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Objective: Laryngeal cancer resections often require excision of portions of the larynx along with sacrifice of the ipsilateral recurrent laryngeal nerve (RLN). In such cases, there are no reconstructive options that reliably restore laryngeal function, rendering patients with severe functional impairment. To address this unmet clinical need, we extend our evaluation of a 3-implant mucosal, muscle, cartilage reconstruction approach aimed at promoting functional laryngeal restoration in a porcine hemilaryngectomy model with ipsilateral RLN transection., Methods: Six Yucatan mini-pigs underwent full-thickness hemilaryngectomies with RLN transection followed by transmural reconstruction using fabricated collagen polymeric mucosal, muscle, and cartilage replacements. To determine the effect of adding therapeutic cell populations, subsets of animals received collagen muscle implants containing motor-endplate-expressing muscle progenitor cells (MEEs) and/or collagen cartilage implants containing adipose stem cell (ASC)-derived chondrocyte-like cells. Acoustic vocalization and laryngeal electromyography (L-EMG) provided functional assessments and histopathological analysis with immunostaining was used to characterize the tissue response., Results: Five of six animals survived the 4-week postoperative period with weight gain, airway maintenance, and audible phonation. No tracheostomy or feeding tube was required. Gross and histological assessments of all animals revealed implant integration and regenerative remodeling of airway mucosa epithelium, muscle, and cartilage in the absence of a material-mediated foreign body reaction or biodegradation. Early voice and L-EMG data were suggestive of positive functional outcomes., Conclusion: Laryngeal reconstruction with collagen polymeric mucosa, muscle, and cartilage replacements may provide effective restoration of function after hemilaryngectomy with RLN transection. Future preclinical studies should focus on long-term functional outcomes., Level of Evidence: NA Laryngoscope, 134:4604-4613, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

A variety of surgical treatment options exist for adductor spasmodic dysphonia (ADSD) with selective adductor recurrent laryngeal nerve denervation and reinnervation (SLAD-R) being one of the more popular. We present a case of bilateral vocal fold paralysis (BVFP) for SLAD-R resulting in the need for total laryngectomy. We suggest BVFP is more common than reported and that we all must insure optimal long term follow up of our surgical patients. Laryngoscope, 134:4582-4584, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Neoadjuvant targeted therapy has emerged as a promising treatment strategy for locally aggressive thyroid cancer. Its impact on tumor and adjacent tissues remains a nascent area of study. Here we report on a series of six subjects with locally advanced thyroid cancer and recurrent laryngeal nerve (RLN) paralysis who experienced recovery of RLN function with neoadjuvant treatment and describe the morphologic and electrophysiologic characteristics of these recovered nerves., Methods: This is a multicenter retrospective review. Descriptive analysis was conducted to examine the following parameters for recovered nerves: (1) nerve morphology, characterized as Type A (involving epineurium only) versus Type B (extending beyond epineurium); (2) proximal stimulability (normal vs. abnormal vs. absent); and (3) surgical management (resection vs. preservation)., Results: Six subjects with unilateral VFP were identified. Median time to return of VF mobility was 3 months (range 2-13.5). All nerves (100%) were noted to have Type A morphology at surgery. Proximal stimulability was normal in four subjects (66.7%), abnormal in one (16.7%), and absent in one (16.7%). Nerves that had improvement of function through neoadjuvant therapy were able to be surgically preserved in five subjects (83.3%)., Conclusions: This represents the first characterization of RLNs that have recovered function with neoadjuvant treatment of locally advanced thyroid cancer. Although much remains unknown, our findings indicate carcinomatous neural invasion is a reversible process and recovered nerves may demonstrate normal morphology and electrophysiologic activity., Level of Evidence: 4 Laryngoscope, 134:3415-3419, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Nonselective laryngeal reinnervation is an effective procedure to improve voice quality after unilateral vocal fold paralysis. Few studies have captured long-term outcome data, and the revision rate for this operation is currently unknown. The objective of this study is to describe the long-term outcomes and revision rates of unilateral, nonselective reinnervation in pediatric and adult patients., Methods: Patients who underwent laryngeal reinnervation from 2000 to 2022 with a single surgeon were identified for inclusion. Patients who underwent bilateral, super selective, deinnervation and reinnervation, and/or concurrent arytenoid adduction procedures were excluded. Outcome measures included maximum phonation time [MPT], voice handicap index score [VHI], patient-reported percent normal voice, revision procedures, and complications. Data were compiled and analyzed using paired t-tests, repeated measures analysis of covariance, and binary logistic regression analysis., Results: One hundred thirty-two patients underwent unilateral, nonselective ansa-recurrent laryngeal nerve [RLN] laryngeal reinnervation. Reinnervation significantly improved MPT and patient-reported percentage of normal voice and significantly decreased VHI. Eleven patients underwent revision procedures, corresponding to a revision rate of 8.3%. Additional procedures included medialization laryngoplasty [n = 3], medialization laryngoplasty with arytenoid adduction [n = 3] and injection augmentation greater than 1 year after reinnervation [n = 5]. The only factor associated with the need for additional surgery was time lapse from nerve injury to reinnervation. The overall complication rate was 6.8%; no patient required reintubation or tracheostomy., Conclusion: Unilateral, nonselective laryngeal reinnervation can provide reliable improvement in vocal symptoms after recurrent laryngeal nerve injury. The revision rate after laryngeal reinnervation is favorable and comparable to framework surgery., Level of Evidence: 4 Laryngoscope, 134:3187-3192, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Patients with bilateral vocal fold paralysis (BVFP) experience airway obstruction because of loss of abductor function of posterior cricoarytenoid (PCA) muscles. We previously reported that implantation of autologous muscle progenitor (stem) cells into thyroarytenoid muscles during reinnervation resulted in improved adductor function. In this study, that same approach was applied to treating PCA muscles in a canine model of BVFP., Design: Animal study., Methods: Two canines underwent baseline measures of glottal resistance (GR), then complete transection and suture repair of both recurrent laryngeal nerves. Muscle stem cells were isolated from skeletal muscle and cultured. Two months later, GR was measured, and then 10 7 stem cells were implanted into one PCA muscle of each animal. After four more months, GR and glottal opening force (GOF) were measured and the muscles were harvested for histologic study. One control dog underwent the same procedures without stem cell implantation, for comparison., Results: GR increased by 21%-25% over baseline at 2 months, but after stem cell implantation, improved to 10%-14% over baseline at 6 months. PCA muscle strength, as determined by GOF, was 61%-65% on control sides (no stem cells), and 78%-83% on treated sides (with stem cells). Histology confirmed survival of stem cells and a 50% higher rate of innervation of motor endplates in the stem cell treated sides., Conclusion: Autologous muscle progenitor (stem) cells show promise as a potential new therapy for patients with bilateral vocal fold paralysis. Additional studies are needed to determine the optimal number of cells, timing of implantation, and other variables before launching a clinical trial., Level of Evidence: NA (animal study) Laryngoscope, 134:324-328, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: No curative injectable therapy exists for unilateral vocal fold paralysis. Herein, we explore the early implications of muscle-derived motor-endplate expressing cells (MEEs) for injectable vocal fold medialization after recurrent laryngeal nerve (RLN) injury., Methods: Yucatan minipigs underwent right RLN transection (without repair) and muscle biopsies. Autologous muscle progenitor cells were isolated, cultured, differentiated, and induced to form MEEs. Three weeks after the injury, MEEs or saline were injected into the paralyzed right vocal fold. Outcomes including evoked laryngeal electromyography (LEMG), laryngeal adductor pressure, and acoustic vocalization data were analyzed up to 7 weeks post-injury. Harvested porcine larynges were examined for volume, gene expression, and histology., Results: MEE injections were tolerated well, with all pigs demonstrating continued weight gain. Blinded analysis of videolaryngoscopy post-injection revealed infraglottic fullness, and no inflammatory changes. Four weeks after injection, LEMG revealed on average higher right distal RLN activity retention in MEE pigs. MEE-injected pigs on average had vocalization durations, frequencies, and intensities higher than saline pigs. Post-mortem, the MEE-injected larynges revealed statistically greater volume on quantitative 3D ultrasound, and statistically increased expression of neurotrophic factors (BDNF, NGF, NTF3, NTF4, NTN1) on quantitative PCR., Conclusions: Minimally invasive MEE injection appears to establish an early molecular and microenvironmental framework to encourage innate RLN regeneration. Longer follow-up is needed to determine if early findings will translate into functional contraction., Level of Evidence: NA Laryngoscope, 134:272-282, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: The recurrent laryngeal nerve (RLN) is at risk during pediatric cervical, thoracic, and cardiac surgery. We aim to determine the feasibility and effectiveness of RLN monitoring techniques in all pediatric patients., Study Design: Retrospective case series., Methods: Retrospective review of patients/procedures with RLN(s) at risk and RLN monitoring at Boston Children's Hospital July 2019-October 2020., Primary Outcomes: pre/postoperative vocal fold mobility by awake flexible fiberoptic laryngoscopy (FFL)., Results: One hundred one patients (median [interquartile range, IQR] age 14.6 months [4.6-49.7 months], weight 10 kg [5.2-16.2 kg]) underwent 122 procedures with RLN(s) at risk. RLN monitoring attempted 111 cases, successful 96 (84%). Surgical indications: esophageal atresia/tracheoesophageal fistula, and tracheobronchomalacia. Sixty-two (56%) procedures in reoperative field. Median follow-up 112 days (IQR 41-230). Pre/postoperative FFL performed 84 procedures (69%), 19 new postoperative RLN injuries (16%), median age 12 months, reoperative fields 11 (18%). Prass probes: 34 cases (28 successful, 82%), 6 injuries (18%), age 12.2 (5.8-23.6) months. Dragonfly electrodes: 45 cases (37 successful, 82%), 8 injuries (18%), age 7.5 (3.8-19) months. Nerve integrity monitoring (NIM) integrated electrode endotracheal tube: 33 cases (33 successful, 100%), 5 injuries (15%), age 90 (58.8-136.7) months. Automatic periodic stimulation (APS): 16 cases, 13 successful (81%), four injuries (25%), age 7.2 (5.3-20.6) months. NIM RLN monitoring is significantly more successful than Prass, Dragonfly (95%CI -0.3 to 0.02, P = .02; and 95%CI 0.05-0.31, P = .008). Rates of injury are not different between types of RLN monitoring (P = .94), with APS use (P = .47), or with monitoring success (95%CI -0.36 to 0.09, P = .28)., Conclusions: RLN monitoring is feasible in pediatric patients of all ages. Although NIM type RLN monitoring success is superior, all forms offer similar rates of nerve protection., Level of Evidence: 3 Laryngoscope, 132:889-894, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Recurrent laryngeal nerve (RLN) injury is a recognized risk during thyroid and parathyroid surgery and can result in significant morbidity. The aim of this review paper is to consider the optimal approach to the immediate intraoperative repair of the RLN during thyroid surgery., Methods: A PubMed literature search was performed from inception to June 2020 using the following search strategy: immediate repair or repair recurrent laryngeal nerve, repair or reinnervation recurrent laryngeal nerve and immediate neurorraphy or neurorraphy recurrent laryngeal nerve., Results: Methods of immediate intraoperative repair of the RLN include direct end-to-end anastomosis, free nerve graft anastomosis, ansa cervicalis to RLN anastomosis, vagus to RLN anastomosis, and primary interposition graft. Techniques of nerve repair include micro-suturing, use of fibrin glue, and nerve grafting. Direct micro-suture is preferable when the defect can be repaired without tension. Fibrin glue has also been proposed for nerve repair but has been criticized for its toxicity, excessive slow reabsorption, and the risk of inflammatory reaction in the peripheral tissues. When the proximal stump of the RLN cannot be used, grafting could be done using transverse cervical nerve, supraclavicular nerve, vagus nerve, or ansa cervicalis., Conclusions: Current evidence is low-level; however, it suggests that when the RLN has been severed, avulsed, or sacrificed during thyroid surgery it should be repaired intraoperatively. The immediate repair has on balance more advantages than disadvantages and should be considered whenever possible. This should enable the maintenance of vocal cord tone, better and prompter voice recovery and avoidance of aspiration. Laryngoscope, 131:1429-1435, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objectives/hypothesis: Arytenoid adduction (AA) is performed to treat unilateral vocal fold paralysis with a large posterior glottal gap. However, the voice effects of AA suture position remain unclear. This study aimed to evaluate voice production and quality as a function of AA suture position on the thyroid ala in a neuromuscularly intact in vivo larynx., Study Design: Animal model., Methods: Unilateral recurrent laryngeal nerve and vagal paralysis were modeled in two canines. AA suture position was varied across five equidistant positions on the anterior inferior thyroid ala, from a paramedian position anteriorly to the oblique line posteriorly. Phonation was performed over 8 × 8 graded level combinations of recurrent and superior laryngeal nerve stimulation per suture position. The primary outcome was percent successful phonatory conditions. Secondary outcomes included fundamental frequency (F0), phonation onset pressure (PTP), cepstral peak prominence (CPP), and laryngeal posture., Results: Anterior suture positions resulted in a greater percentage of successful phonatory conditions compared to posterior sutures. Suture position 2, located at the anterior inferior thyroid ala, resulted in the highest percentage of successful phonatory conditions, lowest PTP, and lower muscle activation levels to achieve higher CPP. Posterior sutures resulted in wider glottal gap and more effective F0 and vocal fold strain increase with cricothyroid muscle contraction, but with fewer successful phonatory conditions and higher PTP. Trends were consistent across both paralysis types., Conclusions: AA suture placed in the anterior inferior thyroid ala resulted in the best acoustic, aerodynamic, and voice quality outcomes. This study provides scientific evidence for maintaining current clinical practice., Level of Evidence: NA Laryngoscope, 131:846-852, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Application of transcartilage needle electrode for intraoperative neuromonitoring (IONM) during thyroidectomy has been considered an alternative method of electromyography (EMG) tube recording. However, needle electrodes must be inserted into both sides of the thyroid cartilage with exposure of the cartilage lamina. We sought to evaluate the feasibility of applying a single ipsilateral transcartilage needle electrode for IONM during unilateral hemithyroidectomy., Methods: Thirty-four patients underwent IONM during unilateral thyroidectomy. A dual disposable needle electrode was inserted obliquely into the inferior lower third of the ipsilateral lamina of the thyroid cartilage. Patients were classified as deep (≥ 5 mm) or superficial (< 5 mm) by the depth of the needle electrode inserted into the thyroid cartilage. Without using an EMG tube, IONM was done according to the standardized procedure using a single needle electrode only., Results: IONM was successful in all nerves at risk. Amplitude of the EMG signal was stable during the surgery, with no cases presenting loss of signal. Amplitude of the signal from vagal and recurrent laryngeal nerve stimulation was significantly lower when needle insertion was superficial (< 5 mm). None of the patients showed postoperative vocal cord paralysis, and complications related to needle electrode were not identified., Conclusion: IONM using a single ipsilateral transcartilage needle electrode during unilateral hemithyroidectomy was feasible with no significant complications. It may serve as an alternative method of IONM with the advantage of minimal exposure of the thyroid cartilage lamina., Level of Evidence: 4 Laryngoscope, 131:448-452, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: This study explored the feasibility and efficiency of main branch of ansa cervicalis nerve (ACN)-to-recurrent laryngeal nerve (RLN) anastomosis for management of paroxysmal laryngospasm due to unilateral vocal cord paralysis (UVCP)., Methods: Thirteen patients who underwent main branch of ACN-to-RLN anastomosis for management of paroxysmal laryngospasm due to UVCP were enrolled in the present study. Multidimensional assessments, including videostroboscopy, voice assessment, and laryngeal electromyography (LEMG), were performed preoperatively and postoperatively., Results: This series was limited to UVCP with iatrogenic causes, including thyroidectomy, cervical spine surgery, and thoracic surgery. After main branch of ACN-to-RLN anastomosis, all cases showed significant airway improvement, and laryngospasm was completely abolished in 92.3% (12 of 13) of cases. Videostroboscopy showed that the bulging and paradoxical adduction of the affected vocal cord during a sniff were abolished immediately after operation, and there was no significant difference in vocal fold position or glottal closure before versus after the operation. LEMG showed that the postoperative recruitment and amplitude of voluntary motor unit potential in the affected thyroarytenoid muscle during a sniff were significantly decreased compared to preoperative values, and postoperative recruitment showed significant improvement during phonation compared to that preoperatively. Voice assessment showed that there were no significant differences in overall grade, roughness, breathiness, jitter (local), shimmer (local), noise-to-harmonics ratio, or maximum phonation time after the operation compared to the preoperative values., Conclusions: Main branch of ACN-to-RLN anastomosis could have long-lasting efficacy in the management of paroxysmal laryngospasm due to UVCP, with no apparent compromise of voice quality., Level of Evidence: 4 Laryngoscope, 130:2412-2419, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Demonstration of voice improvement and long-term stability following nonselective unilateral laryngeal reinnervation (ULR) in patients with unilateral vocal fold paralysis (UVFP) and severe denervation. A subgroup of patients on whom ULR was performed as a salvage technique following unsuccessful medialization was analyzed separately., Study Design: Prospective cohort study., Methods: The ansa cervicalis-recurrent laryngeal nerve anastomosis technique was performed in all patients. Pre- and postoperative voice analysis included voice questionnaires, voice assessment by senior laryngologists using the Hirano Voice Scale, and computer-assisted voice analysis at defined time points over the course of 36 months. Laryngeal electromyography (LEMG) and spirometry were performed before and 1 year after ULR., Results: Significant linear improvement of mean voice quality over time was observed in the majority of parameters measured in 48 ULR patients and in eight ULR salvage patients. LEMG 1 year after ULR showed new recruitment. Mean voice quality remained stable during follow-up in all ULR patients and in the ULR salvage group., Conclusions: Nonselective ULR in UVFP is a reliable and stable therapeutic option for patients with high expectations concerning voice quality. The effect is stable in long-term results. It is also a viable option for patients in whom conventional voice surgery failed to improve voice quality. We therefore propose ULR as salvage option in UVFP., Level of Evidence: 2b Laryngoscope, 130:1756-1763, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: We evaluated the efficacy of a vocal fold reconstruction technique using a vascularized autologous pedicled fat (PEFA) flap in a rabbit model of vocal fold paralysis., Study Design: Animal model., Methods: The study included 30 male New Zealand White rabbits; 20 received vocal fold reconstructions (PEFA group) and 10 served as normal controls (control group). The right recurrent laryngeal nerve was resected, and simultaneous PEFA flap reconstruction was performed. The PEFA flap, including a pre-epiglottic fat and thyroid perichondrium, was elevated and implanted through a window at the inferior border of the thyroid cartilage. Histological and high-speed video analyses of vocal fold vibration were performed 1 month after PEFA reconstruction. The maximum amplitude of vocal fold vibration and the dynamic glottal gap were used to assess vocal fold vibration., Results: The histological findings showed that the lamina propria ratio (lamina propria pixels/total vocal fold pixels) and the total number of vocal fold pixels were similar between the PEFA and control groups. Vocal fold vibration analyses indicated that the maximum amplitude differences in the vibration were slightly lower in the PEFA group. However, the dynamic glottal gap of the vocal fold was not significantly different between the PEFA group and the control group., Conclusions: The PEFA flap vocal fold reconstruction technique maintained the vocal fold area without a significant reduction in vocal fold vibration in a rabbit model., Level of Evidence: NA Laryngoscope, 130:1770-1774, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Non-selective laryngeal reinnervation (NSLR) using the ansa cervicalis to the recurrent laryngeal nerve (RLN) is a promising treatment option for pediatric unilateral neuronal vocal fold movement impairment (VFMI). The aim is to describe our clinical outcomes with this technique and to identify preoperative characteristics that may predict postoperative voice outcomes., Methods: This is a cohort study of pediatric patients with unilateral neuronal VFMI, who underwent NSLR from March 2012 to July 2018. Pre- and postoperative Pediatric Voice Related Quality of Life (PVRQOL) questionnaires, Consensus Auditory Perceptual Evaluation of Voice (CAPE-V) ratings, and objective voice measures were obtained. In addition, patients underwent preoperative laryngeal electromyography (LEMG)., Results: Thirty-two patients were identified. Twenty-one had complete data sets for analysis. The mean duration of VFMI was 9.02 years (range 1.1-26.1 years). There were significant improvements in PVRQOL (P = .0005), in all CAPE-V subsets (P ≤ .0001 to .0195), mean and maximum intensities (P = .0342 and 0.0110, respectively), cepstral peak prominence (P = .0001), and cepstral spectral index of dysphonia (P ≤ .0001). A worse preoperative LEMG correlated with a greater change in maximum phonation time (P = .0162) and maximum intensity (P = .0346). Age at injury and duration of injury had no significant impact on voice outcomes; however, patients with concurrent posterior glottic insufficiency did have smaller changes in PVRQOL (P = .012)., Conclusion: NSLR is an effective treatment for pediatric unilateral neuronal VFMI even many years after initial RLN injury. LEMG may help predict voice outcomes of reinnervation in pediatric patients, but further data is still needed., Level of Evidence: 4 Laryngoscope, 130:1525-1531, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Ansa-to-recurrent laryngeal nerve (ANSA-RLN) reinnervation procedures are now often first-line treatments for some children with unilateral vocal fold immobility. Although many describe that children with prolonged denervation and true vocal fold atrophy should not undergo this procedure, there has been no gold-standard means of identifying true denervation. Here, we describe a novel technique using evoked vagal electromyography to predict degree of chronic nerve injury prior to recurrent laryngeal nerve reinnervation in children. This is a simple, readily available technique that may play an important role in predicting likelihood of success with pediatric ANSA-RLN reinnervation. Laryngoscope, 130:747-751, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: This study aimed to investigate the risk of postoperative recurrent laryngeal nerve paralysis (RLNP) with and without the use of intraoperative nerve monitoring (IONM) during thyroid cancer surgery., Study Design: Retrospective cohort study., Methods: This study utilized a nationwide claims database in Japan. Patients who underwent thyroid cancer surgery with and without IONM were included, and postoperative RLNP incidence was compared., Results: The study included 5,804 patients. Multivariable logistic regression analysis revealed that use of IONM was not associated with increased RLNP risk (odds ratio: 1.15; 95% confidence interval: 0.67-1.96). There was no significant effect on RLNP prevention when stratified by tumor or nodal classification. Rather, the patients who had T4 or N1b classifications who received IONM had higher incidences of RLNP., Conclusions: Use of IONM did not significantly reduce the risk of RLNP. The results for the T4 and N1b populations may be explained by indication bias or unmeasured confounders., Level of Evidence: NA Laryngoscope, 129:1954-1960, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Traditionally, most thyroid surgery utilizes a curvilinear cervical incision with a resulting permanent scar. Minimally invasive and remote access thyroid surgery techniques continue to evolve. Transoral approaches through a vestibular incision have been developed at several centers throughout the world, obviating the need for a cutaneous incision and optimizing aesthetics. To date this technique has been performed using rigid endoscopes or a linear robotic platform. The goal of this study was to test the feasibility of a novel flexible robotic system to perform a transvestibular thyroidectomy in a preclinical cadaver model., Study Design: Preclinical feasibility study., Methods: Right and left thyroid lobectomies were successfully performed via a transvestibular approach in four cadavers., Results: A single vestibular incision between bilateral mental nerves allowed entrance of the flexible robot in a subplatysmal plane in both male and female cadavers. The recurrent laryngeal nerves and parathyroids were identified and preserved. The flexible three-dimensional camera allowed excellent visualization and could be easily repositioned for optimal visualization of right and left structures. The flexible and wristed instruments enabled an atraumatic approach and allowed for precise surgical technique., Conclusions: The transoral vestibular approach to the central neck is a promising technique for thyroidectomy with optimal cosmesis and can be successfully accomplished using this novel flexible robotic system. Improvements in visualization and access offered by this system may improve application of this technique., Level of Evidence: NA Laryngoscope, 129:1482-1487, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Tissue engineering of the larynx requires a complex, multiple tissue layer design. Additionally, spontaneous reinnervation of the larynx after recurrent laryngeal nerve (RLN) injury is often disorganized, resulting in subpar function. This study investigates use of tissue-engineered cartilage and motor endplate-expressing (MEE) tissue-engineered skeletal muscle implants for laryngeal reconstruction and the promotion of organized reinnervation after RLN injury., Methods: F344 rat primary muscle progenitor cells (MPCs) were isolated. Three-dimensional muscle constructs were created by encapsulating MPCs in type I oligomeric collagen under passive tension. Constructs were then cultured in differentiation medium (MPC control constructs) or induced to form motor endplates (MEE constructs) with neurotrophic agents. Three-dimensional cartilage constructs were created with adipose stem cells differentiated in chondrocyte medium. The muscle and cartilage constructs were implanted into surgically created myochondral defects in the F344 rat larynx with injured or intact (control) RLN. At 1-, 3-, and 6-month timepoints, videolaryngoscopy, electromyography (EMG), histology, and immunohistochemistry were used to assess outcomes., Results: At all timepoints, cartilage-muscle implants were well integrated into host tissue. Functionally, there was increased vocal fold adduction and EMG activity in nerve-injured rats treated with the MEE constructs when compared to those treated with the MPC control constructs. Motor endplate-expressing constructs had increased myofiber cross-sectional area compared to MPC control constructs., Conclusion: Although our laboratory previously demonstrated that muscle and cartilage constructs could be used separately for hemilaryngeal reconstruction, this study suggests combining them with the modification of MEEs rather than MPCs, resulting in improved muscle recovery after recurrent laryngeal nerve injury., Level of Evidence: NA Laryngoscope, 129:1293-1300, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Continuous intraoperative nerve monitoring (CIONM) during thyroidectomy is promising technology that may reduce the incidence of recurrent laryngeal nerve (RLN) injuries. However, the current technique for CIONM, in which a stimulating probe is placed on the vagus nerve, has not been widely adopted because of concerns regarding its invasiveness and safety. A new method with the lead positioned on the RLN may overcome these objections and promote greater adoption of CIONM. This study was conducted to serve as the first step in determining the safety and feasibility of an RLN-based CIONM approach., Study Design: Case series with planned data collection., Methods: Fifty patients scheduled to undergo thyroidectomy were enrolled. In all cases, after identification of the RLN, a lead designed for CIONM was placed on the nerve. The lead was then left in place for a minimum of 2 minutes, and CIONM data were recorded. Laryngeal electromyographic (EMG) characteristics were assessed just before the lead was placed on the RLN and after it was removed. Pre- and postoperative fiberoptic laryngoscopy was performed to assess vocal cord function in all patients., Results: In 49 patients (98%), the probe was successfully positioned on the RLN, and CIONM data were generated. On average, 1.4 attempts per patient were required to properly place the lead. No accidental dislodgements of the lead occurred during the experiments. No patients demonstrated significant EMG changes from baseline after manipulation and stimulation of the RLN. The average CIONM time was 175.7 s (range, 138-212 s), and the average CIONM amplitude and latency were 675.2 µV (range, 211.0-1405.2 µV) and 1.8 ms (1.25-1.9), respectively. All patients had normal bilateral vocal cord function preoperatively and at the first postoperative visit., Conclusions: This study demonstrates the apparent safety and viability of a CIONM technique using a lead placed directly on the RLN. Future investigations are warranted of this promising method, which may promote more widespread adoption of CIONM during thyroidectomy to reduce RLN injuries., Level of Evidence: 4 Laryngoscope, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

The purpose of this publication was to inform surgeons as to the modern state-of-the-art evidence-based guidelines for management of the recurrent laryngeal nerve invaded by malignancy through blending the domains of 1) surgical intraoperative information, 2) preoperative glottic function, and 3) intraoperative real-time electrophysiologic information. These guidelines generated by the International Neural Monitoring Study Group (INMSG) are envisioned to assist the clinical decision-making process involved in recurrent laryngeal nerve management during thyroid surgery by incorporating the important information domains of not only gross surgical findings but also intraoperative recurrent laryngeal nerve functional status and preoperative laryngoscopy findings. These guidelines are presented mainly through algorithmic workflow diagrams for convenience and the ease of application. These guidelines are published in conjunction with the INMSG Guidelines Part I: Staging Bilateral Thyroid Surgery With Monitoring Loss of Signal. Level of Evidence: 5 Laryngoscope, 128:S18-S27, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

This publication offers modern, state-of-the-art International Neural Monitoring Study Group (INMSG) guidelines based on a detailed review of the recent monitoring literature. The guidelines outline evidence-based definitions of adverse electrophysiologic events, especially loss of signal, and their incorporation in surgical strategy. These recommendations are designed to reduce technique variations, enhance the quality of neural monitoring, and assist surgeons in the clinical decision-making process involved in surgical management of recurrent laryngeal nerve. The guidelines are published in conjunction with the INMSG Guidelines Part II, Optimal Recurrent Laryngeal Nerve Management for Invasive Thyroid Cancer-Incorporation of Surgical, Laryngeal, and Neural Electrophysiologic Data. Laryngoscope, 128:S1-S17, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: During monitored thyroidectomy, displacement of the recurrent laryngeal nerve (RLN) or vagus nerve (VN) in some complicated cases can increase the risk of injury. Although increasing the stimulus current can facilitate nerve mapping and localization, the safety of a high-current stimulus remains unknown. Therefore, this study evaluated the safety of a high-current stimulus in a porcine model., Methods: Short-duration (1 minute), high-current (3, 5, 10, 15, 20, 25, and 30 mA at 4Hz) stimulus pulses were repeatedly applied to the RLN or VN in six anesthetized piglets. The safety of the high-current stimulus pulses was assessed in terms of hemodynamic stability during VN stimulation and in terms of nerve function integrity after VN and RLN stimulation., Results: During VN stimulation with a high-current stimulus pulse, sinus rhythms in all six piglets showed stable heart rates, and mean arterial pressure was unaffected. High-current stimulation of the VN and the RLN did not affect electromyography amplitude or latency., Conclusion: This porcine study showed that applying a short-duration, high-current stimulus pulse to the VN or RLN during monitored thyroidectomy has no harmful effects. In clinical practice, a short duration of high-current stimulus can be applied to facilitate neural mapping, especially in patients with disoriented nerve positions., Level of Evidence: NA. Laryngoscope, 128:2206-2212, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: After recurrent laryngeal nerve injury (RLN), spontaneous reinnervation of the larynx occurs with input from multiple sources. The purpose of this study was to determine the timing and efficiency of reinnervation across a resected RLN segment in a rat model of RLN injury., Study Design: Animal study., Methods: Twelve male 60-day-old Sprague Dawley rats underwent resection of a 5-mm segment of the right RLN. Rats were sacrificed at 1, 2, 4, and 12 weeks after nerve injury to harvest the larynx and trachea for immunohistologic analysis. The distal RLN segment was stained with neurofilament, and axons were counted and compared to the nonoperated side. Thyroarytenoid (TA) muscles were stained with alpha-bungarotoxin, synaptophysin, and neurofilament to identify intact neuromuscular junctions (NMJ). The number of intact NMJs from the denervated side was compared to the nonoperated side., Results: Nerve fibers regenerated across the resected RLN gap into the distal recurrent laryngeal nerve to innervate the TA muscle. The number of nerve fibers in the distal nerve segment increased over time and reached the normal number by 12 weeks postdenervation. Axons formed intact neuromuscular junctions in the TA, with 48.8% ± 16.7% of the normal number of intact NMJs at 4 weeks and 88.3% ± 30.1% of the normal number by 12 weeks., Conclusion: Following resection of an RLN segment in a rat model, nerve fibers spontaneously regenerate through the distal segment of the transected nerve and form intact NMJs in order to reinnervate the TA muscle., Level of Evidence: NA. Laryngoscope, 128:E117-E122, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: The nonrecurrent laryngeal nerve (NRLN) is a common anatomic variation of the right recurrent laryngeal nerve (RLN), which has been associated with an increased risk of injury during thyroid and parathyroid surgery. We suggest that early successful identification using intraoperative nerve monitoring (IONM) and preservation of this variant will help the surgeon to avoid injury to this nerve. Our objective was to examine the electrophysiological parameters of the NRLN and the efficacy of IONM for successful identification of the NRLN., Study Design: Retrospective database analysis., Methods: This is a retrospective study of a prospectively collected database of all patients who underwent thyroid and parathyroid surgeries by a single surgeon at a tertiary care center over 3 years (n = 481). Patients' demographic data and operative reports, including the IONM reports, were reviewed. Average stimulation thresholds with resulting amplitudes and latencies were compared. Preoperative and postoperative laryngoscopy were performed in all cases., Results: We identified 15 NRLNs (2.2%) in a total 682 laryngeal nerves. No left-sided NRLNs were observed. The average right vagus latency in the NRLN group was shorter than that of the RLN group (2.40 ms ± 0.49 ms vs. 3.43 ms ± 1.03 ms; P < .001). No statistically significant difference was observed between the initial amplitudes of the right vagus nerves in the two groups (713.67 μV ± 208.71 μV vs. 816.22 μV ± 470.45 μV; P = .14). All NRLN cases exhibited normal functioning of vocal cords on postoperative laryngoscopy., Conclusions: IONM is highly effective in the identification of the NRLN. Right vagus nerve latency in the NRLN group was found to be significantly shorter than in the RLN group. Early identification of the NRLN allowed cautious preservation of the NRLN, resulting in excellent postoperative outcomes. The rate of NRLN identification may be improved by routine use of IONM., Level of Evidence: 4 Laryngoscope, 127:2189-2193, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: During intraoperative neural monitoring (IONM) in thyroid and parathyroid surgery, endotracheal (ET) tube migration can result in a decrease in vocalis electromyographic (EMG) amplitude without a concordant latency elevation during stimulation of the recurrent laryngeal nerve (RLN)., Study Design: Retrospective review., Methods: Data were reviewed retrospectively for thyroid and parathyroid surgery patients with IONM of the laryngeal nerves from January 2015 to December 2015. Recordings of vocalis EMG amplitudes and latencies with RLN stimulation were obtained with the neuromonitoring ET tube surface electrodes in optimal baseline position, with vertical displacement away from the vocalis, and with rotational change away from baseline., Results: ET tube surface electrode EMG recordings were obtained with stimulation of seven left and three right RLNs in a total of 10 patients. Mean vocalis EMG amplitudes were reduced with vertical displacement 1 and 2 cm both inferior and superior to baseline and with rotational change (45° and 90° clockwise and counterclockwise, 180°), although amplitude change with 45° clockwise and 180° rotation did not meet statistical significance. Mean EMG latency values did not change significantly from baseline with either rotation or vertical displacement of the ET tube., Conclusions: An isolated decrease in EMG amplitude without concordant latency elevation should warrant re-evaluation of ET tube position during thyroid and parathyroid surgery and is in contrast to a combined event, with both EMG amplitude decrease and concordant latency increase, which is more suggestive of a true neuropraxic injury., Level of Evidence: 4. Laryngoscope, 127:2182-2188, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: This study investigated recurrent laryngeal nerve (RLN) real-time electromyography (EMG) data to define optimal safety parameters of the LigaSure Small Jaw (LSJ) instrument during thyroidectomy., Study Design: Prospective animal model., Methods: Dynamic EMG tracings were recorded from 32 RLNs (16 piglets) during various applications of LSJ around using continuous electrophysiologic monitoring. At varying distances from the RLN, the LSJ was activated (activation study). The LSJ was also applied to the RLN at timed intervals after activation and after a cooling maneuver through placement on the sternocleidomastoid muscle (cooling study)., Results: In the activation study, there was no adverse EMG event at 2 to 5 mm distance (16 RLNs, 96 tests). In the cooling study, there was no adverse EMG event after 2-second cooling time (16 RLNs, 96 tests) or after the LSJ cooling maneuver on the surrounding muscle before reaching the RLNs (8 RLNs, 24 tests)., Conclusion: Based on EMG functional assessment, the safe distance for LSJ activation was 2 mm. Further LSJ-RLN contact was safe if the LSJ was cooled for more than 2 seconds or cooled by touch muscle maneuver. The LSJ should be used with these distance and time parameters in mind to avoid RLN injury., Level of Evidence: N/A. Laryngoscope, 127:1724-1729, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Micronized AlloDerm is a commonly used injectable material for injection laryngoplasty; however, the histologic response to laryngeal implantation and resorption rate over time have not been elucidated. This study aimed to evaluate the in vivo response of micronized AlloDerm over time after laryngeal implantation using a rabbit model., Study Design: Animal model., Methods: The left recurrent laryngeal nerve was sectioned in five New Zealand White rabbits to create a vocal cord paralysis. Two weeks later, injection laryngoplasty was performed with 100 μL of micronized AlloDerm. Animals were sacrificed 4 (two rabbits) and 12 (three rabbits) weeks after injection. Histologic sections were stained and evaluated by a single pathologist. Volume estimates were made by assuming the implant took an ellipsoid shape using dimensions calculated from histologic slides., Results: In all cases, histological analysis revealed a lymphocytic inflammatory response infiltrating the peripheral margins of injection. After 4 weeks, the volume of injected material remaining in two rabbits was 404 and 278 mm 3 (average 341 mm 3 ). After 12 weeks, the volume of injected material remaining in three rabbits was 0, 61, and 124 mm 3 (average 62 mm 3 ), an 82% difference in volume of material between animals sacrificed at 4 weeks versus 12 weeks., Conclusions: Injection laryngoplasty using micronized AlloDerm induces a lymphocytic inflammatory response after injection in a rabbit model. Though a significant amount of material remains after 4 weeks, by 12 weeks the majority has been reabsorbed., Level of Evidence: NA Laryngoscope, 127:E166-E169, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Nerbridge (Toyobo Co., Ltd., Osaka, Japan) is a novel polyglycolic acid (PGA) tube that is filled with collagen fibers and that facilitates nerve fiber expansion and blood vessel growth. It is biocompatible and commercially available, with governmental approval for practical use in Japan. We hypothesized that the PGA-collagen tube would promote regeneration of the recurrent laryngeal nerve (RLN). This hypothesis was examined in a rat axotomy model of the RLN., Study Design: Prospective animal study., Methods: The axotomy model was established by transection of the left RLN in adult Sprague-Dawley rats. The cut ends of the nerve were bridged using Nerbridge (Toyobo Co., Ltd.) with a 1-mm gap (tube-treatment group) or direct sutures (sutured-control group). Left vocal fold mobility, nerve conduction velocity, morphology, and histology were assessed after 15 weeks., Results: Fifteen weeks after treatment, nerve fiber connections were observed macroscopically in both groups, and more clear myelinated fibers and better prevention of laryngeal muscle atrophy were observed in the tube-treatment group compared with the sutured-control group. However, vocal fold movement recovery was not observed in either group, and the conduction velocity of the RLN did not differ between the two groups., Conclusions: Better nerve regeneration was observed in the tube-treatment group. The combination therapy with molecular or gene therapy might be an effective strategy to improve vocal fold movement. The PGA-collagen tube has the potential to promote regeneration of the RLN and to be a scaffold for drug administration in these combination therapies., Level of Evidence: N/A. Laryngoscope, 126:E233-E239, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: During intraoperative neuromonitoring (IONM) of recurrent laryngeal nerve (RLN) in thyroid surgery, the need for frequent shifting between the dissecting instruments and stimulating probe is troublesome and time-consuming. Therefore, use of these two instruments in combination would be a noticeable future direction. This study aimed to investigate the feasibility and safety of using stimulating dissecting instruments (SDIs) that combine the function of surgical dissection and nerve stimulation during IONM., Study Design: Prospective outcomes research., Methods: One hundred consecutive patients with 168 RLNs at risk were enrolled. We developed prototypes of SDIs and applied them to early detect adverse EMG changes during the risky phase of RLN dissection. In the case of substantial EMG change (amplitude decrease > 50%) during dissection, the surgical maneuver was paused and thyroid traction was released immediately., Results: The application of SDIs was feasible in all cases and did not result in any morbidity. Nineteen RLNs were detected with substantial EMG change that was caused by traction stress during dissection with SDIs and that featured progressive gradual EMG recovery after releasing thyroid traction. After thyroid resection, 10 RLNs had a weak point of nerve conduction detected at region of Berry's ligament, but only one nerve with 79% amplitude reduction developed postoperative temporary vocal palsy., Conclusion: The application of SDIs is a simple and effective way to monitor the nerve's function instantly during the risky phase of RLN injury in thyroid surgery. It provides surgeons with real-time feedback of EMG response and can be applied as a tool for the early detection of adverse EMG change caused by traction distress., Level of Evidence: 4., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To establish the benefit of ansa cervicalis-recurrent laryngeal nerve reinnervation (ANSA-RLN) for the management of dysphonia secondary to unilateral vocal cord paralysis (UVCP) in children. Children treated with ANSA-RLN for the management of dysphonia secondary to unilateral vocal fold immobility will have superior acoustic, perceptual, and stroboscopic outcomes compared to injection laryngoplasty and observation., Study Design: Retrospective case-series chart review., Methods: Laryngeal, perceptual, and acoustic analysis of dysphonia was performed in 33 children (age 2-16 years) diagnosed with UVCP. Comparison of pre-post function for treatment groups (no treatment, injection laryngoplasty, ANSA-RLN) with additional comparison between gestational ages, age at initial evaluation, and gender were examined. Perceptual measures included Pediatric Voice Handicap Index (pVHI) and Grade, Roughness, Breathiness, Asthenia, Strain (GBRAS) perceptual rating. Objective measures included semitone (ST) range, jitter%, shimmer%, noise-to-harmonic ratio, voicing, and maximum phonation time., Results: Post-treatment, pVHI, jitter%, and ST were significantly improved for ANSA-RLN subjects compared to injection subjects. Improved function (laryngeal diadochokinesis, pVHI, GRBAS, and/or acoustic) was observed in all ANSA-RLN subjects who had vocal fold paralysis as the only laryngeal diagnosis., Conclusions: This study presents one of the largest studies of pediatric vocal fold paralysis diagnosis and treatment. The study looks at the spectrum of function in patients with UVCP and looks at the outcomes of options: no treatment, injection laryngoplasty, and ANSA-RLN. Although surgical outcomes vary, both injection laryngoplasty and ANSA-RLN show benefit in laryngeal function, voice stability, voice capacity, perceptual rating, and pVHI scores. Both injection laryngoplasty and ANSA-RLN showed improvements post-treatment, and should be considered for management of pediatric UVCP. However, the ANSA-RLN group showed better and longer-lasting perceptual and acoustic parameters in comparison with the injection and control groups. Reinnervation, even long term after the onset of vocal fold paralysis, should be considered a viable permanent treatment for pediatric UVCP., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To examine modulation of M-cadherin, a marker for satellite cells (SCs); and MyoD, which may indicate the myogenic activity following recurrent laryngeal nerve (RLN) denervation and immediate reinnervation; and to elucidate the correlation between their modulations and establishment of neuromuscular junctions (NMJs) in the reinnervated rat thyroarytenoid (TA) muscle., Study Design: Quantitative real-time polymerase chain reaction qPCR and histologic assessment of the TA muscle following RLN transection and anastomosis., Methods: Rats were divided into three groups: 1) denervation alone (DNV) (n = 60), 2) denervation with anastomosis (ANS) (n = 60), and 3) sham-operated controls (n = 12). Animals were sacrificed at 3 days and 1, 3, and 5 weeks after treatment. TA muscles harvested from 40 animals from each DNV and ANS group; all of sham group were subjected to qPCR for assessment of the modulation of M-cadherin and MyoD; and the remaining larynges of DNV and ANS group were used for histologic analysis., Results: The expression levels of messenger RNAs (mRNAs) encoding M-cadherin and MyoD in the TA muscle of the DNV group were significantly higher (P < 0.05) than in the control throughout the study period. These mRNA levels in the ANS group were significantly higher (P < 0.05) at ≤ 1 week than in the controls but fell to control levels at ≥ 3 weeks. In the ANS group, recovery of muscle area and NMJs structure occurred by 3 weeks., Conclusion: These data suggested that NMJ formation following reinnervation might prompt recovery of M-cadherin and MyoD mRNA expression to the quiescent level of SCs., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Medialization thyroplasty (MT) is commonly used to treat glottic insufficiency. In this study, we investigated the phonatory effects of MT implant medialization depth and medial surface shape., Methods: Recurrent laryngeal nerve (RLN) and vagal paralysis were simulated in an in vivo canine. A type 1 MT was performed using a silicone elastomer implant with variable medialization depths and medial surface shapes: rectangular, V-shaped, divergent, and convergent. The effects on phonation onset flow/pressure relationships and acoustics were measured., Results: Increasing depth of medialization led to improvements in fundamental frequency (F0) range and normalization of the slope of pressure/flow relationship toward baseline activation conditions. The effects of implant medial shape also depended on depth of medialization. Outcome measures were similar among the implants at smaller medialization depths. With large medialization depths and vagal paralysis conditions, the divergent implant maintained pressure/flow relationship closer to baseline. The vagal paralysis conditions also demonstrated decreased fundamental frequency range and worse flow/pressure relationship compared to RLN paralysis., Conclusions: The depth and medial shape of a medialization laryngoplasty (ML) implant significantly affect both the F0 range and aerodynamic power required for phonation. These effects become more notable with increasing depth of medialization. The study also illustrates that ML is less effective in vagal paralysis compared to RLN paralysis., Level of Evidence: N/A., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Nonspecific, synkinetic reinnervation is one of the causes of poor functional recovery after a peripheral nerve lesion. Knowledge of the differential expression of neurotrophic factors that subserve axon guidance, as well as neuromuscular junction formation and maintenance in the denervated muscles, may allow appropriate interventions that will improve the functional nonsynkinetic reinnervation., Study Design: Laboratory experiment., Methods: The expression of glial-derived neurotrophic factor (GDNF) was studied in the abductor and adductor muscles of the larynx in the rat utilizing real-time polymerase chain reaction at different times following transection, anastomosis, and reinnervation of the right recurrent laryngeal nerve (RLN). Immunostaining of GDNF, axons, and the motor endplates were performed. This data was correlated with intramuscular mRNA GDNF expression., Results: Significant upregulation of GDNF was observed until 14 days after RLN injury. The highest level of the GDNF expression was reached at different times in posterior cricoarytenoid (PCA), lateral thyroarytenoid (LTA), and medial thyroarytenoid (MTA). These expression peaks correlated with the timing of reinnervation observed on immunohistochemistry, where PCA was reinnervated first, followed by MTA and LTA., Conclusion: Differences of GDNF expression are linked to the differential timing of RLN axon regeneration and individual muscle reinnervation. The present finding suggests the need to further investigate the role of GDNF and other neurotrophic factors in the timing of reinnervation, axon guidance, and neuromuscular junction formation as it relates to synkinetic and nonsynkinetic RLN reinnervation. Future experimental results may provide insight to therapeutic options that could stimulate appropriate neuromuscular junction formation and nonsynkintic functional reinnervation following RLN injury., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To investigate the efficacy of laryngeal reinnervation with ansa cervicalis among unilateral vocal fold paralysis (UVFP) patients with different denervation durations., Study Design: We retrospectively reviewed 349 consecutive UVFP cases of delayed ansa cervicalis to the recurrent laryngeal nerve (RLN) anastomosis. Potential influencing factors were analyzed in multivariable logistic regression analysis. Stratification analysis performed was aimed at one of the identified significant variables: denervation duration., Methods: Videostroboscopy, perceptual evaluation, acoustic analysis, maximum phonation time (MPT), and laryngeal electromyography (EMG) were performed preoperatively and postoperatively. Gender, age, preoperative EMG status and denervation duration were analyzed in multivariable logistic regression analysis. Stratification analysis was performed on denervation duration, which was divided into three groups according to the interval between RLN injury and reinnervation: group A, 6 to 12 months; group B, 12 to 24 months; and group C, > 24 months., Results: Age, preoperative EMG, and denervation duration were identified as significant variables in multivariable logistic regression analysis. Stratification analysis on denervation duration showed significant differences between group A and C and between group B and C (P < 0.05)-but showed no significant difference between group A and B (P > 0.05) with regard to parameters overall grade, jitter, shimmer, noise-to-harmonics ratio, MPT, and postoperative EMG. In addition, videostroboscopic and laryngeal EMG data, perceptual and acoustic parameters, and MPT values were significantly improved postoperatively in each denervation duration group (P < 0.01)., Conclusions: Although delayed laryngeal reinnervation is proved valid for UVFP, surgical outcome is better if the procedure is performed within 2 years after nerve injury than that over 2 years., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Previously, electrical stimulation of denervated canine laryngeal muscle was shown to promote reinnervation by native over foreign motoneurons. The goal of this study was to assess the effect of different stimulus paradigms on reinnervation quality and functional recovery., Study Design: A prospective study of six canines over 8 to 20 months., Methods: A clinical model of laryngeal paralysis was used, where recurrent laryngeal nerves of the animals were sectioned and ventilation compromised. The abductor, posterior cricoarytenoid (PCA) muscles were implanted bilaterally with electrodes from an implantable pulse generator. Animals were randomly assigned to three groups to assess the effect of different stimulus paradigms: 1) 40 pulses per second (pps) train, 2) 10 pps train, 3) no stimulation. Spontaneous vocal fold movement was measured endoscopically during hypercapnia. Exercise tolerance was measured on a treadmill using pulse oximetry. In the terminal session, electromyography (EMG) potentials were recorded during superior laryngeal nerve stimulation to index foreign reinnervation of the PCA by reflex glottic closure (RGC) motoneurons., Results: After reinnervation started, nonstimulated and stimulated 40 pps animals displayed paradoxical closure of the glottis during hypercapnia and severely decreased exercise tolerance due to faulty reinnervation. In contrast, stimulated 10 pps animals displayed minimal paradoxical closure and normal exercise tolerance (12 minutes up to 8 mph). EMG findings in this group demonstrated significantly less PCA reinnervation by foreign RGC motoneurons., Conclusion: PCA stimulation with low frequency reduced synkinetic reinnervation by foreign RGC motoneurons. Paradoxical closure of the glottis with inspiration was reduced and exercise tolerance restored to normal., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: The purpose of this study was to explore a novel strategy to restore vocal gap by using polycaprolactone (PCL) spheres with thermosensitive Pluronic F127 in a paralyzed rabbit vocal fold., Study Design: In vivo study using a rabbit model., Methods: The PCL spheres were fabricated by an isolated particle-melting method. The PCL spheres/Pluronic F127 gel mixture was prepared by a simple mixture of PCL and Pluronic F127 solution. We used 33 New Zealand white rabbits, which were divided into normal (n = 3), vocal fold palsy (VFP, n = 12), PCL/Pluronic F127 gel mixture (PCL, n = 12), and Radiesse (n = 6) groups. After unilateral recurrent laryngeal nerve section, PCL or Radiesse were injected into paralyzed vocal folds. Laryngoscopic exams were performed 1, 2, 4, and 12 weeks after implantation; then larynx specimens were sampled. High-speed camera recording of vocal fold vibration and evaluation by videokymography were performed. Open quotient and asymmetric index were calculated. We evaluated the volume of the implants over time and investigated histologic changes., Results: Endoscopic analysis showed that PCL/Pluronic F127 gel mixture maintained its volume without migration or inflammatory response. Vocal fold gap decreased and asymmetric vocal fold movement was improved compared with the VFP group. Histologically, connective tissue growth was observed between the spheres. The remaining volume of injected material was greater than the Radiesse group, without statistical significance., Conclusions: Locally injected PCL/Pluronic F127 can enhance glottal contact, suggesting it as a potential new therapeutic approach that may lead to better treatment of vocal fold palsy., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: Airway obstruction is an uncommon presentation of unilateral laryngeal paralysis. We have observed two mechanisms of obstruction: arytenoid prolapse and inappropriate adduction of the paralyzed vocal fold. We evaluated arytenoid abduction (AAb) and recurrent laryngeal nerve (RLN) reinnervation as treatments for airway obstruction in patients with unilateral laryngeal paralysis., Study Design: Retrospective case series., Methods: Seven patients with airway obstruction secondary to unilateral laryngeal paralysis were evaluated with flexible laryngoscopy and direct laryngoscopy. Patients with flaccid paralysis and a prolapsing arytenoid were treated with AAb. Airway obstruction due to inspiratory vocal fold adduction was managed by RLN transection and ansa reinnervation of the distal stump., Results: In all cases, paralysis resulted from RLN injury during surgery: thyroidectomy or cervical spine surgery. AAb was performed in four patients with arytenoid prolapse, and all had significant airway improvement, including decannulation of the two patients who had been tracheotomy dependent. RLN reinnervation was performed in five patients, two of whom had inappropriate adduction detected after AAb. The site of RLN injury was identified at surgery in all four patients. Inspiratory stridor and laryngospasm were abolished immediately after RLN transection., Conclusions: Arytenoid prolapse and/or inappropriate laryngeal adduction can cause airway obstruction in patients with unilateral laryngeal paralysis. Treatment of airway obstruction should address the underlying pathophysiology. AAb and RLN transection with ansa reinnervation can be effective in selected patients., (Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: To determine whether nimodipine, an L-type voltage-operated calcium channel antagonist that is an accelerator of axonal regeneration following peripheral nerve injury, can expedite reinnervation of denervated rat thyroarytenoid (TA) muscle following nerve-muscle pedicle (NMP) flap implantation., Study Design: A quantitative histologic and physiologic assessment of the TA muscle following NMP flap implantation, with or without nimodipine treatment., Methods: Using 72 Wistar rats, we performed a transection on the left recurrent laryngeal nerve, followed by NMP flap implantation. Thirty-six animals received nimodipine treatment (NIMO [+] group), and the remaining 36 animals received no nimodipine treatment (NIMO [-] group). As a control, 18 animals were subjected only to transection of the left recurrent laryngeal nerve. We performed a histologic assessment for muscle area, axon, nerve terminals (NTs), and acetylcholine receptors (AchRs) in the TA muscle and electromyography at 2, 4, and 10 weeks after surgery., Results: Muscle area, ratio of the number of NTs to that of AchRs (NT/AchR ratio), and evoked action potential in the TA muscle were significantly greater in the NIMO (+) group than in the NIMO (-) group (P < .05) at 4 weeks. At 10 weeks, the NT/AchR ratio was significantly greater in the NIMO (+) group than in the NIMO (-) group (P < .05)., Conclusions: We found that nimodipine accelerated reinnervation of the denervated TA muscle following NMP flap implantation., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Purpose: Vocal fold medialization laryngoplasty (ML) and laryngeal reinnervation (LR) as treatments for unilateral vocal fold paralysis (UVFP) were compared in a multicenter, prospective, randomized clinical trial., Methods: Previously untreated patients with UVFP were randomized to undergo either ML or LR. Voice results were compared pretreatment and at 6 and 12 months posttreatment using perceptual ratings by untrained listeners (RUL), blinded speech pathologist GRBAS scores, and voice-related quality of life (VRQOL) scores. Other secondary data included maximum phonation time (MPT), cepstral analysis, and electromyography (EMG) findings., Results: Twenty-four patients from nine sites completed the study, 12 in each group. There were no significant intergroup differences in pretreatment variables. At 12 months, both study groups showed significant improvement in RUL, total GRBAS (grade, roughness, breathiness, asthenia, and strain) scores, and VRQOL scores, but no significant differences were found between the two groups. However, patient age significantly affected the LR, but not the ML, group results. The age less than 52 LR subgroup had significantly (P < .05) better scores than the age more than 52 LR subgroup, and had better RUL and GRBAS scores than the age less than 52 ML subgroup. The age more than 52 ML subgroup results were significantly better than the age more than 52 LR subgroup. The secondary data generally followed the primary data, except that the MPTs for the ML patients were significantly longer than for the LR patients., Conclusions: ML and LR are both effective surgical options for patients with UVFP. Laryngeal reinnervation should be considered in younger patients, whereas medialization laryngoplasty should be favored in older patients., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: To evaluate the long-term efficacy of contralateral ansa cervicalis-to-recurrent laryngeal nerve (RLN) anastomosis for unilateral vocal fold paralysis (UVFP), when the ansa cervicalis on the side of the paralyzed vocal fold was absent or there was any question about its viability., Study Design: We retrospectively reviewed 56 consecutive cases of delayed laryngeal reinnervation with contralateral ansa cervicalis for UVFP., Methods: Between January 1996 and January 2008, a total of 56 UVFP patients were enrolled in this study. All patients underwent contralateral ansa cervicalis-to-RLN anastomosis. Videostroboscopy, acoustic analysis, perceptual evaluation and maximum phonation time (MPT), and laryngeal electromyography (LEMG) were performed pre- and postoperatively., Results: Analysis of videostroboscopic findings indicated that the glottic closure, vocal fold edge, vocal fold position, phase symmetry, and regularity were significantly improved (P < .001, post- vs. preoperative). Perceptual evaluation of dysphonia severity showed that overall grade, roughness, breathiness, asthenia, and strain were also significantly decreased postoperatively (P < .001). Postoperative values of jitter (local), shimmer (local), and mean noise-to-harmonics ratio were significantly lower than the corresponding preoperative values (P < .001). The postoperative MPT value was significantly longer than the preoperative one (P < .001). LEMG showed that there was a significant postoperative improvement in voluntary motor-unit recruitment during phonation (P < .001)., Conclusions: In cases with a lack of viable ansa cervicalis on the side of a paralyzed vocal fold, contralateral ansa cervicalis-to-RLN anastomosis is a feasible and effective approach in the treatment of UVFP and can restore physiologic laryngeal phonatory function., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives: To describe the natural evolution of recurrent laryngeal nerve (RLN) reinnervation in an animal model., Study Design: Twenty Sprague Dawley rats underwent unilateral RLN transection and anastomosis. Animals were sacrificed at 4, 8, 12, 16, and 20 weeks. Prior to sacrifice, each rat underwent electromyography (EMG) and visual grading of vocal fold motion. Bilateral RLNs were harvested and evaluated histologically., Results: EMG revealed synkinetic reinnervation at all time periods except at 4 weeks. EMG evolution plateaued at 16 weeks. Vocal fold motion was slight in three rats at 4 weeks but was otherwise absent except for one rat at 12 weeks. Histologic changes of the axons and their myelin sheaths were consistent at each time period. At 16 weeks, histologic changes plateaued., Conclusions: Consistent EMG, histologic, and vocal fold motion changes occur at specific time periods during RLN reinnervation after transection and anastomosis in a rat model. Reinnervation is mature at 16 weeks. Findings corroborate theories of preferential and synkinetic reinnervation after RLN transection. Use of a rat model to investigate the effect of interventions on RLN reinnervation requires a minimum of 16 weeks between transection and investigation to allow for maturation of reinnervation., (Copyright © 2010 The American Laryngological, Rhinological, and Otological Society, Inc.)

Intraoperative neural monitoring (IONM) during thyroid and parathyroid surgery has gained widespread acceptance as an adjunct to the gold standard of visual nerve identification. Despite the increasing use of IONM, review of the literature and clinical experience confirms there is little uniformity in application of and results from nerve monitoring across different centers. We provide a review of the literature and cumulative experience of the multidisciplinary International Neural Monitoring Study Group with IONM spanning nearly 15 years. The study group focused its initial work on formulation of standards in IONM as it relates to important areas: 1) standards of equipment setup/endotracheal tube placement and 2) standards of loss of signal evaluation/intraoperative problem-solving algorithm. The use of standardized methods and reporting will provide greater uniformity in application of IONM. In addition, this report clarifies the limitations of IONM and helps identify areas where additional research is necessary. This guideline is, at its forefront, quality driven; it is intended to improve the quality of neural monitoring, to translate the best available evidence into clinical practice to promote best practices. We hope this work will minimize inappropriate variations in monitoring rather than to dictate practice options.

Objectives: A transoral approach to laser myoneurectomy of the thyroarytenoid muscles was recently reported as an effective technique for treatment of adductor spasmodic dysphonia (ASD). The short-term results were encouraging. In this study, a long-term surgical outcome of this technique is investigated., Study Design: A prospective clinical series., Methods: Fifty-two patients with ASD underwent transoral laryngomicrosurgery with a CO(2) laser to resect the ventricular folds followed by myoneurectomy of the thyroarytenoid muscles. The nerve fibers of recurrent laryngeal nerve terminating at the thyroarytenoid muscle, which were frequently found branching deeply among the posterior belly of this muscle, were vaporized. Care was taken not to damage the vocal ligaments, lateral cricoarytenoid muscles, or arytenoid cartilages. Pre- and postoperative subjective voice assessments, and acoustic and aerodynamic measurements, were performed and statistically analyzed., Results: Twenty-nine of the 52 patients who were followed up for more than 12 months (range, 12-63 months; mean, 31 months) were studied. Moderate and marked vocal improvement was achieved in 90% (26/29) of the patients. Three patients had 30% improvement, which was reported as unsuccessful. Eight of the 26 patients who were satisfied with their postoperative voice still had a mild strain during phonation. Of the eight patients, seven achieved normal or nearly normal voice quality after revision laser surgery. No significant vocal deficit or paralysis was observed in any patient., Conclusions: After long-term follow-up of 31 months on average, approximately 90% of the ASD patients obtained moderate to marked improvement of vocal performance after transoral laser surgery. The long-lasting outcome is encouraging.

Educational Objectives: Describe the clinical presentation and management of tracheoceles., Study Design: Retrospective case review and review of the medical literature., Results: A 56 year old female patient presented with progressive dysphonia and history of benign thyroid nodules. Flexible laryngoscopy revealed a severely paretic right true vocal cord. Computed tomography revealed a right sided air filled sac in the tracheoesophageal groove suspicious for causing compression of the right recurrent laryngeal nerve. The patient underwent an elective right hemithyroidectomy and resection of the air filled sac. Post operative pathology of the air filled sax was consistent with a tracheocele. A laryngoscopy performed 6 months postoperatively demonstrated recovery of right cord function., Conclusions: Tracheoceles are an uncommon entity first described in 1846 by Rokitansky (1) with only a paucity of case reports in the literature describing the surgical management and treatment of this disease. Herein, we report a patient who presented with dysphonia from a tracheocele in the right tracheoesophageal groove who subsequently underwent surgical resection ultimately improving vocal cord function.

Objectives: To evaluate the effects of short-term denervation on the kinetics of satellite cells (SCs) and myocytes in the rat thyroarytenoid (TA) muscle using immunohistochemistry for a myogenic regulatory factor, MyoD, and a cell proliferation marker, Ki-67., Study Design: Quantitative immunohistochemical assessment of MyoD and Ki-67 expression in SCs and myocytes after denervation., Methods: The left recurrent laryngeal nerve (RLN) was transected in 15 adult Wistar rats, which were sacrificed 1, 3, or 7 days after the treatment (n = 5, each group). Fluorescein immunostaining was used to visualize the localization of MyoD+ and Ki-67+ SCs in combination with M-cadherin immunostaining for detection of SCs. We examined the temporal changes of the ratios of MyoD+ and Ki-67+ SCs for all of the counted muscle fibers and M-cadherin+ cells in both the denervated and the contralateral control TA muscle., Results: On the denervated side, the TA muscle contained 3.8 +/- 0.4% MyoD+ SCs and 1.3 +/- 0.4% Ki-67+ SCs. Of the SCs, 22.6 +/- 2.2% were MyoD+, and 14.5 +/- 4.4% were Ki-67+, whereas SCs on the control side did not express these markers., Conclusions: In the rat TA muscle, denervation induces SC activation, and some SCs enter the cell cycle, whereas others are involved in the differentiation process. The number of activated SCs is relatively small compared with all M-cadherin+ SCs. Therefore, SCs might be good targets for a therapy to prevent TA muscle atrophy after RLN paralysis.

Objective: The objective of this prospective study was to assess the long-term effects of immediate reconstruction of the recurrent laryngeal nerve (RLN) during thyroid cancer extirpation on postoperative phonatory function., Subjects and Methods: The subjects were 22 patients with advanced thyroid cancer who underwent resection of the primary lesion and involved RLN. RLN paralysis was seen in 12 patients preoperatively and involvement of the RLN was noted intraoperatively in 10. Immediate reconstruction of the RLN was performed on eight patients using the great auricular nerve and one underwent direct anastomosis of the RLN stumps (group I). Nine patients opted not to have phonosurgical procedures (group II). The remaining four had arytenoid adduction immediately after cancer extirpation (group III). Phonatory function (stroboscopy, maximum phonation time [MPT], mean airflow rate [MFR], harmonics-to-noise ratio [HNR], jitter, and shimmer) was followed for at least 9 months., Results: Minimal or no glottal gap during phonation was observed in six patients in group I, whereas the patients in group II had a large gap along the entire fold. HNR, MPT, and MFR were significantly better in group I (17.7 +/- 3.6 dB, 15.1 +/- 6.3 s, and 100 +/- 32 mL/s, respectively) than in group II (12.1 +/- 2.9 dB, 5.4 +/- 3.1 s, and 430 +/- 207 mL/s, respectively). Patients in group III had a gap of varying degrees along the membranous fold. Although HNR, shimmer, and MPT in group III were comparable to group I, the other parameters were less favorable than in group I., Conclusion: Immediate RLN reconstruction at the time of thyroid cancer extirpation can provide excellent postoperative phonatory function.