Upper Airway Stimulation: Implanted Neurostimulation Device for Treatment of Obstructive Sleep Apnea

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Introduction

Upper airway stimulation is a novel approach to the management of obstructive sleep apnea (OSA). Hypoglossal nerve stimulation (HNS) therapy has been shown to improve objective respiratory and subjective quality-of-life outcomes and is well positioned as a new second-line treatment for moderate to severe OSA.

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Scientific Rationale

The development of HNS therapy has been driven by a need for new OSA treatments, as well as growing recognition of neuromuscular dysfunction as a contributing factor to OSA pathophysiology. Although first-line therapy of continuous positive airway pressure (CPAP) has the most evidence for effectively managing OSA and its comorbid cardiovascular risks, adherence rates are suboptimal. Two recent multicenter studies demonstrated that only 39% to 50% of participants met the minimum CPAP adherence criteria. Alternative treatments to CPAP, including oral appliance therapy, positional therapy, behavioral modifications, weight loss, and upper airway reconstructive surgery, have been shown to be effective in appropriately selected patients, but treatment response can be incomplete, and many patients often require additional therapy.

In addition to the structural upper airway vulnerability of OSA patients, increasing evidence indicates that the changes in the neuromuscular control of breathing during sleep also play a key role in the pathophysiology of OSA. A simplified model of the upper airway neuromuscular reflex has been described as an afferent pathway from the pharynx through the superior laryngeal nerve to the nucleus solitaris and an efferent pathway from the hypoglossal motor nucleus through the hypoglossal nerve to the genioglossus muscle, which is the primary upper airway dilator. Normal healthy subjects have been shown to respond to negative intraluminal pressure with a corresponding increase in genioglossus electromyographic (EMG) activity. The neuromuscular feedback loop is thought to be dysfunctional in patients with OSA. Recent studies have demonstrated abnormal genioglossus EMG patterns resembling that of denervation-renervation injuries, as well as delayed distal hypoglossal nerve latency and low motor amplitude in patients with OSA compared with normative data. Although the etiology of the defective negative pressure reflex remains unclear and is likely multifactorial, augmenting the efferent limb through electrical stimulation of the hypoglossal nerve has emerged as a promising new approach to the management of OSA.

The feasibility of electrical stimulation of the hypoglossal nerve was originally established through multiple animal studies, which demonstrated increases in airflow and airway stability in response to neuromuscular augmentation. Human studies subsequently corroborated these findings, demonstrating that neurostimulation was not only effective in improving airflow and airway stability, but also well tolerated and without adverse sequelae such as arousals, sleep fragmentation, or neuromuscular side effects. Key studies by Oliven et al. showed that selective stimulation of the genioglossus muscle (tongue protrusor) improved airflow and airway stability, whereas selective stimulation of the styloglossus and hyoglossus (tongue retrusors) increased collapsibility of the airway. Coactivation of both protrusor and retrusor muscles produced a net improvement in airflow and reduction in critical closing pressure, confirming the genioglossus as the dominant upper airway muscle. These observations led to advanced analysis of the terminal branches of the hypoglossal neuroanatomy and the use of selective hypoglossal nerve branch stimulation in the development of the first commercially available implantable neurostimulation devices. Furthermore, the use of nasopharyngoscopy demonstrated that selective neurostimulation resulted in an enlargement and stabilization of not only the retrolingual portion of the airway (130% increase), but also the retropalatal space (180%). This finding was one of the first indications that single-modality HNS therapy could provide multilevel upper airway treatment in contrast to many other traditional site-specific pharyngeal surgical procedures ( Fig. 48.1 ).

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