bluuebunny/crossref_metadata_2025 huggingface dataset:
0640 Initial Sleep Center Evaluation and Follow Up Improves Positive Airway Pressure (PAP) Therapy Adherence When Compared to Direct Referrals Without Sleep Physician Follow Up: A Retrospective Study
Authors: Aljarod T , Tran L , Al Ikhwan M , Prasad B
Published: May 2020

Introduction

Obstructive sleep apnea (OSA) affects 26% of adults and positive airway pressure (PAP) is the gold-standard of therapy. Factors affecting PAP adherence—use >4 hours in a 24-hour period—have been studied extensively. We compared of the three months (or other time frame) PAP adherence between patients seen by a sleep specialist prior to OSA diagnosis versus patients referred directly for OSA testing by non-sleep specialist providers. The goal of the study was to understand the impact of sleep consultation on PAP adherence.

Methods

Direct referral (DR) patients underwent polysomnography (PSG) and received PAP devices prior to the sleep clinic visit. In contrast, sleep center patients (SC) had a sleep clinic visit with a sleep physician or APRN prior to PSG.

Eighty-four patients were included in this study, 42 DR and 42 SC patients. Exclusion criteria were age <18 years old, absence of baseline PSG, and lack of 90-day compliance data. Covariates included demographics, body mass index (BMI), AHI, nadir oxygen saturation, demographics, and Epworth Sleepiness Scale (ESS) score. Objective PAP adherence for first 90 days was the primary outcome.

Results

Age (p=0.1), ESS (p=0.3), BMI (p=0.6), and AHI (p=0.9) were not significantly different between the groups. SC patients had greater PAP adherence (4.77 hours, 95%CI: 4.1 to 5.4) compared to DR patients (3.61 hours, 95%CI: 2.88 to 4.33, p=0.02). SC patients were also 8 times more likely to follow up in clinic within 1 year of starting PAP treatment (Likelihood Ratio 8.25, p=0.004).

Conclusion

While possibly more time-efficient for patients, direct referrals may ultimately result in lower PAP adherence due to missed opportunities for receiving education about OSA and PAP therapy. This is consistent with findings from a previous meta-analysis demonstrating that educational interventions improve PAP adherence. Moving forward, we will continue encouraging directly referred patients to follow up in the sleep center after PSG.

Support

None
0650 Impact of Upper Airway Stimulation Therapy on 24 Hour Ambulatory Blood Pressure Monitoring
Authors: De A , Bena J , Wang L , Aylor J , Bhambra R , Kaw S , Lance C , Mehra R , Walia H
Published: May 2020

Introduction

Upper airway stimulation (UAS) is recommended treatment for moderate to severe obstructive sleep apnea (OSA) in select patients. Existing data have not focused on gold standard 24 hour ambulatory blood pressure monitor (ABPM) to elucidate the impact of UAS. We hypothesize that UAS reduces ABPM indices characterized using objective sleep-wake from actigraphy data over 12-month follow-up period.

Methods

A prospective sub-study of the Inspire ® post-approval study at the Cleveland Clinic was designed to examine the effect of UAS on 24-hour ABPM measures post-implantation by examining blood pressure (BP) at baseline, and-2, 6, and 12 months follow-up. Actigraphy data was contemporaneously collected. Paired T-tests were used to evaluate BP changes over time. Repeated measure correlations measured within-patient associations between BP and actigraphy measures.

Results

Average age and BMI were 62.4 +/-12.9) years and 30.1 +/-3.3 kg/m2, 73.3% males and all Caucasian. The mean baseline systolic, diastolic and mean arterial pressure (MAP) were 119.7+/-12.9 mmHg, 74.3+/-7.4 mmHg and 89.3+/- 8.1 mmHg. There were no changes to number, type or dosage of BP medications.

At 12 months, there were non-significant overall mean reduction in systolic [-0.55mmHg, p=0.75], diastolic [-0.73mmHg, p=0.63], and MAP [-0.55mmHg, p=0.71]. Mean sleeping systolic, diastolic and MAP changed by -4.36(p=0.34), -1.45 (p=0.57), -2.18 (p=0.50), respectively. Positive correlations above 0.25 (p<0.10) were observed between all dipping percentage measures and total sleep time. Negative correlations were seen between overall systolic, diastolic and MAP with sleep latency (-0.22, p=0.19, -0.35, p=0.031 and -0.29, p=0.075 respectively). No significant changes in BMI was observed, but average hours of usage decreased over time.

Conclusion

Although consistent reduction of BP measures were observed post-UAS implantation, findings were not statistically significant. It is unclear whether this is due to insufficient sample size or true lack of effect. Larger-scale clinical and mechanistic studies are needed to enhance understanding of UAS-related vascular influences.

Support

Funded: Inspire Medical Systems
0663 The Longterm Effect of CPAP Compared to Mandibular Advancement Device on Metabolic Profile in Mild Obstructive Sleep Apnea
Authors: Togeiro S , Oliveira L S , Guimaraes T M , Luz G P , Coelho G , Badke L N , Tufik S , Bittencourt L
Published: May 2020

Introduction

Moderate and severe Obstructive Sleep Apnea (OSA) have been independently associated to dyslipidemia with controversial results of improvement with CPAP. Less evidence exists regarding this issue in mild OSA. A current treatment for mild OSA is Mandibular Advancement Device (MAD), however its effectiveness on metabolic profile needs to be compared to CPAP.Our aim was to compare MAD with CPAP and no treatment on metabolic profile during one year in mild OSA.

Methods

Cross sectional analyses included 79 mild OSA patients randomized in CPAP group (n: 31), MAD group (n. 25) and Control group (n: 23). Metabolic profile was investigated before and after 6 and months.

Results

Mean age: 47± 9 years, BMI: 28±3.7 kg/m AHI: 9.5±2.9/h. There were no differences in anthropometric data, total cholesterol (TCT) HDL-C, LDL-C, Triglycerides (TC) and glycated Hemoglobin (Hb1c) among groups. MAD and CPAP reduced AHI at 6 and 12 months (9.3 ± 5.2 to 4.2 ± 9.1 to 3.8 ± 12.6 / 10.0 ± 4.6 to 1.2 ± 9.9 to 1.7 ± 14.2, p: 0.01 respectively). BMI did not change in groups at 6 and 12 months. MAD adherence was higher than CPAP at 6 months (5.8 ± 2.8 hs/day vs 3.8 ± 3.0 hs/day; p: 0.01) and 12 months 5.7 ± 2.7 hs/day vs 3.8 ± 3.4 hs/day; p: 0.01). Despite of lower adherence than MAD, CPAP was effective in reduce TCT and LDL- CT at 6 and 12 months (Intention to treat analyses TCT: 189.3±51.4 mg/dl to 186.1±51.4 mg/dl to 174.6±51 mg/dl; p: 0.03 / 112.8±48.7 mg/dl to 110.5±48.7 mg/dl to 95.8±48.7mg/dl; p: 0.03 respectively), however HDL-C, TG and Hbc didn′t change.

Conclusion

Long term CPAP treatment was effective in reducing cholesterol in mild OSA.

Support

Associação Fundo Incentivo à Psicobiologia (AFIP)

CAPES
0673 Effects Of Solriamfetol On Driving Performance In Participants With Excessive Daytime Sleepiness Associated With Obstructive Sleep Apnea
Authors: Vinckenbosch F , Asin J , De Vries N , Vonk P , Donjacour C , Lammers G , Overeem S , Janssen H , Wang G , Chen D , Carter L , Zhou K , Vermeeren A , Ramaekers J
Published: May 2020

Introduction

Excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) is associated with an increased risk of driving accidents. Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved in the US (Sunosi®) for EDS associated with OSA (37.5-150 mg/day). This study evaluated solriamfetol’s effects on on-road driving performance in participants with EDS associated with OSA.

Methods

In each period of this randomized, double-blind, placebo-controlled, crossover study (NCT 02806895; EudraCT 2015-003930-28), driving performance during an on-road driving test was assessed at 2 hours and 6 hours postdose following 7 days of treatment with solriamfetol (150mg/day × 3, then 300mg/day × 4) or placebo. The primary endpoint—standard deviation of lateral position (SDLP), a measure of “weaving,” at 2 hours postdose—was compared between solriamfetol and placebo per time point using a repeated mixed-effects analysis of variance model.

Results

The study included 34 participants. Baseline characteristics reflected the broader OSA population (88% male; mean age=52 years; mean Epworth Sleepiness Scale score=14.4). SDLP at 2 hours postdose was statistically significantly lower following solriamfetol (least squares [LS] mean [standard error; SE], 18.83cm [0.63]) compared with placebo (19.92cm [0.63]): LS mean difference, -1.08cm; 95% confidence interval (CI), -1.85, -0.32; P=0.0062 (incomplete driving tests: solriamfetol, n=1; placebo, n=4), indicating better performance with solriamfetol. At 6 hours postdose, SDLP following solriamfetol (LS mean[SE], 19.24cm [0.63]) was statistically significantly lower compared with placebo (20.04cm [0.63]): LS mean difference, -0.80cm; 95% CI,

-1.58, -0.03; P=0.0432 (incomplete driving tests: solriamfetol, n=3; placebo, n=7). Common adverse events (≥5%) with solriamfetol were headache, nausea, insomnia, dizziness, and agitation.

Conclusion

Solriamfetol (300mg/day) improved SDLP, an important measure of driving performance, at 2 and 6 hours in participants with EDS associated with OSA.

Support

Jazz Pharmaceuticals
0697 Early Sleep Apnea Termination By Bone-conducted Sound Stimulation Reduces Oxygen Desaturation Magnitude And Duration
Authors: Waeber A , Arnal P , Mignot E , Heinzer R
Published: May 2020

Introduction

Obstructive sleep apneas (OSA) usually end with an oxygen desaturation and/or an arousal. In most epidemiological studies, OSA-associated oxygen desaturations are stronger predictors of cardiovascular morbidity than OSA-associated arousals. The aim of this study was to determine if induction of a premature arousal by a bone-conducted sound stimulation shortly after the onset of an event can reduce the magnitude of OSA-associated oxygen desaturation.

Methods

Eight severe OSA patients (2 women, 45 [20-68]y.o.) underwent polysomnography at the Lausanne University Sleep Center (CIRS). Short acoustic stimulations were administered every second sleep apnea by remote control using a Dreem® headband worn by the patients. Acoustic stimulations were administered by bone conduction. The magnitude(%) and the duration(s) of the oxygen desaturations following these prematurely-terminated apneas were compared with previous and following non-acoustic stimulated sleep apnea events.

Results

Analysis of 549 paired (stimulated-unstimulated) respiratory events in N1(14.2%), N2(69.9%), N3(4.2%), and REM sleep (9.6%) showed a 30.3% reduction in oxygen desaturation amplitude (mean difference±SD: -1.9±2.8%, p<0.0001), a 39.6% decrease in desaturation duration (-5.7±9.2 seconds, p<0.0001), and a 21.4% decrease in apnea duration (-3.4±7.2 seconds, p<0.0001) in stimulated apneas compared to the previous and subsequent non-stimulated apnea events. When analyzed individually, each patient showed a significant improvement following acoustic stimulation of events. Sound-associated discomfort was rated 1.14±1.53 on an 8 points scale (8=worst). Of the 68.6±38 administered sound stimuli per patient, only 6.8% of were perceived by the patients. A reduction in the desaturation amplitude occurred in each sleep stage but was milder in N3.

Conclusion

Bone-conducted sound stimuli applied trough a headband during the apneas decreased duration and magnitude of OSA-associated oxygen desaturation. These were well tolerated and often not perceived by the patient. This new treatment approach should be further investigated, with monitoring of its effect on cardiovascular parameters and daytime sleepiness.

Support

Customized Dreem headbands were provided by Dreem company
0703 Transvenous Phrenic Nerve Stimulation Provides Safe And Effective Therapy For Cheyne Stokes Respiration
Authors: Schwartz A R , Sundar K , McKane S , Germany R , Khayat R
Published: May 2020

Introduction

Cheyne-Stokes respiration (CSR), a specific type of central sleep apnea (CSA) is characterized by a waxing and waning pattern of breathing with absent air flow at the ventilatory nadir followed by oxyhemoglobin desaturation. CSR is most common in patients with heart failure (HF) and predicts morbidity/mortality. Therapeutic options remain limited, especially for patients with reduced left ventricular ejection fraction (LVEF).

Methods

Patients (n=151) with predominantly CSA were implanted with a transvenous phrenic nerve stimulation device (TPNS, remedē system, Respicardia Inc.) and randomized to 6-months of active vs. deferred (control) therapy. Patients were divided into subgroups based on percentage of sleep in CSR (<20%, 20-50%, >50%) on their baseline polysomnogram. Response to TPNS, defined by ≥50% reduction in apnea-hypopnea index, and Epworth Sleepiness Scale were assessed. TPNS efficacy and safety was analyzed in each subgroup.

Results

As percentage of CSR during sleep increased, more patients had a history of HF and lower LVEF. The proportion of TPNS responders was similar among CSR subgroups at 6 months (63% [17/27] CSR<20%, 52% [11/21] CSR 20-50%, 54% [7/13] CSR>50%); the corresponding control response rates were ≤16% in each subgroup. Central apnea index decreased from median 33, 17 and 30 events/hour in these subgroups to ≤2 in TPNS-treated subgroups; control subgroups had median ≥17 events/hour at 6 months. Daytime sleepiness improved more in TPNS patients with <20% CSR (4/24 points vs. 2 in >20% CSR subgroups). In the CSR>50% subgroup, cardiovascular death (pump failure) was observed in 2/25 control and 0/14 treatment subjects through 6 months. One cardiovascular death (sudden death) occurred in the TPNS 20-50% CSR subgroup.

Conclusion

TPNS effectively treats CSA regardless of CSR. Risk of cardiovascular death did not differ by CSR severity with TPNS, but may increase in CSR without treatment. TPNS therapy appears safe and efficacious for CSA with and without CSR.

Support

Respicardia and NIH R01 HL 144859
0713 Association Between Obesity Indices And Obstructive Sleep Apnea Is Modified By Age In A Sex-specific Manner
Authors: Liu Y , Meng L , Guan J , Yi H , Yin S
Published: May 2020

Introduction

The beneficial effects of weight loss on obstructive sleep apnea (OSA) are highly variable. Whether the variability is associated with the effects of age and sex remains unclear. This study examined this issue with large cross-sectional data.

Methods

A total of 4600 adult males and 1156 females with suspected OSA were included in the study. Anthropometric measurements, polysomnographic variables, biochemical indicators, and medical history were collected for each subject. Multivariable linear regression with interaction terms was used to estimate the modification effect of age on the associations between OSA severity (assessed by apnea-hypopnea index, AHI) with obesity indices (body mass index, BMI; neck circumference, NC; waist circumference, WC) in a sex-specific manner, and vice versa.

Results

BMI, NC, and WC were all positively correlated with AHI after adjusting for potential confounders in all populations. In males, these associations were much stronger and more significant in younger than older individuals (P for interaction < 0.001). For example, a 10% increase in BMI was independently associated with a 31.6% increase in AHI for males < 40 years old, whereas the corresponding increases were 20.8% and 16.7% for males 40-60 and >60 years old, respectively. By contrast, no modification effect of age was observed in females (P for interaction > 0.05). A 10% increase in BMI was associated with 25.6%, 26.8%, and 23.8% increases in AHI for females < 40, 40-60, and >60 years old, respectively.

Conclusion

Age modifies the associations between obesity indices and OSA severity in a sex-specific manner, and vice versa. These findings may broaden the understanding of age- and sex-related heterogeneities in the pathogenic role of obesity in OSA, and may be beneficial for individualized risk evaluation and treatment management for patients with OSA.

Support

This study was funded by Shanghai Municipal Commission of Science and Technology (grant number.18DZ2260200); the National Key R&D Program of China (grant number: 2017YFC0112500); Multi-Center Clinical Research Project from the School of Medicine, Shanghai Jiao Tong University (grant number: DLY201502); and the Shanghai Shen-Kang Hospital Management Center Project (grant number: SHDC12015101 and 16CR3103B).
0715 Long-term CPAP Adherence In A Public Sleep Clinic
Authors: Rezayat T , Vassar S , Hakopian S , Wallace J
Published: May 2020

Introduction

CPAP adherence may drop substantially over a long time frame. Since minorities including Hispanics and low socioeconomic groups have lower short-term acceptance and adherence, long-term adherence may also be reduced. We adapted a brief motivational enhancement education program (BMEEP) (Lai, CHEST 2014) in a Los Angeles County safety-net sleep clinic and found improved CPAP adherence at 3 months. We now report longitudinal long-term adherence over >=2 years. Our hypothesis: Many patients would meet CMS adherence criteria over >= 2 years.

Methods

During 3/1/2016 - 4/1/17, 118 patients completed BMEEP during CPAP initiation and were scheduled for a reinforcement session and routine clinic visits at 1 and 3 months and every 6 months thereafter. Electronic adherence and efficacy data were accessed each visit. Multivariate regression analyses explored association of adherence variables with demographic, clinical and workflow features.

Results

Baseline characteristics (mean (SD) or percent): Age 57.2 (17.8); Women 44.9%; Hispanic 69.5%, Non-Hispanic-White 22.9%, Other 5%, Black 3%; BMI 37; Epworth score 10.4 (6.05). Home sleep testing (69 patients) respiratory event indices were >=15/hr in 67% and >=30/hr in 57%. Polysomnography (81 patients) apnea hypopnea indices were (AHI) >= 15 in 78% and >=30/hr in 43%. By 7/1/2019, 23 (19%) patients were lost with unknown CPAP use status, while 76 (70.5%) of remaining patients continued to use CPAP. At 2 years, CPAP adherence parameters included: Average nightly use, 75% (27.7); Average hours/night, 4.74 (2.5); Average nightly use >=4 hours, 65.2% (31.6); >=70% nightly use >= 4 hours, 35 (51.5%). Average residual AHI was 2.05 (1.69). Adherence parameters in individual patients remained similar throughout 2 years. Long-term adherence was not associated with the demographic, clinical or workflow variables tested.

Conclusion

Programs that educate, motivate and provide regular follow-up for predominantly Hispanic low income populations can achieve acceptable long-term CPAP adherence rates.

Support

None
0716 The Clinical Characteristics And Therapeutic Efficacy Of Catathrenia
Authors: Wen Y , Xu L , Han F
Published: May 2020

Introduction

Catathrenia/nocturnal groaning, is a rare sleep disorder characterized by repeated groaning in a protracted expiration preceded by a deep inspiration. The classification was moved from ICSD-2 as parasomnia to sleep-disordered breathing(SDB) in ICSD-3. The pathogenesis of catathrenia is unknown.

Methods

To investigate catathrenia’s response to continuous positive airway pressure (CPAP) treatment, and its relationship with SDB. We analyzed patients diagnosed at the Sleep Center of Peking University People’s Hospital from 2009 to 2016. All patients were confirmed with nocturnal groaning by polysomnography(PSG), and recording of the sounds. The patients were recommended for treatment of CPAP.

Results

A total of 49 patients were recruited into this study, including 31 female and 18 male, age ranging from 16 to 64 years. The average onset age was 19.81 ± 8.65 years old, the average BMI was 21.76 ± 2.62 kg/m², the average groaning index (GI) was 11.58 ± 13.32 times per hour, and the average apnea hypopnea index (AHI) was 3.59 ± 8.83 times per hour. The GI in REM and NREM sleep were 39.31 ± 44.39 and 6.74 ± 8.5 times per hour respectively (p <0.01). The GI of 26 patients who received CPAP treatment decreased from 10.57 ± 12.01 to 5.65 ± 7.10 times per hour (p <0.001).

Conclusion

Catathrenia occurs mainly in REM sleep, and treatment with CPAP is effective, although cannot be completely eliminated. Suggest that catathrenia might be a sleep breathing disorder

Support

There is no support of this study
0722 The Association Between Obstructive Sleep Apnea and Neurobehavioural Function in Men: A Large, Population-Based Cohort Study
Authors: Parker J L , Adams R J , Appleton S L , Melaku Y A , Vakulin A
Published: May 2020

Introduction

Obstructive sleep apnea (OSA) is linked with impaired vigilance, attention, memory and executive function. However, this evidence largely comes from small experimental studies or larger studies in clinical samples and therefore the scope and magnitude of OSA driven neurobehavioural dysfunction in the general population remains unclear. This study aimed to examine the cross-sectional association between OSA and neurobehavioural function in a large community sample of men.

Methods

A total of 837 participants from the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study, a longitudinal cohort of men 40+ years, underwent full overnight polysomnography. Participants completed the inspection time (IT) test, mini-mental state examination (MMSE), Fuld object memory evaluation (FOME), and trail-making test (TMT) part A (TMT-A) and part B (TMT-B). Using regression models adjusted for multiple important covariates, we examined the association between neurobehavioural function scores, clinical metrics of OSA severity (Apnea-Hypopnea Index (AHI); percentage total sleep time with oxygen saturation <90% (TST90), and measures of sleep disruption (duration of rapid eye movement (REM) and non-REM (NREM) sleep; and total sleep time (TST).

Results

In multivariable linear regressions, greater TST was associated with worse IT scores (B=13.688, 95% CI [0.134, 27.241], P=0.048) and TMT-B scores (B=19.255, 95% CI [0.931, 37.578], P=0.040). In logistic regressions, greater TST was associated with better MMSE scores (Odds ratio [OR]=0.440, 95% CI [0.194, 0.997], P=0.049); and higher AHI was strongly associated with worse FOME scores in fully adjusted models (OR=1.358, 95% CI [1.252, 1.472], P<0.001).

Conclusion

The AHI and TST were positively, significantly associated with neurobehavioural function across different domains. This cross-sectional data shows that neurobehavioural function deficits in OSA are directly related to sleep and breathing disruptions. Future large prospective studies are needed to determine if OSA and sleep disruption predict future onset of neurobehavioural dysfunction and cognitive decline.

Support

National Health and Medical Research Council and the Adelaide Institute for Sleep Health.
0726 Impact Of Anesthetic Agents On Sleep Apnea Severity
Authors: Albrecht E , Hirotsu C , Bayon V , Heinzer R
Published: May 2020

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

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

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<.001) and at 12 months the average score was 13.11 (t=2.55, 8df, P=.03) documenting clinically meaningful decrease of ESS by >/= 3 points. Three patients had ESS scores </=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

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

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

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>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, (< 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

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

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

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 (>1 and <2 episodes/h of sleep), moderate (>2 and <4 episodes/h of sleep), or high (>4 episodes/h of sleep). PSG diagnose of SB was assumed if RMMA index was >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

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 >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 >10 BG-PVS in 44 (30%). In univariate analyses, silent LI (p=0.035) and the presence of >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.
0806 Prescription Correlates of Nightmare Disorder Among Veterans
Authors: Gross M , Patel R , Schwartz S W , Sebastião Y V , Foulis P , Scheer D , Taylor K A , Anderson W
Published: May 2020

Introduction

In the James A. Haley Veterans Administration (JAHVA) Vista database, the ICD-9 code 307.47 for Nightmare disorder (ND) is infrequently used and appears independently of codes for PTSD. We wanted to determine if certain drugs that may affect sleep are associated with ND.

Methods

All patients with ND visiting JAHVA between 2007 and 2011 were selected along with control patients who visited JAHVA on one of 20 random days, one day each quarter year. Controls were assigned an index date reflecting their selection quarter. Associations with prescriptions for opioids, antidepressants (SSRI’s, SSNI’s, Tricyclics), antihistamines and benzodiazepine/Z-drugs were initially investigated. Two analyses were performed: risk factor analysis- patients with ND diagnosis dates (cases) or index dates (controls) prior to 2008 were excluded and only prescription dates that preceded the ND diagnosis or index date were considered; treatment analysis- cases and controls with a ND diagnosis date or index date after 2010 were excluded and only prescription dates that were subsequent to the ND diagnosis or index date respectively were considered. Logistic regression adjusting for age, gender, race and Hispanic ethnicity was used to determine the association between drug groups and ND.

Results

In risk factor analysis (667 cases, 14,739 controls), opioids and antihistamines were significantly less prevalent among would-be ND patients than controls (OR=0.627 and 0.610 respectively); no drug group was predictive of ND. In contrast, all drug groups were significantly associated with ND in treatment analysis (803 cases, 15,530 controls). The strongest associations were seen with benzodiazepine (OR=3.026; 95% CI: 2.472, 3.703) and SSRI (OR=2.789; 95% CI=2.316, 3.358) prescriptions.

Conclusion

Our data suggest that some JAHVA providers may be treating ND with medication, most notably with benzodiazepines/Z-drugs and antidepressants. The role of anti-histamine and opioid prescriptions needs further elucidation. The ramifications of these treatment decisions should be explored.

Support

This material is the result of work supported with resources and the use of facilities at the James A. Haley Veterans’ Hospital.