SLEEP

Lawati, Nabil M. Al; Ayas, Najib T.

doi: 10.1093/sleep/31.6.772pmid: 18548820

Guilleminault, Christian; Hagen, Chad C.; Khaja, Aliuddin M.

doi: 10.1093/sleep/31.6.774pmid: 18548821

Desseilles, Martin; Dang-Vu, Thanh; Schabus, Manuel; Sterpenich, Virginie; Maquet, Pierre; Schwartz, Sophie

doi: 10.1093/sleep/31.6.777pmid: 18548822

AbstractNeuroimaging methods can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. However, it is still unclear how these new data might improve our understanding of the pathophysiology underlying adult sleep disorders. Here we review functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). The studies reviewed include neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy), metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging), and ligand marker measurements.Based on the current state of the research, we suggest that brain imaging is a useful approach to assess the structural and functional correlates of sleep impairments as well as better understand the cerebral consequences of various therapeutic approaches. Modern neuroimaging techniques therefore provide a valuable tool to gain insight into possible pathophysiological mechanisms of sleep disorders in adult humans.

Hla, Khin Mae; Young, Terry; Finn, Laurel; Peppard, Paul E.; Szklo-Coxe, Mariana; Stubbs, Maryan

doi: 10.1093/sleep/31.6.795pmid: 18548823

AbstractStudy objectives:The association of sleep-disordered breathing (SDB) and blunting of normal nocturnal lowering of blood pressure (BP) (nondipping) has only been examined cross-sectionally. The purpose of this study is to investigate whether SDB is prospectively associated with nondipping.Methods:The longitudinal association between SDB and incident nondipping was examined in a subsample of 328 adults enrolled in the Wisconsin Sleep Cohort Study who completed 2 or more 24-hour ambulatory BP studies over an average of 7.2 years of follow-up. SDB identified by baseline in-laboratory polysomnography was defined by apnea-hypopnea index (AHI) categories. Systolic and diastolic nondipping was defined by systolic and diastolic sleep-wake BP ratios > 0.9. All models were adjusted for age, sex, body mass index at baseline and follow-up, smoking, alcohol consumption, hypertension, sleep time, length of follow-up time, and antihypertensive medication use.Results:There was a dose-response increased odds of developing systolic nondipping in participants with SDB. The adjusted odds ratios (95% confidence interval) of incident systolic nondipping for baseline AHI 5 to < 15 and AHI ≥ 15, versus AHI <5, were 3.1 (1.3–7.7) and 4.4 (1.2–16.3), respectively (P trend = 0.006). The adjusted odds ratios (95% confidence interval) of incident diastolic nondipping for corresponding SDB categories were not statistically significant: 2.0 (0.8–5.6) and 1.3 (0.2–7.1).Conclusions:Our longitudinal findings of a dose-response increase in development of systolic nondipping of BP with severity of SDB at baseline in a population-based sample provide evidence consistent with a causal link. Nocturnal systolic nondipping may be a mechanism by which SDB contributes to increased cardiovascular disease.

Janszky, Imre; Ljung, Rickard; Rohani, Morteza; Hallqvist, Johan

doi: 10.1093/sleep/31.6.801pmid: 18548824

AbstractStudy Objectives:Sleep disordered breathing has been associated with an increased risk for developing coronary heart disease. Data on the effects of sleep disordered breathing on case fatality and prognosis of a myocardial infarction are sparse. The present study aimed to investigate a possible relationship of snoring and case fatality and mortality after an acute myocardial infarction.Design, Settings, Patients, and Measurements:In this study, we enrolled 1660 first acute myocardial infarction cases and examined the effects of self- or relative-reported heavy snoring on case fatality and prognosis. The average follow-up time was 8 years, SD = 262 days.results:There was a variation in the association between snoring and mortality with time, with a strong association in the first 28 days after infarction but not later during the follow-up. Occasional and regular heavy snorers, when compared to those never having heavy snoring, had a 2.04 (95% confidence interval, 1.50 to 2.79) and 3.30 (95% confidence interval, 2.37 to 4.58) hazard ratio for mortality within the first 28 days after controlling for age, gender, obesity, history of diabetes and hypertension, physical activity, smoking, and education, respectively. There was no association between snoring and new myocardial infarction, stroke, or hospitalization for heart failure during the follow-up.Conclusions:Heavy snoring is associated with case fatality and short-term mortality in patients with a first acute myocardial infarction.

Hamilton, Garun S.; Solin, Peter; Walker, Adrian

doi: 10.1093/sleep/31.6.809pmid: 18548825

AbstractStudy Objectives:Patients with obstructive sleep apnea (OSA) and coronary artery disease have a poor long-term prognosis. It is unknown whether the coronary blood flow (CBF) response to OSA is appropriate for myocardial metabolic requirements. Therefore, CBF was assessed during OSA, before and after the development of coronary artery endothelial dysfunction.Setting:University Hospital Animal Laboratory.Patients or participants:Newborn lambs.Interventions:Lambs were surgically instrumented for invasive hemodynamic monitoring and sleep-wake EEG recordings. A tracheostomy was inserted to control the upper airway and model OSA during sleep. Coronary artery endothelial dysfunction was created using infusions of lipopolysaccharide (LPS). The CBF response during OSA was assessed and compared to changes in myocardial work (rate-pressure product [RPP]), O2 saturation, and cortical arousal, before and after the LPS infusions.Measurements and results:During OSA, CBF increased by 8.6% ± 2.4% above baseline in the pre-LPS condition and 8.8% ± 1.9% post-LPS, peaking following termination of the respiratory event. Pre-LPS, change in CBF post-apnea was independently correlated with change in RPP (R2 = 0.50), minimum SpO2 (R2 = 0.11) and the presence of cortical arousal (R2 = 0.04) (P < 0.01, forward stepwise regression analysis). Following LPS, the only predictor of CBF was degree of O2 desaturation (R2 = 0.14, P < 0.05).Conclusion:Under baseline conditions, CBF correlates well with myocardial work following the termination of apnea in lambs. After the creation of coronary artery endothelial dysfunction with LPS, there is uncoupling of the normal CBF-myocardial work relationship.

Sundquist, Jan; Li, Xinjun; Friberg, Danielle; Hemminki, Kari; Sundquist, Kristina

doi: 10.1093/sleep/31.6.817pmid: 18548826

AbstractBackground:Understanding the genetic transmission of obstructive sleep apnea syndrome (OSAS) will help clinicians identify patients at risk and offer opportunities for intervention and treatment at specialist clinics.Objective:To estimate familial risk of hospitalization for OSAS in the adult population of Sweden, and to determine if there are any differences by age and sex.Design, setting, and participants:Using the MigMed database at the Karolinska Institute, we divided the population of Sweden into sibling groups based on a shared mother and father and ascertained the presence or absence of a primary hospital diagnosis of OSAS in each individual during the follow-up period, 1997 to 2004. Individuals were categorized as having or not having a sibling with OSAS, based on the presence or absence of the disorder in at least 1 of their siblings. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were estimated for men and women with a sibling with OSAS, compared with men and women in the reference group (SIR = 1).Results:After accounting for socioeconomic status, age, geographic region, and period of diagnosis, men with at least 1 sibling who had OSAS had a SIR of 3.42 (95% CI, 2.18–5.36); the corresponding SIR in women was 3.25 (95% CI, 1.84–5.65).Conclusions:Our results indicate that physicians should consider family history of OSAS when deciding whether to refer a patient for further sleep examinations.

Marshall, Nathaniel S.; Yee, Brendon J.; Desai, Anup V.; Buchanan, Peter R; Wong, Keith KH; Crompton, Renee; Melehan, Kerri L; Zack, Nadene; Rao, Srinivas G; Gendreau, R. Michael; Kranzler, Jay; Grunstein, Ronald R.

Wulbrand, Henning; McNamara, Frances; Thach, Bradley T.

doi: 10.1093/sleep/31.6.833pmid: 18548828

AbstractDuring obstructive sleep apnea (OSA) in adults upper airway reopening coincides with a sudden burst in activity of pharyngeal dilating muscles. This has been attributed to arousal from sleep as indicated by increased EEG activity. Recovery from OSA in infants often occurs in the absence of cortical arousal. To investigate mechanisms involved in recovery, we performed experimental airway occlusions in sleeping infants. Based on past work, our hypothesis was that a sleep startle combined with an augmented breath and heart rate acceleration would occur during the occlusion, and that such brainstem mediated reflexes might provide an explanation for recovery from OSA in the absence of cortical arousal. However, this is contrary to expectations, since lung inflation is believed to be necessary for occurrence of an augmented breath.We studied 16 healthy infants during sleep. We recorded EEG, EOG, ECG, oxygen saturation, diaphragmatic, nuchal and limb electromyograms, face mask pressure, and airflow. A startle, accompanied by neck extension, limb and nuchal EMG activation, as well as heart rate acceleration occurred during all airway occlusions. The startle occurred simultaneously with a large biphasic inspiratory effort, having characteristics of an augmented breath (sigh). In more than a third of cases, this occurred without any evidence of cortical arousal activity. The magnitude of startles as well as the increase in heart rate correlated positively with peak airway negative pressure, indicating that arousal processes are graded in intensity. We conclude that the neck extension and pharyngeal dilating muscle activity associated with the startle and augmented breath may account for recovery of airway patency in infants as they do adults. Lung inflation is not a prerequisite for the reflex to occur.

Earley, Christopher J.; Ponnuru, Padmavathi; Wang, Xinsheng; Patton, Stephanie M.; Connor, James R.; Beard, John L.; Taub, Dennis D.; Allen, Richard P.

doi: 10.1093/sleep/31.6.847pmid: 18548829

AbstractObjective:Studies using cerebrospinal fluid, magnetic resonance imaging, and autopsy tissue have implicated a primary role for brain iron insufficiency in restless legs syndrome (RLS). If the abnormalities of brain iron regulation reflect a basic disturbance of iron metabolism, then this might be expressed at least partially in some peripheral systems. Thus the study aim was to determine whether patients with RLS and control subjects show differences in lymphocyte iron regulator proteins.Methods:Fasting morning blood samples were used to obtain common serum measures of iron status and to determine lymphocyte iron management proteins. Twenty-four women with early-onset RLS and 25 control women without RLS symptoms were studied.Results:RLS and control subjects were matched for age, hemoglobin, and serum iron profile. However, transferrin receptor (TfR) and DMT1 (divalent metal transporter 1 protein) levels in lymphocytes were significantly higher for RLS patients than for controls. No significant differences in ferritin subtypes or transferrin levels were found. No significant correlations were found between lymphocyte and serum indices of iron status.Interpretation:RLS lymphocytes showed an increase in ferroportin, implying increased cellular iron excretion, in the face of increased iron need (increased TfR and DMT1). In the absence of changes in H-ferritin, the findings indicate a balance between input and output with no net iron change but probable overall increase in iron turnover. The lack of any significant correlation between serum and lymphocyte iron indices indicates that iron management proteins from lymphocytes are at a minimum an alternative and independent marker of cellular iron metabolism.