Lateralized neonatal EEG coherence during sleep predicts language outcome.

BACKGROUND: Enriched language exposure may benefit infants in the neonatal intensive care unit. We hypothesized that changes in neonatal electroencephalogram (EEG) coherence during sleep, in response to maternal voice exposure, predict language development. METHODS: Convalescent neonates underwent 12-h polysomnography. A recording of the mother's voice was randomized to continuous playback in the first or second 6 h. We calculated the imaginary coherence (ICOH-a measure of functional connectivity) between EEG leads. Spearman correlations were computed between ICOH and 18-month Bayley-III language scores. RESULTS: Thirty-five neonates were included (N = 18 33-to-<35 weeks gestation; N = 17 ≥ 35 weeks). Predictive value of ICOH during neonatal non-rapid eye movement (NREM) sleep was left lateralized, and varied with gestational age and voice playback. ICOH in the left-hemispheric (C3-Cz; T3-Cz) channels across multiple EEG frequency bands was associated with 18-month language scores (rho = -0.34 to -0.48). The association was driven by neonates born at 33-34 weeks gestation, and a trend suggested a possible effect of maternal voice at some EEG frequencies. Right hemisphere ICOH (C4-Cz; T4-Cz) was not associated with language outcome. CONCLUSIONS: Left-hemispheric EEG functional connectivity during neonatal NREM sleep shows early signs of physiologic asymmetry that may predict language development. We speculate that sleep analyses could have unique prognostic value. IMPACT: During neonatal NREM sleep, EEG functional connectivity predicts future language development. Left temporal and central EEG coherence-specifically the imaginary component of coherence-is predictive, whereas the same analysis from the right hemisphere is not. These results appear to vary according to the infant's gestational age, and a trend suggests they may be enhanced by measuring functional connectivity during exposure to the mother's voice. These findings identify early evidence of physiologic differentiation within the cerebral hemispheres and raise the possibility that neonatal NREM sleep has a role to play in language development.

Novel metrics of sleep-disordered breathing are associated with outcome after ischemic stroke.

OBJECTIVE/BACKGROUND: Standard measures of sleep-disordered breathing (SDB) that rely on count data may not sufficiently capture SDB severity or reflect downstream consequences of SDB. We hypothesized that novel metrics derived from pulse rate, oxygen saturation, and nasal pressure would be associated with stroke outcomes. PATIENTS/METHODS: Shortly after ischemic stroke, participants in a population-based study were offered ApneaLink Plus testing. Signal analysis was used to generate 166 metrics from the nasal pressure cannula and finger probe, categorized as: autonomic (based on pulse rate variability), oximetry-derived, nasal pressure-derived, and mixed oxygen and nasal pressure-derived measures. Three-month outcome assessments included functional and cognitive outcomes and stroke recurrence. Tobit regression and Cox proportional hazards models were used to examine associations between each sleep apnea metric and the three outcomes, unadjusted and adjusted for multiple potential confounders. Models were adjusted for multiple comparisons. RESULTS: Of the 530 participants, the median age was 65 (IQR: 57, 73), 49 % were female, and 64 % were Mexican American. Without covariate adjustment, 23 of 166 variables were associated with functional outcome, 43 were associated with cognitive outcome, and 1 was associated with stroke recurrence. After adjustment, 7 mixed, oximetry, or nasal pressure-based metrics and 1 autonomic metric were associated with functional outcome, but none was associated with cognitive outcome or stroke recurrence. CONCLUSIONS: Many novel metrics of SDB were associated with important stroke outcomes, and 8 novel metrics were associated with functional outcome in adjusted models. This raises hypotheses about pathways by which SDB may negatively impact stroke outcomes.

Sleep stage dynamics differ between children with and without obstructive sleep apnea.

STUDY OBJECTIVES: Analysis of sleep dynamics--distributions of contiguous sleep and sleep stage durations--reveal exponential distributions and potential clinical utility in adults. We sought to examine these polysomnographic variables for the first time in children, and in the context of childhood sleep disordered breathing (SDB). DESIGN AND SETTING: Analysis of polysomnographic data available from the Washtenaw County Adenotonsillectomy Cohort. PARTICIPANTS: Selected subjects were 48 children aged 5-12 years with SDB (pediatric apnea/hypopnea index > or = 1.5) who were scheduled for adenotonsillectomy and 20 control subjects of similar ages without SDB. Subjects were studied at enrollment and again one year later in almost all cases. RESULTS: Durations of sleep and specific sleep stage bouts generally followed exponential distributions. At baseline, the number of sleep stage changes, proportion of total sleep time occupied by stage 1 sleep, proportion stage 2 sleep, mean stage 2 duration, and mean stage REM duration each distinguished subjects with and without SDB (P < 0.05), but only mean stage 2 duration did so independently after accounting for the other variables (P = 0.03). At one-year follow-up, changes in total sleep time, mean stage 2 duration, and mean stage REM duration distinguished SDB from control subjects, but again only changes in mean stage 2 duration did so independently (P = 0.01). CONCLUSIONS: Durations of uninterrupted sleep and specific sleep stages appear to follow exponential distributions in children with or without SDB. Parameters that describe these distributions--particularly mean duration of stage 2 sleep periods--may provide useful additions to standard sleep stage analyses.

Maternal Voice and Infant Sleep in the Neonatal Intensive Care Unit.

BACKGROUND: Approximately 10% of US newborns require a NICU. We evaluated whether the NICU acoustic environment affects neonatal sleep and whether exposure to the mother's voice can modulate that impact. METHODS: In a level IV NICU with single-infant rooms, 47 neonates underwent 12-hour polysomnography. Their mothers were recorded reading children's books. Continuous maternal voice playback was randomized to either the first or second 6 hours of the polysomnogram. Regression models were used to examine sleep-wake stages, entropy, EEG power, and the probability of awakening in response to ambient noise during and without voice playback. RESULTS: After epochs with elevated noise, the probability was higher with (versus without) maternal voice exposure of neonates staying asleep (P = .009). However, the 20 neonates born at ≥35 weeks' gestation, in contrast to those born at 33 to 34 weeks, showed an age-related increase in percent time awake (R 2 = 0.52; P < .001), a decrease in overall sleep (R 2 = 0.52; P < .001), a reduction in rapid eye movement sleep bouts per hour (R 2 = 0.35; P = .003), and an increase in sleep-wake entropy (R 2 = 0.52; P < .001) all confined solely to the 6 hours of maternal voice exposure. These associations remained significant (P = .02 to P < .001) after adjustment for neurologic examination scores and ambient noise. CONCLUSIONS: Hospitalized newborns born at ≥35 weeks' gestation but not at 33 to 34 weeks' gestation show increasing wakefulness in response to their mother's voice. However, exposure to the mother's voice during sleep may also help protect newborns from awakening after bursts of loud hospital noise.

Respiratory cycle-related EEG changes during sleep reflect esophageal pressures.

STUDY OBJECTIVES: Respiratory cycle-related EEG changes (RCREC) have been demonstrated during sleep by digital analysis and hypothesized to represent subtle inspiratory microarousals that may help to explain daytime sleepiness in patients with sleep-disordered breathing. We therefore examined for the first time associations between RCREC and esophageal pressure swings (deltaPes) that reflect work of breathing. DESIGN: Retrospective analysis. SETTING: Academic sleep laboratory. PATIENTS: Forty adults referred for suspected sleep disordered breathing. INTERVENTIONS: Polysomnography with esophageal pressure monitoring and automatic computation of deltaPes using a novel algorithm. RESULTS: Computed deltaPes for nearly all respiratory cycles during sleep correlated well with visual scoring of selected respiratory cycle samples (Spearman rho = 0.86, P < 0.0001). The RCREC within the sigma EEG range (12.5-15.5 Hz) rather than that within other frequency ranges most often showed significant within-subject inverse correlations with deltaPes. In contrast, in between-subject comparisons, beta (15.5-30.5 Hz) and to a lesser extent theta (4.5-7.5 Hz) RCREC, rather than sigma RCREC, showed significant inverse associations with mean APes. CONCLUSIONS: Variation within subjects of sigma RCREC with APes supports previous evidence that RCREC within this range may reflect microarousals exacerbated by increased work of breathing. Correlation of beta and theta, but not sigma RCREC with deltaPes in between-subject comparisons is more difficult to explain but suggests that ranges other than sigma also deserve further investigation for clinical utility.

Sleep stage dynamics in fibromyalgia patients and controls.

OBJECTIVE: To determine whether previously described sleep stage dynamics, reflecting the mean duration of specific sleep stages, may have clinical utility in a sample of patients with fibromyalgia syndrome (FMS) and controls. METHODS: Women with FMS (n=15, screened to exclude other sleep disorders) and age-matched women in good health (n=15) were studied with nocturnal polysomnography, multiple sleep latency tests, 2-week pain diaries, and a measure of current pain intensity. RESULTS: The FMS subjects, in comparison to controls, did not show differences in several common polysomnographic measures, except for increased numbers of stage shifts (126+/-27 vs. 107+/-22, p=.042). Mean durations for episodes of total sleep, stage 1 sleep, stage 3/4 sleep, and rapid eye movement sleep failed to distinguish FMS and control subjects (Wilcoxon rank sum tests, p>.10 for each), but those for stage 2 sleep were shorter in the FMS subjects (p=.006), possibly because transitions to stage 3/4 sleep occurred more quickly (p=.036). Shorter stage 2 sleep durations predicted higher pain diary scores (Spearman rho=-.56, p=.0014) and current pain intensity (rho=-.71, p<0.0001). CONCLUSIONS: Sleep stage dynamic, and, more specifically, shorter durations of sleep stage 2 periods, distinguish FMS and control female subjects and may predict pain levels experienced in FMS. Analysis of the lengths of individual sleep stages, in addition to the usual sleep stage amounts and percentages listed in standard polysomnogram reports, may have clinical utility.

EMG variance during polysomnography as an assessment for REM sleep behavior disorder.

STUDY OBJECTIVES: In a previous study, we validated a polysomnographic assessment for REM sleep behavior disorder (RBD). The method proved to be reliable but required slow, labor-intensive visual scoring of surface electromyogram (EMG) activity. We therefore developed a computerized metric to assess EMG variance and compared the results to those previously published for visual scoring, bed partner-rated RBD symptom scores, and clinical assessments by sleep medicine specialists. DESIGN: Retrospective validation of new computer algorithm. SETTING: Sleep research laboratory PARTICIPANTS: Twenty-three subjects: 17 with neurodegenerative disorders (9 with probable or possible RBD), and 6 controls. INTERVENTIONS: N/A METHODS: We visually scored 2 consecutive nocturnal polysomnograms for each subject. A computer algorithm calculated the variance of the chin EMG during all 3-second mini-epochs, and compared variances during REM sleep to a threshold defined by variances during quiet NREM sleep. The percentage of all REM mini-epochs with variance above this threshold created a metric, which we refer to as the supra-threshold REM EMG activity metric (STREAM) for each subject. RESULTS: The STREAM correlated highly with the visually-derived score for RBD severity (Spearman rho = 0.87, P < 0.0001). A clinical impression of probable or possible RBD was associated to a similar extent with both STREAM (Wilcoxon rank sum test, P = 0.009) and the visually-derived score (P = 0.018). An optimal STREAM cutoff identified probable or possible RBD with 100% sensitivity and 71% specificity. The RBD symptom score correlated with both STREAM (rho = 0.42, P = 0.046) and the visual score (rho = 0.42, P = 0.048). CONCLUSIONS: These results suggest that a new, automated assessment for RBD may provide as much utility as a more time-consuming manual approach.

Neonatal Sleep-Wake Analyses Predict 18-month Neurodevelopmental Outcomes.

Objectives: The neurological examination of critically ill neonates is largely limited to reflexive behavior. The exam often ignores sleep-wake physiology that may reflect brain integrity and influence long-term outcomes. We assessed whether polysomnography and concurrent cerebral near-infrared spectroscopy (NIRS) might improve prediction of 18-month neurodevelopmental outcomes. Methods: Term newborns with suspected seizures underwent standardized neurologic examinations to generate Thompson scores and had 12-hour bedside polysomnography with concurrent cerebral NIRS. For each infant, the distribution of sleep-wake stages and electroencephalogram delta power were computed. NIRS-derived fractional tissue oxygen extraction (FTOE) was calculated across sleep-wake stages. At age 18-22 months, surviving participants were evaluated with Bayley Scales of Infant Development (Bayley-III), 3rd edition. Results: Twenty-nine participants completed Bayley-III. Increased newborn time in quiet sleep predicted worse 18-month cognitive and motor scores (robust regression models, adjusted r2 = 0.22, p = .007, and 0.27, .004, respectively). Decreased 0.5-2 Hz electroencephalograph (EEG) power during quiet sleep predicted worse 18-month language and motor scores (adjusted r2 = 0.25, p = .0005, and 0.33, .001, respectively). Predictive values remained significant after adjustment for neonatal Thompson scores or exposure to phenobarbital. Similarly, an attenuated difference in FTOE, between neonatal wakefulness and quiet sleep, predicted worse 18-month cognitive, language, and motor scores in adjusted analyses (each p < .05). Conclusions: These prospective, longitudinal data suggest that inefficient neonatal sleep-as quantified by increased time in quiet sleep, lower electroencephalogram delta power during that stage, and muted differences in FTOE between quiet sleep and wakefulness-may improve prediction of adverse long-term outcomes for newborns with neurological dysfunction.

Subjective sleepiness and polysomnographic correlates in children scheduled for adenotonsillectomy vs other surgical care.

STUDY OBJECTIVE: To compare a validated subjective measure of childhood sleepiness to an objective determination, assess the frequency of problematic sleepiness among children with suspected sleep-disordered breathing (SDB), and examine what standard or investigational polysomnographic measures of SDB predict subjective sleepiness. DESIGN: Prospective, cross-sectional. SETTING: University-based sleep disorders laboratory. PARTICIPANTS: Washtenaw County Adenotonsillectomy Cohort. INTERVENTION: Polysomnography followed by Multiple Sleep Latency Tests (MSLTs) in 103 children aged 5 to 12 years old: 77 were scheduled for clinically indicated adenotonsillectomy, usually for suspected SDB, and 26 for unrelated surgical care. Parents completed the previously validated, 4-item Pediatric Sleep Questionnaire-Sleepiness Subscale (PSQ-SS). RESULTS: Thirty-three (43%) of the children scheduled for adenotonsillectomy had high PSQ-SS scores, in comparison with only 3 (12%) of the controls (p = .004). The PSQ-SS scores correlated inversely with mean sleep latencies on the MSLTs (rho = -0.23, p = .006). The obstructive apnea index, apnea-hypopnea index, and respiratory disturbance index (which included respiratory event-related arousals identified by esophageal pressure monitoring) each correlated similarly with PSQ-SS scores, as did investigational quantification of esophageal pressures and respiratory cycle-related electroencephalographic changes (each rho approximately 0.30, p < .02). A stepwise regression identified sigma-frequency respiratory cycle-related electroencephalographic changes as the strongest independent predictor of subjective sleepiness among all subjects and particularly among those without obstructive sleep apnea. CONCLUSIONS: Sleepiness is a frequent problem among children with suspected SDB. Subjective sleepiness (PSQ-SS) reflects MSLT results to a limited extent, as in adults. Standard polysomnographic measures of SDB predict subjective sleepiness, but respiratory cycle-related electroencephalographic changes may offer additional clinical utility.

Method for detection of respiratory cycle-related EEG changes in sleep-disordered breathing.

STUDY OBJECTIVES: In sleep-disordered breathing (SDB), visual or computerized analysis of electroencephalogram (EEG) signals shows that disruption of sleep architecture occurs in association with apneas and hypopneas. We developed a new signal analysis algorithm to investigate whether brief changes in cortical activity can also occur with individual respiratory cycles. DESIGN: Retrospective. SETTING: University sleep laboratory. PARTICIPANTS: A 6 year-old boy with SDB. INTERVENTION: Polysomnography before and after clinically indicated adenotonsillectomy. MEASUREMENTS: For the first 3 hours of nocturnal sleep, a computer algorithm divided nonapneic respiratory cycles into 4 segments and, for each, computed mean EEG powers within delta, theta, alpha, sigma, and beta frequency ranges. Differences between segment-specific EEG powers were tested by analysis of variance. Respiratory cycle-related EEG changes (RCREC) were quantified. RESULTS: Preoperative RCREC were statistically significant in delta (P < .0001), theta (P < .001), and sigma (P < .0001) but not alpha or beta (P > .01) ranges. One year after the operation, RCREC in all ranges showed statistical significance (P < .01), but delta, theta, and sigma RCREC had decreased, whereas alpha and beta RCREC had increased. Preoperative RCREC also were demonstrated in a sequence of 101 breaths that contained no apneas or hypopneas (P < .0001). Several tested variations in the signal-analysis approach, including analysis of the entire nocturnal polysomnogram, did not meaningfully improve the significance of RCREC. CONCLUSIONS: In this child with SDB, the EEG varied with respiratory cycles to a quantifiable extent that changed after adenotonsillectomy. We speculate that RCREC may reflect brief but extremely numerous microarousals.

Correlates of respiratory cycle-related EEG changes in children with sleep-disordered breathing.

STUDY OBJECTIVES: To explore newly-identified respiratory cycle-related electroencephalographic changes (RCREC), which may represent microarousals, as correlates of neurobehavioral outcomes in children with sleep-disordered breathing (SDB). DESIGN: Retrospective. SETTING: University sleep laboratory. PARTICIPANTS: Ten research subjects, aged 6 to 10 years, with and without SDB. INTERVENTION: Polysomnography, Multiple Sleep Latency Tests, and tests of auditory attention before and after clinically-indicated tonsillectomy (n = 9) or hernia repair (n = 1, control). MEASUREMENTS: For the first 3 hours of nocturnal sleep, a computer algorithm quantified the degree to which delta, theta, and alpha electroencephalographic power varied within non-apneic respiratory cycles. Correlations between the RCREC and standard objective measures of SDB, sleepiness, and attention were explored. RESULTS: Five children had SDB (> 1 obstructive apnea per hour of sleep). Preoperative delta, theta, or alpha RCREC were statistically significant (P < .01) in all subjects except 1 without SDB and the 1 control. Theta RCREC correlated with rates of apneas and hypopneas (P = .01) and decreased after the apnea was treated. Postoperative changes in delta and theta RCREC predicted changes in Multiple Sleep Latency Test scores (rho = -0.84, P = .002; rho = -0.64, P = .05), whereas changes in rates of apneas and hypopneas did not (rho = -0.24, P = .50). Postoperative changes in attention tended to correlate with changes in delta RCREC (rho = -0.54, P = .11) more strongly than with changes in rates of apneic events (rho = -0.07, P = .84). CONCLUSIONS: The RCREC may reflect brief but numerous microarousals that could help to explain neurobehavioral consequences of SDB.

Quantitative sleep stage analyses as a window to neonatal neurologic function.

OBJECTIVE: To test the hypothesis that neonatal sleep physiology reflects cerebral dysfunction, we compared neurologic examination scores to the proportions of recorded sleep/wake states, sleep depth, and sleep fragmentation in critically ill neonates. METHODS: Newborn infants (≥35 weeks gestation) who required intensive care and were at risk for seizures were monitored with 8- to 12-hour polysomnograms (PSGs). For each infant, the distribution of sleep-wake states, entropy of the sequence of state transitions, and delta power from the EEG portion of the PSG were quantified. Standardized neurologic examination (Thompson) scores were calculated. RESULTS: Twenty-eight infants participated (mean gestational age 39.0 ± 1.6 weeks). An increased fraction of quiet sleep correlated with worse neurologic examination scores (Spearman rho = 0.54, p = 0.003), but the proportion of active sleep did not (p > 0.1). Higher state entropy corresponded to better examination scores (rho = -0.43, p = 0.023). Decreased delta power during quiet sleep, but not the power at other frequencies, was also associated with worse examination scores (rho = -0.48, p = 0.009). These findings retained significance after adjustment for gestational age or postmenstrual age at the time of the PSG. Sleep stage transition probabilities were also related to examination scores. CONCLUSIONS: Among critically ill neonates at risk for CNS dysfunction, several features of recorded sleep-including analyses of sleep stages, depth, and fragmentation-showed associations with neurologic examination scores. Quantitative PSG analyses may add useful objective information to the traditional neurologic assessment of critically ill neonates.

Sleep-wake cycling and cerebral oxygen metabolism among critically ill neonates.

Among adults, wakefulness and rapid eye movement (REM) sleep, compared to non-REM sleep, require higher overall brain metabolism, but in neonates analogous data are not available. Behavioral states with higher metabolic demand could increase vulnerability to hypoperfusion or hypoxia in the compromised neonatal brain. Using cerebral oximetry (near-infrared spectroscopy), and simultaneous polysomnography, we evaluated whether brain oxygen metabolism varies by sleep-wake state among critically ill newborns. For each of 10 infants, sleep-wake cycling was detectable and cerebral oximetry varied (P < .0001) across behavioral states, but the patterns differed among subjects. We conclude that cerebral oxygen metabolism varies with sleep-wake states in high-risk newborns. The direction and degree of these changes are variable and subject-specific in this initial sample, but could reflect or affect brain injury and vulnerability.

Do respiratory cycle-related EEG changes or arousals from sleep predict neurobehavioral deficits and response to adenotonsillectomy in children?

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory microarousals. METHODS: Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 ± 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. RESULTS: Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] ≥ 1.5, mean 8.3 ± 10.6) and 24 without OSA (AHI 0.9 ± 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p > 0.05, with only scattered exceptions, among all subjects or those with OSA). CONCLUSION: Sleep fragmentation, as reflected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT00233194.

Do snoring sounds arouse the snorer?

STUDY OBJECTIVES: Respiratory cycle-related electroencephalographic (EEG) changes (RCREC), especially in delta and sigma frequencies, are thought to reflect subtle, breath-to-breath inspiratory microarousals that are exacerbated in association with increased work of breathing in obstructive sleep apnea (OSA). We wondered whether snoring sounds could create these microarousals, and investigated whether earplugs, anticipated to alter snoring perception, might affect RCREC. DESIGN: Randomized controlled trial. SETTING: An accredited, academic sleep laboratory. PATIENTS: Adults (n = 400) referred for suspected OSA. INTERVENTIONS: Subjects were randomly assigned to use earplugs or not during a night of diagnostic polysomnography. RESULTS: Two hundred three of the participants were randomized to use earplugs. Earplug use was associated with lower RCREC in delta EEG frequencies (0.5-4.5 Hz), although not in other frequencies, after controlling for potential confounds (P = 0.048). This effect of earplug use was larger among men in comparison with women (interaction term P = 0.046), and possibly among nonobese subjects in comparison with obese subjects (P = 0.081). However, the effect of earplug use on delta RCREC did not differ significantly based on apnea severity or snoring prominence as rated by sleep technologists (P > 0.10 for each). CONCLUSIONS: This randomized controlled trial is the first study to show that perception of snoring sounds, as modulated by earplugs, can influence the cortical EEG during sleep. However, the small magnitude of effect, lack of effect on RCREC in EEG frequencies other than delta, and absence of effect modulation by apnea severity or snoring prominence suggest that perception of snoring is not the main explanation for RCREC.

The face of sleepiness: improvement in appearance after treatment of sleep apnea.

STUDY OBJECTIVES: Anecdote but no formal evidence suggests that facial appearance improves after hypersomnolent patients with obstructive sleep apnea are treated. We investigated whether masked volunteer raters can identify post- rather than pre-treatment images as looking more alert, and whether impressions are predicted by any objective changes on highly precise 3-dimensional digital photogrammetry. METHODS: Participants included 20 adults with obstructive sleep apnea on polysomnography and excessive sleepiness on Epworth Sleepiness Scales. Photogrammetry was performed before and after ≥ 2 months of adherent use of positive airway pressure. Twenty-two raters then assessed pre- and post-treatment facial images, paired side-by-side in random order. RESULTS: Subjects included 14 men and 6 women, with mean age 45 ± 11 (SD) years and mean baseline apnea/hypopnea index of 26 ± 21. The 22 raters twice as often identified post-treatment rather than pre-treatment images to look more alert (p = 0.0053), more youthful (p = 0.026), more attractive (p = 0.0068), and more likely to reflect the treated state (p = 0.015). Photogrammetry documented post-treatment decreases in forehead surface volume and decreased infraorbital and cheek redness, but no narrowing of the interpalpebral fissure. Decreased deep NREM sleep at baseline, and pre- to post-treatment decrements in facial redness showed promise as predictors of improved subjective ratings for alertness. CONCLUSIONS: Patients with obstructive sleep apnea are perceived to appear more alert, more youthful, and more attractive after adherent use of positive airway pressure. Objective changes in facial surface volume and color were identified. Post-treatment decrements in redness may inform subjective impressions of improved alertness.

Limited short-term prognostic utility of cerebral NIRS during neonatal therapeutic hypothermia.

OBJECTIVE: We evaluated the utility of amplitude-integrated EEG (aEEG) and regional oxygen saturation (rSO2) measured using near-infrared spectroscopy (NIRS) for short-term outcome prediction in neonates with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. METHODS: Neonates with HIE were monitored with dual-channel aEEG, bilateral cerebral NIRS, and systemic NIRS throughout cooling and rewarming. The short-term outcome measure was a composite of neurologic examination and brain MRI scores at 7 to 10 days. Multiple regression models were developed to assess NIRS and aEEG recorded during the 6 hours before rewarming and the 6-hour rewarming period as predictors of short-term outcome. RESULTS: Twenty-one infants, mean gestational age 38.8 ± 1.6 weeks, median 10-minute Apgar score 4 (range 0-8), and mean initial pH 6.92 ± 0.19, were enrolled. Before rewarming, the most parsimonious model included 4 parameters (adjusted R(2) = 0.59; p = 0.006): lower values of systemic rSO2 variability (p = 0.004), aEEG bandwidth variability (p = 0.019), and mean aEEG upper margin (p = 0.006), combined with higher mean aEEG bandwidth (worse discontinuity; p = 0.013), predicted worse short-term outcome. During rewarming, lower systemic rSO2 variability (p = 0.007) and depressed aEEG lower margin (p = 0.034) were associated with worse outcome (model-adjusted R(2) = 0.49; p = 0.005). Cerebral NIRS data did not contribute to either model. CONCLUSIONS: During day 3 of cooling and during rewarming, loss of physiologic variability (by systemic NIRS) and invariant, discontinuous aEEG patterns predict poor short-term outcome in neonates with HIE. These parameters, but not cerebral NIRS, may be useful to identify infants suitable for studies of adjuvant neuroprotective therapies or modification of the duration of cooling and/or rewarming.

Respiratory cycle-related EEG changes: response to CPAP.

STUDY OBJECTIVES: Respiratory cycle-related EEG changes (RCREC) quantify statistically significant synchrony between respiratory cycles and EEG spectral power, vary to some extent with work of breathing, and may help to predict sleepiness in patients with obstructive sleep apnea. This study was designed to assess the acute response of RCREC to relief of upper airway obstruction by positive airway pressure (PAP). DESIGN: Comparison of RCREC between baseline diagnostic polysomnograms and PAP titration studies. SETTING: Accredited academic sleep disorders center. PATIENTS: Fifty adults referred for suspected sleep disordered breathing. INTERVENTIONS: For each recording, the RCREC in specific physiologic EEG frequency ranges were computed as previously described for the last 3 h of sleep not occupied by apneic events. RESULTS: The sample included 27 women; mean age was 47 ± 11 (SD) years; and median respiratory disturbance index at baseline was 24 (inter-quartile range 15-43). Decrements in RCREC, from baseline to PAP titration, reached 43%, 24%, 14%, 22%, and 31% for delta (P = 0.0004), theta (P = 0.01), alpha (P = 0.10), sigma (P = 0.08), and beta (P = 0.01) EEG frequency ranges, respectively. Within each specific sleep stage, these reductions from baseline to PAP studies in synchrony between EEG power and respiratory cycles still reached significance (P < 0.05) for one or more EEG frequency ranges and for all frequency ranges during REM sleep. CONCLUSIONS: RCREC tends to diminish acutely with alleviation of upper airway obstruction by PAP. These data in combination with previous observations support the hypothesis that RCREC reflect numerous, subtle, brief, but consequential inspiratory microarousals.

Engineering better sleep.

Sleep medicine is a growing field with multidisciplinary origins in physiological monitoring techniques, on which it still largely depends. Collaborations between engineers and sleep specialists offer substantial opportunities to improve on current approaches to diagnosis and assessment of patients with sleep problems. Such collaborations could also prove key to improved fundamental understanding of the pathophysiology that underlies sleep disorders and their adverse impact on the brain, cardiovascular system, and optimal health.

Electroencephalographic changes during respiratory cycles predict sleepiness in sleep apnea.

Common polysomnographic measures of sleep-disordered breathing have shown a disappointing ability to predict important consequences such as excessive daytime sleepiness. Using novel analytic techniques, this study tested the hypothesis that numerous, brief disruptions in cortical activity could occur on a breath-to-breath basis during nonapneic sleep. Spectral analysis proved the existence of respiratory cycle-related electroencephalographic changes in each of 38 adult patients evaluated by polysomnography for sleep-disordered breathing. Furthermore, the tendency for sigma (13-15 Hz) electroencephalographic power to vary with the respiratory cycle predicted next-day sleepiness as measured by the multiple sleep latency test. The predictive value was enhanced when the analysis was limited to those 27 patients who had sleep-disordered breathing (more than 5 apneas or hypopneas per hour of sleep). In contrast, nocturnal rates of apneas and hypopneas, as well as minimal oxygen saturation, did not predict sleepiness as well. On average, sigma power increased notably during inspiration, whereas delta (1-4 Hz) power showed a simultaneous decrease. We conclude that electroencephalographic activity shows detectable changes during nonapneic respiratory cycles in adults evaluated for sleep-disordered breathing. Quantification of these changes, which may reflect numerous inspiratory microarousals, could prove useful in prediction of excessive daytime sleepiness.