George S. Goding

Treating obstructive sleep apnea with hypoglossal nerve stimulation.

BACKGROUND Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce OSA severity. STUDY OBJECTIVES To examine safety and efficacy of a novel HGNS system (HGNS, Apnex Medical, Inc.) in treating OSA. PARTICIPANTS Twenty-one patients, 67% male, age (mean ± SD) 53.6 ± 9.2 years, with moderate to severe OSA and unable to tolerate continuous positive airway pressure (CPAP). DESIGN Each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by apnea-hypopnea index (AHI) during in-laboratory polysomnography (PSG) at baseline and 3 and 6 months post-implant. Therapy compliance was assessed by nightly hours of use. Symptoms were assessed using the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Calgary Sleep Apnea Quality of Life Index (SAQLI), and the Beck Depression Inventory (BDI). RESULTS HGNS was used on 89% ± 15% of nights (n = 21). On these nights, it was used for 5.8 ± 1.6 h per night. Nineteen of 21 participants had baseline and 6-month PSGs. There was a significant improvement (all P < 0.05) from baseline to 6 months in: AHI (43.1 ± 17.5 to 19.5 ± 16.7), ESS (12.1 ± 4.7 to 8.1 ± 4.4), FOSQ (14.4 ± 2.0 to 16.7 ± 2.2), SAQLI (3.2 ± 1.0 to 4.9 ± 1.3), and BDI (15.8 ± 9.0 to 9.7 ± 7.6). Two serious device-related adverse events occurred: an infection requiring device removal and a stimulation lead cuff dislodgement requiring replacement. CONCLUSIONS HGNS demonstrated favorable safety, efficacy, and compliance. Participants experienced a significant decrease in OSA severity and OSA-associated symptoms. CLINICAL TRIAL INFORMATION NAME: Australian Clinical Study of the Apnex Medical HGNS System to Treat Obstructive Sleep Apnea. REGISTRATION NUMBER NCT01186926. URL: http://clinicaltrials.gov/ct2/show/NCT01186926.

The Relationship Between Cepstral Peak Prominence and Selected Parameters of Dysphonia

Traditional measures of dysphonia vary in their reliability and in their correlations with perceptions of grade. Measurements of cepstral peak prominence (CPP) have been shown to correlate well with perceptions of breathiness. Because it is a measure of periodicity, CPP should also predict roughness. The ability of CPP and other acoustic measures to predict overall dysphonia and the subcategories of breathiness and roughness in pathological voice samples is explored. Preoperative and postoperative speech samples from 19 patients with unilateral recurrent laryngeal nerve paralysis who underwent operative intervention were analyzed by trained listeners and by measures of smoothed CPP (CPPS), noise-to-harmonic ratio (NHR), amplitude perturbation quotient (APQ), relative average perturbation (RAP), and smoothed pitch perturbation quotient (sPPQ). The data were analyzed with bivariate Pearson correlation statistics. Grade of dysphonia and breathiness ratings correlated better with measurements of CPPS than with the other measures. CPPS from samples of connected speech (CPPS-s) best predicted overall dysphonia. None of the measures were useful in predicting roughness.

Reanimation of the Paralyzed Human Larynx With an Implantable Electrical Stimulation Device

Objectives/Hypothesis Electrical stimulation of the posterior cricoarytenoid muscle, when paced with inspiration, offers a physiological approach to restore ventilation in bilateral laryngeal paralysis without any of the disadvantages associated with conventional treatment.

Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS®; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty‐one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single‐arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea–hypopnea index, from in‐laboratory polysomnogram) and sleep‐related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea–hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h−1) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device‐related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.

Relief of upper airway obstruction with hypoglossal nerve stimulation in the canine

Hypoglossal nerve stimulation was investigated as a method to relieve an induced upper airway obstruction. Six dogs were implanted with a cuff electrode applied to each hypoglossal nerve and a pulse generator. After 4 weeks, the hypoglossal nerve was stimulated (50% duty cycle) for up to 8 weeks. At 12 weeks a double tracheotomy was placed, with a negative pressure intermittently applied to the upper limb, simulating inspiratory airway pressure. Unilateral hypoglossal nerve stimulation improved peak upper airway flow from an average of 0.1 L/s to 1.6 L/s (P = 0.0001). Seventy‐seven percent of the maximum possible flow(explanted tracheotomy tube) was obtained with unilateral stimulation. Histopathological evaluation revealed no nerve damage secondary to chronic stimulation. This study provides support for clinical trials of hypoglossal stimulation for obstructive sleep apnea.

Acoustic and perceptual evaluation of laryngeal reinnervation by ansa cervicalis transfer

Objectives/Hypothesis: To evaluate the acoustic and perceptual results of laryngeal reinnervation with ansa cervicalis to recurrent laryngeal nerve anastomosis. Study Design: Retrospective study of voice samples from 12 patients with unilateral recurrent laryngeal nerve paralysis, treated with ansa cervicalis to recurrent laryngeal nerve anastomosis. Samples were recorded before surgery and at least 8 months after surgery. Methods: The samples were subjected to several acoustic analyses sensitive to paralytic dysphonia, including cepstral peak prominence, noise‐to‐harmonics ratio, and measures of frequency and amplitude perturbation. The voice samples from the patients were randomized with age‐ and sexmatched samples from normal subjects and judged by trained listeners for overall dysphonia, roughness, breathiness, asthenia, and strain. The preoperative and postoperative results were compared statistically, and the postoperative results were compared with the matched normal subjects. Results: As a group, the patients showed improvement (P < .05) in cepstral peak prominence, frequency perturbation, and perceptual judgments of overall dysphonia, breathiness, and asthenia. The best results occurred in patients with isolated vocal fold paralysis. The postoperative group as a whole did not improve to the level seen in matched normals. Suboptimal results were seen primarily in patients with untreated laryngeal or extralaryngeal pathology beyond the laryngeal paralysis. Conclusions: These data suggest that laryngeal reinnervation has the potential to bring about a return to normal or near‐normal voice in patients with isolated unilateral vocal fold paralysis.

Myonuclear Addition to Uninjured Laryngeal Myofibers in Adult Rabbits

Objectives: In normal mature limb skeletal muscle, satellite cells are quiescent and myonuclei do not divide after formation of their associated myofibers in the absence of injury. The possibility of myonuclear addition in uninjured laryngeal myofibers of adult rabbits was investigated in an immunohistochemical pilot study. Methods: Bromodeoxyuridine (brdU), a marker for cell division, was administered by intraperitoneal injection over a 12-hour period in rabbits. The number of brdU-positive myonuclei per myofiber was determined on cross sections through the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles. Results: In the TA muscle, 0.13% ± 0.03% (mean ± SEM) of the myofibers counted had a brdU-positive nucleus. In the PCA muscle, 0.13% ± 0.01% of the myofibers counted had a brdU-positive nucleus. Approximately 0.2% and 0.3% of the myofibers of the TA and PCA muscles, respectively, had brdU-positive satellite cells associated with them. Tibialis anterior and pectoralis major muscle controls were negative for brdU-positive myonuclei. Conclusions: These data support the possibility of continuous remodeling in uninjured adult laryngeal myofibers and accentuate the distinct nature of laryngeal muscle relative to limb skeletal muscle in the rabbit model.

Effect of recurrent laryngeal nerve section on the laryngeal muscles of adult rabbits

OBJECTIVE: To examine the effect of recurrent laryngeal nerve section on myonuclear addition and myofiber remodeling in adult rabbit laryngeal muscles. STUDY DESIGN AND SETTING: Unilateral section of the recurrent laryngeal nerve was performed on adult rabbits. Rabbits were labeled with bromodeoxyuridine, euthanized, and the laryngeal muscles were examined for bromodeoxyuridine (brdU) and neonatal myosin heavy chain (MyHC) expression. RESULTS: One week after nerve section, brdU-positive myonuclei were significantly increased on the denervated and contralateral sides. Neonatal MyHC expression significantly increased. By 24 weeks, the upregulation of myonuclear addition returned to control levels. CONCLUSION: Laryngeal muscle denervation results in significant upregulation of myonuclear addition. Denervation also resulted in a significant upregulation of neonatal MyHC expression. SIGNIFICANCE: Laryngeal muscles can be successfully reinnervated after long periods of denervation. This significant and maintained increase in myonuclear addition may contribute to the ability of laryngeal muscles to survive for extended periods following interruption of the recurrent laryngeal nerve.

Hypoglossal Nerve Stimulation and Airway Changes under Fluoroscopy

Objective. To characterize the changes in the anteroposterior dimensions of both the retropalatal and retrolingual airway spaces of the pharynx and hyoid bone position during hypoglossal nerve stimulation under general anesthesia in subjects with obstructive sleep apnea. Study Design. Cross-sectional. Setting. Academic center. Subjects and Methods. Cross-table fluoroscopic images obtained during hypoglossal nerve stimulation were studied in 26 subjects enrolled in the Apnex Medical Hypoglossal Nerve Stimulation (HGNS) system feasibility trials. Changes in the anteroposterior dimensions (2-dimensional) of the retropalatal and retrolingual airway spaces and hyoid bone position were recorded. Measurements were estimated in millimeters and standardized to each subject’s C3 vertebral height. Opening of the pharyngeal airspace was examined relative to body mass index. Results. During hypoglossal nerve stimulation, all subjects demonstrated anterior displacement of the tongue base on fluoroscopy. The average retrolingual airway opening was 0.71 ± 0.23 C3 vertebral body heights (9 ± 3 mm). Opening of the retropalatal airway with stimulation occurred in 65% (15/23) of subjects. When present, the average opening was 0.42 ± 0.14 vertebral heights (5 ± 3 mm). Anterior displacement of the hyoid occurred in 92% (23/25) of subjects. Retrolingual airway opening was independent of baseline body mass index. Conclusion. Unilateral hypoglossal nerve stimulation results in anterior tongue base displacement and an increase in the anterior-posterior retrolingual airway dimensions of the pharynx, independent of body mass index. Opening of the retropalatal airway occurred in a majority of subjects and had a trend toward correlation with body mass index.

Endoscopic cold incision, balloon dilation, mitomycin C application, and steroid injection for adult laryngotracheal stenosis

To describe the presentation, stenosis characteristics, etiological differences, and outcomes of adult laryngotracheal stenosis treated with endoscopic cold incision, balloon dilation, topical mitomycin C application, and steroid injection.