Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study.

STUDY OBJECTIVES: The clinical benefits of positive airway pressure (PAP) therapy for obstructive sleep apnea are assumed to require adherent PAP usage, defined by the Centers for Medicare & Medicaid Services as ≥ 4 hours of use ≥ 70% of nights. However, this definition is based on early data and does not necessarily capture improvements at subthreshold adherence. We explored dose-response relationships between PAP adherence measures and excessive daytime sleepiness from the HomePAP randomized controlled trial. METHODS: Participants aged ≥ 18 years with an apnea-hypopnea index ≥ 15 events/h and baseline sleepiness (Epworth Sleepiness Scale [ESS] ≥ 12) received PAP therapy. Data were collected at baseline, 1-month follow-up, and 3-months follow-up. Regression models and receiver operating characteristic curves evaluated PAP measures as predictors of ESS change and normalization (ESS < 10). RESULTS: In 119 participants (aged 49.4 ± 12.6 years, 66.4% male, 72.3% White), > 50% were PAP nonadherent per Centers for Medicare & Medicaid Services criteria at 3 months. The percentage of nights with PAP use ≥ 4 hours predicted ESS change (P = .023), but not when controlling for the apnea-hypopnea index. The percentage of nights with ≥ 4 hours and average PAP use provided the best discrimination for predicting ESS normalization; each 10% increase in PAP use ≥ 4 hours increased the odds of ESS normalization by 22% (P = .007); those using PAP ≥ 4 hours had a nearly 3-fold greater odds of ESS normalization (P = .025). PAP use for at least 4 hours and on 70% of nights provided the best balance between specificity (0.50) and sensitivity (0.73). CONCLUSIONS: Although subadherent PAP usage may still confer some benefit for patients with obstructive sleep apnea, adherence to current criteria confers the highest likelihood for ESS change and normalization. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Portable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP); URL: https://clinicaltrials.gov/ct2/show/NCT00642486; Identifier: NCT00642486. CITATION: Pascoe M, Bena J, Andrews ND, et al. Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study. J Clin Sleep Med. 2022;18(4):1027-1034.

High prevalence of pathological alertness and wakefulness on maintenance of wakefulness test in adults with focal-onset epilepsy.

BACKGROUND: Excessive daytime sleepiness (EDS) is a common complaint in adults with epilepsy (AWE), but objective evaluation is lacking. We used the maintenance of wakefulness test (MWT) to objectively measure the ability of adults with focal-onset epilepsy to maintain wakefulness in soporific conditions. METHODS: Adults with epilepsy participating in a study investigating the effects of lacosamide on sleep and wakefulness underwent baseline ambulatory polysomnography (PSG)/EEG followed by MWT. Mean sleep latency (MSL) and mean percent sleep time (MST, mean percentage of non-wake EEG scored in 3-sec bins from lights out to sleep onset averaged over the 4 MWT trials) were quantified. Subjective sleepiness was assessed by the Epworth Sleepiness Scale (ESS). Spearman correlation and linear regression assessed relationships between MWT parameters, ESS and relevant sleep and epilepsy-related variables. RESULTS: Maintenance of wakefulness test MSL in 51 AWE (mean age 43.5 ±â€¯13 years, 69% female, mean BMI 24.6 ±â€¯11.2 kg/m2) was 21.7 ±â€¯11.9 min; 45.1% had an abnormally short MSL <19.4 min and 15.7% <8 min. MST was 9.3% [3.3, 19.1]. Mean ESS score was 8.8 ±â€¯5.7; 39% had elevated ESS (>10). No correlation between subjective ESS and objective MSL (p = 0.67) or MST (p = 0.61) was found. MSL was significantly shorter in subjects with focal to bilateral tonic-clonic seizures (FBTCS; 7.9 min [13.6, 22.3]) compared to those without (27.4 min [21.2, 33.6], p = 0.013). Younger subjects had shorter MSL; MSL increased 3.2 min for every 10-year increase in age. CONCLUSION: We found a high prevalence of objective sleepiness/difficulty maintaining wakefulness on the MWT and subjective sleepiness using the ESS in AWE without a correlation between the two. More severe objective sleepiness was found in subjects with a history of FBTCS and younger age. Further research is needed to determine mechanistic underpinnings and optimal measurements of pathological sleepiness in people with epilepsy given the burden of it on quality of life.

The Epworth Sleepiness Scale in epilepsy: Internal consistency and disease-related associations.

BACKGROUND: The Epworth Sleepiness Scale (ESS) is the most common instrument for measuring subjective sleep propensity in people with epilepsy but has not yet been validated in this population. STUDY OBJECTIVES: We aimed to systematically assess the validity, performance, and internal consistency of the ESS, as well as correlations between the ESS and disease-specific variables and patient-reported outcome measures in a cohort of adults with epilepsy (AWE). METHODS: Ninety-five AWE completed sleep and seizure diaries, in-laboratory polysomnography (PSG) and patient-reported outcome measures, including the ESS, Insomnia Severity Index (ISI), and the Beck Depression Inventory (BDI). Demographic information and data from 95 matched controls referred for PSG for suspected obstructive sleep apnea (OSA) was taken from the electronic medical record. Frequencies of high ESS item ratings (item score ≥2) were calculated for each group. Cronbach's α and factor analysis were performed to assess the internal consistency and validity of the ESS within cases and controls. Multivariable linear models were used to assess the association between ESS and predictors of interest, adjusting for demographic and disease-specific variables, including seizure type, frequency, and anti-seizure medication (ASM) therapy. RESULTS: While suspected OSA controls had significantly greater mean ESS total scores (9.9 vs 7.9, p = 0.004) and proportion with ESS >10 (42% vs 25%, p = 0.014), there were no significant differences in the severity of item responses, with the exception of "lying down to rest in the afternoon when circumstances permit," for which more controls rated as likely/very likely (79% vs 64%), p = 0.024). AWE with ESS >10 had higher mean standardized ASM dose (2.5 vs 1.7, p = 0.026). All ESS items were significantly correlated with the total score within each group. Cronbach's α was 0.75 for cases and 0.85 for controls, indicating good internal consistency of the ESS for both groups. After adjusting for demographic and sleep characteristics, higher ESS scores were associated with greater insomnia scores on the ISI (p = 0.024) and depressive symptoms on the BDI (p = 0.018). CONCLUSIONS: This study provides validity for the use of the ESS in adult populations with epilepsy.

Subjective and objective hypersomnia highly prevalent in adults with epilepsy.

INTRODUCTION: Sleepiness is among the most common complaints of people with epilepsy, but objective documentation is lacking. We systematically investigated subjective and objective sleepiness in an observational cross-sectional cohort of adults with epilepsy (AWE). METHODS: This is a prospective study of AWE consecutively recruited without foreknowledge of sleep/wake complaints. Polysomnography (PSG) with 18-channel electroencephalography (EEG) followed by multiple sleep latency testing (MSLT) was performed. Patients completed the Epworth Sleepiness Scale (ESS), a single-item question assessing excessive daytime sleepiness (EDS), and a 7-day sleep and seizure diary. Multivariable linear models were used to assess the association between MSLT mean sleep latency (MSL) and interests with adjustment of covariates of interest. Receiver operating characteristics (ROC) analysis was performed to evaluate the discrimination capability of ESS on MSL < 8 min and <5 min and investigate the optimal cutpoints. RESULTS: Among 127 AWE (mean age: 38.7 ±â€¯13.7 years), abnormal MSL (<8 min) was observed in 49.6% and MSL <5 min in 31.5%. While 78% reported feeling sleepy during the day on a single-item question, only 24% had elevated scores on the ESS (>10/24). The ESS score was associated with MSL even after adjusting for seizure frequency, antiseizure medication (ASM) standardized dose and number, age, gender, depression and insomnia symptom severity, and apnea-hypopnea index (HPI) and total sleep time on PSG (coefficients [95% confidence interval (CI)]: -0.26 [-0.48, -0.05], p = 0.018). The area under the curve (AUC) of the ESS ROC predicting MSL < 8 min and MSL < 5 min were similar: 0.62 (95%CI: 0.52-0.72) and 0.62 (95%CI: 0.51-0.74). CONCLUSIONS: This is the largest prospective cross-sectional observational study to date using MSLT in AWE. We found subjective and objective daytime sleepiness highly prevalent in AWE and not explained by seizure frequency, ASM burden, symptoms of insomnia/depression, or PSG findings although those with MSL < 5 min were more likely to have obstructive sleep apnea (OSA). Pathologic sleepiness with MSL < 8 min was present in half of AWE. Nearly one-third of AWE unselected for sleep/wake complaints had MSL < 5 min, a range typical of narcolepsy.

Dissociation of Objective and Subjective Daytime Sleepiness and Biomarkers of Systemic Inflammation in Sleep-Disordered Breathing and Systolic Heart Failure.

STUDY OBJECTIVES: Subjective versus objective sleepiness in heart failure (HF) remains understudied; therefore, we sought to examine the association of these measures and interrelationships with biochemical markers. METHODS: Participants with stable systolic HF recruited from a clinic-based program underwent attended polysomnography, Multiple Sleep Latency Testing, questionnaire data collection including Epworth Sleepiness Scale (ESS), and morning phlebotomy for biochemical markers. Linear regression was used to assess the association of mean sleep latency (MSL) and ESS (and other reported outcomes) with adjustment of age or body mass index or left ventricular ejection fraction (LVEF) (beta coefficients, 95% confidence interval) and also with biochemical markers (beta coefficients, 95% confidence interval). RESULTS: The final analytic sample comprised 26 participants: 52 ± 14 years with apnea-hypopnea index (AHI): 34 ± 27, LVEF: 34 ± 12%, MSL: 7 ± 5 minutes and ESS: 7 (5, 10). There was no significant association of MSL and ESS (-0.36, -0.81 to 0.09, P = .11), AHI, or other questionnaire-based outcomes in adjusted analyses. Although statistically significant associations of ESS and biomarkers were not observed, there were associations of MSL and cortisol (µg/dL) [-0.05: -0.08, -0.01, P = .012] and interleukin-6 (pg/mL) [-0.11: -0.18, -0.04, P = .006], which persisted in adjusted models. CONCLUSIONS: In systolic HF, although overall objective sleepiness was observed, this was not associated with subjective sleepiness (ie, a discordance was identified). Differential upregulation of systemic inflammation in objective sleepiness was observed, findings not observed with subjective sleepiness. These findings suggest that underlying mechanistic pathways of inflammation may provide the explanation for dissonance of objective and subjective sleepiness symptoms in HF, thus potentially informing targeted diagnostic and therapeutic approaches. COMMENTARY: A commentary on this article appears in this issue on page 1369.

Wake up to sleep: The effects of lacosamide on daytime sleepiness in adults with epilepsy.

OBJECTIVE: The objective of the study was to investigate the effects of lacosamide (LCM) on daytime sleepiness ascertained by the Epworth Sleepiness Scale (ESS) in adults with focal epilepsy in a randomized, controlled design. METHODS: Subjects taking ≤2 AEDs for ≥4weeks underwent polysomnography with EEG followed by the maintenance of wakefulness test (MWT) and completed the ESS and other patient-reported outcomes (PROs) at baseline, LCM 200mg/day, and LCM 400mg/day (Visit 4; V4). Primary endpoint was ESS change (V4 to baseline) between LCM and placebo. Noninferiority test on ESS used a one-sided t-test based on a hypothesized difference of 4-point change between groups. Superiority test used a two-sided t-test to investigate the difference in change in PROs and MWT mean sleep latency (MSL) between groups. Fifty-five subjects provided 80% power to show noninferiority of LCM assuming 10% dropout. RESULTS: Fifty-two subjects (mean age: 43.5±13.2years, 69% female, median monthly seizure frequency: 1 [0, 4.0]) participated. Baseline group characteristics including age, sex, ethnicity, standardized AED dose, seizure frequency, and ESS were similar. Abnormal baseline ESS scores were found in 35% of subjects. Noninferiority test found a ≤4-point increase in ESS (mean [95% CI]) in LCM subjects vs. placebo (-1.2 [-2.9, 0.53] vs. -1.1 [-5.2, 3.0], p=0.027) at V4. No significant difference in change in PROs, MSL, seizure frequency, or AED standardized dose was observed between groups. SIGNIFICANCE: Our interventional trial found that LCM is not a major contributor to daytime sleepiness based on subjective and objective measures. Inclusion of sleepiness measures in AED trials is warranted given the high prevalence of sleep-wake complaints in people with epilepsy.

Severity of self-reported insomnia in adults with epilepsy is related to comorbid medical disorders and depressive symptoms.

BACKGROUND: Few studies have systematically investigated insomnia in adults with epilepsy. METHODS: We performed a prospective cross-sectional investigation of the prevalence, severity, and comorbidities of insomnia in 90 adults with epilepsy using a battery of self-reported instruments and polysomnography. We quantified insomnia severity using the Insomnia Severity Index (ISI). RESULTS: Fifty-nine of 90 (65.5%) adults with epilepsy reported insomnia (ISI≥8), moderate or severe (ISI≥15) in 28.9%. Good agreement between standard clinical diagnostic criteria and ISI was found for patients with ISI scores <8 and ≥15. Scores on the modified Beck Depression Inventory (mBDI) (r=0.25, p=0.021), the original BDI (r=0.32, p=0.002), and self-reported total sleep duration (TSD) (r=-0.3, p=0.006) were significantly related to ISI score. A multiple regression model found that decreased TSD (ß=-0.93, p=0.007), head trauma (ß=4.37, p=0.003), sedative-hypnotic use (ß=4.86, p=0.002), AED polytherapy (ß=3.52, p=0.005), and asthma/COPD (ß=3.75, p=0.014) were predictors of a higher ISI score. For 63 patients with focal epilepsy, an increased mBDI (ß=0.24, p=0.015), decreased TSD (ß=-1.11, p=0.008), asthma/COPD (ß=4.19, p=0.02), and epilepsy surgery (ß=5.33, p=0.006) were significant predictors of an increased ISI score. Patients with temporal lobe epilepsy (TLE) showed a trend for greater severity compared with those with extra-TLE (ß=-2.92, p=0.054). CONCLUSIONS: Our findings indicate that severity of insomnia in adults with epilepsy is more likely to be associated with comorbid medical and depressive symptoms and less likely to be directly related to epilepsy. Good agreement between standard clinical diagnostic criteria for insomnia and the ISI for subjects without insomnia symptoms and for those with moderate-to-severe symptoms supports the use of this instrument in epilepsy research.

Prevalence of Undetected Sleep Apnea in Patients Undergoing Cardiovascular Surgery and Impact on Postoperative Outcomes.

STUDY OBJECTIVE: We examined the prevalence of obstructive sleep apnea (OSA) among patients undergoing cardiac surgery and its impact on postoperative outcomes. METHODS: Subjects were recruited from inpatient cardiovascular surgery units at two tertiary care centers. Crystal Monitor 20-H recorded polysomnograms preoperatively. Regression analyses were performed to explore associations between OSA using different apnea-hypopnea index (AHI) cutoffs and postoperative outcomes adjusting for key covariates. Prevalence of postoperative outcomes was compared among groups defined by AHI and left ventricle ejection fraction (LVEF) median cutoffs. RESULTS: Of 107 participants, the AHI was ≥ 5 in 79 (73.8%), ≥ 10 in 63 (58.9%), ≥ 15 in 51(47.7%), and ≥ 30 in 29 (27.1%). Patients with AHI ≥ 15 had significantly lower LVEF (p < 0.001). Logistic regression analyses with OSA cutoffs as above adjusting for age, gender, race, BMI, and LVEF found no significant increase in odds for any postoperative outcomes. No significant differences were found in %Total sleep time (TST) with SpO2 < 90% between AHI or LVEF groups, or by presence/absence of complications. Patients with any amount of TST with SpO2 < 90% had greater BMI, longer OR tube time, and greater prevalence of prolonged intubation (p = 0.007, 0.035, 0.038, respectively). CONCLUSIONS: OSA is highly prevalent in patients undergoing cardiovascular surgery. It could not be shown that OSA was significantly associated with adverse postoperative outcomes, but this may have been due to an insufficient number of subjects. AHI ≥ 15 was associated with lower LVEF. Larger samples are required to explore the impact of OSA on key postoperative outcomes that have clinical and economic importance in the care of cardiovascular surgery populations. COMMENTARY: A commentary on this article appears in this issue on page 1081.

Impact of sleep duration on seizure frequency in adults with epilepsy: a sleep diary study.

BACKGROUND: Prolonged sleep deprivation activates epileptiform EEG abnormalities and seizures in people with epilepsy. Few studies have addressed the effect of chronic partial sleep deprivation on seizure occurrence in populations with epilepsy. We tested the primary hypothesis that partial sleep deprivation over 24- and 72-hour periods increases seizure occurrence in adults with epilepsy. METHODS: Forty-four subjects completed a series of self-reported instruments, as well as 1-month sleep and seizure diaries, to characterize their sleep and quality of life. Diaries were used to determine the relationship between seizure occurrence and total sleep time 24 and 72h before seizure occurrence using random effects models and a logistic regression model fit by generalized estimating equations. RESULTS: A total of 237 seizures were recorded during 1295 diary days, representing 5.5±7.0 (mean±SD) seizures per month. Random effects models for 24- and 72-hour total sleep times showed no clinically or statistically significant differences in the total sleep time between preseizure periods and seizure-free periods. The average 24-hour total sleep time during preseizure 24-hour periods was 8min shorter than that during seizure-free periods (p=0.51). The average 72-hour total sleep time during preseizure periods was 20min longer than that during seizure-free periods (p=0.86). The presence of triggers was a significant predictor of seizure occurrence, with stress/anxiety noted most often as a trigger. Mean total sleep time was 9h, and subjects took an average of 12±10 naps per month, having a mean duration of 1.9±1.2h. Daytime sleepiness, fatigue, and insomnia symptoms were commonly reported. CONCLUSIONS: Small degrees of sleep loss were not associated with seizure occurrence in our sample of adults with epilepsy. Our results also include valuable observations of the altered sleep times and frequent napping habits of adults with refractory epilepsy and the potential contribution of these habits to quality of life and seizure control.

Effect of positive airway pressure therapy on seizure control in patients with epilepsy and obstructive sleep apnea.

Previous studies suggest that treatment for obstructive sleep apnea (OSA) in patients with epilepsy can improve seizure control. We investigated the effect of positive airway pressure (PAP) therapy on seizures in adults with epilepsy referred to the Cleveland Clinic for polysomnography (PSG) from 1997 to 2010. Seizure outcome at baseline and 1 year later was compared in patients with no OSA (apnea-hypopnea index [AHI] <5), patients with PAP-treated OSA, and patients with untreated OSA. One hundred thirty-two subjects (age: 40.2±13 (18-76) years, 65.4% female) were included. Seventy-six (57.6%) subjects had OSA; of these, 43 (56.6%) were on PAP therapy, and 33 (43.4%) were not on PAP therapy (either PAP-intolerant or refused therapy). Of the group with PAP-treated OSA, 83.7% were adherent (use ≥4 h/night at least 5 nights/week). The percentage of subjects with ≥50% seizure reduction and the mean percentage of seizure reduction were significantly greater in the group with PAP-treated OSA (73.9%; 58.5%) than in subjects with untreated OSA (14.3%; 17.0%). There were significantly more subjects with successful outcomes (with ≥50% seizure reduction or seizure-free at both baseline and follow-up) in the group with PAP-treated OSA (83.7%) than in the groups with no OSA (53.6%) and untreated OSA (39.4%). After adjusting for age, gender, body mass index, AHI, and epilepsy duration, we found that the odds of successful outcomes in subjects in the group with PAP-treated OSA were 9.9 and 3.91 times those of the groups with untreated OSA and no OSA, respectively. The group with PAP-treated OSA had 32.3 times the odds of having a ≥50% seizure reduction compared with the group with untreated OSA and 6.13 times compared with the group with no OSA. Positive airway pressure therapy appears to produce beneficial effects on seizures in adult patients with epilepsy and OSA.

Continuous positive airway pressure therapy for obstructive sleep apnea reduces interictal epileptiform discharges in adults with epilepsy.

Obstructive sleep apnea (OSA) is highly prevalent, affecting 25% of men and 10% of women. We recently reported a prevalence of OSA of 30% among 130 adults with epilepsy unselected for sleep disorder complaints, including 16% with moderate-to-severe disease, rates that markedly exceed general population estimates. Treatment of OSA with continuous positive airway pressure (CPAP) therapy or upper airway surgery reduces seizures in many cases. A single study reported a reduction in interictal spike rate with CPAP in 6 patients with OSA. We explored the effect of CPAP therapy on spike rate in 9 adults with epilepsy and OSA. Interictal epileptiform discharges were quantified during a diagnostic polysomnogram (PSG) and a second PSG using therapeutic CPAP. Spike rates were calculated for each recording during wake and sleep stages. Continuous positive airway pressure therapy was associated with significant reductions in median (quartiles) spike rate overall (77.9 [59.7-90.7] %), in wakefulness (38.5 [0.3-55] %), and in sleep (77.7 [54.8-94.7] %) but not in REM sleep. Continuous positive airway pressure therapy also produced a significant improvement in oxygen saturation and arousals. Our work extends a single prior observation demonstrating beneficial effects of CPAP therapy on interictal EEG in patients with epilepsy with comorbid OSA and supports the hypothesis that sleep fragmentation due to OSA contributes to epileptogenicity.

Use of the Sleep Apnea Scale of the Sleep Disorders Questionnaire (SA-SDQ) in adults with epilepsy.

OBJECTIVE: A growing body of literature supports the importance of sleep comorbidities in epilepsy. The prevalence of obstructive sleep apnea (OSA) in adults with epilepsy exceeds that of the general population, and its presence adversely impacts seizure control in some cases. The Sleep Apnea Scale of the Sleep Disorders Questionnaire (SA-SDQ) is a 12-item screening instrument generally used in clinical research. One prior study suggested modified cutoffs for the prediction of OSA in adults with epilepsy using this instrument. Our purpose was to further investigate the validity of the SA-SDQ in adults with epilepsy. METHODS: Ninety adults with epilepsy who underwent polysomnography (PSG) completed the SA-SDQ. Receiver operating characteristics were constructed to assess optimal sensitivity and specificity for predicting OSA (apnea-hypopnea index [AHI]≥5). RESULTS: Obstructive sleep apnea was diagnosed in 40 (44.4%) subjects. The overall area under the curve for the diagnosis of OSA was 0.771 (0.926 for males, 0.687 for females). For all subjects, a SA-SDQ cutoff score of 25 provided good sensitivity (73%) and specificity (72%) for OSA diagnosis. The same cutoff score provided optimal sensitivity (94%) and specificity (83%) for males, whereas for females, it provided lower sensitivity (55%) and specificity (68%). In females, a cutoff of 24 improved sensitivity (68%) but not specificity (58%). For all subjects with moderate-to-severe OSA (AHI≥15), the area under the curve was 0.766, and the optimal cutoff was 28. SIGNIFICANCE: Our work confirms the validity of the SA-SDQ as a screening instrument for OSA in clinical research involving adults with epilepsy. Further, our findings support the use of cutoffs lower than those applied to the general population and a single cutoff score (25) for predicting any severity of OSA in adults with epilepsy.

Sleep apnea and epilepsy: who's at risk?

Obstructive sleep apnea (OSA) is highly prevalent, affecting 25% of men and 10% of women. Treatment reduces seizures in some patients. Awareness of the comorbidity of sleep disturbances in epilepsy has been increasing. No study has explored OSA predictors in patients unselected for epilepsy severity and sleep disorder symptoms. We assessed cross-sectional OSA prevalence and predictors (apnea-hypopnea index [AHI] ≥10) in 130 consecutive adults using structured interview, subjective assessments, and polysomnography. Obstructive sleep apnea prevalence was 30%, 16% having moderate-severe disease, rates that markedly exceed general population estimates. Obstructive sleep apnea predictors in multivariate modeling included age, dental problems, and standardized AED dose. Male gender, older age, higher BMI, hypertension, and dental problems were associated with higher AHI. Adults with epilepsy appear at increased risk for OSA, increasing with age and AED load, regardless of gender, BMI, and seizure frequency. These findings support the implementation of routine OSA screening in adult epilepsy clinics.

Functional outcomes in patients with REM-related obstructive sleep apnea treated with positive airway pressure therapy.

STUDY OBJECTIVES: To evaluate functional outcomes in adults with REM-related obstructive sleep apnea (OSA) treated with positive airway pressure (PAP) therapy. DESIGN: Retrospective observational study. SETTING: Outpatient sleep clinic. PATIENTS: 330 adults (171 males) with OSA receiving PAP therapy, including 130 with REM OSA and 200 with OSA not restricted to REM. MEASUREMENTS AND RESULTS: REM OSA was defined as a REM apnea-hypopnea index (AHI) / NREM AHI > 2 and NREM AHI < 15. Patients had baseline and post-PAP functional outcomes, including Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Patient Health Questionnaire-9 (PHQ-9), and Functional Outcomes Sleep Questionnaire (FOSQ) scores. We compared functional outcomes, demographic, clinical and polysomnographic features, and PAP adherence in patients with REM OSA and OSA not restricted to REM. Female gender was significantly more common in REM OSA. Age, BMI, neck girth, and baseline ESS, FSS, PHQ-9, and FOSQ were similar between groups. Smoking history and comorbid disorders were also similar except for a higher prevalence of depression and cardiovascular disease in OSA not restricted to REM. All functional outcomes improved significantly after PAP therapy in both groups. Change from baseline to post treatment was similar for all functional outcomes between groups. CONCLUSIONS: The study is the first addressing clinical outcomes in REM OSA using validated measures. Functional outcomes in patients with REM OSA improve after treatment with PAP therapy comparable to that observed in patients with OSA not restricted to REM. COMMENTARY: A commentary on this article appears in this issue on page 249.