Yvonne Pamula

Adenotonsillectomy and neurocognitive deficits in children with Sleep Disordered Breathing.

Background Sleep Disordered Breathing (SDB) is a common childhood disorder that encompasses a range of sleep-related upper airway obstruction. Children with SDB demonstrate significant neurocognitive deficits. Adenotonsillectomy is the first line of treatment for SDB and whilst this improves respiratory disturbance, it remains to be established whether neurocognitive gains also result. Methods A total of 44 healthy snoring children aged 3–12 years awaiting adenotonsillectomy (SDB group), and 48 age and gender matched non-snoring controls from the general community, completed the study. All children underwent polysomnography and neurocognitive assessment at baseline and after a 6-month follow-up (after surgery in the snoring group). Our primary aim was to determine whether neurocognitive deficits in snoring children were significantly improved following adenotonsillectomy. Results Wide ranging neurocognitive deficits were found at baseline in SDB children compared to controls, most notably a 10 point IQ difference (P<.001) and similar deficits in language and executive function. Whilst adenotonsillectomy improved respiratory parameters and snoring frequency at 6 months post surgery, neurocognitive performance did not improve relative to controls. Conclusion Adenotonsillectomy successfully treated the respiratory effects of SDB in children. However, neurocognitive deficits did not improve 6-months post-operatively.

Altered cardio-respiratory response to spontaneous cortical arousals in children with upper airway obstruction

OBJECTIVE Upper airway obstruction (UAO) during childhood is associated with cardiovascular morbidity. The aim of this study was to investigate the cardio-respiratory response to cortical arousal during sleep in children with UAO. METHODS Standard paediatric overnight polysomnography (PSG) was conducted in 40 children with UAO (25M, 7.5±2.7yrs) prior to and 6 months following adenotonsillectomy. For comparison a control group of 40 normal, sex and age matched children (21M, 7.5±2.6yrs) underwent two PSGs without intervention at the same time points. RESULTS Heart rate and respiratory rate were measured during spontaneous and respiratory arousals in stage 2 and REM sleep 15s prior to and 15s immediately following cortical arousal onset. Cortical arousal was associated with a significant increase in heart and respiratory rate in both groups of children. UAO children, however, showed a significantly higher heart rate response in stage 2 sleep (-17.5±6.0 vs. -14.4±4.8%; p<0.05), a lower pre-arousal baseline respiratory rate (stage 2: 17.1±1.4 vs. 18.2±1.7 BPM; p<0.01) and a prolonged increase in respiratory rate compared to control children. Cardiac and respiratory arousal responses were not significantly different from controls following adenotonsillectomy in the UAO children. CONCLUSIONS UAO in children is associated with an altered cardiorespiratory response to spontaneous arousal from sleep, which may indicate early signs of autonomic dysfunction. Surgical treatment of UAO appears to reverse these outcomes.

Cardiorespiratory response to spontaneous cortical arousals during stage 2 and rapid eye movement sleep in healthy children

Arousal from sleep is associated with transient and abrupt cardiorespiratory changes, and elevated arousals associated with sleep disorders may trigger adverse cardiovascular sequela. In this paper, we provide the first data in children on cardiorespiratory responses to cortical arousal. Heart rate and ventilatory responses to arousal from stage 2 and rapid eye movement (REM) sleep were investigated in 40 normal, healthy Caucasian children (age: 7.7 ± 2.6 years; body mass index z‐score: 0.30 ± 0.8). All children underwent overnight polysomnography studies. Cortical arousals were scored according to standard criteria. Heart rate changes were assessed over 30 s, starting 15 s prior to cortical arousal onset. Breathing rates were quantified three breaths before and after arousal onset. Arousals from stage 2 as well as REM sleep resulted in an R–R interval shortening of about 15%, independent of age and gender. The R–R interval shortening initiated at least 3 s before the cortical arousal onset. The breathing interval immediately after cortical arousal onset was significantly shortened (P < 0.001). In conclusion, cortical arousals in children are associated with an increase in breathing rate and significant heart rate accelerations, which typically precede the cortical arousal onset.

Respiratory timing and variability during sleep in children with sleep-disordered breathing

Sleep-disordered breathing (SDB) in children is assessed by quantification of hypopnea and apnea events. Little is known, however, about respiratory timing and breath-to-breath variability during sleep. The aim of this study was to investigate respiratory parameters across sleep stages in children with SDB before and after treatment compared with healthy children. Overnight polysomnography (PSG) was conducted in 40 children with SDB prior to and 6 mo following adenotonsillectomy. For comparison, a control group of 40 healthy sex- and age-matched children underwent two PSGs at equivalent time points but without intervention. The following variables were measured breath by breath during obstruction-free periods in stage 2 nonrapid eye movement (NREM), stage 4 NREM, and REM sleep: inspiratory time (Ti), expiratory time (Te), total time (Ttotal), inspiratory duty cycle (DC; =Ti/Ttotal), respiratory frequency (fR), and SD of the parameters Ti, Te, fR, and DC. Variability in waveform morphology was also computed using the residue of respiratory patterns. The severity of SDB was relatively mild in the study cohort (obstructive apnea hypopnea index: baseline, 5.1 ± 9.4 vs. 0.1 ± 0.2, P < 0.001; follow-up, 0.3 ± 0.3 vs. 0.8 ± 1.0, P < 0.01). Compared with healthy controls, children with SDB showed significantly longer Ti and Te and a lower fR at the baseline study. These differences were not significant after adenotonsillectomy. Sleep stages were associated with significant differences in all of the respiratory measures in both groups of children. In conclusion, children with relatively mild SDB showed prolonged inspiration and expiration indicative of chronic narrowing of the upper airway. Treatment of SDB normalizes respiratory timing. Documentation of these parameters may aid in both understanding and management of children with SDB.

Heartbeat Evoked Potentials during Sleep and Daytime Behavior in Children with Sleep-disordered Breathing

RATIONALE Event-related brain potentials allow probing of cortical information processing, but when evoked with externally induced stimuli may disrupt sleep homeostasis and do not provide insight into intrinsic cortical information processing. To investigate if cortical processing of intrinsic information in children with sleep-disordered breathing (SDB) is different from healthy children and, if so, whether it resolves with treatment, we used heartbeat as a source of interoceptive event-related brain potentials. OBJECTIVES To investigate heartbeat evoked potentials (HEP) during sleep in healthy children and in children with SDB before and after treatment and to explore if there are any associations between HEP and daytime behavioral deficits in children with SDB. METHODS Heartbeat-aligned EEG was assessed for presence of HEP within stage 2, slow-wave sleep, and REM sleep in 40 children with primarily mild to moderate SDB before and after adenotonsillectomy and in 40 matched control subjects at similar time points. MEASUREMENTS AND MAIN RESULTS In both groups, nonrandom HEP were present in all sleep stages analyzed; however, amplitude of HEP were significantly lower in children with SDB during non-REM sleep (stage 2: P = 0.03; slow-wave sleep: P = 0.001). This between-group difference was not significant post adenotonsillectomy. Significant negative associations between HEP and daytime behavioral scores were observed at baseline. CONCLUSIONS Children with SDB displayed reduced HEP amplitude during sleep, which might be indicative of changes in afferent sensory inputs to the brain and/or signify differences in sensory gating of cardiac-related information in the insular cortex. Adenotonsillectomy appears to reverse this effect.

Accurate derivation of heart rate variability signal for detection of sleep disordered breathing in children

The electrocardiogram (ECG) signal is used extensively as a low cost diagnostic tool to provide information concerning the hearts state of health. Accurate determination of the QRS complex, in particular, reliable detection of the R wave peak, is essential in computer based ECG analysis. ECG data from Physionets Sleep-Apnea database were used to develop, test, and validate a robust heart rate variability (HRV) signal derivation algorithm. The HRV signal was derived from pre-processed ECG signals by developing an enhanced Hilbert transform (EHT) algorithm with built-in missing beat detection capability for reliable QRS detection. The performance of the EHT algorithm was then compared against that of a popular Hilbert transform-based (HT) QRS detection algorithm. Autoregressive (AR) modeling of the HRV power spectrum for both EHT- and HT-derived HRV signals was achieved and different parameters from their power spectra as well as approximate entropy were derived for comparison. Poincare plots were then used as a visualization tool to highlight the detection of the missing beats in the EHT method After validation of the EHT algorithm on ECG data from the Physionet, the algorithm was further tested and validated on a dataset obtained from children undergoing polysomnography for detection of sleep disordered breathing (SDB). Sensitive measures of accurate HRV signals were then derived to be used in detecting and diagnosing sleep disordered breathing in children. All signal processing algorithms were implemented in MATLAB. We present a description of the EHT algorithm and analyze pilot data for eight children undergoing nocturnal polysomnography. The pilot data demonstrated that the EHT method provides an accurate way of deriving the HRV signal and plays an important role in extraction of reliable measures to distinguish between periods of normal and sleep disordered breathing (SDB) in children.

Delayed brachial artery dilation response and increased resting blood flow velocity in young children with mild sleep-disordered breathing.

AIM This study aimed to evaluate whether the vascular dysfunction perceived in adults with sleep-disordered breathing (SDB) was also evident in children with snoring referred for evaluation of clinically suspected SDB. OBJECTIVES This study compared flow-mediated dilatation (FMD), measured at the brachial artery, at rest and during hyperaemic stress between children who snore [n = 23; mean standard deviation (SD) age = 7.51 (1.3) years] and healthy, non-snoring children [n = 11; age = 8.0 (1.3) years]. METHODS Children with suspected obstructive sleep apnoea (OSA) and healthy non-snoring controls underwent overnight polysomnography (PSG). Using standard techniques, non-invasive FMD and brachial arterial blood flow velocity during rest and hyperaemia were subsequently measured by ultrasound imaging MEASUREMENTS Resting and hyperaemic velocity time integral (area under the curve of mean systolic velocity × ejection time), maximal dilation response (highest percentage difference from baseline diameter) and the time taken to reach maximal dilation were calculated. RESULTS Children awaiting adenotonsillectomy compared to healthy non-snoring control children had higher velocity time integrals at rest (14 ± 3 m vs. 20 ± 8 m, p < 0.01) and during hyperaemic stress (56 ± 6m vs. 63 ± 13m, p < 0.01) despite having only mild SDB on polysomnographic assessment. Lower nadir oxygen saturation values during non-rapid eye movement sleep were negatively associated with higher resting (r = -0.58, p <0.001) and hyperaemic (r = -0.36, p < 0.05) velocity time integrals. Maximal FMD dilatation response was not significantly different between snoring and non-snoring groups, but the estimated time to reach maximal dilation was significantly delayed in children who snored (60.7 ± 28.4 vs. 39.2 ± 13.2 s, p < 0.05). CONCLUSIONS Children with mild SDB showed increased blood flow velocity at rest and during hyperaemic stress suggesting altered cardiovascular and haemodynamic function. The delay in time to maximal vessel dilatation in children who snored also suggests possible reduced vascular compliance in response to hyperaemic sheer stress. Mild SDB appears to alter the peripheral vascular response in young children. The long-term vascular implications of these changes in the growing child are unknown and warrant further investigation.

Computer-based analysis of heart rate variability signal for detection of sleep disordered breathing in children

A computer-based analysis system was developed to display and analyze heart rate variability (HRV). ECG, oxygen saturation and respiratory signals (airflow, abdominal and thoracic movements), were used as raw data. The heart rate variability signal was derived from ECG by applying a Hilbert transform-based algorithm for reliable QRS complex detection. Following the guidelines suggested by the Task Force of the European Society of Cardiology and the North American Society for Pacing and Electrophysiology, appropriate time-domain and frequency-domain methods were used for HRV signal analysis. Autoregressive modeling of the HRV power spectrum was achieved by implementing the Burg algorithm. Three main spectral features were clearly distinguished in the heart rate variability signal spectrum from polysomnographic recordings of different sleep stages and were correlated with respiratory parameters. The integrated graphical user interface was developed using LabView and the signal processing algorithms were implemented using Matlab application programs. In this paper we present an overview of the system and analyze pilot data for two children undergoing nocturnal polysomnography. The pilot data demonstrated that the HRV analysis system may potentially distinguish between periods of normal and sleep disordered breathing (SDB) in children.

Respiratory Cycle-Related Electroencephalographic Changes during Sleep in Healthy Children and in Children with Sleep Disordered Breathing

STUDY OBJECTIVE To investigate respiratory cycle-related electroencephalographic changes (RCREC) in healthy children and in children with sleep disordered breathing (SDB) during scored event-free (SEF) breathing periods of sleep. DESIGN Interventional case-control repeated measurements design. SETTING Paediatric sleep laboratory in a hospital setting. PARTICIPANTS Forty children with SDB and 40 healthy, age- and sex-matched children. INTERVENTIONS Adenotonsillectomy in children with SDB and no intervention in controls. MEASUREMENTS AND RESULTS Overnight polysomnography; electroencephalography (EEG) power variations within SEF respiratory cycles in the overall and frequency band-specific EEG within stage 2 nonrapid eye movement (NREM) sleep, slow wave sleep (SWS), and rapid eye movement (REM) sleep. Within both groups there was a decrease in EEG power during inspiration compared to expiration across all sleep stages. Compared to controls, RCREC in children with SDB in the overall EEG were significantly higher during REM and frequency band specific RCRECs were higher in the theta band of stage 2 and REM sleep, alpha band of SWS and REM sleep, and sigma band of REM sleep. This between-group difference was not significant postadenotonsillectomy. CONCLUSION The presence of nonrandom respiratory cycle-related electroencephalographic changes (RCREC) in both healthy children and in children with sleep disordered breathing (SDB) during NREM and REM sleep has been demonstrated. The RCREC values were higher in children with SDB, predominantly in REM sleep and this difference reduced after adenotonsillectomy. CITATION Immanuel SA, Pamula Y, Kohler M, Martin J, Kennedy D, Saint DA, Baumert M. Respiratory cycle-related electroencephalographic changes during sleep in healthy children and in children with sleep disordered breathing.

Increased thoracoabdominal asynchrony during breathing periods free of discretely scored obstructive events in children with upper airway obstruction

ObjectiveThis study aims to investigate the impact of upper airway obstruction (UAO) in children by measuring thoracoabdominal asynchrony (TAA) during periods of sleep apnea/hypopnea and during scored-event-free (SEF) breathing periods.MethodsRespiratory inductive plethysmographic signals were extracted from polysomnographic data, recorded before and after adenotonsillectomy in 40 children with UAO and 40 healthy, matched children at equivalent time points. Thoracoabdominal asynchrony was computed using a Hilbert transform-based phase difference estimation method in SEF periods during stage 2, stage 4 non-rapid eye movement (NREM), and rapid eye movement (REM) sleep and compared between the groups.ResultsAt baseline, in the UAO group, TAA during obstructions were significantly higher than TAA during SEF periods in both stage 2 and REM sleep. Compared to controls, children with UAO had a significantly higher TAA during SEF periods in stage 2, stage 4 sleep, and REM sleep. This between-group difference was not significant post adenotonsillectomy. UAO group showed a significant decrease in TAA compared to their baseline during SEF stage 2 and 4 NREM, but not in REM.ConclusionUpper airway obstruction in children is associated with increased TAA during SEF periods, indicative of continuous partial obstruction of the upper airway. Adenotonsillectomy decreased this effect significantly in non-REM sleep as evidenced by reduced asynchrony levels post-surgery. TAA assessment during sleep may therefore provide additional diagnostic information.