Bioluminescence-optogenetics-mediated gene therapy in a sleep-disordered breathing mouse model.

Obstructive sleep apnea (OSA) incurs a huge individual, societal, and economic burden. Specific and selective targeting of hypoglossal motor neurons could be an effective means to treat OSA. Bioluminescent-optogenetics (BL-OG) is a novel genetic regulatory approach in which luminopsins, fusion proteins of light-generating luciferase and light-sensing ion channels, increase neuronal excitability when exposed to a suitable substrate. Here we develop and validate the feasibility of BL-OG for sleep-disordered breathing (SDB). Upon confirming that diet-induced obese mice represent an excellent SDB model, we employed a method of targeting the hypoglossal nucleus (12 N) by peripherally injecting retrogradely transported rAAV2/Retro. With AAV transduction, the eLMO3 protein is expressed in hypoglossal motor neurons (HMN); administration of CTZ results in production of bioluminescence that in turn activates the tethered channelrhodopsin, leading to an increase in the firing of HMN and a 2.7 ± 0.8-fold increase in phasic activity of the genioglossus muscle, a 7.6 ± 1.8-fold increase in tonic activity, and improvements in hypoventilation and apnea index without impacting sleep structure. This is therefore the first study to leverage the rAAV2/Retro vector to execute the BL-OG approach in SDB, which amplified genioglossus muscle discharge activity and increased airflow in mice after activation. This study marks the pioneering utilization of BL-OG in SDB research.

Addressing the gaps: What social media tells us about patient experiences with hypoglossal nerve stimulation.

PURPOSE: Hypoglossal nerve stimulation (HNS) can be an effective treatment for moderate to severe obstructive sleep apnea (OSA) in positive airway pressure (PAP) intolerant patients. To better understand patient perceptions of HNS therapy, we explored three Facebook groups pertaining to HNS therapy. MATERIALS AND METHODS: A retrospective analysis of Facebook posts from three HNS-related Facebook groups, from October 1, 2022 to October 1, 2023, was performed. Posts were analyzed for author attitude, content (adverse events, inquiries, or sharing information), and the inclusion of media within the post. RESULTS: From 737 Facebook posts, 752 events were identified, predominantly authored by patients or family (99.5 %). Few posts included media attachments (7.3 %), primarily photos (85.5 %). Post tone was mainly neutral (79.4 %), rather than positive (12.9 %) or negative (7.7 %). Most posts (53.6 %) were queries to the Facebook group, as opposed to sharing information (28.9 %) or detailing adverse events (17.6 %). Notably queries posed by Facebook group members included those pertaining to the postoperative recovery course (10.17 %), physical activity restrictions (6.20 %), HNS therapy eligibility (4.71 %), financial considerations (4.22 %), and more. CONCLUSION: Overall, Facebook group members reported a predominantly neutral tone, typically posting queries to the group rather than sharing information or detailing adverse events. These findings illustrate how diverse data sources, such as social media, can enhance our understanding of patient experiences and identify gaps in patient education with HNS therapy.

Comparative analysis of pain outcomes in hypoglossal nerve stimulation: Avoiding the digastric tendon.

OBJECTIVE: Upper airway stimulation effectively treats patients with obstructive sleep apnea, especially among those with low long-term compliance with continuous positive airway pressure. Traditional methods to implant the hypoglossal nerve stimulator involve retraction of the digastric tendon to identify the nerve and improve exposure for stimulator implantation. Transient submental pain and discomfort are known side effects of the procedure. Placement without retraction provides an alternative approach to minimize postoperative pain. This study compares post-operative pain outcomes of patients in whom the digastric tendon was and was not retracted. METHODS: Retrospective chart review of patients who received the hypoglossal nerve stimulation implant at a single institution between 2017 and 2021. A combination of descriptive and qualitative data, including age, gender, comorbidities, and postoperative symptoms are analyzed to characterize patient outcomes resulting from this intraoperative technique. The categorical and continuous variables were analyzed using chi-squared tests and independent t-tests, respectively. RESULTS: Patients report overall satisfaction after implantation and titration. A total of 108 patients underwent HGNS implantation between September 2017 and January 2021 using the aforementioned techniques. 1.69 % of patients experienced postoperative submental pain as compared to 18.37 % prior to the change in technique (p < 0.01). CONCLUSION: Avoidance of digastric tendon retraction in the implantation of the stimulating lead is a safe and effective technique that reduces postoperative pain and discomfort. Our institution has demonstrated an alternative technique for hypoglossal stimulator implantation which improves perioperative outcomes. LAY SUMMARY: Upper airway stimulation is an effective treatment for obstructive sleep apnea. During surgery, the digastric tendon is often moved to identify the nerve and improve access. This study shows that avoiding digastric tendon movement safely reduces postoperative pain and discomfort. LEVEL OF EVIDENCE: III.

Real-world data on polysomnography- and patient-reported outcomes in hypoglossal nerve stimulation and auto-titrating positive airway pressure therapy for obstructive sleep apnea.

BACKGROUND: Few data are available comparing first-line positive airway pressure (PAP) therapy of obstructive sleep apnea (OSA), especially auto-adjusting PAP (aPAP), with second-line hypoglossal nerve stimulation (HGNS) therapy. The aim of this study was to directly compare these therapeutic options by standard polysomnography (PSG)-related parameters and patient-reported outcomes in comparable groups. METHODS: 20 patients (aged 57.30 ± 8.56 years; 6 female) were included in the HGNS and 35 patients (aged 56.83 ± 9.20 years; 9 female) were included in the aPAP group. In both groups participants had to fit the current guideline criteria for HGNS treatment. Groups were compared by analysis of covariance (ANCOVA) using inverse propensity score weighting. RESULTS: Propensity scores did not differ between groups. Pre-therapeutic AHI (HGNS: 40.22 ± 12.78/h; aPAP: 39.23 ± 12.33/h) and ODI (HGNS: 37.9 ± 14.7/h, aPAP: 34.58 ± 14.74/h) were comparable between the groups. After 413.6 ± 116.66 days (HGNS) and 162.09 ± 140.58 days (aPAP) of treatment AHI (HGNS: 30.22 ± 17.65/h, aPAP group: 4.71 ± 3.42/h; p < 0.001) was significantly higher in the HGNS group compared to the aPAP group. However, epworth sleepiness scale (ESS) was post-interventionally significantly lower in the HGNS group compared to the aPAP group (pretherapeutic: HGNS: 13.32 ± 5.81 points, aPAP: 9.09 ± 4.71 points; posttherapeutic: HGNS: 7.17 ± 5.06 points; aPAP: 8.38 ± 5.41 points; p < 0.01). CONCLUSION: These are novel real-world data. More research on the key parameters regarding titration of the HGNS neurostimulation parameter tuning and on the impact of factors influencing HGNS adherence is needed.

[Ten years of hypoglossal nerve stimulation in obstructive sleep apnea: a systematic literature review]. / Zehn Jahre Hypoglossusnerv-Stimulation bei obstruktiver Schlafapnoe ­ ein systematischer Literaturreview.

OBJECTIVE: To show the importance of hypoglossal nerve stimulation (HGNS) as a treatment method for obstructive sleep apnea (OSA) in the German healthcare context and to better assess the way patients who do not receive adequate care could benefit from HGNS. METHODS: A systematic literature review in the Medline and Cochrane Library literature database was conducted, including publications using different stimulation technologies for HGNS. The efficacy of HGNS was assessed based on patient-relevant outcomes (daytime sleepiness, quality of life), treatment adherence and the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). The safety of the treatment method was assessed based on adverse events (AEs). RESULTS: Inclusion and analysis of 33 publications: 2 randomized controlled trials (RCTs, level Ib), 1 level IIb trial (n = 1) and 30 level IV trials with a study duration of up to 60 months. The RCTs showed better values for daytime sleepiness and quality of life when using HGNS than in the control group. AHI and ODI showed a deterioration under placebo stimulation or therapy withdrawal in the RCTs. Consistently high adherence was also reported in the long-term course. Severe AEs under HGNS were rare and could usually be resolved by repositioning electrodes or replacing device components. Other AEs were mostly transient or could be resolved by non-invasive measures. All investigated parameters showed similar results in the evaluated studies. The results of different stimulation systems are comparable in type and extent. CONCLUSION: The comprehensive review of the literature shows consistent data that highlight the importance of HGNS as an effective and safe treatment for OSA after unsuccessful CPAP treatment. The evaluation also shows that the different stimulation systems make it possible to better tailor the therapy to the patient's individual requirements. A future systematic evaluation of real-world data on the use of HGNS would help gain additional insights into the relevance of the method in routine clinical practice.

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.

Spontaneous regeneration after resection of various lengths of hypoglossal nerve in rats.

OBJECTIVES: The objective of this study was to investigate spontaneous neural regeneration and functional recovery after resection of various lengths of the hypoglossal (XII) nerve in adult rats. METHODS: Twelve weeks after XII nerve resection at lengths ranging from 0.0 to 15.8 mm, the tongue deviation angle of rats was measured to evaluate the severity of paralysis; thereafter, the XII neurons in the XII nucleus were labeled with Fluoro-Gold (FG), which was injected into the tongue to visualize regenerated XII neurons re-innervating the tongue muscles. RESULTS: In the XII nerve-resected rats, the regenerative rates, that is, the percentage of the total number of FG-positive neurons on the injured side relative to that on the uninjured side, were divided into two groups; the regenerative rates were more than 77% and less than 6%, respectively. Upon comparing the two groups, the boundary resection length was approximately 10.0 mm. Moreover, the former and latter groups demonstrated tongue deviation angles less than or greater than 15°, respectively. CONCLUSIONS: The critical nerve gap length for spontaneous neural regeneration was approximately 10.0 mm in XII nerve-resected adult rats, and nerve regeneration occurred in both morphological and functional aspects after resection at less than the critical length.

Exploring hypoglossal nerve stimulation therapy for obstructive sleep apnea: A comprehensive review of clinical and physiological upper airway outcomes.

Obstructive sleep apnea (OSA) is a chronic disorder characterized by recurrent episodes of upper airway collapse during sleep, which can lead to serious health issues like cardiovascular disease and neurocognitive impairments. While positive airway pressure serves as the standard treatment, intolerance in some individuals necessitates exploration of alternative therapies. Hypoglossal nerve stimulation (HGNS) promises to mitigate OSA morbidity by stimulating the tongue muscles to maintain airway patency. However, its effectiveness varies, prompting research for optimization. This review summarizes the effects of HGNS on upper airway obstruction from human and animal studies. It examines physiological responses including critical closing pressure, maximal airflow, nasal and upper airway resistance, compliance, stiffness, and geometry. Interactions among these parameters and discrepant findings in animal and human studies are explored. Additionally, the review summarizes the impact of HGNS on established OSA metrics, such as the apnea-hypopnea index, oxygen desaturation index, and sleep arousals. Various therapeutic modalities, including selective unilateral or bilateral HGNS, targeted unilateral HGNS, and whole unilateral or bilateral HGNS, are discussed. This review consolidates our understanding of HGNS mechanisms, fostering exploration of under-investigated outcomes and approaches to drive advancements in HGNS therapy.

Persistent glossopharyngeal nerve respiratory discharge patterns after ponto-medullary transection.

Shape and size of the nasopharyngeal airway is controlled by muscles innervated facial, glossopharyngeal, vagal, and hypoglossal cranial nerves. Contrary to brainstem networks that drive facial, vagal and hypoglossal nerve activities (FNA, VNA, HNA) the discharge patterns and origins of glossopharyngeal nerve activity (GPNA) remain poorly investigated. Here, an in situ perfused brainstem preparation (n=19) was used for recordings of GPNA in relation to phrenic (PNA), FNA, VNA and HNA. Brainstem transections were performed (n=10/19) to explore the role of pontomedullary synaptic interactions in generating GPNA. GPNA generally mirrors FNA and HNA discharge patterns and displays pre-inspiratory activity relative to the PNA, followed by robust inspiratory discharge in coincidence with PNA. Postinspiratory (early expiratory) discharge was, contrary to VNA, generally absent in FNA, GPNA or HNA. As described previously FNA and HNA discharge was virtually eliminated after pontomedullary transection while an apneustic inspiratory motor discharge was maintained in PNA, VNA and GPNA. After brainstem transection GPNA displayed an increased tonic activity starting during mid-expiration and thus developed prolonged pre-inspiratory activity compared to control. In conclusion respiratory GPNA reflects FNA and HNA which implies similar function in controlling upper airway patency during breathing. That GPNA preserved its pre-inspiratory/inspiratory discharge pattern in relation PNA after pontomedullary transection suggest that GPNA premotor circuits may have a different anatomical distribution compared HNA and FNA and thus may therefore hold a unique role in preserving airway patency.

Device-related outcomes following hypoglossal nerve stimulator implantation.

STUDY OBJECTIVES: Hypoglossal nerve stimulation (HGNS) has been widely used to treat obstructive sleep apnea in selected patients. Here we evaluate rates of revision and explant related to HGNS implantation and assess types of adverse events contributing to revision and explant. METHODS: Postmarket surveillance data for HGNS implanted between January 1, 2018 and March 31, 2022, were collected. Event rates and risk were calculated using the postmarket surveillance event counts and sales volume over the same period. Indications were categorized for analysis. Descriptive statistics were reported and freedom from explant or revision curves were grouped by year of implantation. RESULTS: Of the 20,881 HGNS implants assessed, rates of explant and revision within the first year were 0.723% and 1.542%, respectively. The most common indication for explant was infection (0.378%) and for revision was surgical correction (0.680%). Of the 5,820 devices with 3-year postimplantation data, the rate of explant was 2.680% and of revision was 3.557%. During this same interval, elective removal (1.478%) was the most common indication, and for revisions, surgical correction (1.134%). CONCLUSIONS: The efficacy of HGNS is comparable in the real world setting to published clinical trial data. Rates of explant and revision are low, supporting a satisfactory safety profile for this technology. CITATION: Moroco AE, Wei Z, Byrd I, et al. Device-related outcomes following hypoglossal nerve stimulator implantation. J Clin Sleep Med. 2024;20(9):1497-1503.

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.

A Protocolized Approach to Awake Endoscopy With Advanced Programming to Optimize Hypoglossal Nerve Stimulation.

Hypoglossal nerve stimulation is a treatment option for patients with obstructive sleep apnea who are intolerant to positive airway pressure therapy. In the post-implant period, awake endoscopy with advanced programming (AEAP) can be employed to optimize apnea-hypopnea index reduction and/or patient comfort and usage. The report herein describes awake endoscopy with AEAP as a guide to providers involved in post-implant care. The first 5 consecutive patients were reviewed to provide general understanding of outcomes and safety when implementing such a protocolized approach.

[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.

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.

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.

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.

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.