Outcome Reporting in Prospective Studies Evaluating Neurostimulation for Obstructive Sleep Apnea.

OBJECTIVE: Due to the controversy surrounding the appropriate outcomes in neurostimulation, we sought to systematically describe ways in which polysomnography and apnea-hypopnea index are reported in prospective studies involving unilateral hypoglossal nerve stimulation. DATA SOURCES: MEDLINE (Ovid), Embase (Ovid), Cochrane Library, and Scopus. REVIEW METHODS: Following the Preferred Reporting items of Systematic Reviews and Meta-analysis (PRISMA) Statement guidelines, a systematic two-reviewer system was used for study screening and quality assessment. Articles that met inclusion criteria were included. Quality was evaluated with either the Newcastle-Ottawa Quality Assessment Scale or the Covidence risk-of-bias tool. RESULTS: Fifteen studies met the inclusion criteria, which included 14 prospective cohort studies and one randomized controlled trial. Titration polysomnography was the primary sleep study used to acquire data in five of the studies compared to only three studies employing exclusively non-titration polysomnography to report outcomes. Three studies compiled data from two or more sleep studies to report a single apnea-hypopnea index. Within the 15 studies, non-titration apnea-hypopnea index was the most reported type (five studies). Titration apnea-hypopnea index was used to report outcomes in one study. Five studies did not specify what type of apnea-hypopnea index was employed to report treatment effectiveness. CONCLUSION: The reported sleep studies and corresponding apnea-hypopnea indices were highly variable across the studies. Because of the high degree of heterogeneity, future research would benefit from consistent use of a standardized apnea-hypopnea index to report outcomes related to hypoglossal nerve stimulation. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Oral appliance therapy and hypoglossal nerve stimulation as non-positive airway pressure treatment alternatives for obstructive sleep apnea: a narrative expert review.

This perspective on alternatives to positive airway pressure (PAP) therapy for the treatment of obstructive sleep apnea (OSA) summarizes the proceedings of a focus group that was conducted by the Sleep Research Society Foundation. This perspective is from a multidisciplinary panel of experts from sleep medicine, dental sleep medicine, and otolaryngology that aims to identify the current role of oral appliance therapy and hypoglossal nerve stimulation for the treatment of OSA with emphasis on the US practice arena. A secondary aim is to identify-from an implementation science standpoint-the various barriers and facilitators for adoption of non-PAP treatment that includes access to care, multidisciplinary expertise, reimbursement, regulatory aspects, current treatment guidelines, health policies, and other factors related to the delivery of care. The panel has contextualized the review with recent events-such as a large-scale PAP device recall compounded by supply chain woes of the pandemic-and emerging science in the field of OSA and offers solutions for multidisciplinary approaches while identifying knowledge gaps and future research opportunities.

Difficulty Falling Asleep is Associated with Poorer Therapeutic Outcomes in Unilateral Hypoglossal Nerve Stimulation.

Purpose: The coexistence of insomnia and obstructive sleep apnea (OSA) is very prevalent. Hypoglossal nerve stimulation (HGNS) is an established second-line therapy for patients suffering OSA. Studies investigating the effect of the different aspects of insomnia on the therapeutic outcome are largely missing. Therefore, this study aimed to understand the impact of the different aspects of insomnia on the therapeutic outcome under HGNS therapy in clinical routine. Patients and Methods: This is a retrospective study including 30 consecutive patients aged 55.40 ± 8.83 years (8 female; 22 male) undergoing an HGNS implantation in our tertiary medical center between 2020 and 2023. All patients underwent preoperative polysomnography (PSG) according to AASM. First follow-up PSG was performed 95.40 ± 39.44 days after activation (30 patients) and second follow-up PSG was performed 409.89 ± 122.52 days after activation (18 patients). Among others, the following PSG-related parameters were evaluated: apnea-hypopnea index (n/h) (AHI) and oxygen desaturation index (n/h) (ODI). Insomnia was assessed by the insomnia severity index (ISI) questionnaire. Preoperatively, all patients included filled out each ISI item. Spearman's-rho correlation coefficient was calculated for correlations. Results: Preoperative score of ISI item 1 (difficulty falling asleep) was 1.93 ± 1.34 and preoperative cumulative ISI score (item1-7) was 18.67 ± 5.32. Preoperative AHI was 40.61 ± 12.02 (n/h) and preoperative ODI was 38.72 ± 14.28 (n/h). In the second follow-up, the mean difference in AHI was ∆ 10.47 ± 15.38 (n/h) and the mean difference in ODI was ∆ 8.17 ± 15.67 (n/h). Strong significant correlations were observed between ISI item 1 (difficulty falling asleep) and both ∆ AHI (r: -0.65, p=0.004) and ∆ ODI (r: -0.7; p=0.001) in the second follow-up. Conclusion: Difficulty falling asleep may hence negatively influence HGNS therapeutic outcome. Insomnia-related symptoms should be considered in the preoperative patient evaluation for HGNS.

Video-assisted thoracoscopic surgery retrieval of a migrated unilateral hypoglossal nerve stimulator sensor lead.

Obstructive sleep apnea is a common chronic condition typically treated with positive airway pressure. However, many patients have difficulty with adherence to this therapy, and for some, implantation of a hypoglossal nerve stimulator has become an option. Though device implantation is generally well-tolerated, a minority of patients will experience serious adverse events. Here we report the unusual complication of the sensor lead migrating to the costophrenic angle and invading the pleural space. Nine months after original implantation, the sensor lead malfunctioned and was found to be displaced. Initial explantation and reimplantation of a new device resulted in the inability to find a portion of the lead. Reimaging showed the missing lead at the costophrenic angle, and the patient underwent thoracoscopic removal. He resumed therapy with the new device without difficulty. This case demonstrates the ability of the lead to migrate far from the implantation site, which has rarely been reported.

Optimizing Inspire Hypoglossal Nerve Stimulator Settings in Pediatric Obstructive Sleep Apnea.

INTRODUCTION: Hypoglossal nerve stimulation (HGNS) is an effective therapy for carefully selected pediatric patients with Down syndrome (DS) and obstructive sleep apnea (OSA), but optimization of device settings has been focused on stimulation settings. The potential benefits of sensing lead setting optimization have not been investigated. We describe a series of three cases of HGNS in children with DS where optimization of both the stimulation lead and sensing lead settings, as well as utilization of drug-induced sleep endoscopy (DISE), when indicated, was more effective than stimulation lead optimization alone. METHODS: Using our novel titration algorithm, among the three identified pediatric patients with DS in whom HGNS initially failed to reduce the apnea-hypopnea index (AHI), two patients in whom sleep studies were characterized as hypopnea-dominant were assigned to advanced titration (optimization of stimulation settings and sensing lead settings). The third patient, with an obstructive apnea-dominant sleep study, was referred for interrogated DISE. Advanced titration included adjustment of both stimulation settings and sensing lead settings. RESULTS: Application of the advanced titration algorithm, tailored to obstructive apnea- versus hypopnea-dominant sleep patterns, resulted in approximately 50% or greater reduction in AHI in all three patients. "Normal to mild OSA" AHI (AHI <5) was achieved in two patients. CONCLUSIONS: A novel diagnostic and therapeutic titration algorithm for the Inspire HGNS system significantly reduced AHI in three pediatric patients with DS and OSA who had failed to respond to the standard device titration that focused solely on stimulation settings. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

The impact of neck circumference on hypoglossal nerve stimulator therapy outcomes.

STUDY OBJECTIVES: Hypoglossal nerve stimulation (HGNS) therapy has historically had strict eligibility requirements including a body mass index (BMI) < 32 kg/m2. However, recent Food and Drug Administration approval expanded indications to a BMI < 40 kg/m2. There is a wide variability in body fat distribution. This study sought to determine if neck circumference is a better surrogate predictive variable for HGNS outcomes than BMI. METHODS: A retrospective chart review was conducted at a tertiary care center on adults who underwent HGNS implantation by a single surgeon from March 2017 to October 2021. Baseline demographic data including neck circumference, diagnostic sleep studies and post-implantation HGNS titration studies were collected. Linear regression and Spearman's Correlation Coefficient (SCC) analysis were utilized to compare neck circumference (NC), percentage of predicted neck circumference (PPNC) and BMI with the apnea-hypopnea index at effective voltage (AHI-v). RESULTS: This study included 43 patients who were middle aged (61.1 years), predominantly male (76.7%), with severe obstructive sleep apnea (median AHI 35) and mean neck circumference of 15.3 inches. Utilizing the NC and PPNC, positive correlations with AHI-v were observed (p = 0.0033, SCC = .438, and p = 0.0029, SCC = .444). While controlling for BMI, a 1-inch increase in neck circumference was associated with a 35% increase in AHI-v (p = 0.0411). CONCLUSIONS: A larger neck circumference was independently associated with worse HGNS outcomes. Further research is needed to support and confirm these findings, particularly across sexes.

Percutaneous Approaches to Hypoglossal Nerve Stimulation: A Pilot Study During Drug-Induced Sleep Endoscopy.

Hypoglossal nerve stimulation (HNS) is a surgical treatment option for select patients with obstructive sleep apnea that currently requires intraoperative dissection of the hypoglossal nerve (HGN) for implantation of an electrode array. Most HNS strategies target select HGN protrusor muscle branches and exclude undesirable retractor branches. We hypothesized that the target HGN branches could instead be selectively stimulated with a percutaneously delivered electrode array under ultrasound guidance via several anatomic approaches. Five different anatomic approaches were iteratively developed and evaluated during drug-induced sleep endoscopy across 14 patients: posterior, intraoral, anteromedial, anterolateral, and paracoronal. The paracoronal and anterolateral approaches were the most successful, with comparable changes in pharyngeal critical closing and opening pressures. Our data suggest that percutaneous delivery of an HGN electrode is feasible and may decrease the morbidity of HNS therapy implantation. Further work is necessary to ascertain what anatomic approach is optimal for percutaneous electrode delivery.

Comprehensive Analysis of Adverse Events Associated With Hypoglossal Nerve Stimulators: Insights From the MAUDE Database.

OBJECTIVE: This study aims to examine the adverse events associated with hypoglossal nerve stimulator (HNS) implantation for treating obstructive sleep apnea (OSA), drawing data from the Manufacturer and User Facility Device Experience (MAUDE) database. We aim to provide a comprehensive and updated account of these adverse events. STUDY DESIGN: Retrospective analysis. SETTING: MAUDE Database review. METHODS: A retrospective analysis was performed on the MAUDE database to collect all HNS-related reports from May 2014 to December 2023. Variables collected included date of event, event description, nature of event, iatrogenic injuries, required interventions, and, if available, root causes. Each event description was analyzed to classify the adverse event, the postevent intervention, and device model number. RESULTS: Out of 1178 reports fulfilling the inclusion criteria, 1312 adverse events were identified. Common adverse events included infection (24.0%), pain (19.7%), and hematoma/seroma (10.2%). Approximately 83.1% of these adverse events necessitated medical and/or surgical intervention. The most frequent procedures included explantation (29.4%) and device repositioning (15.8%). Pneumothorax was reported in 50 cases, with 41 (82.0%) requiring a chest tube to be inserted. Three adverse events described overstimulation in the setting of magnetic resonance imaging (MRI) despite the implantation of MRI-compatible second-generation internal pulse generators. CONCLUSION: While HNS implantation has been established as a reliable intervention for OSA in cases of continuous positive airway pressure failure or intolerance, this study highlights several perioperative and postoperative difficulties and complications. Understanding these challenges is essential for refining surgical practices and enhancing patient consent processes, ultimately aiming to improve therapeutic outcomes.

Effectiveness of Hypoglossal-Facial Anastomosis in the Rehabilitation of Facial Paralysis Following Vestibular Schwannoma Surgery: A Systematic Review.

The facial nerve plays a crucial role in facial expression and sensory functions, with irreversible injuries often demanding rehabilitation therapies, with hypoglossal-facial nerve anastomosis (HFA) being one of the treatment options. This systematic review assessed different HFA techniques for facial paralysis, particularly post vestibular schwannoma resection, focusing on effectiveness and associated morbidities. Fifteen studies, comprising a case series and a retrospective cohort, were analyzed. Techniques included end-to-end, split, side-to-side, end-to-side, and jump interpositional graft hypoglossal-facial anastomosis (JIGHFA). Positive outcomes were observed with end-to-end and side-to-side techniques, while the split technique and JIGHFA showed promise. Comparative analyses favored the 'end-to-side' approach. Shorter intervals between surgery and HFA correlated with improved outcomes. Methodological variations highlight the need for prospective studies with standardized methodologies for robust evidence and informed decision-making on optimal HFA techniques.

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 0.0-15.8 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.

Turicella otitidis hypoglossal nerve stimulator device associated infection.

71-year-old male with history of obstructive sleep apnea presented with persistent drainage from the surgical incision site over the recently implanted hypoglossal nerve stimulator. Wound cultures from device pocket identified the pathogen as Turicella otitidis. Clinical course included treatment with broad-spectrum intravenous antibiotics and device explantation. This case is the first known T. otitidis device associated infection.

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.

Surgical management of large lower cranial nerves schwannomas: long term results of a less aggressive resection strategy.

In an effort to reduce the high morbidity and life-threatening complications after radical resection in large schwannoma surgery, alternative strategies of nontotal resections have emerged. To evaluate the long term clinical and oncological outcome after lower cranial nerves (LCN) schwannoma surgery operated on with a cranial nerve-sparing technique. Single center retrospective cohort study of 8 consecutive patients harboring LCN schwannomas operated on between March 2005 and October 2021. The mean LCN schwannoma diameter was 33 mm (range 26-51). Seven patients (87,5%) underwent a modified retrosigmoid approach. Three patients underwent gross total resection (37,5%), 3 had received neartotal resection (mean tumor residue 0,25 cc) and subtotal resection in 2 patients who presented with an extracranial extension of the tumor (mean tumor residue 2,44 cc). Both patients had received upfront additional GKRS. The three patients who presented with preoperative CN IX & X injuries recovered within 6 months after surgery. All of the five patients freed from any preoperative CNs IX & X symptoms experienced transient (80%) or definitive (one patient) disturbances after surgery. They all improved within 6 months but one who required long term gastrostomy feeding tube. This patient harbored a schwannoma originating from the glossopharyngeal nerve, which could not be anatomically preserved during surgery. Tumor control was achieved in 100% of cases with a mean follow-up of 91 months. LCN schwannomas could be surgically removed through a less aggressive non-radical resection strategy with acceptable functional results and excellent tumor control.

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: Post-market surveillance data for HGNS implanted between January 1, 2018 and March 31, 2022, were collected. Event rates and risk were calculated using the post-market 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 three-year post-implantation 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.

Hypoglossal Nerve Neuropathies-Analysis of Causes and Anatomical Background.

The hypoglossal nerve is the last, and often neglected, cranial nerve. It is mainly responsible for motor innervation of the tongue and therefore the process of chewing and articulation. However, tumors, aneurysms, dissections, trauma, and various iatrogenic factors such as complications after surgeries, radiotherapy, or airway management can result in dysfunction. Correct differential diagnosis and suitable treatment require a thorough knowledge of the anatomical background of the region. This review presents the broad spectrum of hypoglossal neuropathies, paying particular attention to these with a compressive background. As many of these etiologies are not common and can be easily overlooked without prior preparation, it is important to have a comprehensive understanding of the special relations and characteristic traits of these medical conditions, as well as the most common concomitant disorders and morphological traits, influencing the clinical image. Due to the diverse etiology of hypoglossal neuropathies, specialists from many different medical branches might expect to encounter patients presenting such symptoms.

Relationship of Nocturnal Insomnia Symptoms and Outcomes After Hypoglossal Nerve Stimulation.

Objective: In patients undergoing hypoglossal nerve stimulation (HGNS), we examined the Insomnia Severity Index (ISI) to understand how baseline sleep onset insomnia (SOI), sleep maintenance insomnia (SMI), and early morning awakening (EMA) affected postsurgical outcomes. Study Design: Observational. Setting: Multicenter registry. Methods: We included patients from the Adherence and Outcomes of Upper Airway Stimulation for Obstructive Sleep Apnea International Registry (ADHERE) with a baseline ISI from 2020 to 2023. Regression analysis examined the association of ISI question scores for SOI, SMI, and EMA and outcomes: Apnea-Hypopnea Index (AHI) reduction, device usage, changes in the Epworth Sleepiness Scale (ESS) and overall ISI score, final visit (FV) completion, and satisfaction. Results: No relationship was noted between insomnia subtypes and AHI reduction or FV completion. In the subgroup of patients with baseline moderate/severe insomnia, patients with major impairment for SOI used their device 64 min/day longer than those with minimal impairment. Among all patients, those with baseline major impairment for SOI had a 2.3 points greater improvement in ISI from baseline to FV compared to patients with minimal impairment, while patients with baseline major impairment for SMI had a 2.0 and 3.5 points greater improvement in the ESS and ISI than those with minimal impairment. Patients with EMA and moderate/severe baseline insomnia had decreased odds of being satisfied after surgery. Conclusion: In ADHERE, nocturnal symptoms of insomnia did not limit HGNS efficacy or therapy use. Conversely, those with worse insomnia subtype impairments at baseline had improved outcomes related to adherence, sleepiness, and insomnia at the FV.

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.

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.

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.