Warren R. Ruehland

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.

AASM criteria for scoring respiratory events: interaction between apnea sensor and hypopnea definition.

STUDY OBJECTIVES To examine the impact of using a nasal pressure sensor only vs the American Academy of Sleep Medicine (AASM) recommended combination of thermal and nasal pressure sensors on (1) the apnea index (AI), (2) the apnea-hypopnea index (AHI), where the AHI is calculated using both AASM definitions of hypopnea, and (3) the accuracy of a diagnosis of obstructive sleep apnea (OSA). DESIGN Retrospective review of previously scored in-laboratory polysomnography. SETTING A tertiary-hospital clinical sleep laboratory. PATIENTS OR PARTICIPANTS One hundred sixty-four consecutive adult patients with a potential diagnosis of OSA, who were examined during a 3-month period. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Studies were scored with and without the use of the oronasal thermal sensor. AIs and AHIs, using the nasal pressure sensor alone (AI(np) and AHI(np)), were compared with those using both a thermal sensor for the detection of apnea and a nasal pressure transducer for the detection of hypopnea (AI(th) and AHI(th)). Comparisons were repeated using the AASM recommended (AASM(rec)) and alternative (AASM(alt)) hypopnea definitions. AI was significantly different when measured from the different sensors, with AI(np) being 51% higher on average. Using the AASM(rec) hypopnea definition, the mean AHI(np) was 15% larger than the AHI(th); with large interindividual differences and an estimated 9.8% of patients having a false-positive OSA diagnosis at a cutpoint of 15 events and 4.3% at 30 events per hour. Using AASM(alt) hypopnea definition, the mean AHI(np) was 3% larger than the AHI(th), with estimated false-positive rates of 4.6% and 2.4%, respectively. The false-negative rate was negligible at 0.1% for both hypopnea definitions. CONCLUSIONS This study demonstrates that using only a nasal pressure sensor for the detection of apnea resulted in higher values of AI and AHI than when the AASM recommended thermal sensor was added to detect apnea. When the AASM(alt) hypopnea definition was used, the differences in AHI and subsequent OSA diagnosis were small and less than when the AASM(rec) hypopnea definition was used. In situations in which a thermal sensor cannot be used, for example, in limited-channel diagnostic devices, the AHI obtained with a nasal pressure sensor alone differs less from the AHI obtained from a polysomnogram that includes a thermal sensor when the AASM(alt) definition rather than the AASM(rec) definition of hypopnea is used. Thus, diagnostic accuracy is impacted both by the absence of the thermal sensor and by the rules used to analyze the polysomnography. Furthermore, where the thermal sensor is unreliable for sections of a study, it is likely that use of the nasal pressure signal to detect apnea will have modest impact.

Effect of Singing on Respiratory Function, Voice, and Mood After Quadriplegia: A Randomized Controlled Trial

OBJECTIVE To explore the effects of singing training on respiratory function, voice, mood, and quality of life for people with quadriplegia. DESIGN Randomized controlled trial. SETTING Large, university-affiliated public hospital, Victoria, Australia. PARTICIPANTS Participants (N=24) with chronic quadriplegia (C4-8, American Spinal Injury Association grades A and B). INTERVENTIONS The experimental group (n=13) received group singing training 3 times weekly for 12 weeks. The control group (n=11) received group music appreciation and relaxation for 12 weeks. Assessments were conducted pre, mid-, immediately post-, and 6-months postintervention. MAIN OUTCOME MEASURES Standard respiratory function testing, surface electromyographic activity from accessory respiratory muscles, sound pressure levels during vocal tasks, assessments of voice quality (Perceptual Voice Profile, Multidimensional Voice Profile), and Voice Handicap Index, Profile of Mood States, and Assessment of Quality of Life instruments. RESULTS The singing group increased projected speech intensity (P=.028) and maximum phonation length (P=.007) significantly more than the control group. Trends for improvements in respiratory function, muscle strength, and recruitment were also evident for the singing group. These effects were limited by small sample sizes with large intersubject variability. Both groups demonstrated an improvement in mood (P=.002), which was maintained in the music appreciation and relaxation group after 6 months (P=.017). CONCLUSIONS Group music therapy can have a positive effect on not only physical outcomes, but also can improve mood, energy, social participation, and quality of life for an at-risk population, such as those with quadriplegia. Specific singing therapy can augment these general improvements by improving vocal intensity.

Assessment of Breathing Patterns and Respiratory Muscle Recruitment During Singing and Speech in Quadriplegia

OBJECTIVES To explore how respiratory impairment after cervical spinal cord injury affects vocal function, and to explore muscle recruitment strategies used during vocal tasks after quadriplegia. It was hypothesized that to achieve the increased respiratory support required for singing and loud speech, people with quadriplegia use different patterns of muscle recruitment and control strategies compared with control subjects without spinal cord injury. DESIGN Matched, parallel-group design. SETTING Large university-affiliated public hospital. PARTICIPANTS Consenting participants with motor-complete C5-7 quadriplegia (n=6) and able-bodied age-matched controls (n=6) were assessed on physiologic and voice measures during vocal tasks. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Standard respiratory function testing, surface electromyographic activity from accessory respiratory muscles, sound pressure levels during vocal tasks, the Voice Handicap Index, and the Perceptual Voice Profile. RESULTS The group with quadriplegia had a reduced lung capacity (vital capacity, 71% vs 102% of predicted; P=.028), more perceived voice problems (Voice Handicap Index score, 22.5 vs 6.5; P=.046), and greater recruitment of accessory respiratory muscles during both loud and soft volumes (P=.028) than the able-bodied controls. The group with quadriplegia also demonstrated higher accessory muscle activation in changing from soft to loud speech (P=.028). CONCLUSIONS People with quadriplegia have impaired vocal ability and use different muscle recruitment strategies during speech than the able-bodied. These findings will enable us to target specific measurements of respiratory physiology for assessing functional improvements in response to formal therapeutic singing training.

Sensory detection of threshold intensity resistive loads in severe obstructive sleep apnoea

Respiratory related evoked potentials (RREPs) were used to investigate whether sensory detection of small mid-inspiratory resistive loads (≈1.2-6.2 cmH2OL-1s), delivered during wakefulness, was impaired in obstructive sleep apnoea (OSA). It was reasoned that impaired detection of minor airway patency challenge may lead to difficult-to-remedy further collapse. There was a significant reduction in OSA (n=16) vs. control (n=17) participants in the slope of the relationship between the P1 RREP component amplitude, which reflects arrival of somatosensory information at the cortex, and stimulus intensity, expressed as change in epiglottic pressure (mean [95% confidence intervals]: -0.50 [-0.97, -0.03] vs. -1.78 [-2.54, -1.02]; P=0.004), suggesting a reduction in sensitivity to small respiratory loads. However there was no significant difference in sensitivity after background Pepi was taken into account (P=0.268). Additionally, there were no significant group differences in the threshold of the P1 amplitude/stimulus intensity relationship, or in the P1 latency. These results indicate a reduced sensitivity to detection of small upper airway negative pressure stimuli in OSA related to a reduction in mechanoreceptor activation (likely related to increased airway resistance in OSA vs. controls; P=0.002) rather than defective mechanosensory function.

Polysomnography using abbreviated signal montages: impact on sleep and cortical arousal scoring.

OBJECTIVE This study examined the impact of using two abbreviated signal montages on the accuracy, precision and inter-scorer reliability of polysomnography (PSG) sleep and arousal scoring, compared to a standard reference montage, in a cohort of patients investigated for obstructive sleep apnoea (OSA). One abbreviated montage incorporated two signals dedicated to sleep and arousal scoring, and the other incorporated a single signal. METHODS Four scorers from two laboratories each scored 15 PSGS four times in random order: once using each abbreviated montage and twice using the reference montage. RESULTS Use of the two-signal montage resulted in small changes in the distribution of sleep stages, a reduction in the arousal index and resultant reductions in sleep and arousal scoring agreement. For the one-signal montage, although similar magnitude sleep stage distribution changes were observed, there were larger reductions in the arousal index, and sleep and arousal scoring accuracy. Additionally, using the one-signal montage, there were statistically significant reductions in the precision of summary statistics including total sleep time (TST) and the amount of rapid eye movement (REM) sleep scored, and reductions in the inter-scorer reliability of REM sleep and arousal scoring. CONCLUSIONS These findings demonstrate that abbreviated signal montages may result in underestimation of the arousal index and, depending on the montage, poorer precision in TST and REM sleep scoring, with potential consequences for apnoea-hypopnoea index (AHI) measures and OSA diagnosis. The results highlight the importance of careful evaluation of PSG results when using portable devices that have restricted signals, and they offer guidance for future PSG and portable monitoring standards.

Diagnostic accuracy of a two-stage model for detecting obstructive sleep apnoea in chronic tetraplegia

Background Obstructive sleep apnoea (OSA) is highly prevalent in people with spinal cord injury (SCI). Polysomnography (PSG) is the gold-standard diagnostic test for OSA, however PSG is expensive and frequently inaccessible, especially in SCI. A two-stage model, incorporating a questionnaire followed by oximetry, has been found to accurately detect moderate to severe OSA (MS-OSA) in a non-disabled primary care population. This study investigated the accuracy of the two-stage model in chronic tetraplegia using both the original model and a modified version for tetraplegia. Methods An existing data set of 78 people with tetraplegia was used to modify the original two-stage model. Multivariable analysis identified significant risk factors for inclusion in a new tetraplegia-specific questionnaire. Receiver operating characteristic (ROC) curve analyses of the questionnaires and oximetry established thresholds for diagnosing MS-OSA. The accuracy of both models in diagnosing MS-OSA was prospectively evaluated in 100 participants with chronic tetraplegia across four international SCI units. Results Injury completeness, sleepiness, self-reported snoring and apnoeas were included in the modified questionnaire, which was highly predictive of MS-OSA (ROC area under the curve 0.87 (95% CI 0.79 to 0.95)). The 3% oxygen desaturation index was also highly predictive (0.93 (0.87–0.98)). The two-stage model with modified questionnaire had a sensitivity and specificity of 83% (66–93) and 88% (75–94) in the development group, and 77% (65–87) and 81% (68–90) in the validation group. Similar results were demonstrated with the original model. Conclusion Implementation of this simple alternative to full PSG could substantially increase the detection of OSA in patients with tetraplegia and improve access to treatments. Trial registration number Results, ACTRN12615000896572 (The Australian and New Zealand Clinical Trials Registry) and pre-results, NCT02176928 (clinicaltrials.gov).

Genioglossus reflex responses to negative upper airway pressure are altered in people with tetraplegia and obstructive sleep apnoea

Protective reflexes in the throat area (upper airway) are crucial for breathing. Impairment of these reflexes can cause breathing problems during sleep such as obstructive sleep apnoea (OSA). OSA is very common in people with spinal cord injury for unknown reasons. This study shows major changes in protective reflexes that serve to keep the upper airway open in response to suction pressures in people with tetraplegia and OSA. These results help us understand why OSA is so common in people with tetraplegia and provide new insight into how protective upper airway reflexes work more broadly.

Evidence against a subcortical gate preventing conscious detection of respiratory load stimuli

Respiratory related evoked potentials (RREP) were used to examine respiratory stimulus gating. RREPs produced by consciously detected vs. undetected loads, near the detection threshold, were compared. Participants (n = 17) were instrumented with EEG and a nasal mask connected to a loading manifold, which presented a range of mid-inspiratory resistive loads, plus a control, in a random block design. Participants were cued prior to the stimulus and signalled detection by a button press. There were statistically significant differences in peak-to-peak amplitude of the P1 RREP peak for detected (mean ± SD; 3.86 ± 1.45 μV; P =  0.020) and undetected loads (3.67 ± 1.27 μV; P =  0.002) vs. control (2.36 ± 0.81 μV), although baseline-to-peak differences were not significantly different. In contrast peak-to-peak P3 amplitude was significantly greater for detected (5.91 ± 1.54 μV; P <  0.001) but not undetected loads (3.33 ± 0.98 μV; P = 0.189) vs. control (3.69 ± 1.46 μV), with the same pattern observed for baseline-to-peak measurements. The P1 peak, thought to reflect arrival of somatosensory information, appeared to be present in response to both detected and undetected loads, but the later P3 peak, was present for detected loads only. This suggests that for sub-threshold loads sensory information may reach the cortex, arguing against a sub-cortical gating process.