1. INTRODUCTION:

Obstructive sleep apnea (OSA) is a common and potentially serious sleep-disordered breathing condition, characterized by recurrent collapse of the upper airway during sleep. These repeated apnea and hypopnea breathing interruptions of obstruction lead to intermittent hypoxemia, hypercapnia, and disruption of normal sleep architecture, resulting in fragmented sleep and excessive daytime sleepiness^1,3. Moderate-to-severe OSA affects nearly one billion adults worldwide, posing a substantial public health burden due to its high prevalence and association with multiple comorbidities^1,3.

Untreated OSA is linked to a broad spectrum of adverse health outcomes, including hypertension, atrial fibrillation, stroke, heart failure, impaired glucose metabolism, cognitive dysfunction, and increased all-cause mortality^2,3,9. The chronic intermittent hypoxia and sleep fragmentation characteristic of OSA contribute to sympathetic nervous system overactivity, endothelial dysfunction, oxidative stress and systemic inflammation, which collectively increase cardiovascular and metabolic risk^2,9.

Continuous positive airway pressure (CPAP) therapy remains the gold standard first-line treatment, effectively maintaining airway patency and normalizing respiratory parameters during sleep. However, long-term adherence remains a major challenge, with 30-60% of patients discontinuing therapy due to mask discomfort, pressure intolerance, claustrophobia, or aerophagia⁴. Surgical interventions, such as uvulopalatopharyngoplasty and multilevel procedures, offer moderate efficacy but are limited by higher perioperative morbidity, variable long-term outcomes and invasiveness⁵.

In this context, hypoglossal nerve stimulation (HGNS) has emerged as a promising minimally invasive neuromodulation therapy. By selectively activating the upper airway dilator muscles, particularly the genioglossus, HGNS improves airway patency during sleep without tissue resection^6,11. The pivotal STAR trial and subsequent studies have demonstrated that HGNS is effective in patients with moderate-to-severe OSA who are intolerant of CPAP, providing durable improvements in apnea hypopnea index (AHI), oxygen saturation, daytime sleepiness, and quality of life^6,13.

2. Pathophysiology of Obstructive Sleep Apnea:

Obstructive sleep apnea (OSA) is a complex disorder resulting from the interplay of anatomical, neuromuscular, and ventilatory control factors. The pathophysiology is multifactorial, with several mechanisms contributing to recurrent upper airway collapse during sleep:

1. Anatomical narrowing: Structural features such as excess soft tissue in the palate, tongue, or lateral pharyngeal walls, craniofacial abnormalities, retrognathia, or obesity-related fat deposition can reduce upper airway caliber, predisposing to collapse during sleep⁸.

2. Neuromuscular hypotonia during sleep: Sleep-associated reduction in the activity of upper airway dilator muscles, particularly the genioglossus and tensor veli palatini, diminishes airway stability and contributes to obstruction⁸.

3. Ventilatory control instability (high loop gain): Patients with an unstable ventilatory control system may overreact to small changes in blood oxygen or carbon dioxide levels, resulting in repeated cycles of fast and slow breathing and multiple pauses in breathing⁹.

4. Abnormal arousal threshold: Altered sensitivity to airway obstruction can result in premature arousals or delayed response to hypoxemia and hypercapnia, perpetuating sleep fragmentation and instability in airway patency⁹.

5. Impaired upper airway motor responsiveness: In some individuals, compensatory activation of airway dilator muscles is insufficient to prevent collapse despite obstruction-related stimuli, exacerbating apneic events¹⁰.

The genioglossus muscle plays a central role in maintaining pharyngeal patency. During wakefulness, sufficient neuromuscular tone stabilizes the airway, but during sleep, reduced muscle activation leads to airway collapse in susceptible individuals⁸. Recurrent obstruction causes intermittent hypoxemia, hypercapnia and arousals, which trigger sympathetic nervous system overactivity, endothelial dysfunction, oxidative stress and systemic inflammation, all of which contribute to long-term cardiovascular and metabolic complications such as hypertension, arrhythmias, stroke, insulin resistance and dyslipidemia^9,10.

Furthermore, repeated airway obstruction can alter sleep architecture, reducing slow-wave and REM sleep, which are essential for metabolic regulation, memory consolidation, and cognitive function. Chronic sleep disruption in OSA is associated with neurocognitive deficits, impaired executive function, mood disorders, and decreased quality of life^9,10.

Hypoglossal nerve stimulation (HGNS) addresses this pathophysiology by delivering timed electrical stimulation to the hypoglossal nerve, activating the genioglossus and other upper airway dilator muscles in synchrony with inspiration. By compensating for diminished neuromuscular tone, HGNS stabilizes the airway, reduces the frequency of apneic events, improves oxygenation and mitigates the downstream cardiovascular, metabolic, and neurocognitive consequences of OSA^10,11.

3. Mechanism of Hypoglossal Nerve Stimulation:

Hypoglossal nerve stimulation (HGNS) is a targeted neuromodulation therapy designed to improve upper airway patency in patients with obstructive sleep apnea (OSA) by electrically activating the muscles responsible for tongue protrusion and airway stabilization. The therapy works by selectively stimulating the hypoglossal nerve branches that innervate the genioglossus and other pharyngeal dilator muscles, thereby compensating for the diminished neuromuscular tone that occurs during sleep^10,11.

Modern HGNS systems typically consist of the following components:

· Cuff electrode: Placed around the selective branches of the hypoglossal nerve to deliver precise electrical stimulation.

· Respiratory sensing lead: Positioned between the intercostal muscles to detect inspiratory effort and synchronize stimulation with the patient’s natural breathing pattern.

· Implantable pulse generator (IPG): Implanted subcutaneously in the chest, it serves as the central control unit that delivers stimulation according to the detected respiratory signals.

· External patient controller: Allows the patient to initiate or adjust therapy nightly, providing user-friendly control over the stimulation sessions.

HGNS operates by timing electrical pulses with inspiration, resulting in forward protrusion and stiffening of the tongue, which increases retrolingual airway space, reduces pharyngeal collapsibility, and lowers critical closing pressure. This mechanism effectively prevents upper airway collapse during sleep while minimizing interference with natural breathing patterns^10,11.

Unlike conventional surgical interventions, such as uvulopalatopharyngoplasty or multilevel airway surgery, HGNS targets neuromuscular function without resecting tissue, making it a minimally invasive option that preserves normal airway anatomy and function. By addressing the neuromuscular deficiency at the core of OSA pathophysiology, HGNS improves sleep quality, reduces apnea hypopnea events and mitigates downstream cardiovascular and metabolic consequences^10,11.

4. Available HGNS Systems:

Several hypoglossal nerve stimulation (HGNS) systems are currently available for the treatment of moderate-to-severe obstructive sleep apnea (OSA), each with distinct design features, stimulation strategies, and clinical evidence. Selection of a specific system depends on patient anatomy, disease severity, and regulatory approvals.

4.1 Inspire Upper Airway Stimulation System:

The Inspire Upper Airway Stimulation System is the most extensively studied HGNS device in the published literature. It comprises a cuff electrode placed around selective hypoglossal nerve branches, a respiratory sensing lead implanted between the intercostal muscles to detect inspiration, and an implantable pulse generator (IPG) positioned in the chest. An external patient controller allows the user to activate therapy nightly^6,13,14.

The Inspire system delivers timed electrical stimulation synchronized with the patient’s inspiratory effort, which protrudes and stabilizes the tongue, expands the retrolingual airway, and reduces critical closing pressure. This targeted approach preserves normal airway anatomy while preventing upper airway collapse during sleep.

4.2 Genio® (Nyxoah) System:

The Genio® System (Nyxoah, Belgium) represents a novel approach to hypoglossal nerve stimulation by employing a bilateral stimulation strategy without the need for an implanted battery. Instead, the system uses a minimally invasive, submentally implanted lead connected to an external wearable stimulator, which delivers electrical pulses to the hypoglossal nerve branches responsible for tongue protrusion¹¹.

This design offers several advantages, including simplified implantation, reduced invasiveness, and elimination of an internal pulse generator, which may improve patient comfort and reduce potential device-related complications. The system coordinates stimulation with respiration, similar to other HGNS devices, thereby enhancing upper airway patency, reducing collapsibility, and preventing apneic events during sleep.

4.3 ImThera Targeted Hypoglossal Neurostimulation:

The ImThera system represents a unique approach to hypoglossal nerve stimulation by targeting multiple branches of the hypoglossal nerve rather than a single branch. This strategy is designed to provide broader activation of upper airway dilator muscles, including the genioglossus and other pharyngeal muscles, thereby enhancing airway patency throughout the oropharyngeal region¹².

The device consists of an implantable lead array positioned around the hypoglossal nerve branches and an implantable pulse generator (IPG) that delivers stimulation. Unlike some other HGNS systems, ImThera does not rely on a respiratory sensing lead, instead, it provides continuous stimulation during sleep based on pre-programmed parameters, which can be adjusted according to patient-specific needs.

Early clinical studies have demonstrated reductions in apnea hypopnea index (AHI) and improvements in oxygen saturation, although outcomes have shown variability in individual response, likely reflecting differences in airway anatomy, neuromuscular responsiveness, and stimulation parameters¹². Despite this variability, the system has been shown to be well-tolerated with a favorable safety profile, and ongoing trials aim to optimize patient selection criteria and stimulation protocols to maximize therapeutic efficacy.

5. Surgical Technique and Patient Selection:

Successful hypoglossal nerve stimulation (HGNS) therapy requires careful patient selection and precise surgical implantation to ensure optimal outcomes and minimize complications. Patient evaluation focuses on anatomical, physiological, and behavioral factors that predict responsiveness to HGNS.

5.1 Drug-Induced Sleep Endoscopy (DISE):

Drug-induced sleep endoscopy (DISE) is a critical diagnostic procedure used to assess dynamic upper airway collapse patterns during sedated sleep. It provides direct visualization of the soft palate, velum, lateral pharyngeal walls, tongue base, and epiglottis, allowing clinicians to identify the specific sites and patterns of obstruction that contribute to obstructive sleep apnea⁷.

Patients exhibiting complete concentric collapse (CCC) at the velum have been shown to respond poorly to HGNS therapy and are typically excluded from implantation, as stimulation of the hypoglossal nerve is unlikely to overcome the circumferential airway collapse at the level of the soft palate. In contrast, patients with anteroposterior or lateral collapse patterns at the tongue base or retrolingual airway often demonstrate better therapeutic response to HGNS⁷.

DISE also guides personalized surgical planning, including optimal placement of the cuff electrode on the hypoglossal nerve branches and ensures that the selected patients have anatomical features amenable to neuromodulation By integrating DISE findings with other selection criteria, such as body mass index (BMI), apnea hypopnea index (AHI) and CPAP intolerance, clinicians can maximize the likelihood of successful outcomes and minimize adverse events^7,18.

5.2 Implantation Procedure and Standard Patient Selection Criteria:

HGNS implantation is a minimally invasive surgical procedure performed under general anesthesia. The procedure typically involves two to three small incisions: one for placement of the cuff electrode around selective branches of the hypoglossal nerve, another for the implantable pulse generator (IPG) in the chest, and, if applicable, a third for the respiratory sensing lead positioned between the intercostal muscles⁶.

The electrode is carefully positioned to selectively stimulate the tongue protrusor muscles, primarily the genioglossus, while avoiding stimulation of muscles that could worsen airway obstruction or cause dysphagia. After implantation, the device is programmed and calibrated based on the patient’s respiratory patterns, and therapy activation typically occurs 4-6 weeks post-surgery to allow for wound healing and tissue integration⁶.

Standard Patient Selection Criteria:

Appropriate patient selection is critical to achieving optimal therapeutic outcomes. Candidates for HGNS are typically screened based on the following criteria:

· Moderate-to-severe OSA (apnea–hypopnea index [AHI] 15 - 65 events/hour)

· CPAP intolerance or non-adherence, as HGNS is primarily indicated for patients who cannot tolerate first-line therapy^4,6

· Body mass index (BMI) <32-35 kg/m², as higher BMI may reduce efficacy due to increased airway collapsibility

· Age ≥22 years, consistent with current regulatory approvals and clinical trial populations

· Absence of complete concentric collapse (CCC) at the velum on DISE, since CCC predicts poor response to HGNS^7,18

6. Evidence of HGNS Efficacy:

6.1 STAR Trial:

The Stimulation Therapy for Apnea Reduction (STAR) trial was a pivotal multicenter, prospective clinical study evaluating the efficacy and safety of hypoglossal nerve stimulation (HGNS) in patients with moderate-to-severe obstructive sleep apnea (OSA) who were intolerant to continuous positive airway pressure (CPAP)⁶. A total of 126 participants underwent HGNS implantation and were followed for at least 12 months post-therapy initiation.

The trial demonstrated significant improvements in both objective and subjective measures of OSA severity:

· Apnea Hypopnea Index (AHI): Mean AHI decreased from 29.3 events/hour at baseline to 9.0 events/hour, representing a clinically meaningful reduction in respiratory events during sleep.

· Oxygen Desaturation Index (ODI): ODI improved from 25.4 to 7.4, reflecting enhanced nocturnal oxygenation.

· Epworth Sleepiness Scale (ESS): Daytime sleepiness decreased, with ESS scores improving from 11.6 to 6.0, indicating reduced daytime somnolence and improved functional alertness.

· Functional Outcomes of Sleep Questionnaire (FOSQ): Quality-of-life scores increased from 14.3 to 18.2, demonstrating better social, emotional, and daily functioning.

· Therapy Success Rate: Approximately 66% of patients met predefined response criteria, which included ≥ 50% reduction in AHI and AHI < 20 events/hour.

The STAR trial provided robust evidence supporting HGNS as an effective long-term therapeutic option for carefully selected patients with moderate-to-severe OSA who cannot tolerate CPAP. Furthermore, the study established the safety profile of HGNS, with low rates of serious adverse events and mostly mild, transient complications. These results have informed clinical guidelines and patient selection criteria for HGNS therapy⁶.

6.2 Long-Term Outcomes:

Long-term follow-up studies have demonstrated the durability and sustained efficacy of hypoglossal nerve stimulation (HGNS) in patients with moderate-to-severe obstructive sleep apnea (OSA). Woodson et al. reported five-year outcomes from patients who underwent HGNS implantation, confirming that therapeutic benefits are maintained over extended periods¹³.

Key findings included:

· Sustained reduction in Apnea Hypopnea Index (AHI): Patients maintained significant improvements in AHI compared to baseline, indicating long-term control of upper airway obstruction.

· Persistent improvement in daytime sleepiness: Epworth Sleepiness Scale (ESS) scores remained significantly lower than baseline, reflecting continued enhancement of daytime alertness and overall quality of life.

· Low incidence of serious adverse events: Serious complications were reported in less than 1% of patients, highlighting the favorable long-term safety profile of HGNS. Minor adverse events, such as tongue soreness or mild dysphagia, were generally transient and resolved without intervention.

These findings underscore that HGNS is not only effective in the short term but also provides durable improvements in both objective measures (AHI) and patient-reported outcomes (ESS and quality of life) while maintaining a high safety standard. This long-term evidence supports HGNS as a reliable alternative to CPAP therapy for appropriately selected patients¹³.

6.3 Real-World Evidence: ADHERE Registry:

Beyond controlled clinical trials, real-world evidence provides critical insight into the effectiveness and usability of hypoglossal nerve stimulation (HGNS) in broader patient populations. The ADHERE Registry, reported by Thaler et al. (2020), included outcomes from over 2,800 patients who underwent HGNS implantation across multiple centers, reflecting routine clinical practice¹⁴.

Key findings from this registry included:

· Apnea–Hypopnea Index (AHI): Patients experienced a substantial reduction from 32.8 events/hour at baseline to 9.5 events/hour, confirming the therapy’s effectiveness in real-world settings.

· Daytime sleepiness (Epworth Sleepiness Scale, ESS): ESS scores improved from 12.3 to 7.1, indicating meaningful decreases in excessive daytime sleepiness and enhanced daily functioning.

· Therapy adherence: Average nightly usage was approximately 6 hours, demonstrating excellent patient compliance and usability of the implanted device in a real-world context.

· Quality-of-life improvements: Patients reported significant enhancements in functional outcomes, social engagement, and overall well-being, supporting the broad impact of HGNS on patient-centered measures.

The ADHERE Registry highlights that HGNS provides durable and clinically meaningful benefits outside the controlled environment of clinical trials. High adherence rates and consistent improvements in both objective and subjective outcomes further reinforce HGNS as a practical and effective therapy for CPAP-intolerant patients with moderate-to-severe OSA¹⁴.

6.4 Meta-Analyses:

Meta-analyses provide a comprehensive evaluation of hypoglossal nerve stimulation (HGNS) by pooling data from multiple studies, offering robust evidence of efficacy and safety across diverse patient populations. Recent systematic reviews and meta-analyses have consistently demonstrated that HGNS produces clinically significant improvements in both objective and patient-reported outcomes^15,16.

· Apnea Hypopnea Index (AHI) reduction: Pooled analyses, such as those reported by Alrubasy et al. (2024), showed 60-70% reductions in AHI, indicating substantial improvement in nocturnal breathing events across study populations¹⁵.

· Oxygen Desaturation Index (ODI): Meta-analytic data demonstrated 50-60% reductions in ODI, reflecting enhanced nocturnal oxygenation and reduced intermittent hypoxemia.

· Daytime sleepiness (Epworth Sleepiness Scale, ESS): Patients experienced a 4-7 point decrease in ESS, signifying clinically meaningful relief of daytime somnolence.

· Quality of life (Functional Outcomes of Sleep Questionnaire, FOSQ): Consistent improvements in FOSQ scores were reported, indicating better physical, emotional, and social functioning¹⁶.

Importantly, meta-analyses also confirmed the favorable safety profile of HGNS. Adverse events were generally minor and transient, such as tongue soreness or mild dysphagia, while serious complications (e.g., device infection or lead dislodgment) remained rare.

Overall, these meta-analytic findings corroborate results from clinical trials and real-world registries, reinforcing HGNS as a durable, effective, and well-tolerated therapy for CPAP-intolerant patients with moderate-to-severe OSA. By integrating evidence across study types, meta-analyses provide strong support for HGNS in routine clinical practice and inform guidelines for patient selection, safety monitoring, and long-term management^15,16.

7. Safety and Adverse Events:

Table 1: Common Adverse Events of HGNS Therapy

Adverse Event	Frequency	Severity	Reference
Tongue soreness	20–30%	Mild	6,13,14
Mild dysphagia	10–15%	Mild	6,13
Speech changes	5–10%	Mild	14
Incisional discomfort	5–15%	Mild	13
Device infection	<2%	Serious, may require revision	13,17
Lead dislodgment	<2%	Serious, may require revision	13,17

7.1 Common Minor Effects:

Hypoglossal nerve stimulation (HGNS) is generally well tolerated, with most adverse events being mild, transient, and manageable. These minor effects are typically observed during the early postoperative period or during initial therapy titration, and they rarely necessitate device removal or revision. Common minor effects include:

· Tongue soreness: Mild discomfort or tenderness in the tongue is frequently reported, particularly in the first few weeks after device activation. This is usually temporary and resolves as patients adapt to nightly stimulation.

· Mild dysphagia: Some patients may experience minor swallowing difficulties, which generally improve over time without intervention.

· Speech changes: Temporary alterations in speech, such as mild articulation changes or a sensation of altered tongue movement, can occur but are typically transient and resolve with continued therapy.

· Incisional discomfort: Discomfort or mild pain at the sites of electrode or pulse generator implantation is common immediately post-surgery but diminishes as healing progresses.

These minor adverse effects are considered acceptable and manageable, especially when weighed against the substantial improvements in sleep-disordered breathing, daytime sleepiness, and quality of life provided by HGNS therapy. Proper patient education, gradual device titration, and postoperative follow-up can further minimize the impact of these minor events^6,13,14.

7.2 Serious Adverse Events:

Device-related complications such as infection, lead dislodgment, or the need for revision surgery have been reported, with an overall incidence of less than 2-4%¹⁷.

Overall, hypoglossal nerve stimulation (HGNS) demonstrates a favorable safety profile, with serious adverse events being relatively uncommon and typically manageable with appropriate clinical intervention.

8. Predictors of Response:

Table 2: Predictors of Response to HGNS Therapy

Predictor	Impact on Response	Evidence	Reference
BMI <32 kg/m²	Higher therapy success	Multicenter cohort studies	18
Absence of complete concentric collapse (CCC)	Strong predictor	DISE-based selection	7,18
Predominant retrolingual collapse	Positive correlation	STAR trial & European cohorts	6,11
Younger age	Slightly higher success	Registry analyses	14
Female sex	Better response in some studies	Meta-analysis	15

Key predictors of success include:

· Lower body mass index (BMI), which is associated with reduced upper airway collapsibility

· Absence of complete concentric collapse (CCC) at the level of the soft palate

· Predominantly retrolingual airway collapse, indicating favorable tongue-base responsiveness

· Female sex and younger age, both of which have been correlated with improved therapeutic outcomes¹⁸

9. Comparison with Other Therapies:

Table 3: Comparison of HGNS with Other Therapies for OSA

Therapy	AHI Reduction	Patient Adherence	Safety Profile	Reference
CPAP	80–90%	Low-moderate long-term adherence	Generally safe, mask-related side effects	4
Oral Appliances	30–50%	Moderate adherence	Mild TMJ/muscle discomfort	5
UPPP / Multilevel Surgery	40–60%	NA	Surgical morbidity, variable long-term success	5
HGNS	55–70%	High in selected patients	Low serious AE; minor tongue/neck symptoms	6,13–16

9.1 CPAP:

CPAP is highly effective in eliminating respiratory events and normalizing the apnea-hypopnea index; however, its real-world effectiveness is frequently limited by suboptimal patient adherence and long-term tolerance.

9.2 Oral Appliances:

Oral appliances demonstrate variable effectiveness in patients with moderate-to-severe obstructive sleep apnea, with inconsistent reductions in respiratory events, in comparison, hypoglossal nerve stimulation HGNS has demonstrated greater and more durable reductions in AHI in appropriately selected patients.

9.3 Surgical Therapy:

Traditional surgical approaches, such as uvulopalatopharyngoplasty (UPPP) and multilevel airway surgery, are associated with higher morbidity and variable long-term efficacy. In contrast, hypoglossal nerve stimulation (HGNS) avoids tissue resection, preserves airway anatomy, and offers a more targeted and physiologic approach to maintaining upper airway patency.

10. Limitations of Current Evidence:

Despite encouraging clinical outcomes, several limitations constrain the current body of evidence for hypoglossal nerve stimulation (HGNS). Only a small number of randomized controlled trials have been conducted beyond the landmark STAR trial, limiting the robustness of high-level comparative data. Study populations are often defined by narrow eligibility criteria, which restricts the generalizability of findings to patients who fall outside these carefully selected cohorts.

Additionally, Differences among commercially available HGNS devices, as reported in published studies, may contribute to variability in reported outcome, making it challenging to draw uniform conclusions across studies. There remains a relative paucity of data in key subgroups, particularly individuals with higher body mass index (BMI) and those with mild obstructive sleep apnea, who represent a substantial portion of the clinical population.

Economic considerations are also incompletely addressed, as comprehensive cost-effectiveness analyses comparing HGNS with established therapies are limited. Finally, heterogeneity in outcome definitions, reporting standards, and follow-up durations across studies impedes meaningful cross-study comparisons and underscores the need for standardized outcome reporting in future research^6,12,15.

11. Future Directions:

Future research directions discussed in the published literature highlight opportunities to further refine hypoglossal nerve stimulation (HGNS) therapy through improved patient characterization, optimization of stimulation parameters, and expanded understanding of long-term clinical outcomes.

Academic reports and expert commentaries have described growing interest in patient-specific stimulation approaches, broader evaluation of HGNS in patient populations that remain underrepresented in clinical trials, and continued use of established sleep assessment tools for longitudinal outcome monitoring. These discussions emphasize the importance of refined anatomical and functional phenotyping to better predict therapeutic response and durability.

The literature has also noted the potential role of adjunctive, non-invasive sleep monitoring modalities and standardized follow-up frameworks to support therapy optimization and post-implantation assessment, rather than to define specific device architectures, stimulation algorithms, or system designs.

Importantly, these areas represent research hypotheses and observational insights derived from published evidence, rather than established clinical standards, validated therapeutic protocols, or device development pathways. Based on existing published clinical studies, these efforts will help refine the integration of hypoglossal nerve stimulation into established obstructive sleep apnea management frameworks, ensuring optimal patient selection and continued monitoring of safety and effectiveness.

12. CONCLUSION:

Hypoglossal nerve stimulation (HGNS) has emerged as a clinically effective, durable, and well-tolerated therapeutic option for carefully selected patients with moderate-to-severe obstructive sleep apnea (OSA) who are intolerant of continuous positive airway pressure therapy. By directly addressing the neuromuscular dysfunction underlying upper airway collapse, HGNS offers a targeted, physiologic, and tissue-preserving alternative to traditional surgical interventions.

Evidence from pivotal randomized trials, long-term follow-up studies, large real-world registries, and contemporary meta-analyses consistently demonstrates sustained reductions in apnea–hypopnea index, improvements in nocturnal oxygenation, alleviation of daytime sleepiness, and meaningful gains in quality of life, with therapeutic benefits maintained for up to five years. Importantly, HGNS is associated with high patient adherence and a favorable safety profile, with serious device-related adverse events occurring infrequently and typically amenable to clinical management.

Successful outcomes with HGNS are strongly dependent on appropriate patient selection, particularly lower body mass index, absence of complete concentric palatal collapse on drug-induced sleep endoscopy, and favorable patterns of retrolingual airway obstruction. These factors underscore the importance of advanced phenotyping and individualized evaluation in optimizing therapeutic response.

Despite its demonstrated efficacy and durability, current evidence is limited by relatively few randomized controlled trials, narrow eligibility criteria, and heterogeneity in device platforms and outcome reporting. Furthermore, data remain limited in patients with higher BMI, mild OSA, and special populations, and comprehensive cost-effectiveness analyses are still evolving.

Looking forward, ongoing advances in personalized stimulation algorithms, minimally invasive and non-invasive neuromodulation technologies, integration with home-based sleep monitoring, and refined anatomical and functional phenotyping are expected to further enhance the role of HGNS in the OSA treatment landscape. As evidence continues to mature, Based on current evidence, HGNS represents an important and evolving therapeutic option within the management framework for obstructive sleep apnea for obstructive sleep apnea, bridging the gap between CPAP therapy and conventional surgical interventions.

13. CONFLICT OF INTEREST STATEMENT:

The authors are employees of Meril Medical Innovations Pvt. Ltd., a medical device manufacturer. This review is based exclusively on analysis of publicly available, peer-reviewed literature and does not describe proprietary technologies, unpublished data, investigational devices, or product development activities of Meril Medical Innovations Pvt. Ltd. The content is intended for academic discussion only and does not constitute product promotion, regulatory claims, or clinical recommendations.

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Received on 19.01.2026 Revised on 14.02.2026

Accepted on 12.03.2026 Published on 25.04.2026

Available online from April 28, 2026

Research J. Science and Tech. 2026; 18(2):190-198.

DOI: 10.52711/2349-2988.2026.00027

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.