Hypoglossal nerve stimulation (HNS) has emerged as an established treatment option for selected patients with obstructive sleep apnoea (OSA) who are intolerant to continuous positive airway pressure (CPAP). Over the past decade, technological developments have expanded the field from unilateral stimulation systems (e.g. Inspire) to bilateral stimulation approaches (e.g. Genio), raising important clinical questions regarding patient selection and expected outcomes.
Diagram illustrating the Inspire (unilateral) hypoglossal nerve stimulation system, showing the chest pulse generator implant connected to the stimulation cuff via a subcutaneous cable. © Inspire Medical Systems, Inc.
Pictorial diagram illustrating the Genio bilateral hypoglossal nerve stimulation system overlying the genioglossus muscles and hypoglossal nerves bilaterally [1].
The hypoglossal nerve (cranial nerve XII) represents an ideal target for neuromodulation in OSA. It is a purely motor nerve that innervates the intrinsic and extrinsic tongue muscles, particularly the genioglossus muscle, which is responsible for tongue protrusion and airway stabilisation. Stimulation directly counteracts upper airway collapse, especially at the retrolingual level, by advancing and stiffening the tongue. This results in an immediate mechanical enlargement of the airway. Several features make the hypoglossal nerve particularly suitable for stimulation: predictable motor response without sensory side effects, anatomical accessibility and the ability to synchronise stimulation with respiration. These characteristics underpin the strong clinical efficacy observed in both trials and real-world settings.
Initial HNS systems focused on unilateral stimulation. The Inspire system is currently the most widely used device and consists of an implantable pulse generator, a stimulation electrode placed on the hypoglossal nerve, and a sensing lead detecting respiratory effort. This closed-loop system delivers stimulation synchronised with inspiration, closely mimicking physiological activation of upper airway dilator muscles. Clinical studies have consistently demonstrated significant reductions in apnoea–hypopnoea index (AHI) and oxygen desaturation index (ODI), as well as improvements in daytime sleepiness and quality of life. Long-term data confirm the durability and safety of the therapy. However, the system requires implantation of a pulse generator and sensing lead, which increases surgical complexity.
Observations of cross-innervation within the hypoglossal nerve led to the hypothesis that bilateral stimulation may improve outcomes. Approximately half of patients demonstrate bilateral tongue movement following unilateral stimulation, suggesting that symmetric activation may be advantageous. This concept has been realised in newer systems such as Genio, which provide bilateral hypoglossal nerve stimulation. The Genio system uses a submental implanted stimulation unit without an implanted pulse generator. Activation occurs via an external wearable patch, delivering stimulation to both hypoglossal nerves. Physiologically, bilateral stimulation produces more symmetric tongue protrusion and stronger activation of suprahyoid muscles. Preclinical and early clinical data indicate that this leads to greater airway opening and improved palatal coupling. These effects may be particularly relevant in patients with more complex patterns of airway collapse. The DREAM trial, a prospective multicentre study, demonstrated significant reductions in AHI and ODI with bilateral stimulation, alongside improvements in quality of life. Safety outcomes were acceptable, with low rates of serious adverse events. Transient tongue weakness was observed in a minority of patients but was generally self-limiting.
When comparing unilateral and bilateral systems, both approaches are effective when applied to appropriately selected patients. However, differences in mechanism and design may influence outcomes in specific subgroups. Unilateral stimulation offers the advantage of extensive clinical experience, robust long-term data and respiratory synchronisation. Bilateral stimulation, on the other hand, provides a more physiological activation pattern and avoids implantation of a chest device, potentially reducing invasiveness.
"Shared decision-making is essential, as device handling and lifestyle implications differ"
OSA is a heterogeneous condition, and treatment success depends on multiple factors including site and pattern of airway collapse, body mass index, positional dependency and sleep stage distribution. Drug-induced sleep endoscopy (DISE) remains essential for appropriate patient selection. Based on current experience, a simplified clinical algorithm can be proposed. Candidates for HNS should have moderate-to-severe OSA (AHI 15–65 events per hour), intolerance to CPAP, and a body mass index typically below 35 kg/m². Complete concentric collapse at the level of the soft palate should be excluded in unilateral HNS, but can be included in patients with bilateral HNS. In patients with predominantly retrolingual collapse, both unilateral and bilateral systems are suitable. In cases with significant palatal involvement or more complex collapse patterns, bilateral stimulation may offer advantages due to improved symmetry of airway opening.
Device selection should also consider patient-specific factors. Patients preferring a fully implanted system and automatic respiratory synchronisation may favour Inspire. Those wishing to avoid a chest implant or prioritising a less invasive procedure may prefer Genio. Shared decision-making is essential, as device handling and lifestyle implications differ.
Although HNS is primarily indicated for OSA, reduction of snoring is a consistent secondary benefit. By stabilising the upper airway and reducing tissue vibration, both systems can significantly decrease snoring intensity. However, HNS should not be considered a primary treatment for simple snoring without OSA.
In conclusion, hypoglossal nerve stimulation represents a major advance in the surgical management of OSA. Unilateral systems such as Inspire have established strong long-term efficacy and safety, while bilateral systems such as Genio introduce a promising, more physiological approach. Both modalities are effective when applied to the appropriate patient population. Future research should focus on direct comparative studies and further refinement of patient selection criteria to optimise outcomes and personalise therapy in this evolving field.
References
1. Karagama Y. First UK hypoglossal nerve stimulation implant in the treatment for moderate to severe OSA. ENT & Audiology News 2023.
www.entandaudiologynews.com/development/
spotlight-on-innovation/post/first-uk-hypoglossal-nerve
-stimulation-implant-in-the-treatment-for-moderate-to-severe-osa
[Link last accessed June 2026].
2. Cheong RCT. First UK Genio Nyxoah bilateral hypoglossal nerve stimulator implant for obstructive sleep apnoea. ENT & Audiology News 2025;34(3):26-7.
Further reading
1. Woodson BT, Kent DT, Huntley C, et al. Bilateral hypoglossal nerve stimulation for obstructive sleep apnea: a nonrandomized clinical trial. J Clin Sleep Med 2025; 21(11):1883–91.
2. Wirth M, Bautz M, von Meyer F, et al. Obstruction level associated with outcome in hypoglossal nerve stimulation. Sleep Breath 2021;26(1):419–27.
3. Heiser C, de Vries N. Upper Airway Stimulation in Obstructive Sleep Apnea: Best Practices in Evaluation and Surgical Management. Springer Cham; 2022.
4. Cé PS, Melo MES, Machado AA, et al. Review of Neurostimulation Therapies for Obstructive Sleep Apnea: Hypoglossal Nerve Stimulation and Beyond. J Clin Med 2025;14(15):5494.
5. Heiser C, Maurer JT, Hofauer B, et al. Outcomes of Upper Airway Stimulation for Obstructive Sleep Apnea in a Multicenter German Postmarket Study. Otolaryngol Head Neck Surg 2017;156(2):378–84.
Declaration of competing interests: CH has received research grants from Inspire Medical Systems, Nyxoah and Löwenstein Medizintechnik; consultancy fees from Nyxoah, Jazz Pharmaceuticals and XM Consult, and has previously served as a consultant for Inspire Medical Systems; travel support from XM Consult, Inspire Medical Systems and Nyxoah. CH is founder of the Institute for Sleep Medicine and LunaLab.
