Orexin receptor 2 agonist activates diaphragm and genioglossus muscle through stimulating inspiratory neurons in the pre-Bötzinger complex, and phrenic and hypoglossal motoneurons in rodents.

Orexin-mediated stimulation of orexin receptors 1/2 (OX[1/2]R) may stimulate the diaphragm and genioglossus muscle via activation of inspiratory neurons in the pre-Bötzinger complex, which are critical for the generation of inspiratory rhythm, and phrenic and hypoglossal motoneurons. Herein, we assessed the effects of OX2R-selective agonists TAK-925 (danavorexton) and OX-201 on respiratory function. In in vitro electrophysiologic analyses using rat medullary slices, danavorexton and OX-201 showed tendency and significant effect, respectively, in increasing the frequency of inspiratory synaptic currents of inspiratory neurons in the pre-Bötzinger complex. In rat medullary slices, both danavorexton and OX-201 significantly increased the frequency of inspiratory synaptic currents of hypoglossal motoneurons. Danavorexton and OX-201 also showed significant effect and tendency, respectively, in increasing the frequency of burst activity recorded from the cervical (C3-C5) ventral root, which contains axons of phrenic motoneurons, in in vitro electrophysiologic analyses from rat isolated brainstem-spinal cord preparations. Electromyogram recordings revealed that intravenous administration of OX-201 increased burst frequency of the diaphragm and burst amplitude of the genioglossus muscle in isoflurane- and urethane-anesthetized rats, respectively. In whole-body plethysmography analyses, oral administration of OX-201 increased respiratory activity in free-moving mice. Overall, these results suggest that OX2R-selective agonists enhance respiratory function via activation of the diaphragm and genioglossus muscle through stimulation of inspiratory neurons in the pre-Bötzinger complex, and phrenic and hypoglossal motoneurons. OX2R-selective agonists could be promising drugs for various conditions with respiratory dysfunction.

Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea in a Young Child With Down Syndrome.

Obstructive sleep apnea (OSA) is common in children with Down syndrome (DS). Adenoidectomy and/or tonsillectomy are the usual first interventions employed to treat OSA in children with DS but sometimes do not achieve adequate resolution of clinical signs. Positive airway pressure treatment is often used next, but this treatment is poorly tolerated by this population. Persistent OSA can adversely affect a child's health and cognitive development. Hypoglossal nerve stimulation (HGNS), previously shown to be safe and effective in adults with OSA, has been used in children as young as 10 years old with DS and has achieved measurable neurocognitive benefits. The US Food and Drug Administration recently lowered the age for HGNS implantation to 13 years for children with DS. However, questions remain regarding treatment of refractory OSA in younger children. Here, we report the case of a 4-year-old boy with DS and treatment-refractory OSA who underwent successful HGNS implantation. The decision to proceed with HGNS implantation in such a young child involved discussions about anatomic feasibility and potential neurocognitive benefits. The device was implanted without complication and with minimal postoperative bulk. This case suggests a possible treatment option that can be discussed in the course of shared decision-making between clinicians and families of young children with DS and treatment-refractory OSA.

Swallowing-like activity elicited in neonatal rat medullary slice preparation.

Swallowing is induced by a central pattern generator in the nucleus tractus solitarius (NTS). We aimed to create a medullary slice preparation to elucidate the neural architecture of the central pattern generator of swallowing (Sw-CPG) and record its neural activities. Experiments were conducted on 2-day-old Sprague-Dawley rats (n = 46). The brainstem-spinal cord was transected at the pontomedullary and cervicothoracic junctions; the medulla was sliced transversely at thicknesses of 600, 700, or 800 µm. The rostral end of the slice was 100 µm rostral to the vagus nerve. We recorded hypoglossal nerve activity and electrically stimulated the vagus nerve or microinjected bicuculline methiodide (BIC) into the NTS. The 800-µm slices generated both rhythmic respiratory activity and electrically elicited neural activity. The 700-µm slices generated only respiratory activity, while the 600-µm slices did not generate any neural activity. BIC microinjection into the NTS in 800-µm slices resulted in the typical activity that closely resembled the swallowing activity reported in other experiments. This swallowing-like activity consistently lengthened the respiratory interval. Despite complete inhibition of respiratory activity, weak swallowing-like activity was observed under bath application of a non-NMDA receptor antagonist. Contrastingly, bath application of NMDA receptor antagonists resulted in a complete loss of swallowing-like activity and no change in respiratory activity. These results suggest that the 800-µm medullary slice preparation contains both afferent and efferent neural circuits and pattern generators of swallowing activity. Additionally, NMDA receptors may be necessary for generating swallowing activity. This medullary slice preparation can therefore elucidate Sw-CPG neural networks.

Response to Hypoglossal Nerve Stimulation Changes With Body Mass Index and Supine Sleep.

Importance: Hypoglossal nerve stimulation (HGNS) is a potential alternative therapy for obstructive sleep apnea (OSA), but its efficacy in a clinical setting and the impact of body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) on treatment response remain unclear. Objective: To investigate whether HGNS therapy is effective for patients with OSA, whether HGNS can treat supine OSA, and whether there are associations between BMI and treatment response. Design, Setting, and Participants: In this cohort study, adult patients with OSA implanted with HGNS at the Washington University Medical Center in St Louis from April 2019 to January 2023 were included. Data were analyzed from January 2023 to January 2024. Exposure: HGNS. Main Outcomes and Measures: Multivariable logistic regression was performed to assess associations between HGNS treatment response and both BMI and supine sleep. Treatment response was defined as 50% reduction or greater in preimplantation Apnea-Hypopnea Index (AHI) score and postimplantation AHI of less than 15 events per hour. Results: Of 76 included patients, 57 (75%) were male, and the median (IQR) age was 61 (51-68) years. A total of 59 patients (78%) achieved a treatment response. There was a clinically meaningful reduction in median (IQR) AHI, from 29.3 (23.1-42.8) events per hour preimplantation to 5.3 (2.6-12.3) events per hour postimplantation (Hodges-Lehman difference of 23.0; 95% CI, 22.6-23.4). In adjusted analyses, patients with BMI of 32 to 35 had 75% lower odds of responding to HGNS compared with those with a BMI of 32 or less (odds ratio, 0.25; 95% CI, 0.07-0.94). Of 44 patients who slept in a supine position, 17 (39%) achieved a treatment response, with a clinically meaningful reduction in median (IQR) supine AHI from 46.3 (33.6-63.2) events per hour preimplantation to 21.8 (4.30-42.6) events per hour postimplantation (Hodges-Lehman difference of 24.6; 95% CI, 23.1-26.5). In adjusted analysis, BMI was associated with lower odds of responding to HGNS with supine AHI treatment response (odds ratio, 0.39; 95% CI, 0.04-2.59), but the imprecision of the estimate prevents making a definitive conclusion. Conclusions and Relevance: This study adds to the growing body of literature supporting the use of HGNS for OSA treatment. Sleep medicine clinicians should consider informing patients that higher BMI and supine sleeping position may decrease therapeutic response to HGNS. Future research is needed to replicate these findings in larger, more diverse cohorts, which would facilitate the optimization of treatment strategies and patient counseling for HGNS therapy.

Extracranial Hypoglossal Schwannoma: Case Report and Literature Review.

BACKGROUND: Schwannomas are solitary neurogenic tumors originating from the myelin sheath of peripheral nerves. Extracranial hypoglossal schwannomas comprise <5% of all head and neck schwannomas and can mimic submandibular salivary gland tumors. CASE REPORT: We report the diagnostic imaging, surgical treatment, and histopathological findings of a rare case of extracranial schwannoma of the hypoglossal nerve in a 73-year-old female, presented with an asymptomatic swelling in the left submandibular region that had been persisted for approximately three years. CONCLUSION: Accurate diagnosis of this rare clinical entity requires comprehensive diagnostics. The optimal therapeutic strategy is nerve-sparing surgical excision, although it can be challenging.

[Postoperative effect analysis of different surgical techniques used in facial nerve reconstruction].

Objective:To investigate the factors and efficacy of different surgical techniques used in facial nerve（FN） reconstruction. Methods:A retrospective analysis was conducted on 24 patients who underwent facial nerve reconstruction surgery in our department from January 2016 to January 2021. The duration of total facial nerve paralysis was less than 18 months. The study included 5 surgical techniques, including 6 cases of FN anastomosis（Group A）, 5 cases of FN grafting（sural nerve or great auricular nerve）（Group B）, 5 cases of side-to-end facial-hypoglossal nerve anastomosis（Group C）, 4 cases of side-to-end FN grafting（sural nerve or great auricular nerve） hypoglossal nerve anastomosis（Group D）, and 4 cases of dual nerve reanimation（Group E）. The postoperative follow-up period was ≥1 year. Results:The HB-Ⅲ level of FN function at 1 year after surgery was 83.3%（5/6） in group A, 60.0%（3/5） in group B, 40.0%（2/5） in group C, 25.0%（1/4） in group D, and 50.0%（2/4） in group E. In patients without multiple FN repair, the incidence of synkinesis was 15.0%（3/20）, while no cases of synkinesis were observed in patients with dual nerve reanimation. The patients who underwent hypoglossal-facial side-to-end anastomosis showed no hypoglossal nerve dysfunction. Conclusion:Different FN repair techniques result in varying postoperative FN function recovery, as personalized repair should be managed. Among the various techniques, FN end-to-end anastomosis after FN transposition is recommended as to reduce the number of anastomotic stoma, while hypoglossal-facial side-to-end anastomosis is advocated as to prevent postoperative hypoglossal nerve dysfunction. Additionally, dual nerve repair can effectively improve smile symmetry and reduce synkinesis, which enhances patients' quality.

Polysomnographic airflow shapes and site of collapse during drug-induced sleep endoscopy.

BACKGROUND: Differences in the pharyngeal site of collapse influence efficacy of non-continuous positive airway pressure therapies for obstructive sleep apnoea (OSA). Notably, complete concentric collapse at the level of the palate (CCCp) during drug-induced sleep endoscopy (DISE) is associated with reduced efficacy of hypoglossal nerve stimulation, but CCCp is currently not recognisable using polysomnography. Here we develop a means to estimate DISE-based site of collapse using overnight polysomnography. METHODS: 182 OSA patients provided DISE and polysomnography data. Six polysomnographic flow shape characteristics (mean during hypopnoeas) were identified as candidate predictors of CCCp (primary outcome variable, n=44/182), including inspiratory skewness and inspiratory scoopiness. Multivariable logistic regression combined the six characteristics to predict clear presence (n=22) versus absence (n=128) of CCCp (partial collapse and concurrent tongue base collapse excluded). Odds ratios for actual CCCp between predicted subgroups were quantified after cross-validation. Secondary analyses examined complete lateral wall, tongue base or epiglottis collapse. External validation was performed on a separate dataset (ntotal=466). RESULTS: CCCp was characterised by greater scoopiness (ß=1.5±0.6 per 2sd, multivariable estimate±se) and skewness (ß=11.4±2.4) compared with non-CCCp. The odds ratio for CCCp in predicted positive versus negative subgroups was 5.0 (95% CI 1.9-13.1). The same characteristics provided significant cross-validated prediction of lateral wall (OR 6.3, 95% CI 2.4-16.5), tongue base (OR 3.2, 95% CI 1.4-7.3) and epiglottis (OR 4.4, 95% CI 1.5-12.4) collapse. CCCp and lateral wall collapse shared similar characteristics (skewed, scoopy), diametrically opposed to tongue base and epiglottis collapse characteristics. External validation confirmed model prediction. CONCLUSIONS: The current study provides a means to recognise patients with likely CCCp or other DISE-based site of collapse categories using routine polysomnography. Since site of collapse influences therapeutic responses, polysomnographic airflow shape analysis could facilitate precision site-specific OSA interventions.

Impact of Hypoglossal Nerve Stimulation on Consumer Sleep Technology Metrics and Patient Symptoms.

OBJECTIVES: Obstructive sleep apnea (OSA) is usually assessed at discrete and infrequent timepoints. Wearable consumer sleep technologies (CST) may allow for more granular and longitudinal assessments of OSA therapy responses and OSA-related symptoms. METHODS: In this case series, we enrolled hypoglossal nerve stimulator (HGNS) patients who had an effective treatment response for an 8-week study using a wearable CST. Participants started with "HGNS-on," were randomized to turn off HGNS therapy during either week 4 or 5 ("HGNS-off"), followed by a return to therapy, "HGNS-resume." Participants completed validated symptom questionnaires assessing sleepiness, insomnia symptoms, functional status, and overall sleep health (Satisfaction, Alertness, Timing, Efficiency, and Duration, SATED) each week. CST metrics and survey scores were compared between HGNS treatment phases. Associations between CST metrics and survey scores were assessed. RESULTS: Seven participants with a total of 304 nights of CST data showed no statistically significant changes in total sleep time (TST), wake time after sleep onset, or sleep efficiency (SE) across the study periods. During HGNS-off, survey scores indicated significantly worsened OSA-related symptom scores. Two participants had significantly higher heart rate variability (HRV) during HGNS-off (by 3.3 and 6.3 ms) when compared to HGNS active therapy periods. Amongst CST metrics, SATED scores correlated with TST (r = 0.434, p < 0.0001), HRV (r = -0.486, p < 0.0001), and SE (r = 0.320, = 0.0014). In addition, FOSQ-10 scores correlated with average HR during sleep (r = -0.489, p < 0.001). CONCLUSION: A 1-week HGNS therapy withdrawal period impacted OSA-related sleep symptoms. Sleep-related metrics measured by a wearable CST correlated with symptom scores indicating potential value in the use of CSTs for longitudinal sleep-tracking in OSA patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3406-3411, 2024.

Case report of hypoglossal nerve stimulation therapy failure due to significant underlying central sleep apnea.

Hypoglossal nerve stimulation is indicated for obstructive sleep apnea but is ineffective in treating central sleep apnea. We describe 2 patients implanted with hypoglossal nerve stimulation after being diagnosed with obstructive sleep apnea at outside sleep laboratories and failing a trial of continuous positive airway pressure therapy. Despite successful hypoglossal nerve stimulation implantation, the patients continued to have persistent symptoms with residual apnea-hypopnea indices above 25 events/h. Although obstructive sleep apnea was the presenting diagnosis, we discovered a significant central sleep apnea component in the original diagnostic sleep data upon careful review. One patient was confirmed to have a central sleep apnea-predominant sleep disorder and improved with adaptive servo-ventilation therapy. The other was diagnosed with central sleep apnea and severe periodic limb movement disorder, and improved with medication. Based on these sleep apnea cases, we propose guidelines emphasizing the importance of reviewing basic clinical information upon treatment failure and initiating multidisciplinary collaboration early in the treatment course. CITATION: Banerjee D, Lee C-H, Im K. Case report of hypoglossal nerve stimulation therapy failure due to significant underlying central sleep apnea. J Clin Sleep Med. 2024;20(6):1003-1007.

Neurostimulation for Pediatric Obstructive Sleep Apnea.

Up to 80% of children with Down syndrome (DS) are affected by obstructive sleep apnea (OSA), and only 16% to 30% will have resolution of their OSA with adenotonsillectomy. Hypoglossal nerve stimulation is a well-established therapy for adults with OSA and was recently approved by the Food and Drug Administration for use in children with DS and residual OSA. There is robust experience with this therapy in adults that has led to well-established care pathways. However, given the challenges inherent to caring for a complex pediatric population, these pathways are not directly transferrable to children with DS.

Neurostimulation for Obstructive Sleep Apnea.

Neurostimulation of hypoglossal nerve has emerged as an effective treatment option of obstructive sleep apnea (OSA). Since FDA approval in 2014, therapy has been widely used in select patients with moderate-to-severe OSA who do not benefit from positive airway pressure. Ongoing research and technological developments continue to advance the therapy to deliver personalized and efficient treatment to patients with OSA.

Extracranial transport of brain lymphatics via cranial nerve in human.

Extracranial waste transport from the brain interstitial fluid to the deep cervical lymph node (dCLN) is not extensively understood. The present study aims to show the cranial nerves that have a role in the transport of brain lymphatics vessels (LVs), their localization, diameter, and number using podoplanin (PDPN) and CD31 immunohistochemistry (IHC) and Western blotting. Cranial nerve samples from 6 human cases (3 cadavers, and 3 autopsies) were evaluated for IHC and 3 autopsies for Western blotting. The IHC staining showed LVs along the optic, olfactory, oculomotor, trigeminal, facial, glossopharyngeal, accessory, and vagus nerves. However, no LVs present along the trochlear, abducens, vestibulocochlear, and hypoglossal nerves. The LVs were predominantly localized at the endoneurium of the cranial nerve that has motor components, and LVs in the cranial nerves that had sensory components were present in all 3 layers. The number of LVs accompanying the olfactory, optic, and trigeminal nerves was classified as numerous; oculomotor, glossopharyngeal, vagus, and accessory was moderate; and facial nerves was few. The largest diameter of LVs was in the epineurium and the smallest one was in the endoneurium. The majority of Western blotting results correlated with the IHC. The present findings suggest that specific cranial nerves with variable quantities provide a pathway for the transport of wastes from the brain to dCLN. Thus, the knowledge of the transport of brain lymphatics along cranial nerves may help understand the pathophysiology of various neurological diseases.

Effect of hypoglossal nerve stimulation on snoring: an evaluation using objective acoustic parameters.

STUDY OBJECTIVES: Hypoglossal nerve stimulation is an established therapy for sleep apnea syndrome. Whether or not this therapy on snoring and nighttime noise exposure is effective and how strong this effect may be has not been objectively investigated thus far and was the aim of this study. METHODS: In 15 participants (14 males; age: 30-72 years; mean: 51.7 years), polysomnography and acoustic measurements were performed before and after hypoglossal nerve stimulation. RESULTS: The therapy led to a significant improvement in sleep apnea (apnea-hypopnea index from 35.8 events/h to 11.2 events/h, P < .001). Acoustic parameters showed a highly significant reduction in the average sound pressure level (42.9 db[A] to 36.4 db[A], P < .001), averaged sound energy, A-weighted (LAeq; 33.1 db[A] to 28.7 db[A], P < .001), snoring index (1,068 to 506, P < .001), percentage snoring time (29.7-14.1%, P < .001), and psychoacoustic snore score, the latter being a measure of annoyance due to snoring (47.9 to 24.5, P < .001). CONCLUSIONS: This study was able to show for the first time by means of objective acoustic and psychoacoustic parameters that hypoglossal nerve stimulation can not only cause a significant improvement in sleep apnea but also has a positive effect on snoring and thus noise annoyance experienced by the bed partner. CLINICAL TRIAL REGISTRATION: Registry: German Clinical Trials Register; Name: Effect of Hypoglossal Nerve Stimulation on Snoring: An Evaluation Using Objective Acoustic Parameters; URL: https://drks.de/search/de/trial/DRKS00032354; Identifier: DRKS00032354. CITATION: Fischer R, Vielsmeier V, Kuehnel TS, et al. Effect of hypoglossal nerve stimulation on snoring: an evaluation using objective acoustic parameters. J Clin Sleep Med. 2024;20(3):363-370.

Hypoglossal nerve stimulation over-titration.

This case report reviews worsening obstructive sleep apnea (OSA) events in a patient over-titrated with a hypoglossal nerve stimulator. A healthy 57-year-old man underwent hypoglossal nerve stimulator implantation for moderate OSA. During an in-laboratory hypoglossal nerve stimulator titration the patient had improvement of his OSA at 2.1 V. However, a further increase of voltage resulted in worsening of obstructive events. The pathophysiology behind this finding is unknown but may result from unfavorable changes in the upper anatomy due to higher energy delivered to the hypoglossal nerve and surrounding structures. This high energy may also lead to genioglossus muscle fatigue. This finding highlights the importance of hypoglossal nerve stimulation titration with a dedicated sleep study. CITATION: Chang M, Moore V, Eng K, Ryden A, Zeidler M. Hypoglossal nerve stimulation over-titration. J Clin Sleep Med. 2024;20(6):999-1001.

Right Versus Left Cuff Position for Upper Airway Stimulation.

OBJECTIVE: Upper airway stimulation (UAS) is a treatment option for obstructive sleep apnea in which electrical stimulation is applied to the hypoglossal nerve. Nerve branches that control tongue protrusion are located inferiorly. Due to positioning, left-sided implants are typically placed with an inferiorly oriented electrode cuff (L-down) as opposed to superiorly on the right (R-up). In this study, we assess the impact of left- versus right-sided UAS on patient outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary Academic Medical Center. METHODS: Patients who underwent UAS implantation between 2016 and 2021 with an L-down or R-up oriented cuff as confirmed by X-ray were included. Data were collected retrospectively. Most recent sleep study variables were used for analysis. RESULTS: A total of 190 patients met the inclusion criteria. The average age was 61.0 ± 11.0 years, with 55 (28.9%) females. L-down orientation was present in 21 (11.1%) patients vs 169 (88.9%) R-up. Indications for L-down included hunting/shooting (n = 15), prior radiation/surgery (n = 4), central port (n = 1), and brachial plexus injury (n = 1). Adherence was higher among L-down patients (47.1 vs 41.0 hours use/week, P = .037) in univariate analysis, with a similar time to adherence data collection (4.4 vs 4.2 months, P = .612), though this finding was not maintained in the multivariate regression analysis. Decrease in apnea-hypopnea index (21.3 vs 22.8, P = .734), treatment success (76.5% vs 84.0%, P = .665), functional threshold (1.5 vs 1.6, P = .550), therapeutic amplitude (2.3 vs 2.4, P = .882), and decrease in Epworth Sleepiness Scale (4.9 vs 2.6, P = .060) were not significantly different between cohorts. CONCLUSION: This study is the first to examine the orientation of the UAS electrode cuff concerning the electrodes' natural position and the potential effect on postoperative outcomes. Our study found no significantly different treatment outcomes between the L-down versus R-up cohort, with the exception of device adherence, which was significantly higher in the L-down group on univariate analysis though not on multivariate analysis. Future studies with larger patient cohorts are needed to further investigate this potential relationship between treatment outcomes and electrode cuff orientation.

Electromyography findings in radiation-induced unilateral tongue immobility.

BACKGROUND: We used electromyography to characterize hypoglossal nerve function among radiation-treated head and neck cancer survivors with later onset unilateral tongue immobility. METHODS: Patients with unilateral tongue immobility without evidence of recurrent cancer were seen at a tertiary academic institution between February and September 2021. All patients were at least 2 years post-treatment with radiation therapy for head and neck squamous cell carcinoma. Participants were under annual surveillance and displayed no evidence of operative injury to the hypoglossal nerve. RESULTS: The median symptom-free interval for the 10 patients included in this study was 13.2 years (range 2-25 years). Myokymia alone was present in 3 of 10 patients, fibrillation potentials alone were present in 3 of 10 patients, and 1 subject displayed both fibrillation and myokymia. Three out of 10 patients had normal hypoglossal nerve function. DISCUSSION: These findings highlight how disparate mechanisms may underlie similar clinical presentations of radiation-induced neuromuscular dysfunction.

Treatment of Residual Palatal Collapse in Hypoglossal Nerve Stimulation Using a Palatal Device.

Hypoglossal nerve stimulation (HNS) has increasingly become an alternative therapy for obstructive sleep apnea patients with CPAP intolerance. Stimulation of the hypoglossal nerve during sleep enhances airway patency and alleviates collapse. Suboptimal responses to HNS often stem from insufficient palatal coupling and residual velar collapse. Combining palatal devices, such as Velumount®, with HNS represents a simple and cost-effective strategy to treat residual palatal collapse. Patients desiring conservative treatment for residual palatal obstruction under HNS may consider this combined approach. Laryngoscope, 134:3412-3414, 2024.

Pediatric Down Syndrome Upper Airway Stimulation: Patient Selection and Post-Implantation Optimization.

OBJECTIVE: The Food and Drug Administration recently approved upper airway stimulation (UAS) for children with Down Syndrome and persistent obstructive sleep apnea who meet certain inclusion and exclusion criteria. Although there is a robust experience with this therapy in the adult population, established protocols used in adults are not directly transferrable to a complex pediatric population. This review aims to combine the protocols from several institutions for patient selection and postimplantation optimization, including a protocol for Drug-Induced Sleep Endoscopy in children with Down Syndrome, preactivation threshold measurements, device titration, and follow-up sleep studies. STUDY DESIGN: Expert panel development of best Practice algorithm. SETTING: Multi-institutional investigator review. METHODS: An expert panel was assembled of pediatric otolaryngologists with extensive experience in hypoglossal nerve stimulation in children with Down Syndrome. Thirty statements were created during an initial drafting session. A modified Delphi method was used assess consensus among the panel. RESULTS: After 2 rounds of Delphi surveys, 29 statements met criteria for consensus. One statement did not meet consensus. The statements were grouped into several categories to facilitate presentation. CONCLUSIONS: A standardized approach to UAS for children with Down Syndrome must take into account the unique challenges inherent to treating a complex pediatric population with a high rate of sensory processing disorders. This expert panel has met consensus on several statements that will guide clinicians as this novel therapy is adopted.

Patient-reported experience with hypoglossal nerve stimulation in the treatment of obstructive sleep apnea.

BACKGROUND: Breathing-synchronized hypoglossal nerve stimulation (HNS) is routinely used as an alternative treatment for patients with obstructive sleep apnea (OSA). Significant and clinically relevant improvements in disease severity and OSA symptoms such as daytime sleepiness as well as overall quality of life have been reported in randomized-controlled trials and large real-world cohort studies. However, so far, few data exist on patient-reported experience with the treatment. METHODS: A structured survey with 22 questions was constructed using five-level Likert scales (1 = no agreement, 5 = complete agreement) to evaluate patient experience with HNS and perception of the treatment in the domains "Overall experience with therapy," "Experience with treatment process," and "Side-effects from treatment." Additional data were collected on current symptom status, measured with Epworth sleepiness scale (ESS) questionnaire, and OSA disease history. Multiple linear regression analysis was conducted to test associations of medical variables and response behavior. Correlations between variables and domains, as well as individual items, were assessed using Spearman rank test. RESULTS: A total of 75 patients from Germany who were treated with breathing-synchronized HNS were enrolled (mean age 57.3 years, 78% male), and 71 questionnaires with complete data were included for analysis. Two-thirds of participants (67%) had a history of OSA history for 5 years or longer. Of all patients, 76% had normalized OSA symptoms at time of the study (ESS: 6.4 ± 5.0) and 98% reported using stimulation therapy every night. Regression analysis revealed an association of current symptoms measured with ESS and response behavior. Hence, patients with normalized daytime sleepiness reported significantly more positive experience across all domains assessed, compared to patients with residual daytime sleepiness. Overall, only 2% of participants reported side effects that made them reduce or discontinue stimulation therapy. The rate of reported side effects was associated with current symptom control under therapy. CONCLUSIONS: Overall patient-reported experience with breathing-synchronized HNS therapy was positive and high satisfaction with the treatment process was observed. Side effects occurred, but rarely affected subjective use of the therapy or satisfaction. Subjective experience and perception are influenced by residual daytime sleepiness with stimulation therapy.