Maree Barnes

Treating obstructive sleep apnea with hypoglossal nerve stimulation.

BACKGROUND Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce OSA severity. STUDY OBJECTIVES To examine safety and efficacy of a novel HGNS system (HGNS, Apnex Medical, Inc.) in treating OSA. PARTICIPANTS Twenty-one patients, 67% male, age (mean ± SD) 53.6 ± 9.2 years, with moderate to severe OSA and unable to tolerate continuous positive airway pressure (CPAP). DESIGN Each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by apnea-hypopnea index (AHI) during in-laboratory polysomnography (PSG) at baseline and 3 and 6 months post-implant. Therapy compliance was assessed by nightly hours of use. Symptoms were assessed using the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Calgary Sleep Apnea Quality of Life Index (SAQLI), and the Beck Depression Inventory (BDI). RESULTS HGNS was used on 89% ± 15% of nights (n = 21). On these nights, it was used for 5.8 ± 1.6 h per night. Nineteen of 21 participants had baseline and 6-month PSGs. There was a significant improvement (all P < 0.05) from baseline to 6 months in: AHI (43.1 ± 17.5 to 19.5 ± 16.7), ESS (12.1 ± 4.7 to 8.1 ± 4.4), FOSQ (14.4 ± 2.0 to 16.7 ± 2.2), SAQLI (3.2 ± 1.0 to 4.9 ± 1.3), and BDI (15.8 ± 9.0 to 9.7 ± 7.6). Two serious device-related adverse events occurred: an infection requiring device removal and a stimulation lead cuff dislodgement requiring replacement. CONCLUSIONS HGNS demonstrated favorable safety, efficacy, and compliance. Participants experienced a significant decrease in OSA severity and OSA-associated symptoms. CLINICAL TRIAL INFORMATION NAME: Australian Clinical Study of the Apnex Medical HGNS System to Treat Obstructive Sleep Apnea. REGISTRATION NUMBER NCT01186926. URL: http://clinicaltrials.gov/ct2/show/NCT01186926.

Cognition and daytime functioning in sleep-related breathing disorders

Sleep-related breathing disorders encompass a range of disorders in which abnormal ventilation occurs during sleep as a result of partial or complete obstruction of the upper airway, altered respiratory drive, abnormal chest wall movement, or respiratory muscle function. The most common of these is obstructive sleep apnea (OSA), occurring in both adults and children, and causing significant cognitive and daytime dysfunction and reduced quality of life. OSA patients experience repetitive brief cessation of breathing throughout the night, which causes intermittent hypoxemia (reductions in hemoglobin oxygen levels) and fragmented sleep patterns. These nocturnal events result in excessive daytime sleepiness, and changes in mood and cognition. Chronic excessive sleepiness during the day is a common symptom of sleep-related breathing disorders, which is assessed in sleep clinics both subjectively (questionnaire) and objectively (sleep latency tests). Mood changes are often reported by patients, including irritability, fatigue, depression, and anxiety. A wide range of cognitive deficits have been identified in untreated OSA patients, from attentional and vigilance, to memory and executive functions, and more complex tasks such as simulated driving. These changes are reflected in patient reports of difficulty in concentrating, increased forgetfulness, an inability to make decisions, and falling asleep at the wheel of a motor vehicle. These cognitive changes can also have significant downstream effects on daily functioning. Moderate to severe cases of the disorder are at a higher risk of having a motor vehicle accident, and may also have difficulties at work or school. A number of comorbidities may also influence the cognitive changes in OSA patients, including hypertension, diabetes, and stroke. These diseases can cause changes to neural vasculature and result in neural damage, leading to cognitive impairments. Examination of OSA patients using neuroimaging techniques such as structural magnetic resonance imaging and proton magnetic resonance spectroscopy has observed significant changes to brain structure and metabolism. The downstream effects of neural, cognitive, and daytime functional impairments can be significant if left untreated. A better understanding of the cognitive effects of these disorders, and development of more effective assessment tools for diagnosis, will aid early intervention and improve quality of life of the patient.

Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS®; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty‐one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single‐arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea–hypopnea index, from in‐laboratory polysomnogram) and sleep‐related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea–hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h−1) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device‐related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.

Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment

STUDY OBJECTIVES To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA. DESIGN Observational, before and after CPAP treatment. SETTING Two tertiary hospital research institutes. PARTICIPANTS 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM). MEASUREMENTS AND RESULTS Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01). CONCLUSIONS OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia.

Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea.

RATIONALE Hypoglossal nerve stimulation (HGNS) recruits lingual muscles, reduces pharyngeal collapsibility, and treats sleep apnea. OBJECTIVES We hypothesized that graded increases in HGNS relieve pharyngeal obstruction progressively during sleep. METHODS Responses were examined in 30 patients with sleep apnea who were implanted with an HGNS system. Current (milliampere) was increased stepwise during non-REM sleep. Frequency and pulse width were fixed. At each current level, stimulation was applied on alternating breaths, and responses in maximal inspiratory airflow (V(I)max) and inspiratory airflow limitation (IFL) were assessed. Pharyngeal responses to HGNS were characterized by the current levels at which V(I)max first increased and peaked (flow capture and peak flow thresholds), and by the V(I)max increase from flow capture to peak (ΔV(I)max). MEASUREMENTS AND MAIN RESULTS HGNS produced linear increases in V(I)max from unstimulated levels at flow capture to peak flow thresholds (215 ± 21 to 509 ± 37 ml/s; mean ± SE; P < 0.001) with increasing current from 1.05 ± 0.09 to 1.46 ± 0.11 mA. V(I)max increased in all patients and IFL was abolished in 57% of patients (non-IFL subgroup). In the non-IFL compared with IFL subgroup, the flow response slope was greater (1241 ± 199 vs. 674 ± 166 ml/s/mA; P < 0.05) and the stimulation amplitude at peak flow was lower (1.23 ± 0.10 vs. 1.80 ± 0.20 mA; P < 0.05) without differences in peak flow. CONCLUSIONS HGNS produced marked dose-related increases in airflow without arousing patients from sleep. Increases in airflow were of sufficient magnitude to eliminate IFL in most patients and IFL and non-IFL subgroups achieved normal or near-normal levels of flow, suggesting potential HGNS efficacy across a broad range of sleep apnea severity.

Effects of Maternal Obstructive Sleep Apnoea on Fetal Growth: A Prospective Cohort Study

Objective The objective of this study is to determine whether obstructive sleep apnea (OSA) is associated with reduced fetal growth, and whether nocturnal oxygen desaturation precipitates acute fetal heart rate changes. Study Design We performed a prospective observational study, screening 371 women in the second trimester for OSA symptoms. 41 subsequently underwent overnight sleep studies to diagnose OSA. Third trimester fetal growth was assessed using ultrasound. Fetal heart rate monitoring accompanied the sleep study. Cord blood was taken at delivery, to measure key regulators of fetal growth. Results Of 371 women screened, 108 (29%) were high risk for OSA. 26 high risk and 15 low risk women completed the longitudinal study; 14 had confirmed OSA (cases), and 27 were controls. The median (interquartile range) respiratory disturbance index (number of apnoeas, hypopnoeas or respiratory related arousals/hour of sleep) was 7.9 (6.1–13.8) for cases and 2.2 (1.3–3.5) for controls (p<0.001). Impaired fetal growth was observed in 43% (6/14) of cases, vs 11% (3/27) of controls (RR 2.67; 1.25–5.7; p = 0.04). Using logistic regression, only OSA (OR 6; 1.2–29.7, p = 0.03) and body mass index (OR 2.52; 1.09–5.80, p = 0.03) were significantly associated with impaired fetal growth. After adjusting for body mass index on multivariate analysis, the association between OSA and impaired fetal growth was not appreciably altered (OR 5.3; 0.93–30.34, p = 0.06), although just failed to achieve statistical significance. Prolonged fetal heart rate decelerations accompanied nocturnal oxygen desaturation in one fetus, subsequently found to be severely growth restricted. Fetal growth regulators showed changes in the expected direction- with IGF-1 lower, and IGFBP-1 and IGFBP-2 higher- in the cord blood of infants of cases vs controls, although were not significantly different. Conclusion OSA may be associated with reduced fetal growth in late pregnancy. Further evaluation is warranted to establish whether OSA may be an important contributor to adverse perinatal outcome, including stillbirth.

Sleep disordered breathing in chronic stroke survivors. A study of the long term follow-up of the SCOPES cohort using home based polysomnography.

Prevalence of sleep-disordered breathing (SDB) (apnea-hypopnea index [AHI] > or = 5) in acute stroke patients ranges between 44% and 95%, compared to the community prevalence, 9 to 35% for women and 8 to 57% for men [age range 30-60 years]. Limited data exists beyond 3 months following stroke. We assessed the prevalence of SDB amongst stroke survivors at 3 years and compared results to data reported in normal and elderly populations. 90/143 eligible stroke survivors from an existing cohort underwent a home based sleep study. Mean age of the 78 subjects with a valid sleep study was 64 years (SD 15). Prevalence of SDB (AHI > or = 5) was 81% (95% CI 72% to 90%) and sleep apnoea syndrome (AHI > or = 5 plus ESS score > or =11) was 20% (95% CI 11% to 29%). Important predictors for AHI > or = 15 were haemorrhagic stroke (aOR12.06 [1.42-102.74]) and stroke severity at 1 month (aOR4.15 [1.05-16.38]). Large case-control studies are needed.

Factors associated with maintenance of wakefulness test mean sleep latency in patients with mild to moderate obstructive sleep apnoea and normal subjects

This study investigated the possible factors related to the Maintenance of Wakefulness Test (MWT) mean sleep latency. A second analysis explored the characteristics of subjects who had discrepant Epworth Sleepiness Scale (ESS) and MWT scores. A total of 151 subjects (110 mild to moderate obstructive sleep apnoea (OSA) patients and 41 control subjects) were recruited for the study. The subjects completed an overnight Polysomnography (PSG), MWT, cognitive, performance and vigilance tasks and answered self‐report questionnaires on mood and sleepiness. A forward stepwise multiple regression was performed on MWT mean sleep latency. The predictor variables age (r = 0.28), subjective sleep history for 1 week prior to MWT (sleep diary; r = 0.19) and number of >4% SaO2 Dips during the PSG (r = −0.21) best explained the MWT results, but only accounted for 12.8% of the variance in the test. It was found that 33% of subjects had discrepant ESS and MWT scores. A new variable was created to analyse these subjects (MWT/ESS discrepancy score; MED). A forward stepwise multiple regression analysis found that depression, performance errors and sleep disordered breathing explained 13.4% of the variance in MED scores. The MWT is a complex behavioural test whose scores do not seem to have a very robust relationship with potential predictors and co‐correlates. Further comprehensive study is needed if the test is to be used in a diagnostically meaningful way.

Decreased sleep efficiency, increased wake after sleep onset and increased cortical arousals in late pregnancy

Background:  Anecdotal reports of sleep disturbance during pregnancy are abundant; however, objective measurement of sleep changes has so far produced conflicting results.

Obstructive sleep apnea and pregnancy: the effect on perinatal outcomes.

Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper airway obstruction, resulting in hypoxemia, hypercapnia and sleep fragmentation. Pathophysiological sequelae include sympathetic activation, increased oxidative stress and a generalized inflammatory response, culminating in endothelial dysfunction. These are the proposed mechanisms that mediate the increased risk of hypertension and cardiovascular disease among patients with OSA outside of pregnancy. It is intriguing to consider the consequences of these events on pregnancy outcomes. There is a growing literature on the impact of maternal OSA on hypertensive disorders of pregnancy, gestational diabetes and impaired fetal growth. The data, while promising, require confirmation with larger numbers to verify the findings. OSA may be an important mediator of the poor perinatal outcomes associated with maternal obesity; moreover, one which may be amenable to treatment. This review discusses OSA and summarizes the current literature linking OSA with adverse perinatal outcomes.