Electrical Stimulation of Vocal Fold Adduction Triggered by Laryngeal Electromyography Using a Custom Implant.

PURPOSE: Medialization procedures for unilateral vocal fold (VF) paralysis generally improve voice but do not fully replace dynamic VF adduction. Paralyzed VFs typically experience synkinetic reinnervation, which makes it feasible to elicit movement through electrical stimulation. We tested a novel laryngeal pacing implant capable of providing closed-loop (automatic) stimulation of a VF triggered by electromyography (EMG) potentials from the contralateral VF. METHOD: A custom, battery-powered, microprocessor-based stimulator was tested in eight dogs with bipolar electrodes implanted for recording EMG from the left VF and stimulating adduction of the right VF. A cuff electrode on the left recurrent laryngeal nerve (RLN) stimulated unilateral VF adduction, modeling voluntary control in anesthetized animals. Closed-loop stimulation was tested in both acute and chronic experiments. Synkinetic reinnervation was created in two animals by right RLN transection and suture repair to model unilateral VF paralysis. RESULTS: In all animals, left VF activation through RLN stimulation generated a robust EMG response that rapidly triggered stimulation of contralateral thyroarytenoid and lateral cricoarytenoid muscles, causing nearly simultaneous bilateral adduction. Optimal triggering of VF stimulation from elicited EMG was achieved using independent onset and offset thresholds. Real-time artifact blanking allowed closed-loop stimulation without self-perpetuating feedback, despite the proximity of recording and stimulation electrodes. CONCLUSIONS: Using a custom implant system, we demonstrated real-time closed-loop stimulation of one VF triggered by the activation of the contralateral VF. This approach could potentially restore dynamic glottic closure for reflexive behaviors or phonation in cases of unilateral VF paralysis with synkinetic reinnervation. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24492133.

Surgical Treatment Strategies for Laryngeal Chondrosarcomas: A Single Institution Investigation.

OBJECTIVES/HYPOTHESIS: Laryngeal chondrosarcomas are rare malignancies with a spectrum of presentations due to varying size, local extension, and biological behavior. Moreover, these neoplasms have differing effects on respiration, phonation, and deglutition. Consequently, it is valuable to assess endoscopic and transcervical treatment strategies. STUDY DESIGN: Retrospective case series. METHODS: A retrospective review was done from 2001 to 2020; 25 patients were identified with laryngeal chondrosarcomas. Their tumor pathology and treatment were analyzed. RESULTS: All 25 chondrosarcomas were in the posterior cricoid and arose in proximity to at least one cricoarytenoid joint: 23 of 25 grade I-II (low-mid), one of 25 grade II-III (mid-high), and one of 25 grade III (high). Some tumor was left in 23 of 25 to preserve cricoarytenoid-joint function. There were no known disease-specific deaths (~8-year median follow-up). Final surgical treatment in 24 of 25 was: 13 of 25 transcervical partial laryngectomy, 7 of 25 transoral-endoscopic removal, 4 of 25 total laryngectomy, and 1 of 25 observation. CONCLUSIONS: In this series, unresected intercurrent disease with laryngeal chondrosarcomas was not life-threatening. Therefore, disease was typically left in the posterior cricoid region to preserve mobility of at least one cricoarytenoid joint. This philosophy employed an ultra-function-sparing conservation approach that preserved and/or restored optimal voice, airway patency and swallowing. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:169-176, 2022.

Direct measurement and modeling of intraglottal, subglottal, and vocal fold collision pressures during phonation in an individual with a hemilaryngectomy.

The purpose of this paper is to report on the first in vivo application of a recently developed transoral, dual-sensor pressure probe that directly measures intraglottal, subglottal, and vocal fold collision pressures during phonation. Synchronous measurement of intraglottal and subglottal pressures was accomplished using two miniature pressure sensors mounted on the end of the probe and inserted transorally in a 78-year-old male who had previously undergone surgical removal of his right vocal fold for treatment of laryngeal cancer. The endoscopist used one hand to position the custom probe against the surgically medialized scar band that replaced the right vocal fold and used the other hand to position a transoral endoscope to record laryngeal high-speed videoendoscopy of the vibrating left vocal fold contacting the pressure probe. Visualization of the larynx during sustained phonation allowed the endoscopist to place the dual-sensor pressure probe such that the proximal sensor was positioned intraglottally and the distal sensor subglottally. The proximal pressure sensor was verified to be in the strike zone of vocal fold collision during phonation when the intraglottal pressure signal exhibited three characteristics: an impulsive peak at the start of the closed phase, rounded peak during the open phase, and minimum value around zero immediately preceding the impulsive peak of the subsequent phonatory cycle. Numerical voice production modeling was applied to validate model-based predictions of vocal fold collision pressure using kinematic vocal fold measures. The results successfully demonstrated feasibility of in vivo measurement of vocal fold collision pressure in an individual with a hemilaryngectomy, motivating ongoing data collection that is designed to aid in the development of vocal dose measures that incorporate vocal fold impact collision and stresses.

Subcutaneous Ports for Chronic Nerve Cuff and Intramuscular Electrode Stimulation in Animal Models.

OBJECTIVE: Tracking recovery after nerve injury may require many intermittent assessments over long periods, preferably with non- or minimally invasive methods. We developed subcutaneous electrical connection ports (ECPs) for repeated connection to nerve cuff or intramuscular electrodes via transdermal needles and evaluated them during studies of laryngeal reinnervation. STUDY DESIGN: Animal experiment. SETTING: Laboratory. METHODS: ECPs were designed and 3-dimensionally printed for connection to bipolar electrodes with biocompatible polymers. Dual compartments filled with conductive silicone capped with nonconductive silicone were used to make the connections between electrode leads and transdermally inserted needles. Ten dogs (19-29 kg) were implanted with 22 ECPs. In 7 dogs, 11 electrodes were placed on recurrent laryngeal nerves proximal to transection and suture repair to track laryngeal reinnervation. In 6 dogs, 8 spinal accessory nerve cuff electrodes were used to stimulate neck muscle contraction. In 2 dogs, 3 electrodes were implanted in the thyroarytenoid muscle. Stimulation thresholds, electromyography, and videolaryngoscopic imaging were obtained in 156 tests over survival periods up to 32 months. Stimulation data provided information about ECP performance. RESULTS: ECPs added negligible resistance to electrodes (mean ± SD, 2.14 ± 0.9 Ω). Despite some electrode leads breaking distally, ECPs were reliable and well tolerated at implant sites and enabled periodic assessment of nerve and muscle function over the time course of laryngeal reinnervation. Histology showed ECP encapsulation as thin layers of connective tissue and minimal acute inflammation. CONCLUSION: Custom ECPs are easily fabricated and cause little tissue reaction over months to years of subcutaneous implantation, facilitating long-term physiologic studies.

Changes in a Daily Phonotrauma Index After Laryngeal Surgery and Voice Therapy: Implications for the Role of Daily Voice Use in the Etiology and Pathophysiology of Phonotraumatic Vocal Hyperfunction.

Purpose This study attempts to gain insights into the role of daily voice use in the etiology and pathophysiology of phonotraumatic vocal hyperfunction (PVH) by applying a logistic regression-based daily phonotrauma index (DPI) to predict group-based improvements in patients with PVH after laryngeal surgery and/or postsurgical voice therapy. Method A custom-designed ambulatory voice monitor was used to collect 1 week of pre- and postsurgery data from 27 female patients with PVH; 13 of these patients were also monitored after postsurgical voice therapy. Normative weeklong data were obtained from 27 matched controls. Each week was represented by the DPI, standard deviation of the difference between the first and second harmonic amplitudes (H1-H2). Results Compared to pretreatment, the DPI significantly decreased in the patient group after surgery (Cohen's d effect size = -0.86) and voice therapy (d = -1.06). The patient group DPI only normalized after voice therapy. Conclusions The DPI produced the expected pattern of improved ambulatory voice use across laryngeal surgery and postsurgical voice therapy in a group of patients with PVH. The results were interpreted as providing new objective information about the role of daily voice use in the etiology and pathophysiology of PVH. The DPI is viewed as an estimate of potential vocal fold trauma that relies on combining the long-term distributional characteristics of two parameters representing the magnitude of phonatory forces (neck-surface acceleration magnitude) and vocal fold closure dynamics (H1-H2). Further validation of the DPI is needed to better understand its potential clinical use.

Efficacy of Videostroboscopy and High-Speed Videoendoscopy to Obtain Functional Outcomes From Perioperative Ratings in Patients With Vocal Fold Mass Lesions.

OBJECTIVES: A major limitation of comparing the efficacy of videostroboscopy (VS) and high-speed videoendoscopy (HSV) is the lack of an objective reference by which to compare the functional assessment ratings of the two techniques. For patients with vocal fold mass lesions, intraoperative measures of lesion size and depth may serve as this objective reference. This study compared the relationships between the pre- to postoperative change in VS and HSV visual-perceptual ratings to intraoperative measures of lesion size and depth. DESIGN: Prospective visual-perceptual study with intraoperative measures of lesion size and depth. METHODS: VS and HSV samples were obtained preoperatively and postoperatively from 28 patients with vocal fold lesions and from 17 vocally healthy controls. Two experienced clinicians rated amplitude, mucosal wave, vertical phase difference, left-right phase asymmetry, and vocal fold edge on a visual-analog scale using both imaging techniques. The change in perioperative ratings from VS and HSV was compared between groups and correlated to intraoperative measures of lesion size and depth. RESULTS: HSV was as reliable as VS for ratings of amplitude and edge, and substantially more reliable for ratings of mucosal wave and left-right phase asymmetry. Both VS and HSV had mild-moderate correlations between change in perioperative ratings and intraoperative measures of lesion area. Change in function could be obtained in more patients and for more parameters using HSV than VS. Group differences were noted for postoperative ratings of amplitude and edge; however, these differences were within one level of the visual-perceptual rating scale. The presence of asynchronicity in VS recordings renders vibratory features either uninterpretable or potentially distorted and thus should not be rated. CONCLUSIONS: Amplitude and edge are robust vibratory measures for perioperative functional assessment, regardless of imaging modality. HSV is indicated for evaluation of subepithelial lesions or if asynchronicity is present in the VS image sequence.

Aerodynamically driven phonation of individual vocal folds under general anesthesia in canines.

OBJECTIVES/HYPOTHESIS: We previously developed an instrument called the Aerodynamic Vocal Fold Driver (AVFD) for intraoperative magnified assessment of vocal fold (VF) vibration during microlaryngoscopy under general anesthesia. Excised larynx testing showed that the AVFD could provide useful information about the vibratory characteristics of each VF independently. The present investigation expands those findings by testing new iterations of the AVFD during microlaryngoscopy in the canine model. STUDY DESIGN: Animal model. METHODS: The AVFD is a handheld instrument that is positioned to contact the phonatory mucosa of either VF during microlaryngoscopy. Airflow delivered through the AVFD shaft to the subglottis drives the VF into phonation-like vibration, which enables magnified observation of mucosal-wave function with stroboscopy or high-speed video. AVFD-driven phonation was tested intraoperatively (n = 26 VFs) using either the original instrument design or smaller and larger versions three-dimensionally printed from a medical grade polymer. A high-fidelity pressure sensor embedded within the AVFD measured VF contact pressure. Characteristics of individual VF phonation were compared with typical two-fold phonation and compared for VFs scarred by electrocautery (n = 4) versus controls (n = 22). RESULTS: Phonation was successful in all 26 VFs, even when scar prevented conventional bilateral phonation. The 15-mm-wide AVFD fits best within the anteroposterior dimension of the musculo-membranous VF, and VF contact pressure correlated with acoustic output, driving pressures, and visible modes of vibration. CONCLUSIONS: The AVFD can reveal magnified vibratory characteristics of individual VFs during microlaryngoscopy (e.g., without needing patient participation), potentially providing information that is not apparent or available during conventional awake phonation, which might facilitate phonosurgical decision making. LEVEL OF EVIDENCE: NA Laryngoscope, 130: 1980-1988, 2020.

Glottic Carcinoma in Young Patients.

INTRODUCTION:: Recent reported evidence indicates that vocal cord carcinoma is evolving similarly to oropharyngeal cancer with an increasing number of patients without a smoking history having human papillomavirus (HPV) disease. Observations also suggest that an increasing number of patients who present with glottic carcinoma are younger than has been reported in the past. Therefore, an investigation was done to examine the incidence of glottic carcinoma in patients 30 years old (y/o) or younger. METHODS:: A retrospective review was done with Institutional Review Board approval to evaluate the incidence of patients 30 y/o or younger presenting with glottic carcinoma in 2 symmetric-length time periods over 28 years. These data were comprised from glottic cancer patients evaluated by the senior author (S.M.Z.) at the Massachusetts Eye and Ear Infirmary (July 1990-June 2004) and subsequently at the Massachusetts General Hospital (July 2004-June 2018). HPV testing was done on those patients identified as having a disease process at 30 y/o or younger. RESULTS:: Between July 1990 and June 2018, 353 patients were diagnosed with glottic carcinoma. From July 1990 to June 2004, there were 112 patients, with none being 30 y/o or younger. From July 2004 to June 2018, 241 patients were diagnosed with glottic carcinoma; 11 patients (7 females, 4 males) were 30 y/o or younger. Of the 11 patients, 3 (1 female, 2 males) were 10 to 19 y/o, 3 (2 females, 1 male) were 20 to 25 y/o, and 5 (4 females, 1 male) were 26 to 30 y/o. Moreover, 10 of the 11 cases were tested and were positive for high-risk HPV. None of the 11 glottic cancer patients had been previously treated for benign recurrent respiratory papillomatosis although it was initially suspected prior to biopsy due to the morphology of the lesions and the patients' young age. Three of 11 had a history of smoking; all 3 had less than 3 pack-years. One of the 11 glottic cancer patients was treated with serial Cidofovir injections that resulted in dramatic acceleration in the growth of the cancer. CONCLUSION:: Historically, glottic carcinoma is considered to be a tobacco-induced disease associated with a multidecade process of initiation, promotion, transformation, and progression. However, recent published evidence shows that glottic carcinoma can be an HPV-related disease with increasing incidence in nonsmokers. It isn't surprising that alternate malignant pathways may have a different timeline. In this investigation, an increased incidence of HPV-positive glottic cancer in patients 30 y/o or younger was documented in the past 14 years. This finding further supports the concept that glottic carcinoma is an evolving disease, and it demonstrates the increasing importance of discriminating potential glottic carcinomas in young patients from benign low-risk HPV recurrent respiratory papillomatosis.

Vocal Fold Injection of Absorbable Materials: A Histologic Analysis With Clinical Ramifications.

OBJECTIVES:: Gels composed of carboxymethylcellulose (CMC) and cross-linked hyaluronic acid are commonly used as temporary or resorbable injectable materials for vocal fold medialization. However, there is limited information about tissue injection patterns, soft tissue reaction, degradation, and residence time, particularly for the newer CMC gels. STUDY DESIGN:: Prospective, laboratory. METHODS:: Ten canines underwent paraglottic (deep to the vocal ligament) microlaryngoscopic injection with about 100 µL (0.1 mL) of cross-linked hyaluronic acid (Restylane) in the right vocal fold and about 100 µl (0.1 mL) of CMC gel in the left vocal fold. Two commercial CMC gels of similar formulation (Prolaryn Gel and Renú Gel) were used in 5 animals each. Two subjects were sacrificed for histologic analysis at 3, 13, 29, 42, and 55 days. RESULTS:: Histology showed that injected Restylane formed cohesive ovoid-shaped aggregated implants with minimal dispersion, inflammation, or cellular invasion in all subjects. Approximately 86% of Restylane injected remained at 8 weeks, as estimated from postmortem, high-resolution magnetic resonance imaging scans. In contrast, histology showed that both CMC gels dispersed widely through fascial planes during and after injection within and outside the thyroarytenoid muscle fascicles. There was a robust macrophage and histiocyte phagocytic response, with moderate to severe inflammation noted around residual CMC gel at early time points, and at 6 to 8 weeks, very little free gel was observed. CONCLUSIONS:: None of the studied materials induced a clinical inflammatory reaction on laryngoscopy such that they would be considered problematic or dangerous. Restylane demonstrated superior injection localization, tissue compatibility, and residence time. Both CMC gels did not localize well in the paraglottic region, and there was a robust inflammatory response, with clearance by macrophages and short residence time. These results suggest that CMC gels may have a more limited application than previously thought for vocal fold medialization in patients in whom the injection is being used to achieve voice enhancement while awaiting reinnervation. Level of Evidence: NA.

Glottic Stenosis: An Anatomic Analysis and New Treatment With a Self-Retaining Interarytenoid Spring.

INTRODUCTION:: Endotracheal (ET) intubation is a common cause of acquired glottic stenosis. Severe cases often require an irreversible arytenoidectomy/cordectomy, which typically results in poor voice quality. Adult human cadaver larynges were studied to gain insights about ET tube-induced posterior glottic injuries, hoping to create a less invasive remedy. STUDY DESIGN:: Human cadaver investigation and case reports. METHODS:: Microlaryngeal assessments were done on 10 human cadaver larynges (5 men, 5 women) with and without ET tubes. After supracricoid soft tissue resection, measurements were obtained, including the distance between the outer diameter of the ET tube and the medial aspect of the cricoarytenoid joint facet. Additionally, measurements of the circumferential arc of differently sized ET tubes were made alongside both cricoarytenoid joint capsules. This information was used to design a silastic stent that would function as a self-retaining interarytenoid spring to treat posterior glottic stenosis in 5 patients. Four of 5 patients included in the clinical study were tracheotomy dependent, primarily because of glottic stenosis. The human surgical technique is described in detail. RESULTS:: The shortest distance between the outer diameter of the ET tube to the medial cricoid facet averaged 5.02 mm in men and 3.62 mm in women. On the basis of the diameter of the intralaryngeal component of the initially round stent, and the position of the cricoarytenoid joint facets, the interarytenoid spring would have a subtended arc between 110° and 175°. These data helped fashion parameters for modifying a conventional T-tube to form a new self-retaining silastic interarytenoid spring. The first 5 human cases have been successful, allowing effective tracheotomy tube decannulation and excellent voice quality. CONCLUSIONS:: The anatomic investigation herein provided key insights into ET tube-induced glottic stenosis and facilitated a new straightforward procedure to surgically improve the airway yet preserve excellent vocal function in patients with acquired glottic stenosis. Level of Evidence: NA.

Development of a Closed-Loop Stimulator for Laryngeal Reanimation, Part 1: Devices.

OBJECTIVE:: The goal of this work was to create implantable stimulator systems that could be used in animal experiments on laryngeal paralysis, including "closed-loop" stimulation of impaired muscles triggered by electromyographic (EMG) potentials from healthy muscles. STUDY DESIGN:: Iterative device design and testing. METHODS:: A series of microcontroller-based implantable devices were built that incorporated increasingly sophisticated features for stimulation, EMG recording, and communication across the skin. Specific engineering challenges included minimizing power consumption, achieving charge-balanced and relatively high stimulation capacity, implementing noninvasive communication across the skin, providing real-time processing of EMG signals, and mitigating effects of shock artifacts. Bench testing was used to verify performance. RESULTS:: Two prototypes are described in detail. Each system is based on an "implant" and an external "communication adapter" that interfaces both with the implant and with external computers for adjustments and monitoring. The first version described is inductively powered and referred to as the "inductive laryngeal stimulator." It uses inductive coupling for both power and communication and performs EMG processing in the communication adapter module. The second version, a "battery-powered laryngeal stimulator," consists of an autonomous battery-powered implant with onboard EMG processing and artifact control; it communicates by infrared light with the external communication adapter for setup and monitoring. CONCLUSIONS:: The devices met design and performance specifications and have proved useful in the animal experiments that are described in Part 2 of this series. Detailed descriptions of the circuits and their firmware are made available in the Appendix. Level of Evidence: NA.

A Method for Reconstruction of Anterior Commissure Glottal Webs With Endoscopic Fibro-Mucosal Flaps.

BACKGROUND:: Anterior-commissure (AC) cicatrization and web formation is a difficult problem that can result from a variety of clinical scenarios. An advancement-rotation flap utilizing papillomatous epithelium and subepithelial fibrous tissue has been previously described. For patients in whom there was not excessive redundant papillomatosis covering the AC web, including other clinical scenarios, a microlaryngoscopic procedure was designed to lengthen the glottal/subglottal aperture using substantial local fibro-mucosal tissue. Although it has been done for over a decade, this approach is not widely known and to our knowledge not photo-documented. STUDY DESIGN:: Retrospective. MATERIAL AND METHODS:: An analysis was done with Institutional Review Board approval that identified 42 patients who underwent 53 procedures to treat AC webs, which were reconstructed with local soft-tissue flaps and without any device/stent to maintain the glottal aperture. The microlaryngoscopic method and technical nuances for this approach with and without diseased epithelium are described and photo-documented. Tactical mucosal incisions were made to facilitate advancement and/or rotation of fibro-mucosal flaps with enough length to resurface the medial aspect of 1 vocal fold. The scarred submucosal soft tissue in the AC region was separated with cold instruments, and the flaps were sutured in position. Variations of this method are demonstrated mobilizing fibro-mucosal soft tissue from different locations, including the web itself, contralateral vocal fold, infrapetiole region, and/or the inner aspect of the thyroid lamina below the anterior-commissure tendon. RESULTS:: Of the 53 cases in which anterior commissure glottal webs were reconstructed with endoscopic fibro-mucosal flaps, 31 of 53 had recurrent respiratory papillomatosis (RRP). Redundant RRP comprised the majority of the flap in 14 of 31 RRP cases. Fibro-mucosal tissue without a substantial amount of disease occurred in 17 of 31 RRP cases. Of the remaining 22 AC web cases, the primary diagnoses observed were: glottic cancer = 7 of 22, intraepithelial dysplasia = 10 of 22, glottic trauma = 3 of 22, congenital = 1 of 22, and radiotherapy = 1 of 22. CONCLUSION:: Endolaryngeal utilization of local fibro-mucosal tissue to lengthen the glottal/subglottal aperture for AC webs is an effective strategy. It can be done without using devices or keels for webs that are congenital or from nonsurgical trauma, idiopathic disease, or postsurgical traumatic cicatrization of the anterior commissure subsequent to treatment of epithelial disease (eg, cancer, dysplasia, and RRP). Normalizing the architecture of the anterior commissure was a valuable asset in patients who require future treatment of epithelial diseases, especially in an office-based setting.

Development of a Closed-Loop Stimulator for Laryngeal Reanimation: Part 2. Device Testing in the Canine Model of Laryngeal Paralysis.

OBJECTIVE:: Laryngeal paralysis of central or peripheral origin can potentially be treated using functional electrical stimulation (FES) of laryngeal muscles. Experiments in canines (dogs) were performed using implant prototypes capable of closed-loop FES to refine engineering designs and specifications, test surgical approaches for implantation, and better understand the in vivo effects of laryngeal muscle stimulation on short- and long-term glottic function. STUDY DESIGN:: Prospective, laboratory. METHODS:: We designed and tested a series of microprocessor-based implantable devices that can stimulate glottic opening or closing based on input from physiological control signals (real-time processing of electromyographic [EMG] signals). After acute device testing experiments, 2 dogs were implanted for 8 and 24 months, with periodic testing of closed-loop laryngeal muscle stimulation triggered from EMG signals. In total, 5 dogs were tested for the effects of laryngeal muscle stimulation on vocal fold (VF) posturing in larynges with nerve supplies that were intact (7 VFs), synkinetically reinnervated (2 VFs), or chronically denervated (1 VF). In 3 cases, the stimulation was combined with airflow-driven phonation to study the consequent modulation of phonatory parameters. RESULTS:: Initial device prototypes used inductive coupling for power and communication, while later iterations used battery power and infrared light communication (detailed descriptions are provided in the Part 1 companion paper). Two animals were successfully implanted with the inductively powered units, which operated until removed at 8 months in 1 animal or for more than 16 months in the second animal. Surgically, the encapsulated implants were well tolerated, and procedures for placing, attaching, and connecting the devices were developed. To simulate EMG control signals in anesthetized animals, we created 2 types of nerve/muscle signal sources. In one approach, a neck muscle had a cuff electrode placed on its motor nerve that was connected to transdermal electrical connection ports for periodic testing. In the second approach, the recurrent laryngeal nerve on one side of the larynx was stimulated to generate a VF EMG signal, which was then used to trigger FES of the paralyzed contralateral side (eg, restoring VF movement symmetry). Implant testing identified effective stimulation parameters and closed-loop stimulation artifact rejection techniques for FES of both healthy and paralyzed VFs. Stimulation levels effective for VF adduction did not cause signs of discomfort during awake testing. CONCLUSION:: Our inductive and battery-powered prototypes performed effectively during in vivo testing, and the 2 units that were implanted for long-term evaluation held up well. As a proof of concept, we demonstrated that elicited neck strap muscle or laryngeal EMG potentials could be used as a control signal for closed-loop stimulation of laryngeal adduction and vocal pitch modulation, depending on electrode positioning, and that VFs were stimulable in the presence of synkinetic reinnervation or chronic denervation.

The Art and Craft of Phonomicrosurgery in Grammy Award-Winning Elite Performers.

BACKGROUND:: Since the renowned opera maestro Manuel Garcia presented "Observations on the Human Voice" using mirror laryngoscopy in 1855, there has been an inextricable link between performing vocalists and laryngologists. Today, specialized laryngeal surgeons continue the tradition of integrating medical and surgical management of performers with those skilled in vocal arts, voice science, and voice therapy. With advances in surgical instrumentation and techniques, increasing opportunities have evolved to surgically restore lost performing voices. However, it is especially challenging because of a range of factors, including the need for optimal technical precision, management of expectations, complexity of informed consent, public visibility of these patients, and the economics related to the success and failure of surgery. A number of these key issues apply to phonomicrosurgical procedures in nonsingers as well. Consequently, reviewing the art and craft of phonomicrosurgery in elite performers provides valuable insights into the optimal management of any patient. METHODS:: A retrospective review was done of microlaryngeal procedures for the past 20 years, and 18 elite performers were identified who were Grammy Award winners. Microsurgical methods for different lesions are illustrated. Composite analyses of the group along with their associated pathology was done to provide insights into key issues. RESULTS:: The 18 patients in this cohort have won 80 Grammy Awards, which were garnered from 242 nominations. All 18 had substantial deterioration in voice quality and could retain more than 1 pathology. Significant loss of superficial lamina propria (SLP) pliability was present in 15 of 18, varices and/or ectasias leading to vocal hemorrhage in 6, vocal polyps in 9, fibrovascular nodules in 6, arytenoid granuloma in 1, sulcus from prior microlaryngeal surgery leading to vocal fold SLP scarring in 4, sulcus from long-term phonotrauma leading to vocal fold SLP scarring in 4, benign cyst in 1, precancerous dysplasia in 2, and invasive carcinoma in 2. Subsequent to phonomicrosurgery, all reported improvement in their performance. CONCLUSIONS:: Laryngologists and laryngeal surgeons have shouldered a burden of responsibility for elite performing vocalists since the origin of our specialty. Most lesions and diagnoses that are encountered result from phonotrauma. Optimizing singers' care provides surgeons with extremely complex technical, emotional, social, and financial challenges. Focused analysis of managing elite performing vocalists effectively integrates a range of essential issues, which provide key insights to assist clinicians treating nonperforming patients requiring phonomicrosurgery.

Lubricin/proteoglycan 4 detected in vocal folds of humans and five other mammals.

OBJECTIVES/HYPOTHESIS: Lubricin/proteoglycan-4 (PRG4) lubricates connective tissues such as joints and tendon sheaths, enabling them to better withstand shearing and frictional forces during motion. We wondered whether PRG4 might play a role in phonation, as normal vocal folds withstand repetitive, high-velocity deformations remarkably well. As a first step, we tested whether PRG4 is expressed in vocal folds. STUDY DESIGN: Laboratory study. METHODS: Anatomical and molecular methods were applied to 47 larynges from humans, macaque (Macaca fascicularis), canines, pigs, calves, and rats. Immunohistochemistry (IHC), Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) methods were used to test for the presence of PRG4. RESULTS: In all species, the true vocal fold lamina propria (TVF-LP) was positive for PRG4 by IHC, whereas immunoreactivity of the false vocal fold was weak or absent, depending on the species. Human TVF-LP was strongly stained across all layers. Immunoreactivity was seen variably on the vocal fold surface and within the vocal fold epithelium, in the conus elasticus and thyroglottic ligament, and at the tip of vocal process. Western blots of four humans and six pigs demonstrated immunoreactivity at appropriate molecular weight. qRT-PCR of pig tissues confirmed PRG4 mRNA expression, which was highest in the TVF-LP. CONCLUSIONS: PRG4 was found in phonatory tissues of six mammals. We suggest it might act as a lubricant within the lamina propria and possibly on the vocal fold surface, limiting phonation-related damage to vocal fold extracellular matrix and epithelium, and enhancing vocal efficiency by reducing internal friction (viscosity) within the vocal fold. LEVEL OF EVIDENCE: NA Laryngoscope, 129:E229-E237, 2019.

Toward Development of a Vocal Fold Contact Pressure Probe: Bench-Top Validation of a Dual-Sensor Probe Using Excised Human Larynx Models.

A critical element in understanding voice production mechanisms is the characterization of vocal fold collision, which is widely considered a primary etiological factor in the development of common phonotraumatic lesions such as nodules and polyps. This paper describes the development of a transoral, dual-sensor intraglottal/subglottal pressure probe for the simultaneous measurement of vocal fold collision and subglottal pressures during phonation using two miniature sensors positioned 7.6 mm apart at the distal end of a rigid cannula. Proof-of-concept testing was performed using excised whole-mount and hemilarynx human tissue aerodynamically driven into self-sustained oscillation, with systematic variation of the superior-inferior positioning of the vocal fold collision sensor. In the hemilarynx experiment, signals from the pressure sensors were synchronized with an acoustic microphone, a tracheal-surface accelerometer, and two high-speed video cameras recording at 4000 frames per second for top-down and en face imaging of the superior and medial vocal fold surfaces, respectively. As expected, the intraglottal pressure signal exhibited an impulse-like peak when vocal fold contact occurred, followed by a broader peak associated with intraglottal pressure build-up during the de-contacting phase. As subglottal pressure was increased, the peak amplitude of the collision pressure increased and typically reached a value below that of the average subglottal pressure. Results provide important baseline vocal fold collision pressure data with which computational models of voice production can be developed and in vivo measurements can be referenced.

Comparison of Videostroboscopy to Stroboscopy Derived From High-Speed Videoendoscopy for Evaluating Patients With Vocal Fold Mass Lesions.

Purpose: Videostroboscopy (VS) uses an indirect physiological signal to predict the phase of the vocal fold vibratory cycle for sampling. Simulated stroboscopy (SS) extracts the phase of the glottal cycle directly from the changing glottal area in the high-speed videoendoscopy (HSV) image sequence. The purpose of this study is to determine the reliability of SS relative to VS for clinical assessment of vocal fold vibratory function in patients with mass lesions. Methods: VS and SS recordings were obtained from 28 patients with vocal fold mass lesions before and after phonomicrosurgery and 17 controls who were vocally healthy. Two clinicians rated clinically relevant vocal fold vibratory features using both imaging techniques, indicated their internal level of confidence in the accuracy of their ratings, and provided reasons for low or no confidence. Results: SS had fewer asynchronous image sequences than VS. Vibratory outcomes were able to be computed for more patients using SS. In addition, raters demonstrated better interrater reliability and reported equal or higher levels of confidence using SS than VS. Conclusion: Stroboscopic techniques on the basis of extracting the phase directly from the HSV image sequence are more reliable than acoustic-based VS. Findings suggest that SS derived from high-speed videoendoscopy is a promising improvement over current VS systems.

Quantitative differentiation of normal and scarred tissues using second-harmonic generation microscopy.

The aim of this study was to differentiate normal and scarred hamster cheek pouch samples by applying a quantitative image analysis technique for determining collagen fiber direction and density in second-harmonic generation microscopy images. This paper presents a collagen tissue analysis of scarred cheek pouches of four adult male Golden Syrian hamsters as an animal model for vocal fold scarring. One cheek pouch was scarred using an electrocautery unit and the other cheek was used as a control for each hamster. A home-built upright microscope and a compact ultrafast fiber laser were used to acquire depth resolved epi-collected second-harmonic generation images of collagen fibers. To quantify the average fiber direction and fiber density in each image, we applied two-dimensional Fourier analysis and intensity thresholding at five different locations for each control and scarred tissue sample, respectively. The resultant depth-resolved average fiber direction variance for scarred hamster cheek pouches (0.61 ± 0.03) was significantly lower (p < 0.05) than control tissue (0.73 ± 0.04), indicating increased fiber alignment within the scar. Depth-resolved average voxel density measurements indicated scarred tissues contained greater (p < 0.005) fiber density (0.72 ± 0.09) compared to controls (0.18 ± 0.03). In the present study, image analysis of both fiber alignment and density from depth-resolved second-harmonic generation images in epi-detection mode enabled the quantification of the increased collagen fiber deposition and alignment typically observed in fibrosis. The epi-detection geometry is the only viable method for in vivo imaging as well as imaging thick turbid tissues. These quantitative endpoints, clearly differentiating between control and scarred hamster cheek pouches, provide an objective means to characterize the extent of vocal fold scarring in vivo in preclinical and clinical research. In particular, this non-invasive method offers advantages for monitoring scar treatments in live animals and following the effects of scarring-related treatments such as application of steroids or drugs targeting pathways involved in fibrosis. SCANNING 38:684-693, 2016. © 2016 Wiley Periodicals, Inc.

Glottic Cancer: A Metamorphosing Disease.

OBJECTIVE: Conventional wisdom is that the overwhelming majority of glottic cancer patients have a smoking history. However, in recent years observations suggested that an increasing number of glottic cancer patients had never been smokers. Therefore, an investigation was done examining the incidence of having a smoking history in a recent cohort of glottic cancer patients. METHOD: Retrospective review of 100 patients with glottic cancer to determine those reporting never having smoked. RESULTS: Thirty-one of 100 did not have a smoking history. Clinical observations of those cases revealed that the disease morphology tended to be exophytic, papillary, and very vascular, often resembling recurrent respiratory papillomatosis (RRP). Remarkably, 2 of 31 were initially treated elsewhere assuming they had RRP and underwent 5 cidofovir injections. Both presented with advanced cancer, and the disease growth markedly accelerated coincident with the injections. CONCLUSIONS: Observations herein provide new insights that glottic cancer may be an evolving disease in which smoking is less exclusive, not unlike HPV-induced pharynx cancer. Similar to RRP, the angiogenic papillary disease morphology is well suited for voice-preserving angiolytic KTP laser treatment. Given the resemblance of some glottic cancers to RRP, great care should be taken when using cidofovir for papillary glottic neoplasms.

Transoral and Transcervical Surgical Innovations in the Treatment of Glottic Cancer.

Transoral and transcervical surgery to treat glottic cancer has advanced substantially over the past decade. There have been considerable innovations that enhance vocal function for early disease and airway function for advanced disease. The fiber-based angiolytic 532 nm potassium titanyl phosphate laser has provided a new foundational strategy to maintain high cure rates with enhanced vocal outcomes for the treatment of early glottic disease. For advanced glottic cancer, transplanting cryopreserved aortic homograft to reconstruct wide-field laryngotracheal airway defects can provide an adequate airway caliber such that a long-term tracheotomy can frequently be avoided.