Recurrent Laryngeal Nerve Transection Research Articles

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

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. 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. 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. 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. https://doi.org/10.23641/asha.24492133.

Early Changes in Porcine Larynges Following Injection of Motor-Endplate Expressing Muscle Cells for the Treatment of Unilateral Vocal Fold Paralysis.

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. 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. 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. 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. NA Laryngoscope, 134:272-282, 2024.

Changes in vocal fold gene expression and histology after injection augmentation in a recurrent laryngeal nerve injury model.

To investigate changes in neuroregenerative pathways with vocal fold denervation in response to vocal fold augmentation. Eighteen Yorkshire crossbreed swine underwent left recurrent laryngeal nerve transection, followed by observation or augmentation with carboxymethylcellulose or calcium hydroxyapatite at two weeks. Polymerase chain reaction expression of genes regulating muscle growth (MyoD1, MyoG and FoxO1) and atrophy (FBXO32) were analysed at 4 and 12 weeks post-injection. Thyroarytenoid neuromuscular junction density was quantified using immunohistochemistry. Denervated vocal folds demonstrated reduced expression of MyoD1, MyoG, FoxO1 and FBXO32, but overexpression after augmentation. Healthy vocal folds showed increased early and late MyoD1, MyoG, FoxO1 and FBXO32 expression in all animals. Neuromuscular junction density had a slower decline in augmented compared to untreated denervated vocal folds, and was significantly reduced in healthy vocal folds contralateral to augmentation. Injection augmentation may slow neuromuscular degeneration pathways in denervated vocal folds and reduce compensatory remodelling in contralateral healthy vocal folds.

Effects of early local administration of high-dose bFGF on a recurrent laryngeal nerve injury model

BackgroundResearch on regenerative medicine using basic fibroblast growth factor (bFGF) has recently advanced in the field of laryngology. We previously reported that local administration of bFGF 1 month after recurrent laryngeal nerve (RLN) paralysis compensated for atrophy of the thyroarytenoid muscle. The objective of this study was to elucidate the effects of early bFGF administration on the thyroarytenoid muscle after RLN transection and to investigate the underlying mechanisms.MethodsA rat model of RLN paralysis was established in this study. One day after RLN transection, low- (200 ng) or high-dose (2000 ng) bFGF or saline (control) was administered to the thyroarytenoid muscle. The larynges were excised for histological and immunohistochemical examinations at 1, 7, 14, 28, and 56 days after administration.ResultsThe cross-sectional thyroarytenoid muscle area was significantly larger in the high-dose group than in the saline and low-dose groups on days 28 and 56. Immunohistochemistry indicated that bFGF significantly increased the number of satellite cells in the thyroarytenoid muscle up to day 14 and that of neuromuscular junctions on days 28 and 56.ConclusionsA single, early local administration of high-dose bFGF prevented atrophic changes in the thyroarytenoid muscles by activating satellite cell proliferation and reforming neuromuscular junctions. As increased neuromuscular junctions are expected to maintain myofiber volume, bFGF administration may prevent thyroarytenoid muscle atrophy in the mid to long term.Graphical abstract

Augmentation and vocal fold biomechanics in a recurrent laryngeal nerve injury model.

Objectives/hypothesisComposite vocal fold (VF) biomechanical data are lacking for augmentation after recurrent laryngeal nerve (RLN) injury. We hypothesize resulting atrophy decreases VF stiffness and augmentation restores native VF biomechanics.MethodsSixteen Yorkshire Crossbreed swine underwent left RLN transection and were observed or underwent carboxymethylcellulose (CMC) or calcium hydroxyapatite (CaHa) augmentation at 2 weeks. Biomechanical measurements (structural stiffness, displacement, and maximum load) were measured at 4 or 12 weeks. Thyroarytenoid (TA) muscle cross‐sectional area was quantified and compared with two‐way ANOVA with Tukey's post hoc test.ResultsAfter 4 weeks, right greater than left structural stiffness (mean ± SE) was observed (49.6 ± 0.003 vs. 28.4 ± 0.002 mN/mm), left greater than right displacement at 6.3 mN (0.54 ± 0.01 vs. 0.46 ± 0.01 mm, p < .01) was identified, and right greater than left maximum load (72.3 ± 0.005 vs. 40.8 ± 0.003 mN) was recorded. TA muscle atrophy in the injured group without augmentations was significant compared to the noninjured side, and muscle atrophy was seen at overall muscle area and individual muscle bundles. CMC augmentation appears to maintain TA muscle structure in the first 4 weeks with atrophy present at 12 weeks.ConclusionsVF biomechanical properties match TA muscle atrophy in this model, and both CMC and CaHa injection demonstrated improved biomechanical properties and slower TA atrophy compared to the uninjured side. Taken together, these data provide a quantifiable biomechanical basis for early injection laryngoplasty to improve dysphonia and potentially improve healing in reversible unilateral vocal fold atrophy.Level of evidenceN/A

Towards Personalized Musculoskeletal Interventional Oncology: Enhanced Image-Guided Biopsies and Interventions

Studies comparing endocrine-specific outcomes following parathyroidectomy (PTx) versus concurrent parathyroidectomy and thyroidectomy (PTx + Tx) are few.10,019 patients were selected from the Collaborative Endocrine Surgery Quality Improvement Program (2014–2019). Baseline characteristics and short-term (≤30 days) outcomes for PTx + Tx vs PTx patients were compared using bivariate and multivariable methods.PTx + Tx patients were more likely to experience clinical hypoparathyroidism (6.7% vs 0.5%, p < 0.001), recurrent laryngeal nerve transection, (0.4% vs 0.1%, p = 0.002) and hematoma requiring evacuation (1.0% vs 0.2%, p < 0.001). Readmissions and ED visits for hypocalcemia were more frequent after PTx + Tx vs PTx. Concurrent surgery was associated with an 8-fold increase in risk of short-term complications (Odds Ratio (OR): 8.0, 95% Confidence Interval (CI): 5.7–11.1, p < 0.001).Patients undergoing PTx + Tx have increased rates of postoperative complications, ED visits, and readmissions compared to patients undergoing parathyroidectomy alone. These findings could help guide surgeon-patient discussions on the risks of concurrent surgery.

Outcomes of concurrent parathyroidectomy and thyroidectomy among CESQIP surgeons

BackgroundStudies comparing endocrine-specific outcomes following parathyroidectomy (PTx) versus concurrent parathyroidectomy and thyroidectomy (PTx + Tx) are few. Methods10,019 patients were selected from the Collaborative Endocrine Surgery Quality Improvement Program (2014–2019). Baseline characteristics and short-term (≤30 days) outcomes for PTx + Tx vs PTx patients were compared using bivariate and multivariable methods. ResultsPTx + Tx patients were more likely to experience clinical hypoparathyroidism (6.7% vs 0.5%, p < 0.001), recurrent laryngeal nerve transection, (0.4% vs 0.1%, p = 0.002) and hematoma requiring evacuation (1.0% vs 0.2%, p < 0.001). Readmissions and ED visits for hypocalcemia were more frequent after PTx + Tx vs PTx. Concurrent surgery was associated with an 8-fold increase in risk of short-term complications (Odds Ratio (OR): 8.0, 95% Confidence Interval (CI): 5.7–11.1, p < 0.001). ConclusionsPatients undergoing PTx + Tx have increased rates of postoperative complications, ED visits, and readmissions compared to patients undergoing parathyroidectomy alone. These findings could help guide surgeon-patient discussions on the risks of concurrent surgery.

MRI imaging versus histologic volumetric estimation of residual injection laryngoplasty material.

ObjectivesTo examine the degree of agreement between MRI and histologically generated volumetric measurements of residual injection laryngoplasty material.MethodsFollowing left recurrent laryngeal nerve transection, rabbit vocal cords were injected with jellyfish collagen, Cymetra®, or Restylane®. Laryngeal tissue was harvested 4 or 12 weeks post injection followed by MRI imaging and histologic cross‐sectioning. Two raters estimated the volume of remaining injection material in specimens within MRI and histologic axial cross sections. Wilcoxon signed rank tests were employed to detect gross differences between inter‐rater measurements and between imaging modalities across time. Agreement between rater measurements and imaging (histology and MRI) was assessed using intra‐class correlation coefficients.ResultsData was available from 16 rabbits sacrificed at 4 weeks (n = 8) and 12 weeks (n = 8). Inter‐rater testing of MRI imaging revealed no significant differences (p > .05) between rater measurements across time points, and excellent agreement (0.93; 95% confidence interval 0.80–0.98) while histologically estimated volumes demonstrated a significant difference at 4 weeks (p < .05) and overall good agreement (0.89; 95% confidence interval 0.59–0.97). Comparison of MRI and histologically estimated volume measurements revealed significant differences at the 4‐week time point (p < .05) but not at 12 weeks (p > .05). Overall, there is only moderate agreement between MRI and histology estimates (0.72; 95% confidence interval 0.22–0.90).ConclusionsMRI imaging demonstrates good reliability and similar estimates of volume to histologically estimated measurements of residual injection laryngoplasty material at time points clinically relevant for future injection laryngoplasty experiments.Level of EvidenceNA.

Incidence of Dysphonia and Dysphagia Exceeds Recurrent Laryngeal Nerve Injury During Thyroid Surgery

To determine the prevalence of separate and combined voice and swallowing impairments before and after total thyroidectomy and to delineate risk factors for these symptoms. Retrospective review of 592 consecutive patients who underwent total thyroidectomy from July 2003 to August 2015. Combined voice and swallowing problems occurred preoperatively in 4.7% (11/234), 3.3% (3/92), and 6.0% (16/266) of patients with malignancy, hyperthyroidism, and benign euthyroid disease, respectively. Postoperatively, prevalence was 5.1%, 2.2%, and 1.9%, respectively. Benign euthyroid disease (20.7%) had the greatest risk of preoperative dysphagia (P = 0.003) and the largest glands (P < 0.001). Comparing before and after surgery, the cancer and benign euthyroid groups had decreased dysphagia (cancer: 11.5% vs. 6.0%, P = 0.034; benign: 20.7% vs. 3.8%, P < 0.001) but increased dysphonia (cancer: 19.2% vs. 28.6%, P = 0.017; benign: 15.8% vs. 27.1%, P = 0.002). Overall, 23/592 (3.9%) developed new dysphagia and 122/592 (20.6%) developed new dysphonia after surgery. Intraoperative recurrent laryngeal nerve transection occurred in 12 cases (2.0%). Total thyroidectomy resolved dysphagia but increased dysphonia in benign and malignant euthyroid patients. Voice and swallowing problems following thyroidectomy occurred more frequently than intraoperative recurrent laryngeal nerve transection, confirming symptoms often occur in the absence of suspected nerve injury.

Co-transplantation of Schwann cells and neural stem cells in the laminin-chitosan-PLGA nerve conduit to repair the injured recurrent laryngeal nerve in SD rats.

The objective of this paper is to investigate the possibility and efficacy of recurrent laryngeal nerve repair by transplantation of co-cultured Schwann cells and neural stem cells (NSCs) in laminin-chitosan-poly-lactic-co-glycolic acid (laminin-chitosan-PLGA) nerve conduits in rats. A laminin-chitosan-PLGA conduit was used in a rat recurrent laryngeal nerve transection model. The rat recurrent laryngeal nerve was dissected to generate a 5 mm defect. Then, a laminin-chitosan-PLGA nerve conduit with or without Schwann cells and NSCs in the lumen was transplanted into the defect. A total of 96 female rats were randomised into six groups: co-culture of NSCs and Schwann cells in the nerve conduit group (CO), Schwann cells only in the nerve conduit group (SC), neural stem cells only in the nerve conduit group (NSC-only), nerve conduit group (null), autologous nerve graft group (autograft) and sham operation group (sham). Regenerated nerves were evaluated by histological and functional assessment at 8 and 12 weeks after surgery. The diameter and area of the regenerated myelin sheath, as well as the secretion of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor in laryngeal muscle or regenerated nerve tissue in the CO group, were significantly better than they were in the SC, NSC-only and null groups (all P values < 0.05). Immunofluorescence showed that the CO group had significantly more neurofilament-200 immunoreactive and S-100 immunoreactive fibres than the SC, NSC-only and null groups (all P values < 0.05). The performance of the CO groups and autograft groups was found to be similar by laryngoscopy. Arytenoid cartilage motion recovery in these two groups was significantly better than it was in the other groups (all P values < 0.05). Our results indicated that co-culture of Schwann cells and NSCs in laminin-chitosan-PLGA conduits might promote injured nerve regeneration. This method might be a promising alternative for defective nerve repair.

Post-thyroidectomy emergency room visits and readmissions: Assessment from the Collaborative Endocrine Surgery Quality Improvement Program (CESQIP)

BackgroundThis study analyzed independent factors associated with post-thyroidectomy Emergency Room (ER) visits and Hospital Readmissions (HR). MethodsThis is a retrospective review from the CESQIP registry of 8381 thyroidectomy patients by 173 surgeons at 46 institutions. A total of 7142 ER visits and 7265 HR were analyzed. Multivariable logistic regression analysis was performed to determine the risk factors for an ER visit or HR. ResultsWithin 30-days of surgery, rates of all ER visits were 3.4% (n = 250) and all HR were 2.3% (n = 170). Hypocalcemia was the reason for 21.9% of ER encounters and 36.4% of HR. BMI >40 kg/m2 was a risk factor for both ER visit (OR1.86) and HR (OR1.94). Surgical duration >3 h (OR2.63), and transection of recurrent laryngeal nerve (OR4.58) were risk factors for HR. ConclusionsStrategies to decrease hypocalcemia and improve perioperative care of patients with BMI >40 kg/m2 may improve post-thyroidectomy outcome.

Recurrent laryngeal nerve transection in mice results in translational upper airway dysfunction.

The recurrent laryngeal nerve (RLN) is responsible for normal vocal-fold (VF) movement, and is at risk for iatrogenic injury during anterior neck surgical procedures in human patients. Injury, resulting in VF paralysis, may contribute to subsequent swallowing, voice, and respiratory dysfunction. Unfortunately, treatment for RLN injury does little to restore physiologic function of the VFs. Thus, we sought to create a mouse model with translational functional outcomes to further investigate RLN regeneration and potential therapeutic interventions. To do so, we performed ventral neck surgery in 21 C57BL/6J male mice, divided into two groups: Unilateral RLN Transection (n = 11) and Sham Injury (n = 10). Mice underwent behavioral assays to determine upper airway function at multiple time points prior to and following surgery. Transoral endoscopy, videofluoroscopy, ultrasonic vocalizations, and whole-body plethysmography were used to assess VF motion, swallow function, vocal function, and respiratory function, respectively. Affected outcome metrics, such as VF motion correlation, intervocalization interval, and peak inspiratory flow were identified to increase the translational potential of this model. Additionally, immunohistochemistry was used to investigate neuronal cell death in the nucleus ambiguus. Results revealed that RLN transection created ipsilateral VF paralysis that did not recover by 13 weeks postsurgery. Furthermore, there was evidence of significant vocal and respiratory dysfunction in the RLN transection group, but not the sham injury group. No significant differences in swallow function or neuronal cell death were found between the two groups. In conclusion, our mouse model of RLN injury provides several novel functional outcome measures to increase the translational potential of findings in preclinical animal studies. We will use this model and behavioral assays to assess various treatment options in future studies.

Laryngeal adductor function following potassium titanyl phosphate laser welding of the recurrent laryngeal nerve.

Recurrent laryngeal nerve (RLN) transection injuries may occur during thyroidectomy and other surgical procedures. Laser nerve welding has been shown to cause less technique-related axonal damage than the traditional suture method. We compared functional adductor results using these two methods of RLN repair. Animal model. Canine hemilarynges underwent pretreatment testing of laryngeal adductor function, followed by RLN transection and repair using potassium titanyl phosphate (KTP) laser welding (n = 8) or microneural suture (n = 16) techniques. Six months later, adductor function was measured again and expressed as a proportion of the pretreatment value. The mean laryngeal adductor pressure ratios were 82.4% (95% confidence interval [CI]: 72.8%-92.0%) for the laser repair group and 55.5% (95% CI: 49.4%-61.6%) for the suture control group, with a difference of 26.9% (95% CI: 15.3%-38.5%). Both spontaneous and stimulated glottic closure was observed in the laser welding and microsuture repair groups. Laser nerve welding resulted in greater strength of adduction than suture repair of an acutely transected RLN. Suture anastomosis may traumatize more axons than the laser. Stronger vocal fold adduction is associated clinically with better protection from aspiration and improved voice outcomes. KTP laser welding should be considered for anastomosis of the RLN and other nerves. NA Laryngoscope, 130:1764-1769, 2020.

Compound Motor Action Potential Measures Acute Changes in Laryngeal Innervation.

Vocal fold paralysis is caused by injury to the recurrent laryngeal nerve (RLN). Current clinical measures of laryngeal innervation are often nonquantitative. Compound motor action potentials (CMAP) measure motor innervation. The goal of this study was to determine whether CMAP can quantify laryngeal innervation following acute nerve injury. Animal study. Twelve canine hemilaryngeal preparations were used. The RLN was serially stimulated with increasing intensities until the nerve was maximally stimulated. The CMAP amplitude was measured for each intensity stimulation and correlated. Next, the RLN was incompletely transected, and the reduction in CMAP amplitude was correlated to the percentage of transected axons. The percentage of transected axons was determined using horseradish peroxidase (HRP) staining. Combining all hemilaryngeal preparations, the submaximal stimulation of the RLN linearly correlated with the resultant CMAP amplitude (r = 0.83; 95% CI, 0.76-0.88). Following partial RLN transection, the percentage of remaining axons linearly correlated with the CMAP amplitude (r = 0.87; 95% CI, 0.34-0.98). CMAP amplitude is a quantitative measure that may correlate with the degree of vocal fold innervation in canines. Following RLN injury, CMAP may help clinicians quantify the number of intact axons, assess the likelihood of recovery, and counsel patients on their prognosis.

Revisiting the autoconditioning hypothesis for acquired reactivity to ultrasonic alarm calls.

Rats emit 22 kHz ultrasonic vocalizations (USVs) in association with pain, fear, or distress. Whereas the capacity to produce USVs is innate, reactivity to them appears to require experience. Specifically, 22 kHz USVs fail to elicit freezing behavior in naïve laboratory rats. However, these "alarm calls" do elicit freezing in rats that previously experienced foot shocks. These findings led to the hypothesis that acquired reactivity is based on "autoconditioning"-learning in which self-generated 22 kHz USVs serve as Pavlovian cues that become associated with foot shocks. The current study tested the autoconditioning hypothesis by devocalizing rats through a unilateral transection of the recurrent laryngeal nerve (Experimental group). Subsequently, animals in both the Experimental and sham-operated Control groups received five unsignaled foot shocks. One or two days later, both groups were tested for USV-elicited freezing in a novel context. Recurrent laryngeal nerve transection failed to prevent or even diminish USV-elicited freezing. In fact, both groups showed large and comparable increases in freezing to USV presentations. A subset of Control animals failed to vocalize during conditioning, while some Experimental animals did vocalize during conditioning. Animals were therefore re-grouped and reanalyzed based on whether they vocalized during conditioning. Again, both groups showed large and comparable increases in USV-elicited freezing. These results disconfirm the essential tenet or prediction of the autoconditioning hypothesis. Alternative mechanisms for acquired reactivity to 22 kHz USVs are therefore considered.

Involvement of hypoglossal and recurrent laryngeal nerves on swallowing pressure.

Swallowing pressure generation is important to ensure safe transport of an ingested bolus without aspiration or leaving residue in the pharynx. To clarify the mechanism, we measured swallowing pressure at the oropharynx (OP), upper esophageal sphincter (UES), and cervical esophagus (CE) using a specially designed manometric catheter in anesthetized rats. A swallow, evoked by punctate mechanical stimulation to the larynx, was identified by recording activation of the suprahyoid and thyrohyoid muscles using electromyography (EMG). Areas under the curve of the swallowing pressure at the OP, UES, and CE from two trials indicated high intrasubject reproducibility. Effects of transecting the hypoglossal nerve (12N) and recurrent laryngeal nerve (RLN) on swallowing were investigated. Following bilateral hypoglossal nerve transection (Bi-12Nx), OP pressure was significantly decreased, and time intervals between peaks of thyrohyoid EMG bursts and OP pressure were significantly shorter. Decreased OP pressure and shortened times between peaks of thyrohyoid EMG bursts and OP pressure following Bi-12Nx were significantly increased and longer, respectively, after covering the hard and soft palates with acrylic material. UES pressure was significantly decreased after bilateral RLN transection compared with that before transection. These results suggest that the 12N and RLN play crucial roles in OP and UES pressure during swallowing, respectively. We speculate that covering the palates with a palatal augmentation prosthesis may reverse the reduced swallowing pressure in patients with 12N or tongue damage by the changes of the sensory information and of the contact between the tongue and a palates. NEW & NOTEWORTHY Hypoglossal nerve transection reduced swallowing pressure at the oropharynx. Covering the hard and soft palates with acrylic material may reverse the reduced swallowing function caused by hypoglossal nerve damage. Recurrent laryngeal nerve transection reduced upper esophageal sphincter negative pressure during swallowing.

Recovery of Voice After Reconstruction of the Recurrent Laryngeal Nerve and Adjuvant Nimodipine

BackgroundTransection injury to the recurrent laryngeal nerve (RLN) has been associated with permanent vocal fold palsy, and treatment has been limited to voice therapy or local treatment of vocal folds. Microsurgical repair has been reported to induce a better function. The calcium channel antagonist nimodipine improves functional recovery after experimental nerve injury and also after cranial nerve injury in patients. This study aims to present voice outcome in patients who underwent repair of the RLN and received nimodipine during regeneration.MethodsFrom 2002–2016, 19 patients were admitted to our center with complete unilateral injury to the RLN and underwent microsurgical repair of the RLN. After nerve repair, patients received nimodipine for 2–3 months. Laryngoscopy was performed repeatedly up to 14 months postoperatively. The Voice Handicap Index (VHI) was administered, and patients’ maximum phonation time (MPT) was recorded during the follow-up.ResultsAll patients recovered well after surgery, and nimodipine was well tolerated with no dropouts. None of the patients suffered from atrophy of the vocal fold, and some patients even showed a small ab/adduction of the vocal fold on the repaired side with laryngoscopy. During long-term follow-up (>3 years), VHI and MPT normalized, indicating a nearly complete recovery from unilateral RLN injury.ConclusionsIn this cohort study, we report the results of the first 19 consecutive cases at our center subjected to reconstruction of the RLN and adjuvant nimodipine treatment. The outcome of the current strategy is encouraging and should be considered after iatrogenic RLN transection injuries.

Improved adductor function after canine recurrent laryngeal nerve injury and repair using muscle progenitor cells.

Muscle progenitor cells (MPCs) can be isolated from muscle samples and grown to a critical mass in culture. They have been shown to survive and integrate when implanted into rat laryngeal muscles. In this study, the ability of MPC implants to enhance adductor function of reinnervated thyroarytenoid muscles was tested in a canine model. Animal study. Sternocleidomastoid muscle samples were harvested from three canines. Muscle progenitor cells were isolated and cultured to 107 cells over 4 to 5 weeks, then implanted into right thyroarytenoid muscles after ipsilateral recurrent laryngeal nerve transection and repair. The left sides underwent the same nerve injury, but no cells were implanted. Laryngeal adductor force was measured pretreatment and again 6 months later, and the muscles were harvested for histology. Muscle progenitor cells were successfully cultured from all dogs. Laryngeal adductor force measurements averaged 60% of their baseline pretreatment values in nonimplanted controls, 98% after implantation with MPCs, and 128% after implantation with motor endplate-enhanced MPCs. Histology confirmed that the implanted MPCs survived, became integrated into thyroarytenoid muscle fibers, and were in close contact with nerve endings, suggesting functional innervation. Muscle progenitor cells were shown to significantly enhance adductor function in this pilot canine study. Patient-specific MPC implantation could potentially be used to improve laryngeal function in patients with vocal fold paresis/paralysis, atrophy, and other conditions. Further experiments are planned. NA. Laryngoscope, 2017.

Selective recurrent laryngeal nerve stimulation using a penetrating electrode array in the feline model.

Laryngeal muscles (LMs) are controlled by the recurrent laryngeal nerve (RLN), injury of which can result in vocal fold (VF) paralysis (VFP). We aimed to introduce a bioelectric approach to selective stimulation of LMs and graded muscle contraction responses. Acute experiments in cats. The study included six anesthetized cats. In four cats, a multichannel penetrating microelectrode array (MEA) was placed into an uninjured RLN. For RLN injury experiments, one cat received a standardized hemostat-crush injury, and one cat received a transection-reapproximation injury 4 months prior to testing. In each experiment, three LMs (thyroarytenoid, posterior cricoarytenoid, and cricothyroid muscles) were monitored with an electromyographic (EMG) nerve integrity monitoring system. Electrical current pulses were delivered to each stimulating channel individually. Elicited EMG voltage outputs were recorded for each muscle. Direct videolaryngoscopy was performed for visualization of VF movement. Stimulation through individual channels led to selective activation of restricted nerve populations, resulting in selective contraction of individual LMs. Increasing current levels resulted in rising EMG voltage responses. Typically, activation of individual muscles was successfully achieved via single placement of the MEA by selection of appropriate stimulation channels. VF abduction was predominantly observed on videolaryngoscopy. Nerve histology confirmed injury in cases of RLN crush and transection experiments. We demonstrated the ability of a penetrating MEA to selectively stimulate restricted fiber populations within the feline RLN and selectively elicit contractions of discrete LMs in both acute and injury-model experiments, suggesting a potential role for intraneural MEA implantation in VFP management. NA. Laryngoscope, 128:1606-1614, 2018.

Regenerative Effects of Basic Fibroblast Growth Factor on Restoration of Thyroarytenoid Muscle Atrophy Caused by Recurrent Laryngeal Nerve Transection

Vocal fold atrophy following unilateral vocal fold paralysis is caused by atrophy of the thyroarytenoid (TA) muscle and remains a challenge. Medialization procedures are popular treatment options; however, hoarseness often remains due to the reduction in mass or tension of the TA muscle. Therefore, in addition to medialization procedures, TA muscle reinnervation is desirable. In vivo studies have shown the potential for basic fibroblast growth factor (bFGF) to affect muscular and nerve regeneration. The present study aimed to examine the regenerative effects of bFGF on restoration of TA muscle atrophy caused by recurrent laryngeal nerve transection. Prospective animal experiments with controls. TA muscle atrophy was induced by unilateral transection of the recurrent laryngeal nerve. One month after transection, different doses (200 ng, 100 ng, 10 ng) of bFGF in 50 µL were repeatedly injected into the TA muscle four times with an interval of 1 week between injections. Saline only was injected in the sham group. Larynges were harvested for histologic and immunohistochemical examination 4 weeks after the final injection. The cross-sectional TA muscle area was significantly larger in the bFGF-treated groups compared with the sham-treated groups. Immunohistochemistry indicated that bFGF significantly increases the number of neuromuscular junctions and satellite cells in the TA muscle. These results suggest that local application of bFGF to the TA muscle may improve TA muscle atrophy caused by recurrent laryngeal nerve paralysis. Furthermore, bFGF may have regenerative effects on both nerves and muscles.