Supplement Grant)
0609 Samelisant, Histamine 3 Receptor Agonist for the Potential Treatment of Excessive Daytime Sleepiness in Patients with Narcolepsy
Authors: Nirogi Ramakrishna , Ravula Jyothsna , Jayarajan Pradeep , Goyal Vinod Kumar , Jetta Satish , Shinde Anil , Benade Vijay 
Published: May 2023

Abstract

Introduction
Samelisant (SUVN-G3031) is a potent and selective histamine 3 receptor inverse agonist. In orexin knockout mice, samelisant produced wake-promoting and anticataplectic effects suggesting its potential therapeutic utility in the treatment of narcolepsy. Safety and tolerability studies in animals and healthy human volunteers suggested a favorable risk/benefit profile for samelisant.

Methods
Samelisant is currently being evaluated in a double blind, Phase-2 proof of concept study in USA and Canada for narcolepsy with or without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). The study is recruiting subjects diagnosed with narcolepsy as per ICSD-3 criteria, aged between 18 to 65 years with an Epworth Sleepiness Scale (ESS) score of ≥12 and mean Maintenance of Wakefulness Test (MWT) time of &lt; 12 min. A total of 171 subjects are expected to be randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in 1:1:1 ratio. Each subject will receive either placebo or study drug once daily for 2 weeks. The primary efficacy endpoint is change in MWT score from baseline to week 2. Key secondary endpoint is change in ESS from baseline to week 2. Safety will be monitored throughout the study by medical monitor and by data safety monitoring committee. As the study is still recruiting, demographics and baseline characteristic data for the currently enrolled subjects is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion.

Results
At the data cutoff date of Nov 30, 2022, a total of 155 subjects were randomized in the study. The median age of subjects was 30 years (range: 18-57 years) with mean BMI of 28.5 kg/m2 (range: 18.3- 43.9 kg/m2). Overall, 57% subjects were of narcolepsy type-1, 71% were female and 71% were Caucasian. Mean (SD) baseline values of MWT and ESS scores were 6.1 (4.4) and 17.2 (2.8), respectively.

Conclusion
Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling subjects with narcolepsy and the data readout is expected in Q2 2023.

Support (if any)
0610 The effects of wakefulness promoting agents on neuronal activity in nucleus accumbens
Authors: MacLean Jennifer , Nataraj Jaya , Mousavi S A Seyyed , Galion Anjalee , Sanger Terence 
Published: May 2023

Abstract

Introduction
Both modafinil and methylphenidate are frequently utilized for maintenance of wakefulness in narcolepsy and other sleep disorders. Both have been demonstrated to affect dopamine transporter, leading to an increase extracellular dopamine. Subsequent functional connectivity changes between nucleus accumbens and pallidum are noted. Animal studies demonstrate changes in neuronal activity with methylphenidate in nucleus accumbens. To our knowledge there has been no direct examination of human neural activity in nucleus accumbens after administration of modafinil or methylphenidate, compared to baseline.

Methods
Two subjects with placement of stereotactic electroencephalographic (sEEG) electrodes to identify optimal location for permanent deep brain stimulation electrodes in nucleus accumbens were given wakefulness promoting agents to optimize testing of stimulation sites during inpatient hospitalization. Assessment occurred at least 48 hours following surgical electrode insertion under inhaled general anesthesia. Retrospective analysis was performed on neural activity in nucleus accumbens during rest on and off medication. Frequency content was calculated in the following bands: delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz), gamma (30-50 Hz), and high gamma (70-100 Hz). Power in each band is reported as the percentage contribution of each band to summed power across all bands.

Results
Total power was noted to be lower with both modafinil and methylphenidate. With modafinil, the beta band ratio was decreased (22.3% vs. 30.5%), the gamma band ratio was increased (24% vs. 22.4%), and the high gamma band was increased (39.5% vs. 32.9%). With methylphenidate, only the high gamma band was increased (40.3% vs. 22.9%).

Conclusion
Both methylphenidate and modafinil increase high gamma band neural activity in nucleus accumbens, while modafinil has additional effects on beta and gamma bands. Further assessment of modafinil and methylphenidate’s effects on neural activity are indicated to help better understand their mechanism of action and appropriate use as wakefulness promoting agents.

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