A reduction of sleep spindles heralds seizures in focal epilepsy

ObjectivesSleep has profound effects on epilepsy. It may alter the occurrence of interictal discharges (IEDs) and seizures. Vice versa, an active epilepsy changes sleep. Sleep spindles are typically associated with an increase of IEDs. We examined whether seizures change the number and power of spindles preceding nightly seizures.MethodsWe retrospectively examined the nightly EEG recordings of presurgical epilepsy patients from our EEG-video-monitoring unit. We evaluated the 200 s before the EEG seizure onset for spindle density (spindles per minute) and spindle power and compared that to the interictal baseline sleep.ResultsThe spindle density and the spindle power decreased significantly before the first seizure. The reduction before secondarily generalized seizures (8.7 ± 2.5; p = 0.001) was more pronounced than before focal seizures (10.5 ± 2.5; p = 0.003) compared to baseline (12.2 ± 2.7). This finding was more pronounced in extratemporal lobe epilepsies than in temporal lobe epilepsies. The reduction of spindle power was also significant and was more pronounced in XTLE. These results were consistent for all other seizures during sleep, the mean spindle density decreased significantly in all focal (10.2 ± 1.9; p = 0.001) and generalized preictal period (8.8 ± 2.4; p = 0.001) compared to the mean interictal period (12.1 ± 2.1). These were also more significant in XTLE than TLE group.ConclusionsOur data demonstrate that the occurrence of seizures and propensity of seizure generalisation in focal epilepsy is modulated by specific characteristics of light sleep such as sleep spindles.SignificanceThis study supports the notion that changes in the epileptic network precede the seizure onset and have an influence on seizure generation and termination.     

Functional MRI of sleep spindles and K-complexes

ObjectiveSleep spindles and K-complexes are EEG hallmarks of non-REM sleep. However, the brain regions generating these discharges and the functional connections of their generators to other regions are not fully known. We investigated the neuroanatomical correlates of spindles and K-complexes using simultaneous EEG and fMRI.MethodsEEGs recorded during EEG-fMRI studies of 7 individuals were used for fMRI analysis. Higher-level group analyses were performed, and images were thresholded at Z ? 2.3.ResultsfMRI of 106 spindles and 60 K-complexes was analyzed. Spindles corresponded to increased signal in thalami and posterior cingulate, and right precuneus, putamen, paracentral cortex, and temporal lobe. K-complexes corresponded to increased signal in thalami, superior temporal lobes, paracentral gyri, and medial regions of the occipital, parietal and frontal lobes. Neither corresponded to regions of decreased signal.ConclusionsfMRI of both spindles and K-complexes depicts signal subjacent to the vertex, which likely indicates each discharges’ source. The thalamic signal is consistent with thalamic involvement in sleep homeostasis. The limbic region’s signal is consistent with roles in memory consolidation. Unlike the spindle, the K-complex corresponds to extensive signal in primary sensory cortices.SignificanceIdentification of these active regions contributes to the understanding of sleep networks and the physiology of awareness and memory during sleep.     

Spindles insufficiency in sleepwalkers’ deep sleep

ObjectivesSleepwalkers have consistently shown N3 sleep discontinuity, especially after sleep deprivation. In healthy subjects, sleep spindles activity has been positively correlated to sleep stability. We aimed to compare spindles density during N3 sleep between sleepwalkers and healthy controls.MethodsTwo cohorts of 10 and 21 adult sleepwalkers respectively controlled with 10 and 18 healthy volunteers underwent one baseline and one recovery sleep recording after 38 h (cohort 1) and 25 h (cohort 2) of sleep deprivation. For the two recordings, we performed an automatic detection of spindles (11–16 Hz) from EEG signal during N3 sleep, restricted to the first sleep cycle and repeated for all cycles. For better interpretation of results, we extended the analysis to N2 sleep and we also measured the density of slow waves oscillation (SWO) (0.5–4 Hz) during the same periods.ResultsCompared to controls, sleepwalkers showed significantly lower spindle densities during N3 sleep considering the first sleep cycle (both cohorts) or all cycles (cohort 1). SWO densities did not differ (cohort 1) or were lower (cohort 2) for sleepwalkers. The effect of sleep deprivation did not interact with the effect of group on spindles and SWO densities.ConclusionThis work suggests that the instability of N3 sleep inherent to sleepwalkers may be underpinned by a specific alteration of spindles activity.     

Clinical and polysomnographic characteristics and response to continuous positive airway pressure therapy in obstructive sleep apnea patients with nightmares

ObjectiveTo assess the characteristics of obstructive sleep apnea (OSA) patients with nightmares and the effects of continuous positive airway pressure (CPAP) therapy on nightmares.MethodsConsecutive patients referred with a clinical suspicion of OSA underwent attended overnight sleep studies. OSA and nightmares were diagnosed according to the American Academy of Sleep Medicine (AASM) criteria, and CPAP titration was performed in accordance with the AASM guidelines. A follow-up visit was performed 3 months later, and the patients with nightmares were divided into two groups: group 1 used CPAP with good compliance, whereas group 2 refused CPAP treatment and did not use other alternative treatments for OSA.ResultsThe study included 99 patients who had been diagnosed with OSA with nightmares. Their mean age was 47.2 ± 11.2 years, and they had a mean apnea–hypopnea index (AHI) of 36.5 ± 34.3/h. Also included were 124 patients with OSA without nightmares. The mean age of these patients was 45.4 ± 13.9 years, and they had a mean AHI of 40.2 ± 35/h. The patients with nightmares had a significantly higher AHI during rapid eye movement sleep (REM) compared with the patients without nightmares (51.7 ± 28.1 vs 39.8 ± 31.9/h). Logistic regression analysis revealed that the REM-AHI and interrupted sleep at night were independent predictors of nightmares in the OSA patients. Nightmares disappeared in 91% of the patients who used CPAP compared with 36% of patients who refused to use CPAP (p < 0.001).ConclusionNightmares in OSA patients are associated with a higher REM-AHI. CPAP therapy results in a significant improvement in nightmare occurrence.     

Continuous positive airway pressure deepens sleep in patients with Alzheimer’s disease and obstructive sleep apnea

ObjectivePatients with Alzheimer’s disease (AD) and obstructive sleep apnea (OSA) experience disrupted sleep. This study examined the effect of continuous positive airway pressure (CPAP) on sleep parameters in AD patients with OSA.MethodsA randomized placebo-controlled trial of 3 weeks of therapeutic CPAP (tCPAP) vs. 3 weeks placebo CPAP (pCPAP) followed by 3 weeks tCPAP in patients with AD and OSA. Polysomnography data from screening after one night and after 3 weeks of treatment were analyzed. Records were scored for percent of each sleep stage, total sleep time (TST), sleep efficiency (SE), sleep period (SP), time in bed (TIB), sleep onset (SO), wake time after sleep onset (WASO), and arousals. A randomized design comparing one night of pCPAP to tCPAP and a paired analysis combining 3 weeks of tCPAP were performed.ResultsFifty-two participants (mean age = 77.8 years, SD = 7.3) with AD and OSA were included. After one treatment night, the tCPAP group had significantly less % Stage 1 (p = 0.04) and more % Stage 2 sleep (p = 0.02) when compared to the pCPAP group. In the paired analysis, 3 weeks of tCPAP resulted in significant decreases in WASO (p = 0.005), % Stage 1 (p = 0.001), arousals (p = 0.005), and an increase in % Stage 3 (p = 0.006).ConclusionIn mild to moderate AD patients with OSA, the use of tCPAP resulted in deeper sleep after just one night, with improvements maintained for 3 weeks.     

Age,drugs, or disease: What alters the macrostructure of sleep in Parkinson’s disease?

ObjectiveTo describe the alterations in the macrostructure of sleep in a large cohort of sleep-disturbed patients with Parkinson’s disease (PD) and investigate influencing factors.MethodsA cohort of sleep-disturbed but otherwise unselected PD patients (n = 351) was investigated with video-supported polysomnography. We analyzed the influence of age, disease duration, disease severity, and dopaminergic medication on subjective sleep perception, sleep efficiency, the amount of slow wave sleep, awakenings, periodic leg movements in sleep (PLMS), and REM sleep behavior disorder (RBD).ResultsSleep efficiency and slow wave sleep decreased with age (p = 0.003 and p = 0.041, respectively). The number of awakenings and the frequency of RBD increased with age (p = 0.028 and p = 0.006, respectively). Higher Hoehn & Yahr stages were associated with more PLMS (p = 0.017). A higher daily dose of levodopa corresponded to more RBD (p < 0.001). Neither disease duration nor levodopa dosage had any influence on sleep efficiency, slow wave sleep, awakenings, or PLMS. Dopamine agonists increased awakenings (p < 0.001) and lowered PLMS (p < 0.001). Subjective sleep perception was not influenced by any of the factors analyzed. The only path model that could be replicated identified disease severity and dopamine agonists as interdependent factors influencing awakenings and PLMS.ConclusionAge leads to less sleep and a higher risk for RBD, and disease severity increases motor phenomena such as PLMS; dopamine agonists reduce PLMS but increase awakenings. No single factor analyzed influenced subjective sleep perception in this cohort of sleep disturbed PD patients.     

Association between body mass index and sleep duration assessed by objective methods in a representative sample of the adult population

IntroductionSleep duration has been associated with overweight individuals in many epidemiological studies; however, few studies have assessed sleep using objective methods. Our study was designed to evaluate the association between body mass index (BMI) and sleep duration measured by actigraphy (Acti), polysomnography (PSG) and the Pittsburgh Sleep Quality Index questionnaire (PSQIO). Furthermore, we evaluated other biochemical and polysomnographic parameters.MethodsA representative sample of 1042 individuals from Sao Paulo, Brazil, including both genders (20–80 yrs), participated in our protocol. Weight and other anthropometric parameters were measured at the onset of the study. Sleep duration was calculated by Acti, PSG, and the PSQIQ. The population was sorted by sleep duration, body, slow wave sleep (SWS) and REM sleep (REMS) duration subsets. In addition, other biochemical and polysomnographic parameters were analyzed. Differences between population subsets were analyzed by one-way analysis of variance (ANOVA). Linear regression analysis was performed between sleep and anthropometric parameters.ResultsShorter sleep duration was associated with higher BMI and waist and neck circumference when measured by Acti and PSG (p < 0.05). Lower leptin levels were associated with short sleep in normal-weight (BMI > 18 and ⩽25) individuals (p < 0.01). The association between short sleep duration Acti and higher BMI was present when apnea-hypopnea index (AHI) was less than 15 (p = 0.049). Shorter REMS and SWS also were associated with higher BMI (p < 0.01). Normal-weight individuals tended to sleep longer, have higher sleep efficiency and longer SWS and REMS than obese individuals (Acti, PSG; p = 0.05). Sleep duration was negatively correlated with BMI (Acti, PSG; p < 0.05). Short SWS and REMS were associated with higher cardiovascular risk factors (p < 0.05).ConclusionShorter sleep, SWS, and REMS duration were associated with higher BMI, central adiposity measurements, and cardiovascular risk factors when measured by objective methods.     

Sleep maintenance insomnia complaints predict poor CPAP adherence: A clinical case series

BackgroundAlthough CPAP is a highly efficacious treatment for obstructive sleep apnea (OSA), low adherence presents a significant challenge for sleep medicine clinicians. The present study aimed to evaluate the relationship between insomnia symptoms and CPAP use. We hypothesized that pre-treatment insomnia complaints would be associated with poorer CPAP adherence at clinical follow-up.MethodsThis was a retrospective chart review of 232 patients (56.5% men, mean age = 53.6 ± 12.4 years) newly diagnosed with OSA (mean AHI = 41.8 ± 27.7) and prescribed CPAP in the Johns Hopkins Sleep Disorder Center. Difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening were measured via three self-report items. CPAP use was measured via objective electronic monitoring cards.ResultsThirty-seven percent of the sample reported at least one frequent insomnia complaint, with 23.7% reporting difficulty maintaining sleep, 20.6% reporting early morning awakening and 16.6% reporting difficulty initiating sleep. After controlling for age and gender, sleep maintenance insomnia displayed a statistically significant negative relationship with average nightly minutes of CPAP use (p < .05) as well as adherence status as defined by the Centers for Medicaid and Medicare Services (p < .02).ConclusionsTo our knowledge, these are the first empirical data to document that insomnia can be a risk factor for poorer CPAP adherence. Identifying and reducing insomnia complaints among patients prescribed CPAP may be a straightforward and cost-effective way to increase CPAP adherence.     

The effect of childhood obstructive sleep apnea on ambulatory blood pressure is modulated by the distribution of respiratory events during rapid eye movement and nonrapid eye movement sleep

ObjectiveWe aimed to investigate if different childhood obstructive sleep apnea (OSA) subtypes, namely rapid eye movement (REM)-related, nonrapid eye movement (NREM)-related and stage-independent OSA would exert different effects on ambulatory blood pressure (ABP).MethodsData from our previous school-based cross-sectional study were reanalyzed. Subjects who had an obstructive apnea–hypopnea index (OAHI) between 1 and 10 events per hour and a total REM sleep duration of >30 min were included in our analysis. REM-related and NREM-related OSA were defined as a ratio of OAHI in REM sleep (OAHI_REM) to OAHI in NREM sleep (OAHI_NREM) of >2 and <0.5, respectively. The others were classified as stage-independent OSA.ResultsA total of 162 subjects were included in the analysis. In the mild OSA (OAHI, 1–5 events/h) subgroup, no significant differences in any ABP parameters were found between OSA subtypes. On the other hand, in subjects with moderate OSA (OAHI, 5–10 events/h), the REM-related OSA subtype had a significantly lower daytime systolic blood pressure (SBP) z score (−0.13 ± 0.90 cf 1.15 ± 0.67; P = .012) and nighttime SBP z score (0.29 ± 1.06 cf 1.48 ± 0.88, P = .039) than the stage-independent OSA subtype. Linear regression analyses revealed that OAHI_NREM but not OAHI_REM was significantly associated with both daytime (P = .008) and nighttime SBP (P = .042) after controlling for age, gender, and body size.ConclusionChildren with obstructive events mainly in REM sleep may have less cardiovascular complications than those with stage-independent OSA.     

Restless legs syndrome in end-stage renal disease: Clinical characteristics and associated comorbidities

BackgroundDespite being frequently described in patients with end-stage renal disease (ESRD), clinical characteristics and comorbidities in association with restless legs syndrome (RLS) are still to be confirmed.ObjectivesThe aim of this study was to investigate clinical factors associated with RLS in ESRD patients in hemodialysis.MethodsThis is a cross-sectional study of 400 patients on hemodialysis, evaluating RLS, clinical features and other sleep abnormalities.ResultsOut of 400, 86 patients presented RLS (21.5%; mean age 48.8 ± 13.8 y), being more frequent in females (p < 0.005). Forty-eight individuals (12% mean age 50.7 ± 13.1 y) had moderate/severe RLS, 14 reported symptoms prior to hemodialysis, 13 described family history of RLS, and eight described symptoms as disturbing during dialysis. RLS cases showed lower hemoglobin (p < 0.005), poorer quality of sleep (Pittsburgh Sleep Quality Index >5, p = 0.002), higher scores on the Beck Depression Inventory Scale (p < 0.005), greater scores on the Charlson Comorbidity Index (p = 0.01) and the Epworth Sleepiness Scale (p = 0.001) and higher risk of obstructive sleep apnea (OSA; Berlin questionnaire, p = 0.01). Hypertension was more frequent in cases with moderate/severe RLS (p = 0.01) and remained after controlling for the risk of OSA (p = 0.02).ConclusionIn ESRD patients in hemodialysis, RLS is present in 21.5%; 16% report symptoms prior to hemodialysis and a family history of RLS. Symptoms are disturbing during hemodialysis in 9% of cases. RLS is associated with lower hemoglobin, worse sleep quality, excessive daytime sleepiness, depressive symptoms and higher risk of OSA. Hypertension is associated with moderate/severe RLS.     

The effects of pregabalin on sleep disturbance symptoms among individuals with fibromyalgia syndrome

ObjectivesSleep disturbances are common in patients with fibromyalgia (FM). The objective of this analysis was to evaluate the effects of pregabalin on sleep in patients with FM.MethodsAnalyses were based on two randomized, double-blind, placebo-controlled trials of pregabalin (300 mg, 450 mg, and 600 mg daily) in adult FM patients. Sleep outcomes included the Medical Outcomes Study (MOS) Sleep Scale and a daily diary assessment of sleep quality. Treatment effects were evaluated using analysis of covariance. Clinically important differences (CID) in the Sleep Quality Diary and MOS Sleep Disturbance scores were estimated using mixed-effects models of changes in scores as a function of patients’ global impressions of change. Mediation modeling was used to quantify the direct treatment effects on sleep in contrast to indirect influence of the treatment on sleep via pain.ResultsA total of 748 and 745 patients were randomized in the respective studies. Patients were predominantly Caucasian females, average age 48–50 years, on average had FM for 9–10 years, and experienced moderate to severe baseline pain. Pregabalin significantly improved the Sleep Quality Diary (P < 0.001), MOS Sleep Disturbance (P < 0.01), MOS Quantity of Sleep (P < 0.003), and MOS Sleep Problems Index scores (P < 0.02) relative to placebo. Treatment effects for the 450 mg and 600 mg groups exceeded the estimated CID thresholds of 0.83 and 7.9 for the Sleep Quality Diary and MOS Sleep Disturbance scores, respectively. Mediation models indicated that 43–80% of the benefits on sleep (versus placebo) were direct effects of pregabalin, with the remainder resulting from an indirect effect of treatment via pain relief.ConclusionsThese data demonstrate improvement in FM-related sleep dysfunction with pregabalin therapy. The majority of this benefit was a direct effect of pregabalin on the patients’ insomnia, while the remainder occurred through the drug’s analgesic activity.     

Sleep apnea increased incidence of primary central nervous system cancers: a nationwide cohort study

IntroductionObstructive sleep apnea (OSA) was associated with increased incidence of all cancers. We aimed to determine the risk for primary central nervous system (CNS) cancers in patients with sleep apnea syndrome.MethodsA total of 23,055 incident cases of newly diagnosed sleep apnea syndrome (sleep apnea group) were identified between 2000 and 2003 in the medical claims database of Taiwan’s National Health Institute (NHI) program and were matched by age and gender to patients without OSA (comparison group) in the same period. The occurrence of primary malignant CNS cancers was measured 2 years after the index date over a 10-year period.ResultsThe incidence density of primary CNS cancers (per 10,000 individual-years) was 2.14 and 1.28, respectively, for the OSA and comparison groups. The overall risk for developing primary CNS cancers was significantly higher in the OSA group (adjusted hazard ratio [HR], 1.54; P = 0.046) after adjusting for age, gender, and obesity, among other variables. Subgroup analysis revealed a significantly higher risk for primary brain cancers but not primary spinal cord cancers in the OSA subgroup (adjusted HR, 1.71; P = 0.027). The analysis also revealed a significantly higher risk for primary CNS cancers in the insomnia with OSA subgroup (adjusted HR, 2.20; P = 0.001) and in the OSA without surgical treatment subgroup (adjusted HR, 1.831; P = 0.003).ConclusionsOSA, especially with insomnia, may increase the risk for primary CNS cancer development, though surgical treatment may reduce this risk in participants with OSA.     

The effect of sildenafil on sleep respiratory parameters and heart rate variability in obstructive sleep apnea

ObjectiveTo evaluate the magnitude of effects of sildenafil on respiratory parameters and heart rate variability (HRV) in slow wave sleep (SWS) and REM sleep of patients with severe obstructive sleep apnea (OSA).MethodsThirteen male patients with untreated severe OSA (aged 43 ± 10 years, body mass index of 26.7 ± 1.9 kg/m²) were studied on two nights, one with sildenafil 50 mg and one with a placebo, in a double-blind, randomized fashion. All-night polysomnography and HRV were simultaneously recorded. Short-term HRV measures were performed in apnea-free intervals. Respiratory parameters were separately assessed in non-REM and REM sleep and compared to total sleep time (TST). Short-term HRV analysis was conducted in samples with regular respiration obtained in SWS and REM sleep.ResultsComparing to placebo, during sildenafil night there was an increase in apnea–hypopnea index (AHI) in TST and also in non-REM and REM sleep. Increase in central AHI occurred in non-REM sleep; increase in obstructive AHI and decrease in oxyhemoglobin saturation occurred in both non-REM and REM sleep. Additionally, an increase in arousal index and in low/high frequency component of HRV ratio (LF/HF) was significant only in REM sleep. Correlation between sleep architecture and respiratory parameters were more frequent in non-REM sleep for placebo and in REM sleep for sildenafil.ConclusionIn severe OSA, the use of sildenafil 50 mg at bedtime plays a detrimental role on respiratory parameters in both non-REM and REM sleep, fragmentation in REM sleep, and a prolonged increase in LH/HF component of HRV after resumption of ventilation.     

Impaired blood pressure control in children with obstructive sleep apnea

BackgroundObstructive sleep apnea (OSA) in adults has been associated with hypertension, low baroreflex sensitivity (BRS), a delayed heart rate response to changing blood pressure (heart period delay [HPD]), and increased blood pressure variability (BPV). Poor BRS may contribute to hypertension by impairing the control of blood pressure (BP), with increased BPV and HPD. Although children with OSA have elevated BP, there are scant data on BRS, BPV, or HPD in this group.Methods105 children ages 7–12 years referred for assessment of OSA and 36 nonsnoring controls were studied. Overnight polysomnography (PSG) was performed with continuous BP monitoring. Subjects were assigned to groups according to their obstructive apnea–hypopnea index (OAHI): primary snoring (PS) (OAHI ⩽1 event/h), mild OSA (OAHI > 1–⩽5 events/h) and moderate/severe (MS) OSA (OAHI > 5 events/h). BRS and HPD were calculated using cross spectral analysis and BPV using power spectral analysis.ResultsSubjects with OSA had significantly lower BRS (p < .05 for both) and a longer HPD (PS and MS OSA, p < .01; mild OSA, p < .05) response to spontaneous BP changes compared with controls. In all frequencies of BPV, the MS group had higher power compared with the control and PS groups (low frequency [LF], p < .05; high frequency [HF], p < .001).ConclusionsOur study demonstrates reduced BRS, longer HPD, and increased BPV in subjects with OSA compared to controls. This finding suggests that children with OSA have altered baroreflex function. Longitudinal studies are required to ascertain if this dampening of the normal baroreflex response can be reversed with treatment.     

Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

BackgroundThe angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity.MethodsMale OSA patients (apnea-hypopnea index [AHI] > 5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping.ResultsWe studied 266 males with OSA (age = 48 ± 13y, body mass index = 29 ± 5kg/m², AHI = 34 ± 25events/h). HTN was present in 114 patients (43%) who were older (p < 0.01), heavier (p < 0.05) and had more severe OSA (p < 0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p < 0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast, the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR = 1.12) and II genotype (OR = 0.27).ConclusionsOur results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe OSA.     

Prognostic implication of obstructive sleep apnea diagnosed by post-discharge sleep study in patients presenting with acute coronary syndrome

ObjectiveWe aimed to determine the prognostic implications of obstructive sleep apnea (OSA) diagnosed during the recovery phase of acute coronary syndrome (ACS).MethodsPatients presenting with ACS and treated with percutaneous coronary intervention were recruited prospectively for a home-based sleep study within 30 days of hospital discharge. Major adverse cardiac and cerebrovascular events (MACCEs) assessed included cardiac death, myocardial infarction, stroke, unplanned revascularization, and hospitalization for heart failure.ResultsOf the 85 patients recruited, 68 successfully completed the study. The median time from percutaneous coronary intervention to sleep study was 14 days (interquartile range: 7.5–27 days). OSA was diagnosed in 24 patients (35.3%) (apnea–hypopnea index ⩾15). A drug-eluting stent was implanted into the target lesion in 45 patients (66.2%). None of the study patients had received treatment for OSA. At 24-month follow-up, the MACCE incidence was 34.9% in the OSA group and 5.1% in the non-OSA group (P = 0.008, log-rank test). After adjusting for the possible confounding effect of age, gender, coronary intervention indications, hypertension, smoking, and body mass index, OSA remained an independent predictor of MACCEs (adjusted hazard ratio, 6.95; 95% confidence interval, 1.17–41.4; P = 0.033).ConclusionOSA diagnosed in patients treated with percutaneous coronary intervention for ACS by post-discharge sleep studies conducted 2 weeks after percutaneous coronary intervention was independently associated with MACCEs at 24-month follow-up.     

Obstructive sleep apnea and neurocognitive performance: the role of cortisol

BackgroundObstructive sleep apnea (OSA) is a prevalent disorder with multiple consequences including negative effects on neurocognitive function. Several domains of cognitive function are impaired in OSA patients, but the mechanisms through which this sleep disorder results in impairment are not clear. Given the well-known effects of cortisol on cognitive function, in particular memory, the dysregulating effects of OSA on cortisol levels are hypothesized as a potential pathway leading to cognitive impairment.MethodsFifty-five participants with OSA (mean apnea-hypopnea index [AHI], 30.3) were assessed over 2 days. Over a 24-h period, blood samples were collected every 2 h to examine cortisol levels. The following night, sleep was monitored with polysomnography (PSG). Participants were given a battery of neurocognitive tests, which assessed seven cognitive domains.ResultsOSA severity assessed by oxygen desaturation index (ODI) was associated with 24-h cortisol levels. AHI, ODI, and nighttime cortisol levels were associated with global deficit scores (GDS) in cognitive functioning, particularly in domains of learning, memory, and working memory (P < .05 for all). Hierarchical linear regression analysis revealed that nighttime cortisol accounted for 9–16% of variance in learning (P = .018), memory (P = .003), and working memory (P = .016) domains, though apnea severity did not significantly predict any additional variance.ConclusionsIn our sample of patients with OSA, nocturnal cortisol levels were associated with neuropsychologic functioning above and beyond the influence of covariates and apnea severity. These findings suggest that OSA-related alterations in cortisol activity may partially explain the pathophysiology of neuropsychologic impairments in sleep apnea.     

Functional respiratory imaging as a tool to assess upper airway patency in children with obstructive sleep apnea

ObjectiveWe aim to investigate if anatomical and functional properties of the upper airway using computerized 3D models derived from computed tomography (CT) scans better predict obstructive sleep apnea (OSA) severity than standard clinical markers.MethodsConsecutive children with suspected OSA underwent polysomnography, clinical assessment of upper airway patency, and a CT scan while awake. A three-dimensional (3D) reconstruction of the pharyngeal airway was built from these images, and computational fluid dynamics modeling of low inspiratory flow was performed using open-source software.ResultsThirty-three children were included (23 boys; mean age, was 6.0 ± 3.2 y). OSA was diagnosed in 23 patients. Children with OSA had a significantly lower volume of the overlap region between tonsils and the adenoids (median volume, 1408 mm compared to 2173 mm; p = 0.04), a lower mean cross-sectional area at this location (median volume, 69.3 mm² compared to 114.3 mm²; p = 0.04), and a lower minimal cross-sectional area (median volume, 17.9 mm² compared to 25.9 mm²; p = 0.05). Various significant correlations were found between several imaging parameters and the severity of OSA, most pronounced for upper airway conductance (r = −0.46) (p < 0.01) for correlation between upper airway conductance and the apnea-hypopnea index. No differences or significant correlations were observed with clinical parameters of upper airway patency. Preliminary data after treatment showed that none of the patients with residual OSA had their smallest cross-sectional area located in segment 3, and this frequency was significantly lower than in their peers whose sleep study normalized (64%; p = 0.05).ConclusionFunctional imaging parameters are highly correlated with OSA severity and are a more powerful correlate than clinical scores of upper airway patency. Preliminary data also showed that we could identify differences in the upper airway of those subjects who did not benefit from a local upper airway treatment.     

Relationship between delta power and the electrocardiogram-derived cardiopulmonary spectrogram: possible implications for assessing the effectiveness of sleep

ObjectivesThe physiologic relationship between slow-wave activity (SWA) (0–4 Hz) on the electroencephalogram (EEG) and high-frequency (0.1–0.4 Hz) cardiopulmonary coupling (CPC) derived from electrocardiogram (ECG) sleep spectrograms is not known. Because high-frequency CPC appears to be a biomarker of stable sleep, we tested the hypothesis that that slow-wave EEG power would show a relatively fixed-time relationship to periods of high-frequency CPC. Furthermore, we speculated that this correlation would be independent of conventional nonrapid eye movement (NREM) sleep stages.MethodsWe analyzed selected datasets from an archived polysomnography (PSG) database, the Sleep Heart Health Study I (SHHS-I). We employed the cross-correlation technique to measure the degree of which 2 signals are correlated as a function of a time lag between them. Correlation analyses between high-frequency CPC and delta power (computed both as absolute and normalized values) from 3150 subjects with an apnea-hypopnea index (AHI) of ⩽5 events per hour of sleep were performed.ResultsThe overall correlation (r) between delta power and high-frequency coupling (HFC) power was 0.40 ± 0.18 (P = .001). Normalized delta power provided improved correlation relative to absolute delta power. Correlations were somewhat reduced in the second half relative to the first half of the night (r = 0.45 ± 0.20 vs r = 0.34 ± 0.23). Correlations were only affected by age in the eighth decade. There were no sex differences and only small racial or ethnic differences were noted.ConclusionsThese results support a tight temporal relationship between slow wave power, both within and outside conventional slow wave sleep periods, and high frequency cardiopulmonary coupling, an ECG-derived biomarker of “stable” sleep. These findings raise mechanistic questions regarding the cross-system integration of neural and cardiopulmonary control during sleep.     

MRI of the pharynx in ischemic stroke patients with and without obstructive sleep apnea

BackgroundObstructive sleep apnea (OSA) is common after stroke and associated with poor stroke outcomes. Whether OSA after acute stroke is caused by anatomic, physiologic, or both etiologies has not been studied. We therefore used brain magnetic resonance imaging (MRI) scans to assess oropharyngeal anatomy in stroke patients with and without OSA.MethodsPatients within 7 days of ischemic stroke underwent nocturnal polysomnography. Sagittal T1-weighted MRI performed for clinical purposes was used to measure retropalatal distance, soft palatal length, soft palatal thickness, retroglossal space, and tongue length. Nasopharyngeal area and high retropharyngeal area were measured from axial T2-weighted images, and lateral pharyngeal wall thickness from coronal T1-weighted images.ResultsAmong 27 subjects, 18 (67%) had OSA (apnea/hypopnea index (AHI) ? 5). Demographics, vascular risk factors, and stroke severity were similar in the two groups. Median retropalatal distance was shorter in subjects with OSA (Wilcoxon rank-sum test, p = 0.03). Shorter retropalatal distance was associated with higher AHI (linear regression, p = 0.04). None of the other morphological characteristics differed.ConclusionsAnatomic difference between awake acute stroke patients with and without OSA shows that the sleep disorder cannot be attributed solely to sleep, sleeping position, or changes in neuromuscular control that are specific to the sleep state.