Hypoglossal nerve stimulation for adult patients with obstructive sleep apnea

INTRODUCTION — Obstructive sleep apnea (OSA) is a disorder characterized by airway collapse during sleep, leading to complete or partial episodes of breathing cessation. Positive airway pressure (PAP) is the first-line treatment for OSA [1]. Despite advancing technology, poor tolerance and low adherence to PAP therapy remains a major barrier, leaving many patients untreated [2]. For patients with OSA who cannot tolerate or decline PAP, hypoglossal nerve stimulation (HNS) is being increasingly used as a therapy.

Treatment of OSA using HNS is discussed in this topic. Treatment of OSA and management of nonadherence to PAP therapy are discussed separately. (See "Obstructive sleep apnea: Overview of management in adults" and "Assessing and managing nonadherence with continuous positive airway pressure (CPAP) for adults with obstructive sleep apnea".)

ANATOMY AND MECHANISM OF ACTION

Anatomy — The hypoglossal nerve is cranial nerve 12 (CN XII), which innervates the extrinsic and intrinsic muscles of the tongue (figure 1) [3].

Mechanism of action of the device — The HNS device is an implantable system [4-6] that includes the following (figure 2):

●An implantable pulse generator (IPG), which generates an electrical impulse at the start of anticipated inspiration.

●A neurostimulation lead with a cuff that connects the IPG.

●A neurostimulation lead cuff (with three electrodes) encases and stimulates the medial division of the hypoglossal nerve and the C1/C2 nerve (if included) at the level of the neck in the submandibular region.

●A respiratory sensing lead that connects to IPG and monitors respirations to allow synchronization of neurostimulation with initiation of inspiration.

●An external remote that controls impulse settings.

During sleep, HNS activates upper airway muscles, predominantly the genioglossus muscle, to produce tongue protrusion and airway opening at several levels by increasing retropalatal, retroglossal, and retroepiglottic airway space. Retropalatal opening is thought to be secondary to anterior movement of the palatoglossus muscle, which is anchored to the musculature of the tongue. Epiglottic engagement and hypopharyngeal expansion is likely secondary to incorporation of the C1 nerve branch, which innervates the geniohyoid muscle.

To avoid muscle fatigue, the device uses phasic stimulation wherein neurostimulation only occurs at the initiation of each breath.

Implantation of the device and long-term effects of stimulation do not alter airway anatomy or physiology; thus, therapy can be discontinued without sequelae.

PATIENT SELECTION — HNS is an option for patients with moderate to severe OSA who are unable to use or benefit from positive airway pressure (PAP) therapy. Other treatment options include positional or weight loss therapy; mandibular advancement devices; ablative and reconstructive surgery for the oropharynx, hypopharynx, epiglottis, and base of tongue; or maxillomandibular advancement. (See "Obstructive sleep apnea: Overview of management in adults", section on 'Weight loss and exercise' and "Oral appliances in the treatment of obstructive sleep apnea in adults" and "Surgical treatment of obstructive sleep apnea in adults" and "Obstructive sleep apnea: Overview of management in adults", section on 'Patients who fail, do not tolerate, or decline PAP therapy'.)

Indications and efficacy — HNS therapy has emerged as a novel second-line treatment option for patients who meet specific selection criteria. Current US Food and Drug Administration (FDA) recommendations are the following (note that payor criteria may vary) (table 1):

●Adults older than 18 years of age.

●A diagnosis of moderate to severe OSA with an apnea-hypopnea index (AHI) between 15 and 100 events per hour (of which less than 25 percent of events are central and mixed apneas).

●Failure or intolerance of PAP therapy.

●Body mass index (BMI) less than 40 kg/m².

●Absence of complete concentric collapse (CCC) at the level of velopharynx or soft palate on drug-induced sleep endoscopy. (See "Upper airway imaging in obstructive sleep apnea in adults", section on 'Nasopharyngoscopy and drug-induced sleep endoscopy'.)

HNS therapy is not recommended for patients with mild OSA (AHI <15 events per hour). Since the major trial that demonstrated benefit was conducted in patients with a BMI <32 kg/m², most United States commercial insurances require a BMI <32 kg/m². However, limited clinical evidence supports benefit in patients with BMI <35 kg/m² such that Medicare coverage and coverage in Europe extends to patients with BMI <35 kg/m² [7]. In 2023, the FDA expanded indications to AHI <100 events per hour and BMI to <40 kg/m².

Data to support HNS are largely derived from the Stimulation Therapy for Apnea Reduction (STAR) trial, which demonstrated efficacy of HNS in select patients with OSA [8] and Adherence and Outcome of Upper Airway Stimulation for the OSA International Registry (ADHERE) global registry.

●The STAR trial was a prospective cohort study that used HNS to treat 126 patients with moderate to severe OSA in whom PAP had failed or was not tolerated [8]. At 12 months following HNS, the AHI decreased from 29.3 to 9 events per hour and the oxygen desaturation index decreased from 25.4 to 7.4 events per hour. Approximately two-thirds had a successful outcome (defined as a reduction of AHI by 50 percent to below 20 events per hour). Subjective measures, including the Epworth Sleepiness Scale (calculator 1) and the Functional Outcomes of Sleep Questionnaire, showed clinically significant improvement from baseline. Serious adverse events occurred at a rate of less than 2 percent. Randomized therapy withdrawal showed recurrence of symptoms and evidence of at least moderate OSA.

●Multiple single-center studies and one multicenter study following the STAR trial have also demonstrated similar effectiveness of HNS therapy in the clinical (eg, improved blood pressure control) and real-world settings [9-16].

●Additional data from ADHERE has prompted the FDA to expand approval to include patients with an AHI between 65 and 100 events per hour and patients with a BMI between 35 and 40 kg/m² (ie, a patient group not studied in STAR) [7].

Data also suggest that the benefit is long lasting, provided patients adhere to therapy. Follow-up of the STAR trial at 60 months demonstrated persistent reduction in AHI with HNS therapy [9,17-20]. The ADHERE registry reported an average therapy compliance of approximately 5.6 hours per night and AHI reduction from 36 to 14.5 events per hour at one to two years [21]; at nine years, there was a 50 percent reduction in the AHI from baseline to the latest follow-up and the mean therapy use was 7.2 hours/night, although only a small number of patients were assessed [22].

Patients also subjectively report benefit. The ADHERE registry reported that 92 percent of patients had a better experience than with PAP therapy [21].

Patients with apnea-predominant OSA appear to respond similarly to patients who have hypopnea-predominant OSA [23].

Contraindications — There are few absolute contraindications to HNS therapy. We consider central apnea events that comprise more than 25 percent of the total AHI and hypoglossal neve palsy or paralysis as definitive contraindications.

When assessing patients for HNS therapy, additional considerations should be taken into account that may limit candidacy, including the following:

●The presence of neuromuscular disease where HNS may not be as effective or tolerated.

●Severe cardiovascular, pulmonary, or other comorbidities that impact the risk of general anesthesia.

●Active and uncontrolled comorbid sleep disorders that would not respond to HNS.

●Pregnancy (since HNS is an elective surgery).

●Active psychiatric disease that may impact adherence.

One additional relative contraindication is an anticipated need for body magnetic resonance imaging (MRI). While in the past HNS devices were not MRI compatible, patients with newer second-generation devices can undergo full body MRI with a 1.5 Tesla magnet.

Implantation of the HNS device is not contraindicated in patients who have had other implanted medical devices (eg, permanent pacemaker, defibrillator) as long as the devices are placed far enough apart to avoid any device interactions. However, external cardioversion can disrupt or damage the HNS device, and this should be discussed with patients with known cardiovascular disease.

Predictors of a response — Despite the recommended selection criteria for HNS therapy, there is still no consensus as to what the best predictors of therapy success are [24]. Data suggest that older age, lower BMI, and possibly female sex are associated with therapy success [25,26].

The following are considered as predictors of a poor therapy success:

●BMI (>32 kg/m²) – It has been demonstrated that patients with a high BMI (>32 kg/m²) are less likely to meet surgical success criteria and achieve an AHI reduction by 50 percent to below 20 events per hour [21]. However, patients still demonstrated therapy benefit based on reduction of the disease burden.

●CCC at the velopharynx and complete lateral collapse of the oropharyngeal wall on drug induced sleep endoscopy – These features have been shown to be predictive of a reduced response to HNS [27].

●Comorbid insomnia – Comorbid insomnia may potentially also predict a poor response to HNS therapy due to poor adherence (eg, difficulty falling asleep when experiencing tongue movement). We typically assess patients for the presence of insomnia preoperatively, and if found, we counsel patients on the possibility of a poor response. However, recent data analysis from ADHERE [28] demonstrated similar response rates in patients with and without comorbid insomnia. (See "Evaluation and diagnosis of insomnia in adults".)

PROCEDURE, POSTOPERATIVE CARE, ADVERSE EVENTS

Surgical technique — The following is our general approach:

●Choice of left or right positioning – Most commonly, we place the device on the right side. This leaves access for cardiac devices, which are usually placed on the left. Nerve access and surgery is the same regardless of the side chosen. We consider the left side in select patients, such as patients with specific occupational or recreational activities that require right arm or shoulder motion, patients with an implantable medical device on the right, patients with prior surgery on the right neck or chest (which distorts anatomy), prior radiation of the right neck or chest (increases the risk of poor wound healing, infection, extrusion), or a history of right hypoglossal nerve palsy.

●Preoperative antibiotics – Patients usually receive a single dose of antibiotics prophylactically one hour prior to surgery. Bacitracin or gentamicin irrigation can be used during surgery.

●Anesthesia – HNS device placement is performed under general anesthesia with endotracheal intubation. Transoral intubation is the most utilized approach. However, some surgeons prefer a transnasal intubation to facilitate intraoral access for placement of nerve integrity monitoring (NIM) needles and assessment of tongue movement. Preoperative evaluation of patients with OSA is discussed separately. (See "Surgical risk and the preoperative evaluation and management of adults with obstructive sleep apnea".)

●Positioning – The patient is placed in the supine position. We usually turn the bed 180 degrees to allow for the head of bed to be positioned away from anesthesia while patient is supine, to allow for full access to the patient’s head and neck. The arms are tucked tightly to the body to allow access to the chest for the implantable pulse generator (IPG) and the respiratory sensor placement. Standard monitors (eg, telemetry leads, blood pressure cuff, and pulse oximetry) should be kept out of the anticipated surgical field.

●NIM – We utilize intraoperative NIM to assess hypoglossal nerve activity by analyzing electromyography (EMG) responses to neurostimulation. Since the genioglossus muscle protrudes the tongue and is the main airway dilator, it is the primary target for neurostimulation. We place one set of 18 mm paired EMG electrodes vertically in the floor of mouth on the ipsilateral side off the midline into the genioglossus muscle. We also place a second set of electrodes in the lateral aspect of the ipsilateral tongue just under the mucosa 3 to 4 cm from the tip of the tongue. This allows monitoring of the hyoglossus and styloglossus muscles, which are undesirable targets for neurostimulation as they retract the tongue.

●Procedure – Our procedural approach is the following:

•Placing the stimulation lead – A 3 to 5 cm incision is placed in the neck crease in the submandibular area from the midpoint of the submandibular gland and extending anteriorly. The platysma muscle is divided. The anterior border of the submandibular gland is identified, and the gland is retracted posteriorly. The tendon of the digastric muscle is then identified and retracted inferiorly. Further dissection is carried out to identify the posterior border of the mylohyoid muscle that is then retracted anteriorly. The hypoglossal nerve and the associated ranine vein are then visualized (figure 1).

In most cases, we preserve the ranine vein and dissect it away from the hypoglossal nerve. In some cases, ligation of the ranine vein or its branches might be necessary to access and visualize the hypoglossal nerve. Further nerve dissection is carried out to isolate the medial branches of the nerve and also the adjacent C1 nerve branch.

We identify the separation of the lateral and medial branches of the hypoglossal nerve often marked by an accompanying vasa nervorum. NIM is used to confirm anatomic identification of the medial and lateral branches by observing characteristic EMG signals and by visual observation of corresponding muscle contraction in response to neurostimulation at 0.1 to 0.3 volts. (See 'Anatomy' above.)

Because stimulation of even tiny retractor branches within the hypoglossal nerve can compromise therapy outcome as a result of undesirable tongue motion, nerve stimulation is additionally performed at the superior edge of the medial division to identify and isolate late takeoff retractor nerve fibers. If found or suspected, further dissection should be performed to separate the retractor branch(es) prior to placement of the stimulation cuff. This action minimizes the risk of undesirable tongue retraction postoperatively.

We next place the stimulation lead cuff on the medial branch of the hypoglossal nerve (ensuring that no retractor branches are trapped within the cuff). We also typically include C1 nerve fibers within the cuff. Once in place, the stimulation lead anchor is secured to the digastric muscle tendon.

•Inserting the IPG and respiratory sensor lead – To insert the IPG and respiratory sensor lead, we use a horizontal 4 to 5 cm incision on the anterior chest wall, approximately 4 to 6 cm below the clavicle on the ipsilateral side. Rarely, the lead may need to be implanted on the contralateral side (eg, revision cases with an infected or damaged lead).

The IPG pocket is then created superficial to the pectoralis major muscle. We use a two-incision approach that allows for the respiratory sensor lead placement through the same incision as the IPG [6,17]. The pectoralis major muscle is bluntly dissected over the second or third intercostal space, and fibers are separated to allow exposure of the intercostal muscles. The external intercostal muscle is identified and dissected to allow the exposure of underlying internal intercostal muscle.

The respiratory sensor is placed in a medial to lateral direction in between the external and internal intercostal muscles. The respiratory sensor should be placed closer to the superior border of the rib away from the neurovascular bundle running on inferior aspect of the rib. The sensor lead anchors are sutured to the external intercostal muscle fascia, and the pectoralis fascia.

The neurostimulation lead is tunneled from the neck incision into the IPG pocket in the subplatysmal plane. Neurostimulation and respiratory sensor leads are connected to the IPG. The excess lead wire is coiled posterior to the IPG. The IPG is placed into the pocket and secured to the pectoralis major fascia.

Placement of the respiratory sensor lead has a possibility of causing pneumothorax. If clinically suspected and a small pneumothorax is found (eg, ultrasound or chest radiography) and the patient stable, the respiratory lead should be immediately removed, the overlying muscle layer should be closed, and respiratory sensor can be placed in a different intercostal space. If pneumothorax is significant, a chest tube or catheter needs to be placed immediately. Once the patient is stable, the respiratory sensor lead can then be placed in a separate intercostal space away from the chest tube to avoid device infection. Pneumothorax is best avoided by staying between the intercostal muscles and avoiding entering the pleural space.

•Interrogating the system – Once the device placement is complete, prior to incision closure, the system is interrogated to assess its proper function. The respiratory sensor function is tested utilizing an external programmer. It is important to observe a clear rise and fall of the respiratory wave tracing corresponding to inspirations and expirations. If the expected tracing is not observed, the placement and function of the sensor lead should be explored.

Testing of nerve stimulation by the IPG is performed at various intensities and polarities to confirm unrestricted forward tongue protrusion [29]. If tongue retraction or mixed activation (ie, both protrusion and retraction) is identified, we re-explore the previously dissected submandibular region to exclude any entrapment of late retractor branches in the stimulation lead cuff; if identified, we reposition the cuff ensuring that there are no retractor branches included in the cuff before incisions are closed.

If no tongue movement is observed with device interrogation, it is likely due to poor electrode contact with the nerve or trapped air within the cuff. Irrigation within the properly placed cuff often resolves the problem. If the problem does not resolve, we check the lead connection to the IPG and assess the device for a defect. Rarely, devices may be damaged during dissection or electrocautery. Hardware damage requires immediate replacement of the relevant parts.

•Closure – Once a comprehensive electric testing of the implant is completed, we irrigate with antibiotic-containing solutions and close the incisions. Neck and chest incisions are covered with pressure dressings. Noteworthy is that the device is not activated at this point. (See 'Initial activation' below.)

Postoperative care

Immediate — We obtain anterior-posterior chest and lateral neck radiographs in the recovery area to rule out pneumothorax and document the baseline position of the IPG, stimulation cuff, and respiratory sensor lead, respectively [4-6]. Some surgeons will prescribe postoperative antibiotics.

Unless there are concerns for postoperative complications, most patients are discharged home once they meet postoperative care unit observation criteria. If pneumothorax is identified, observation or chest tube thoracostomy may be needed. Details regarding choosing among these options are provided separately. (See "Treatment of primary spontaneous pneumothorax in adults".)

We ask patients to avoid strenuous activity and limit arm and shoulder motion on the side of the implant for at least two weeks. Pain is usually managed with over-the-counter analgesics; opiate use is rarely required. We also counsel patients to expect minor procedure-associated symptoms, which can be experienced postoperatively but generally resolve over time. (See 'Follow-up for early surgery-related adverse events' below.)

Other issues pertaining to the postoperative management of patients with OSA are discussed separately. (See "Postoperative management of adults with obstructive sleep apnea".)

Follow-up for early surgery-related adverse events — We see patients in the office one week after surgery for evaluation of incisions and assessment for any adverse effects listed below. In general, HNS has a low rate of serious adverse events (<2 percent), both in clinical trials and real-world settings [8,21,26].

The next visit is scheduled four weeks from the date of the surgery for device activation and programming. (See 'Initial activation' below.)

Hypoglossal nerve injury (tongue weakness) — Since the introduction of HNS therapy, there have been no reports of permanent hypoglossal nerve paralysis as a result of implant placement. However, postoperative tongue weakness is reported in less than 1 percent of patients (eg, asymmetry on tongue protrusion and limited movement of the tongue from side to side). It is typically associated with neuropraxia resulting from hypoglossal nerve manipulation (ie, focal demyelination from mild injury at the surgical site resulting in blockage of nerve conduction and transient weakness).

We typically expect tongue weakness to fully recover over time without any intervention. However, if neuropraxia is present a month after surgery, we postpone device activation until the tongue movement is fully recovered.

Tongue numbness or taste changes are rare and indicative of lingual nerve injury.

Intraoperative nerve injury can be prevented by adherence to proper surgical technique and knowledge of the anatomy.

Platysma muscle weakness and marginal mandibular nerve injury — Lower lip weakness, which may present as an asymmetric smile, is often noted postoperatively as a result of the incision through the ipsilateral platysma muscle. It typically resolves with time.

However, lower lip weakness can also be due to neuropraxia of the marginal mandibular nerve. Similar to hypoglossal neuropraxia, this is usually temporary. However, if the marginal mandibular nerve was inadvertently transected during dissection, it will result in permanent lower lip weakness.

Permanent injury is best avoided by knowledge of the relevant neuroanatomy and careful dissection.

Pneumothorax — Parietal pleural injury and subsequent pneumothorax can occur due to a breach of the parietal pleura due to dissection deeper than intended when the respiratory sensor lead is being placed between the internal and external intercostal muscles. Pneumothorax can occur intraoperatively (see 'Surgical technique' above) or be found postoperatively on routine chest radiography, performed in the recovery area (see 'Postoperative care' above). Pneumothorax after discharge is unusual.

Infection — In rare cases, infection related to the implanted system can present during the immediate postoperative period. Signs may include worsening of erythema, swelling, drainage, and pain at the surgical sites.

While deep or persistent implant infections may require hardware removal, superficial infections can typically be treated with oral antibiotics with skin flora coverage.

To prevent infections, it is critical to adhere to sterile techniques during implantation. We also typically administer a single dose of antibiotics one hour prior to surgery and use bacitracin or gentamicin irrigation during surgery. Some experts also administer three days of antibiotics postoperatively.

Hematoma — HNS implant placement is not generally associated with significant bleeding, although patients on anticoagulant medications are more prone to intraoperative and postoperative bleeding.

Some intraoperative bleeding can be encountered during dissection, especially around the ranine vein or its branches, or during tunneling of the stimulation lead into the IPG pocket. In most patients, bleeding can be managed with bipolar electrocautery or by application of pressure. In controlling any bleeding related to the ranine vein, particular care must be taken to avoid any injury to the hypoglossal nerve given its immediate proximity. Bleeding encountered during the lead tunneling can be controlled by direct visualization and cautery of the bleeding vessel and application of pressure. In rare cases, additional incision over the site of bleeding and exploration to identify the source of bleeding might be required.

Postoperative hematoma formation is a rare complication of HNS implant surgery. In most cases, a hematoma or seroma can be managed conservatively (observation). We typically do not aspirate fluid or blood in order to avoid introduction of skin pathogens into the surgical site and development of a subsequent infection. If the hematoma continues to expand, we explore the surgical site and control bleeding in an operating room under sterile conditions.

Postoperative pain — Postoperative pain and discomfort after HNS implant are usually managed with nonopioid analgesics. Pain typically resolves within a few weeks after surgery. Pain with swallowing is expected postoperatively and resolves over time. Pain at the IPG site can be due to implant movement during upper body movement. We often suggest activity restriction of the upper body until the discomfort is completely resolved.

INITIAL ACTIVATION — We typically activate the HNS device four weeks after implant placement. We delay activation when patients have residual neuropraxia of the tongue or a possible infection and wait for full resolution before device activation. Initial activation is performed in the office setting while the patient is awake.

●Device check – We initially perform a device check and assess respiratory sensor lead function by confirming the expected respiratory wave tracing changes with inspiration and expiration using an external program similar to that used intraoperatively. (See 'Surgical technique' above.)

The respiratory sensor or stimulation leads can be damaged intraoperatively due to improper handling while using cautery or sharp instruments. This can lead to breach of insulation, lead fractures, and current leaks that will cause the device to malfunction postoperatively (if not detected at the time of damage). In most cases, this requires revision. Assessment and management are discussed below. (See 'Device malfunction and damage' below and 'Revision surgery/replacement' below.)

In patients with absent tongue movement, stimulation cuff dislodgement should be suspected. When suspected, we perform a lateral neck radiograph or computed tomography of the neck to assess the position of the cuff. If dislodgement is confirmed, revision is required to reposition the cuff. (See 'Revision surgery/replacement' below.)

●Initial programming – We next perform electrode programming. Each of the three stimulation lead electrodes can be programmed as a cathode (−) or anode (+) and be selectively turned on or off. The implantable pulse generator (IPG) can also be programmed to function as an anode. The initial (or default) programming setting is a bipolar electrode configuration (ie, + ─ +), with a pulse width of 90 microseconds, and a rate of 33 Hz.

In patients with suboptimal tongue motion, a unipolar electrode configuration (eg, ─ 0 ─; 0 ─ 0; ─ ─ ─) may be trialed. In this case, the IPG is programmed as an anode (+) and either one, two, or three cuff electrodes can be turned on and programmed as a cathode (─). This allows for a wide current field and engagement of more nerve fibers.

●Establishing the functional threshold – The functional threshold (FT) is established by gradually increasing the stimulation voltage to identify and set the lowest amplitude at which tongue protrusion passes the mandibular incisors (eg, 1.1 volts).

●Therapy start delay – This is the time that stimulation starts after the device is turned on to allow patients to fall asleep. It is typically set for 30 minutes or per the patient’s preference.

●Therapy pause time – This setting allows pausing of the therapy if patient were to wake up in the middle of the night. It is usually set for 15 minutes (or any other time that the patient desires). The therapy automatically turns on once pause time is up.

●Home titration – The patient is instructed to use the device nightly and educated on the remote functions, which include turning therapy on and off, pausing therapy, and adjustment of the voltage. The patient is instructed on therapy self-titration at home to optimize comfort and efficacy. Each night prior to sleep, they are asked to gradually increase the stimulation amplitude from the set FT by 0.1 volt increments within a 10-step range (up to a maximum of 5 volts). For example, if the FT is 1.1 volts, the patient is usually set to have a range 1.0 to 2.0 volts.

FOLLOW-UP — Follow-up is scheduled for one to two months after therapy initiation. At that time, we perform a clinical and formal sleep assessment and address any complications that may be impacting therapy.

Assess sleep apnea symptoms and sleep study — We typically assess for symptomatic benefit (eg, daytime fatigue, sleep quality, snoring, awakenings, headaches) by direct questioning of the patient and their sleep partner. Information about therapy compliance and nightly usage is also downloaded from the remote control. The introduction of Bluetooth communication between the remote control and phone application now allows for web-based remote monitoring of therapy use. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults", section on 'Clinical features'.)

We also typically perform a sleep study, either home sleep apnea test or in-laboratory polysomnographic sleep study (PSG), with the device in place and active. When performing PSG, therapy setting adjustment and optimization can be performed, if needed. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults", section on 'Diagnostic tests'.)

Address therapy-related issues — We assess and address therapy-related discomfort or early adverse events that may impact the efficacy of and compliance with the device.

Therapy-related discomfort includes stimulation-associated tongue discomfort, tongue abrasions, insomnia or frequent awakenings, and neck, jaw, or occipital pain triggered by stimulation. As examples:

●In most patients with tongue discomfort, we typically lower the stimulation intensity by adjusting electrode configuration, pulse width, and frequency.

●In patients with insomnia or other sleep disturbances, we sometimes optimize therapy start delay and pause time. (See 'Initial activation' above.)

●For those with tongue abrasions, we typically decrease therapy intensity or advise wearing a dental guard during sleep.

●Pain in the supraclavicular, postauricular, and occipital regions can be referred pain due to stimulation of the cervical nerve branches. It often resolves over time but if persistent, it can be relieved by lowering the stimulation intensity or adjusting stimulation settings.

Other adverse issues including absent or abnormal tongue movement, device malfunction or damage, and device extrusion and migration can be seen in the early postoperative period but are more likely to occur later in the course of HNS therapy. (See 'Long-term adverse effects' below.)

PATIENTS WITH OPTIMAL RESPONSE — Following therapy initiation, approximately two-thirds of patients experience immediate therapy benefit. If symptoms improve and the sleep study confirms adequate OSA control with HNS therapy, patients are instructed on nightly therapy use and are scheduled for a clinical follow-up and a device check in 6 to 12 months.

What is considered an optimal response is poorly defined. We consider HNS a success if therapy results in mild or no OSA, or an apnea-hypopnea index (AHI) <10 events per hour. A reduction of the AHI by 50 percent and below 20 events per hour are surgical success criteria.

PATIENTS WITH SUBOPTIMAL RESPONSE — Approximately one-third of patients have a suboptimal response to HNS therapy. Patients might experience therapy-related discomfort that impacts adherence or continue to have OSA-related symptoms and/or an elevated apnea-hypopnea index on sleep testing.

Adjust device settings — For most patients with a suboptimal response to HNS, we address complications and reasons for poor adherence, which often underlie the suboptimal response. (See 'Address therapy-related issues' above.)

In most patients, we further adjust settings including electrode configuration (polarity), amplitude, pulse width, and rate to optimize therapy comfort and effectiveness.

If further therapy optimization is needed, we can adjust settings in the office with direct awake endoscopic airway visualization, but this may require assessment by an ear, nose, and throat specialist with expertise in sleep.

For patients in whom these in-office therapy adjustments do not achieve desired therapeutic benefit, drug-induced sleep endoscopy (DISE)-directed therapy reprogramming can be considered. DISE gives the clinician the opportunity to assess and program the device while the patient is sleeping.

Adjunctive therapy for OSA or other sleep disorders — When adequate OSA control is not achieved with HNS, and discomfort and adherence are not an issue, we sometimes combine HNS stimulation with other OSA treatments.

As examples:

●If it is felt that additional airway opening is needed, a mandibular advancement device may be used to further open the airway by advancing the jaw during sleep. (See "Oral appliances in the treatment of obstructive sleep apnea in adults".)

●For patients with troublesome mouth breathing during sleep, a chin strap or mouth tape may be used. (See "Assessing and managing nonadherence with continuous positive airway pressure (CPAP) for adults with obstructive sleep apnea", section on 'Oral air leaks'.)

●In patients with residual sleep apnea with HNS therapy use who have nasal obstruction or oropharyngeal obstruction due to redundant palatal tissue or tonsillar hypertrophy or patients who have epiglottic collapse or large lingual tonsils on DISE, additional upper airway surgery can be considered. (See "Surgical treatment of obstructive sleep apnea in adults".)

●For patients with residual supine OSA, positional therapy, such as pillows and position-adjusting devices, can be used to optimize the HNS therapy response.

●If insomnia is suspected, sleep hygiene and cognitive behavioral therapy should be initiated in combination with HNS. (See "Overview of the treatment of insomnia in adults".)

LONG-TERM ADVERSE EFFECTS — During long-term follow-up (eg, every 6 to 12 months), we clinically reassess for recurrent sleep symptoms and look for complications that may occur later during the postoperative course. The incidence of long-term complications is generally low (eg, <1 percent).

Device malfunction and damage — Lead damage and fracture can occur spontaneously several months or years after the device placement.

Device malfunction or hardware damage should be suspected if patients report new therapy-associated discomfort, inappropriate or absent tongue movement, changes in stimulation requirements, or pain at the incision sites.

When suspected, we perform a device check with external device programmer to check or change the settings and evaluate impedances. Indices of device malfunction or damage include the presence of abnormal impedances (abnormalities in electric circuit) on device interrogation, or abnormal respiratory sensor wave.

Although less common, implantable pulse generator (IPG) damage and malfunction can also occur (eg, following cardioversion). During electrophysiology procedures, care should be taken to avoid placement of the defibrillation pads directly over the IPG. Sensor lead damage may be suggested by a nonphysiologic pattern of the respiratory waveform during a device check.

The clinician should be aware of “Twiddler syndrome” that was first reported in association with cardiac and deep brain stimulation implants. Twiddler syndrome is intentional manipulation or rotation of the IPG by the patient that can result in lead damage and device malfunction. (See "Deep brain stimulation for treatment of obsessive-compulsive disorder".)

In any case of device malfunction or suspected hardware damage, therapy should be discontinued and revision surgery undertaken to replace the damaged device. (See 'Revision surgery/replacement' below.)

Implant exposure and migration — Pain, erythema, or swelling months or years after HNS placement may suggest extrusion or displacement.

●Exposure – Lead or IPG exposure is rare (ie, erosion through the skin). Meticulous surgical technique to avoid superficial placement of the implanted system components can help avoid wound dehiscence and exposure of the IPG or leads. If exposure occurs, the exposed components or the entire HNS system should be removed. Surgical sites should be allowed to fully heal before reimplantation.

●Migration – IPG migration can occur, which, in some cases, can put tension on the stimulation or respiratory sensing leads. A large IPG pocket, inadequate fixation of the IPG at the time of implantation, obesity, increasing age, or issues with tissue laxity can contribute to IPG movement and displacement. When suspected, we obtain a chest radiograph to assess the position of the IPG and the leads. Repositioning or revision may be required.

Others — Other late adverse events include infection and scarring.

Infection — Pain, erythema, or swelling months or years after HNS placement may suggest infection, although infection is more common in the early postoperative period. The management of suspected infection is discussed above. (See 'Infection' above.)

Scarring — Visible scarring at the incision sites and fibrosis at the site of the stimulation lead tunneling can occur.

Placement of the incisions within skin creases or tension lines, tension-free closures, and postoperative wound care can reduce visibility of scarring.

Fibrosis around the stimulation lead can occasionally be visible with neck extension. Tunneling of the lead in the subplatysmal plane (assuring laxity of the tunneled wire), neck stretching, and massage of the area after the surgery can help avoid noticeable fibrosis.

REVISION SURGERY/REPLACEMENT — The need for revision, replacement, or removal of the implanted HNS system or its components is rare (eg, device damage or fracture, infection, need for magnetic resonance imaging, or patient request) [21].

Revision and replacement surgeries are performed with a similar setup as initial device implantation (see 'Surgical technique' above). However, revision surgeries are technically more challenging due to obscured visualization of anatomic structures and are often complicated by fibrosis. For example, lead coiling under the implantable pulse generator (IPG) and the tunneled leads between incisions are often scarred and can have an unpredictable path. Removal of all lead-securing sutures and dissection along the tunneled course of the leads can facilitate removal of the implant and prevent inadvertent damage of the intact device parts.

Limited data suggest that parts replacement has a low complication rate. Data from the ADHERE registry reported safe IPG replacement in 14 patients, 2 of whom needed lead replacement as well. The operative time was, in general, shorter than that associated with the original implant [22].

DEVICES UNDER INVESTIGATION — Several newer HNS implantable devices have been developed. They are commercially available in parts of Europe but not yet approved in the United States.

One device consists of an implantable rechargeable unit connected to a six-electrode stimulation cuff lead. The neurostimulator is implanted below the clavicle, and the stimulation cuff is placed through a submandibular incision on the main trunk of the hypoglossal nerve. It delivers continuous stimulation that cyclically targets various tongue muscles, and stimulation is not synchronized with respirations [30].

Another device consists of two sets of paired stimulating electrodes and a receiving antenna and is implanted under the chin on top of the genioglossus muscles bilaterally. The electrode paddles are placed over the medial division branches of the hypoglossal nerve bilaterally. The system does not contain a respiratory sensor and implantable battery. It uses an external activation unit that is applied externally with an adhesive patch. Preliminary data suggest apnea-hypopnea index reduction from 24 to 13 events per hour and a success rate of 50 percent after six months of device use [31,32].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sleep-related breathing disorders in adults".)

SUMMARY AND RECOMMENDATIONS

●Mechanism of action – Hypoglossal nerve stimulation (HNS) is being increasingly used to treat obstructive sleep apnea (OSA). During sleep, HNS activates upper airway muscles, predominantly the genioglossus muscle, thereby opening the airway to prevent obstructive events (figure 1 and figure 2). (See 'Anatomy and mechanism of action' above.)

●Patient selection – HNS is a second-line therapy that is an option for patients with OSA who are unable to use or benefit from positive airway pressure therapy. Our selection criteria simulate those in a major prospective study that demonstrated efficacy of HNS in select patients with OSA who fulfill all of the criteria listed in the table (table 1). (See 'Patient selection' above.)

●Surgical procedure and postoperative care

•Technique – The procedure involves placing an electrode cuff of the neurostimulation lead on the medial division fibers of the hypoglossal nerve in the submandibular region of the neck (figure 2 and figure 1). We connect the stimulation lead to an implantable pulse generator (IPG) in the chest wall. The IPG is also connected to a respiratory sensor lead, which is placed in between the internal and external intercostal muscles. We interrogate the system to ensure tongue protrusion without retraction. (See 'Surgical technique' above.)

•Immediate and early postoperative care – We obtain anterior-posterior chest and lateral neck radiographs in the recovery area to rule out pneumothorax and document the baseline position of the device components. Patients are generally discharged on the same day. (See 'Postoperative care' above.)

One week after the procedure, patients are assessed for wound healing and other adverse events including tongue and lip weakness, asymmetric smile, infection, hematoma, and pain. Most of these complications resolve over a few weeks. (See 'Follow-up for early surgery-related adverse events' above.)

●Follow-up and device activation – We typically activate the HNS device in the office four weeks after implant placement. Settings are titrated to identify the lowest amplitude at which tongue protrusion passes the mandibular incisors. The patient is then instructed on self-titration and asked to use the device nightly. One to two months later, we assess patients for compliance and OSA symptoms and obtain a sleep test either at home or in laboratory. (See 'Initial activation' above.)

•For those whose symptoms improve, and the sleep study confirms adequate OSA control with HNS therapy (approximately two-thirds), we instruct patients on nightly HNS therapy use and schedule clinical follow-up and a device check in 6 to 12 months. (See 'Patients with optimal response' above.)

•For patients with a suboptimal response to HNS, we assess and treat reasons for this, and perform device setting adjustment, if needed. Occasionally, awake or drug-induced sleep endoscopy-directed HNS reprogramming or the addition of adjunctive therapy may be needed. (See 'Patients with suboptimal response' above.)

•The need for revision, replacement, or removal of the implanted HNS system or its components is rare (eg, device damage or fracture, infection, need for magnetic resonance imaging, or patient request). However, revision surgeries are technically more challenging due to obscured visualization of anatomic structures and are often complicated by fibrosis. (See 'Revision surgery/replacement' above.)