Electrical stimulation of the hypoglossal nerve: a potential therapy

Abstract

Obstructive sleep apnea is characterized by recurrent episodes of pharyngeal collapse, which result from a decrease in pharyngeal dilator muscle tone. The genioglossus is a major pharyngeal dilator that maintains airway patency during sleep. Early studies in animal and humans have demonstrated that electrical stimulation of this muscle reduces pharyngeal collapsibility, increases airflow, and mitigates obstructive sleep apnea. These findings impelled the development of fully implantable hypoglossal nerve stimulating systems (HGNS), for which feasibility trial results are now available. These pilot studies have confirmed that hypoglossal nerve stimulation can prevent pharyngeal collapse without arousing patients from sleep. Potentially, a substantial segment of the patient population with obstructive sleep apnea can be treated with this novel approach. Furthermore, the feasibility trial findings suggest that the therapeutic potential of HGNS can be optimized by selecting patients judiciously, titrating the stimulus intensity optimally, and characterizing the underlying function and anatomy of the pharynx. These strategies are currently being examined in ongoing pivotal trials of HGNS.

Keywords: hypoglossal nerve stimulating systems; hypopnea; obstructive sleep apnea; pharyngeal collapse.

Fig. 1.

Left: hypoglossal nerve stimulating system components. Cuff electrode around the hypoglossal nerve, lead connected to implantable pulse generator, and respiratory sensing lead(s) to synchronize stimulation with inspiration. Right: flat electrode array used for asynchronous electrical stimulation. See text for details.

Fig. 2.

Apnea-hypopnea indices (means ± SD) for each of four feasibility trials of hypoglossal nerve stimulation therapy. Baseline, before initiating hypoglossal nerve stimulation (solid bars) and at 6 mo, 12 mo, or last follow-up after the initiation of stimulation (open bars) (Plotted from data provided in Refs. 4, 25, 38, 46).

Fig. 3.

Representative recording example in one patient showing response in breathing pattern at the onset of hypoglossal stimulation during a continuous period of non-rapid eye movement sleep. Left: before stimulation was started, three obstructive hypopneas were evident, with periodic reductions in airflow terminated by microarousals from sleep [see rise in submental electromyogram (EMG) amplitude with resumption of tidal airflow] and oxyhemoglobin desaturations. Right: ∼20 s after the onset of the stimulus, tidal airflow stabilized, esophageal pressure swings were reduced, and arousals and oxyhemoglobin desaturations were abolished. EOG indicates electro-oculogram; EEG, C3-A2 electroencephalogram; P_ES, esophageal pressure; and Sa_O2, oxyhemoglobin saturation. *Inspirations in which stimulation was not applied, showing immediate reduction in airflow to unstimulated levels. Airflow increased promptly during subsequent stimulated breaths (38).

Fig. 4.

Left: maximal inspiratory airflow (V_Imax) responses to increasing levels of stimulation current (mA, milliamperes) on every other inspiration demonstrates progressive increases in inspiratory flow and the elimination of inspiratory flow limitation without arousing the patient from sleep. The findings imply that responses can be optimized by titrating stimulation intensity to maximize V_Imax (pharyngeal patency) during sleep. (37). Right: maximal inspiratory airflow (V_Imax) vs. stimulation current (milliamperes) in groups with (solid circles) and without (open circles) inspiratory flow limitation at the peak flow threshold. The flow response slope in the non-flow-limited group was greater than that in the flow-limited subgroup (1,241 ± 199 vs. 674 ± 167 ml·s⁻¹·mA⁻¹; n = 25; P < 0.05). Lower levels of stimulation current were required to achieve peak airflow in the non-flow-limited compared with flow-limited subgroup (1.23 ± 0.10 vs. 1.80 ± 0.20 mA; n = 25; P < 0.05), although peak inspiratory airflow did not differ between non-flow-limited and flow-limited subgroups (564 ± 58 vs. 438 ± 35 ml/s). Both groups attained normal or near-normal levels during sleep of ∼400 ml/s or greater (shaded region). (37).