Bilateral Selective Laryngeal Reinnervation for Bilateral Vocal Fold Paralysis in Children.

Importance: Bilateral vocal fold paralysis (BVFP) in pediatric patients is a challenging entity with multiple causes. Traditional approaches to managing BVFP include tracheostomy, arytenoidectomy, suture lateralization, cordotomy, and posterior cricoid enlargement. These interventions are used to create a stable airway but risk compromising voice quality. Objectives: To assess the use of bilateral selective laryngeal reinnervation (SLR) surgery to manage BVFP and restore dynamic function to the larynx in pediatric patients. Design, Setting, and Participants: In this case series performed at 2 tertiary care academic institutions, 8 pediatric patients underwent bilateral SLR to treat BVFP (5 patients with iatrogenic BVFP and 3 with congenital BVFP) from November 2004 to August 2018 with follow-up for at least 1.5 years. Interventions: Bilateral selective laryngeal reinnervation surgery. Main Outcomes and Measures: Flexible laryngoscopy findings, subjective and objective measures of voice quality, subjective swallowing function, and decannulation in patients who were previously dependent on a tracheostomy tube. Results: Participants included 6 boys and 2 girls with a median age of 9.3 (range, 2.2 to 18.0) years at the time of surgery. All 8 patients were decannulated; 6 patients had preoperative tracheostomies and 2 had perioperative tracheostomies. Voice quality, as measured using the GRBAS (grade, roughness, breathiness, asthenia, strain) scale, improved in 6 of 8 patients after reinnervation, and swallowing was not impaired in any patients. In 2 patients, GRBAS scale scores remained the same before and after surgery. Inspiratory vocal fold abduction was observed on both sides in 5 patients and on 1 side in 2 patients, with no active abduction observed in 1 patient. The follow-up period was more than 5 years in 7 of 8 patients and at least 1.5 years in all patients. Conclusions and Relevance: Bilateral SLR appears to be a promising treatment option for children with BVFP; it is currently the only option, to our knowledge, with the potential to restore abductor and adductor vocal fold movement. In patients with complete paralysis, this procedure may provide a strategy for airway management and restoration of the dynamic function of the larynx. It could be considered as a first-line technique before endolaryngeal or airway framework procedures, which carry a risk of compromising voice quality.

Nerve branches to the posterior cricoarytenoid muscle may complicate the laryngeal reinnervation procedure.

OBJECTIVES/HYPOTHESIS: To better understand the reason for the low success rate of posterior cricoarytenoid (PCA) muscle reinnervation, we attempted to identify the communicating branches that may exist between the nerve branch to the PCA muscle and the other laryngeal adductors in addition to the interarytenoid (IA) muscle. STUDY DESIGN: Quantitative histological assessment. METHODS: Twenty human hemilarynges from patients with laryngeal or hypopharyngeal cancer were obtained after surgery and stained with Sihler's stain, which rendered the muscle translucent while counterstaining the neuroanatomy of the recurrent laryngeal nerve (RLN) inside the larynges. RESULTS: The nerve supply to the PCA muscle was separated into two main branches. One upper branch supplied the horizontal compartment, and the lower branch supplied the vertical/oblique compartment. In 14 specimens, two nerve branches to the PCA muscle arose separately from the RLN. In six specimens, one single main branch arose from the RLN and immediately ramified into two secondary branches. In all specimens except one, the nerve branch to the horizontal compartment was connected to the IA muscle. However, no communicating branches were observed between the nerve to the PCA muscle and the other laryngeal adductors. No anastomosis between nerve branches to the horizontal and vertical/oblique compartments or other variations of nerve distribution were observed. CONCLUSIONS: The communicating branches between the nerve branches to the PCA muscle and the IA muscle may be the only branch, complicating the reinnervation procedure. More investigations are needed to identify variations in the terminal branch distribution from the RLN. LEVEL OF EVIDENCE: NA.

Airway obstruction due to unilateral vocal fold paralysis.

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.

Laryngeal reinnervation for bilateral vocal fold paralysis.

PURPOSE OF REVIEW: Laryngeal reinnervation for bilateral vocal fold paralysis (BVFP) patients is a promising technique to achieve good airway, although preserving a good quality of voice. On the other hand, the procedure is not simple. This review explores the recent literature on surgical technique and factors that may contribute to the success. RECENT FINDINGS: Research and literature in this area are limited due to variability and complexity of the nerve supply. The posterior cricoarytenoid (PCA) muscle also receives nerve supply from the interarytenoid branch. Transection of this nerve at the point between interarytenoid and PCA branch may prevent aberrant reinnervation of adductor nerve axons to the PCA muscle. A varying degree of regeneration of injured recurrent laryngeal nerves (RLN) in humans of more than 6 months confirms subclinical reinnervation, which may prevent denervation-induced atrophy. SUMMARY: Several promising surgical techniques have been developed for bilateral selective reinnervation for BVFP patients. This involves reinnervation of the abductor and adductor laryngeal muscles. The surgical technique aims at reinnervating the PCA muscle to trigger abduction during the respiratory cycle and preservation of good voice by strengthening the adductor muscles as well as prevention of laryngeal synkinesis.

Evidence of return of function in patients with vocal fold paresis.

Unilateral vocal fold paresis (UVFP) patients were examined over time for achievement of partial or full functional return or no functional return in the extent of arytenoid movement, clarity of laryngeal articulation, maximum phonation time (MPT), and flow. Effects of treatment type and initial laryngeal electromyography (EMG) results were examined. A retrospective chart review was completed for patients a year or less after onset evaluated between April 1999 and December 2005 and treated between 2 and 20 months after onset. Twenty-one individuals were evaluated (11 males, age: 34-89 years) and subsequently treated (10 by injection and 11 by thyroplasty). Evidence of full functional return was found for the extent of arytenoid movement in 25% of individuals, for clarity of laryngeal articulation in 71%, for MPT in 58%, and for flow in 50%. No evidence of functional return was found for the extent of arytenoid movement in 33% of the individuals, for clarity of laryngeal articulation in 8%, for MPT in 32%, and for flow in 22%. All pairs of outcome measures showed poor agreement in the level to which they functionally returned. More individuals with signs of reinnervation demonstrated MPTs with full functional return than expected. Patients with UVFP, even after treatment and at least 12 months postinjury did not demonstrate full functional return for all measures. Differences across measures in the percentage of individuals demonstrating each level of function and the lack of agreement of function level between measures within individuals suggest the need to use multiple outcome measures.

A "fenestration approach" for arytenoid adduction through the thyroid ala combined with type I thyroplasty.

OBJECTIVE: To develop and evaluate the voice outcomes of an approach of arytenoid adduction (AA) through a fenestration of the thyroid ala for unilateral vocal cord paralysis. STUDY DESIGN: Twelve consecutive patients with severe unilateral vocal cord paralysis, whose maximum phonation times (MPTs) were less than or equal to 5 seconds, underwent laryngoplasty using an approach of AA performed through a fenestration of the thyroid ala combined with type I thyroplasty. METHOD: Two surgical windows were made in the lower part of the thyroid ala. The anterior window was for typical type I thyroplasty, and the posterior window was for AA. AA was performed by pulling the lateral cricoarytenoid muscle (LCA) (5 patients) or muscular process (7 patients) through the posterior fenestration in the contractile direction of the LCA without releasing the cricoarytenoid joint. The operation was performed under local anesthesia with sedation except in two patients who underwent general anesthesia using a laryngeal mask. The vocal cord medialization was confirmed endoscopically during the operation. For all patients, the MPT and mean airflow rate (MFR) were measured before and after the operation. The postoperative voices were analyzed using shimmer and jitter. RESULT: All patients achieved a MPT of over 12 seconds. The MFR, which ranged from 340 to 1902 mL/second before the operation, improved to less than 200 mL/second, except in one patient whose MFR was 210 mL/second. Shimmer and jitter improved significantly after the operation. Perceptual evaluation using the GRBAS (grade, roughness, breathiness, aesthenia, strain) scale also improved significantly. CONCLUSION: A fenestration-based approach simplified the combination of AA and type I thyroplasty because the two treatments could be performed in the same operating field and provided good voice improvement. Pulling the AA braid in the contractile direction of the LCA and endoscopic vocal cord observation during surgery may have contributed to the positive results.

Useful landmarks in arytenoid adduction and laryngeal reinnervation surgery.

OBJECTIVE: Knowledge of the location of the muscular process of the arytenoid cartilage and the recurrent laryngeal nerve is essential to performing a successful arytenoid adduction and laryngeal reinnervation surgery. We describe external landmarks useful in locating these structures. STUDY DESIGN: Cadaveric laryngeal dissection. METHODS: Posterior laryngeal dissection was performed in 16 human larynges. The position of the muscular process of the arytenoid was measured bilaterally relative to the inferior and superior borders of the thyroid lamina. The recurrent laryngeal nerve was followed distally from slightly below the level of the cricothyroid joint to its genu where its vertical course changes to an oblique intralaryngeal course. RESULTS: The muscular process of the arytenoid was usually found halfway between the roots of the superior and inferior cornu of the thyroid lamina. The recurrent laryngeal nerve was found just deep to the cricothyroid joint and lateral to the posterior cricoarytenoid muscle. There were no other nerves in this area. CONCLUSIONS: This study finds that the superior and inferior borders of the thyroid lamina are useful intraoperative landmarks to locate the muscular process of the arytenoid. The cricothyroid joint provides a good starting point to locate the recurrent laryngeal nerve, which can be identified slightly deeper between it and the posterior cricoarytenoid muscle.

Aging effects on motor units in the human thyroarytenoid muscle.

OBJECTIVES: To determine whether age differences are present in the human laryngeal thyroarytenoid muscle that would indicate that different normative values would be needed for identifying motor unit abnormalities. STUDY DESIGN: Twenty-six consecutively recruited healthy subjects between the ages of 21 and 72 years participated in a laryngeal electromyography study. METHODS: Bipolar needle electrodes were used to record motor unit action potentials from several locations in the right and left thyroarytenoid muscles of each subject. The duration of a motor unit was measured when at least 10 firings of the same motor unit could be identified. On the average, four units were measured per muscle. RESULTS: In the subjects less than 60 years of age, motor unit duration did not increase significantly with age. However, motor units from subjects greater than 60 years of age had longer durations than those from subjects less than 60 years of age (P < .00005), and 25% of the units measured in subjects greater than 60 years of age had longer durations than any of the units measured in subjects less than 60 years of age. Further, the older subjects differed from each other in their mean unit durations (P < .0001). In subjects less than 60 years of age, significantly longer durations were found for units innervated by the longer, left-side recurrent laryngeal nerve in comparison with the right-side nerve (P = .005). CONCLUSIONS: Different mean and SD values should be used for patients less than and greater than 60 years of age and for the right and left sides, when evaluating motor units in the thyroarytenoid muscles.

Three-dimensional anatomic characterization of the canine laryngeal abductor and adductor musculature.

The biomechanics of vocal fold abduction and adduction during phonation, respiration, and airway protection are not completely understood. Specifically, the rotational and translational forces on the arytenoid cartilages that result from intrinsic laryngeal muscle contraction have not been fully described. Anatomic data on the lines of action and moment arms for the intrinsic laryngeal muscles are also lacking. This study was conducted to quantify the 3-dimensional orientations and the relative cross-sectional areas of the intrinsic abductor and adductor musculature of the canine larynx. Eight canine larynges were used to evaluate the 3 muscles primarily responsible for vocal fold abduction and adduction: the posterior cricoarytenoid, the lateral cricoarytenoid, and the interarytenoid muscles. Each muscle was exposed and divided into discrete fiber bundles whose coordinate positions were digitized in 3-dimensional space. The mass, length, relative cross-sectional area, and angle of orientation for each muscle bundle were obtained to allow for the calculations of average lines of action and moment arms for each muscle. This mapping of the canine laryngeal abductor and adductor musculature provides important anatomic data for use in laryngeal biomechanical modeling. These data may also be useful in surgical procedures such as arytenoid adduction.

Intracellular recording from posterior cricoarytenoid motoneurons in the rat.

The ability to maintain coordinated vocal cord abduction and upper airway patency is dependent on the integrity of the posterior cricoarytenoid (PCA) motoneurons and their multiple neural connections. Study of the PCA motoneurons represents the initial step in understanding the complex mechanisms responsible for coordinated vocal cord abduction and may provide an insight into the possible pathological processes underlying the various clinical presentations of vocal cord dysfunction. Intracellular recordings were made from 11 PCA motoneurons in Sprague-Dawley rats, which all showed an inspiratory augmenting discharge pattern that is also characteristic of phrenic nerve activity. The resting membrane potential was -56+/-11 mV. Two PCA motoneurons were injected with Neurobiotin to demonstrate neuronal morphology, which was found to be similar to that obtained by retrograde labeling with cholera toxin B subunit. The technique described for intracellular recording of PCA motoneurons should allow more detailed morphological, electrophysiological, and immunohistochemical information to be obtained, to thereby identify some of the factors responsible for maintaining normal function of the PCA muscle.

Beaded nerve terminals in feline laryngeal mucosa.

To investigate the mechanism of airway defense reflex, beaded nerve terminals were studied by immunohistochemical techniques. In the supraglottic region the density of PGP 9.5-immunoreactive nerve fibers was the highest at the base of the glottic surface in the epiglottis, and in the glottic region it was the highest in the arytenoid region. In the subglottic region the number of positive nerve fibers was less than the number at the base of the glottic surface in the epiglottis, and when the laryngeal mucosa was processed with NaOH to dissolve the epithelium, it was possible to observe beaded nerve terminals more clearly. These beaded nerve terminals were found just beneath, in the epithelial basement membrane. Electron microscopic examination of beaded nerve terminals revealed a large quantity of secretory granules and mitochondria, suggesting that their structure is similar to that of nerve terminals. Thus these beaded nerve terminals may function as mechanoreceptors.

Morphologic study of the laryngeal taste buds in the cat.

The distribution of laryngeal taste buds (TBs) and their neutral components in the cat were investigated by immunohistochemistry and electron microscopy. The antisera used in this study were against cytokeratin, protein gene product 9.5 (PGP9.5), neuron-specific enolase (NSE), S-100 protein, calbindin D, calcitonin gene-related peptide (CGRP), and substance P (SP). Taste bud cells were specifically immunoreactive to the antibodies of human cytokeratin subtypes 8 and 18 (CAM5.2). On observation with CAM5.2, TBs were seen distributed on the laryngeal surface of the epiglottis and spread caudally along the aryepiglottic folds, reaching peak density at the laryngeal side of the arytenoid tubercle. The PGP9.5 and NSE immunoreactivities were recognized in TB cells and nerve fibers, both within the TBs and in the subepithelial connective tissue. S-100 protein immunoreactivities were not found in any of the cells in the TBs but were found exclusively in the subepithelial neural elements. The calbindin-D, CGRP, and SP immunoreactivities were confined to a part of the neural elements that was very thin. Taste pores, taste villi, neuronal varicosity, and synapselike structures were observed by scanning and transmission electron microscopic study. From these results it is considered that the TBs act as a chemical receptor.

The innervation of the human posterior cricoarytenoid muscle: evidence for at least two neuromuscular compartments.

Recent work has demonstrated that the dog posterior cricoarytenoid (PCA) muscle is composed of three neuromuscular compartments: a vertical, an oblique, and a horizontal. In this study, the human PCA muscle was examined for evidence of neural compartments. Fifteen human PCA muscles were processed by Sihler's stain, which renders the muscle translucent while counterstaining the nerve supply. The results clearly show that in all specimens the nerve supply of the human PCA muscle is separated into at least two main branches: one supplies the horizontal compartment and a second further subdivides to innervate both the vertical and oblique compartments. In 10 of the specimens, these nerve branches arose as separate branches from the recurrent laryngeal nerve. In all specimens, the nerve branch to the horizontal compartment was either combined or connected with the nerve branch to the interarytenoid muscle. The results suggest that the different compartments of the PCA muscle have distinct functions. In addition, the strong connections with the interarytenoid nerve complicate reinnervation procedures to reanimate a paralyzed or transplanted larynx.

[Motor innervation of the canine arytenoid muscle].

Dual motor innervation by the bilateral recurrent laryngeal nerves (RLNs) has been demonstrated in the human arytenoid muscle (AR). Whether AR of the dog receives dual motor innervation remains to be cleared yet, although the canine larynx is frequently used in experimental studies. To answer this question, the author observed the muscular structure in detail and anastomotic nerve branch between the bilateral RLNs, and then carried out glycogen depletion experiments on AR of dog compared with typical unpaired ARs of monkey and of guinea pig. 1) Muscular structure AR of the dog consisted of three parts of muscle bundles: the transverse arytenoid muscle (TVA), ventricular muscle (VT) and anonymous small bundle provisionally named the smaller interarytenoid muscle (IAm). While TVA and VT were paired type, IAm was unpaired type and lay horizontally on the dorsal aspect of the sesamoid cartilage around the midline. So the canine AR displayed a trigastric muscle as a whole. 2) Anastomotic nerve branch By the vital staining with methylene blue, the arytenoid branch of canine RLN ramified in three directions: anteriorly to the bellies of TVA and VT, medially to the anastomotic branch and superomedially to IAm. By the silver impregnation method of Barker and Ip, the bilateral IAm ramuli were found to form collateral anastomoses and terminate disorderly on the individual fibers. 3) Glycogen depletion experiments When an electrical stimulation was applied to the unilateral RLN in the monkey and the guinea pig, about one half of AR fibers were unstained with PAS staining and, in turn, these unstained fibers were known to be innervated by the ipsilateral RLN. While these unpaired ARs receive dual motor innervation as a whole muscle, every individual fiber is innervated by the unilateral RLN. In the canine VT and TVA, almost 90% of fibers were depleted of glycogen on the belly of the stimulated side, while the reverse was on the nonstimulated side. This finding suggests that most fibers of canine VT and TVA are ipsilaterally and the remaining fibers are contralaterally innervated. About one half of fibers of IAm were unstained and the others were stained. This pattern was similar to that observed in the monkey and the guinea pig. Therefore, IAm receives dual motor innervation from both RLNs as a whole muscle.

Clinical evaluation of laryngeal sensation in horses.

Sensory innervation of the larynx was examined by tactile stimulation with a blunt biopsy forceps passed through a flexible videoendoscope. Twenty horses with no evidence of laryngeal motor deficit were stimulated on 10 sites by touch with the forceps. Unilateral neurectomies of the internal branch of the left cranial laryngeal nerve were performed on 5 other horses. These horses were stimulated by touch on the same sites preoperatively and up to 1 week postoperatively. In all 25 horses the motor response of the larynx was recorded on videotape and evaluated by 2 observers blind as to treatment and time of evaluation. Normal horses responded to touch by adduction of both arytenoid cartilages, swallowing or both. This response was not altered by sedation with xylazine hydrochloride. Left cranial laryngeal neurectomized horses failed to respond to tactile stimulation of the left side, while adduction of both cartilages, swallowing or both was observed following stimulation on the right side. Laryngeal stimulation by touch with a biopsy forceps was accurate in identifying horses with complete deficits of the internal branch of the cranial laryngeal nerve.

Substance P immunoreactive nerve fibers of the canine laryngeal mucosa.

Substance P (SP) immunoreactive nerve endings in the laryngeal mucosa were studied by PAP immunohistochemistry with light and electron microscopy. SP immunoreactive sensory endings were observed in the epithelium as intra-epithelial free nerve endings and taste bud-like structures. A small number of autonomic SP immunoreactive nerve fibers were observed running parallel to arterioles which were over 30 micron in diameter and terminated in glandular cells. Contrary to findings by silver impregnation, intraepithelial free nerve endings were more frequently observed on the lower surface of the vocal cord. The taste bud-like structures were classified into two different types: simple terminations and reticular terminations, according to the mode of the SP immunoreactive nerve fiber. Immature or degenerated taste bud-like structures in the larynx were assumed to be mechanical receptors because these receptors lacked outer taste pores and taste hairs.