Recurrent Laryngeal Nerve Reinnervation Research Articles

A meta-analysis on the improvement of vocal function in unilateral vocal cord paralysis by reinnervation of the recurrent laryngeal nerve

Objective:To conduct a systematic description and meta-analysis of the treatment of unilateral vocal cord paralysis（UVCP） with recurrent laryngeal nerve reinnervation through literature search, and to analyze the therapeutic effect of recurrent laryngeal nerve reinnervation on improving vocal function in UVCP. Methods:Electronic databases Pubmed, Web of Science, EMBASE, Cochrane Library, CNKI, and Wanfang databases were searched using relevant keywords and screened in strict accordance with the inclusion and exclusion criteria, and quality evaluations were conducted. Reported treatment outcomes were measured by relevant data extracted from literature, such as auditory perception assessment（GRBAS）, voice handicap index（VHI）, maximal phonation time（MPT）, jitter, shimmer, and noise harmonic ratio（NHR）, etc. Meta-analysis was performed by Revman5.3 and heterogeneity was analyzed using fixed effects or random effects models. Results:Eight articles were included in this study, all of which showed that the postoperative maximum phonation time of patients was significantly prolonged compared to preoperative, while the postoperative GRBAS score, Jitter, Shimmer, and NHR decreased compared to preoperative with statistical significance. Conclusion:The innervation of the internal laryngeal muscle was obtained through the reinnervation of the recurrent laryngeal nerve, which effectively improved the patient's vocal function and had a good long-term therapeutic effect. Although there was no difference in the efficacy of surgical methods for reconstructing the recurrent laryngeal nerve, the anastomosis between ansa cervicalis nerve and the recurrent laryngeal nerve is more ideal. Further randomized controlled studies with longer follow-up periods and larger samples will increase the credibility of their effectiveness.

Paediatric recurrent laryngeal nerve reinnervation at The Children’s Hospital at Westmead: a case series

Paediatric recurrent laryngeal nerve reinnervation at The Children’s Hospital at Westmead: a case series

Iatrogenic pediatric unilateral vocal cord paralysis after cardiac surgery: a review.

Unilateral vocal cord paralysis (UVCP) is a growing area of research in pediatrics as it spans across many specialties including otolaryngology, cardiology, general surgery, respirology, and speech language pathology. Iatrogenic injury is the most common cause of UVCP, however there is a wide range of data reporting the prevalence, symptom burden, and best treatment practice for this condition. The literature included systematic reviews and meta-analyses, retrospective studies and limited prospective studies. Overall, the literature lacked consistency in the diagnosis, treatment, and long-term outcomes of patients with UVCP. Many articles conflated bilateral vocal cord paralysis (BVCP) with UVCP and had limited data on the natural history of the condition. There was no consensus on objective and subjective measurements to evaluate the condition or best indications for requiring surgical intervention. Thyroplasty, injection medialization (IM) and recurrent laryngeal nerve reinnervation (RLNR) were the reported surgical interventions used to treat UVCP, however there was limited data on short and long-term surgical outcomes in children. More research is needed to determine the true prevalence, natural history, indications for surgical intervention and long-term outcomes for pediatric patients with this condition.

The Feasibility of Outpatient Type I Thyroplasty with Laryngeal Reinnervation.

Type I thyroplasty has increasingly been performed on an outpatient basis. Laryngeal reinnervation is recognized for its long-term and functional benefits but is typically performed inpatient under general anesthesia. Herein we report the first published outpatient type I thyroplasty with laryngeal reinnervation performed under monitored anesthesia care (MAC). Three adults underwent type I thyroplasty with ansa cervicalis to recurrent laryngeal nerve (RLN) reinnervation. A 23-year-old female with a history of generalized idiopathic epilepsy s/p vagal nerve stimulator implantation presented with persistent dysphonia. She developed longstanding left vocal fold paralysis. She underwent left type I thyroplasty with silastic implant and ansa cervicalis to RLN neurorrhaphy under MAC-local anesthesia. The patient was discharged home on the day of surgery. Two additional patients underwent the same procedure, including a 58-year-old male with postsurgical dysphonia who was admitted for overnight observation due to a small amount of incisional crepitus and a 23-year-old female with postsurgical vocal cord paralysis who was admitted overnight due to multiple comorbidities. Both were discharged on post-operative day one without issue and demonstrated improvement in voice at follow up. Outpatient type I thyroplasty with laryngeal reinnervation under MAC is feasible with proper patient selection.

Understanding Risk and Recovery in Vocal Fold Paralysis

To summarize and critically review recent literature on spontaneous recovery from unilateral vocal fold paralysis (UVFP), with emphasis on the time to vocal recovery and its implications for the physiology of recurrent laryngeal nerve (RLN) injury and repair. Analyses of the time to spontaneous vocal recovery in UVFP have generated probabilities of recovery that can be used to counsel patients within the first 12 months of the onset of UVFP, replacing the traditional recommendation of waiting 12 months prior to pursuing permanent intervention. In addition, mathematical modeling of the recovery times has yielded insights into the physiology of RLN reinnervation following injury. Most patients with UVFP who experience vocal recovery do so within 6–9 months. The recovery pattern differs between idiopathic UVFP and iatrogenic UVFP. For iatrogenic UVFP, the severity of RLN injury dictates the time to recovery and the eventual probability of recovery, not the distance between the injury site and the larynx.

Arytenoid adduction combined with reinnervation of recurrent laryngeal nerve at inside thyroid cartilage for unilateral recurrent laryngeal nerve

Arytenoid adduction combined with reinnervation of recurrent laryngeal nerve at inside thyroid cartilage for unilateral recurrent laryngeal nerve

Medical and Surgical Advances in the Treatment of Unilateral Vocal Fold Paralysis

Purpose In this chapter, unilateral vocal fold paralysis is described, and treatment options are discussed with emphasis on recent developments in treatment. Conclusion Unilateral vocal fold paralysis is a disorder commonly encountered by otolaryngologists and speech-language pathologists alike and is caused by dysfunction of one of the recurrent laryngeal nerves leading to dysphonia and dysphagia. The etiology of this disorder can include malignancy, iatrogenic injury, or traumatic injury or may be due to idiopathic causes, and evidence has suggested that the rates of different etiologies have changed over time. Treatment options include a variety of approaches and range from expectant management, voice therapy, as well as surgical and procedural approaches. Surgical approaches generally aim to augment the affected vocal fold to medialize its position, thereby reducing glottic insufficiency, and can include injection laryngoplasty and laryngeal framework surgery. Recurrent laryngeal nerve reinnervation is also an option for certain patients and can improve vocal fold bulk by restoring basal neurologic stimulation. Though it is a well-described phenomenon, with new developments in procedural interventions, unilateral vocal fold paralysis remains a dynamic entity in the field.

Type Ⅰ thyroplasty with recurrent laryngeal nerve reinnervation for the severe aspiration due to bilateral nerve paralysis

Type Ⅰ thyroplasty with recurrent laryngeal nerve reinnervation for the severe aspiration due to bilateral nerve paralysis

Recurrent laryngeal nerve reinnervation: is this the standard of care for pediatric unilateral vocal cord paralysis?

Ansa to recurrent laryngeal nerve reinnervation, otherwise known as a nonselective laryngeal reinnervation (NSLR), is growing in popularity for the management of pediatric unilateral neuronal vocal fold movement impairment (VFMI). In this chapter, we will review the current treatment options for neuronal VFMI and role that NSLR plays in the treatment algorithm. In 2018, Bouhabel and Hartnick published a survey of fellowship trained pediatric otolaryngologists and found an increasing comfort level with NSLR. Respondents felt that NSLR resulted in favorable subjective and objective postsurgical voice outcomes. Furthermore, NSLR may decrease the risk of aspiration in children with neuronal VFMI. Although NSLR appears to work, the voice results are not perfect for all children. Further work is being done to understand which preoperative variables, such as age, time from injury, and preop laryngeal electromyography, may predict a better voice outcome. A variety of treatment options exist for unilateral neuronal VFMI. Recent data and developments demonstrate the effectiveness of reinnervation as a potential first-line surgical intervention in children with unilateral neuronal VFMI.

Improved reinnervation of recurrent laryngeal nerve by ansa cervicalis for iatrogenic unilateral vocal fold paralysis

Improved reinnervation of recurrent laryngeal nerve by ansa cervicalis for iatrogenic unilateral vocal fold paralysis

Immunohistologic analysis of spontaneous recurrent laryngeal nerve reinnervation in a rat model

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. Animal study. 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. 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. 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. NA. Laryngoscope, 128:E117-E122, 2018.

Influence of Netrin-1 on reinnervation of laryngeal muscles following recurrent laryngeal nerve injury

Following recurrent laryngeal nerve (RLN) injury, recovery results in poor functional restitution of the paralyzed vocal fold. Netrin-1 has been found to be upregulated in the rat posterior cricoarytenoid muscle (PCA) during nerve regeneration. We evaluated the effect of ectopic Netrin-1 in the PCA during RLN reinnervation. The right RLN was transected and Netrin-1 was injected into the PCA (2.5, 5, 10, 15, 20μg/ml). At 7 days post injury fluorescent retrograde tracer was injected into the PCA and Thyroarytenoid (TA) muscles. At 9 days tissues were harvested. Immunostaining showed reinnervation patterns in the laryngeal muscles and labelled motoneurons in the nucleus ambiguus. Lower concentrations of Netrin-1 (2.5 and 5μg/ml) showed no significant changes in laryngeal muscles reinnervation. Higher concentrations of Netrin-1 significantly reduced motor end plate innervation. The most effective dose was 10μg/ml showing reduced number of innervated motor endplates in the PCA. The somatotopic organization of the nucleus ambiguus was altered in all concentrations of Netrin-1 injection. These findings indicate that injection of Netrin-1 into the PCA changes the reinnervation pattern of the RLN.

Blockade of glial-derived neurotrophic factor in laryngeal muscles promotes appropriate reinnervation.

Synkinetic reinnervation of the laryngeal muscles is one of the causes of the poor functional recovery after a recurrent laryngeal nerve (RLN) injury. Glial-derived neurotrophic factor (GDNF) is elevated in rat laryngeal muscles during RLN reinnervation. The specific aim of this investigation was to evaluate the effect of anti-GDNF on RLN reinnervation. Anti-GDNF antibody was injected into the posterior cricoarytenoid (PCA) 3 days following RLN transection and anastomosis. Larynges were harvested at 7, 14, 28, 56, and 112 days post injury (DPI). Prior to sacrifice, the vocal fold mobility was assessed. Immunostaining to identify neuromuscular junctions was used to evaluate the extent of axonal reinnervation of the PCA, lateral thyroarytenoid (LTA), and medial thyroarytenoid (MTA). After anti-GDNF injection into PCA, RLN reinnervation in all muscles was altered when compared to the controls. PCA innervation was delayed. At 7 DPI, only a few axons made synapses in the PCA. In contrast, axons prematurely innervated the LTA and MTA when compared to controls. Innervation was similar to controls at 56 and 112 DPI. Vocal fold motion was enhanced in 10 of 24 animals studied. After injection of anti-GDNF into the PCA, early arriving axons bypass the PCA and enter the LTA. Later arriving axons innervate the PCA and MTA. Vocal fold function is improved as compared to controls. Anti-GDNF injection into the PCA influences the pattern of reinnervation and may result in less synkinetic, more functional innervation. NA Laryngoscope, 126:E337-E342, 2016.

Pediatric recurrent laryngeal nerve reinnervation: A case series and analysis of post-operative outcomes

ObjectiveTo provide detailed information about recurrent laryngeal nerve (RLN) reinnervation outcomes in children using objective measures. MethodsThe records of three pediatric patients with unilateral vocal cord paralysis that underwent RLN reinnervation were retrospectively reviewed. Fundamental frequency (F0), jitter, shimmer, noise-to-harmonic ratio (NHR), and voice phonation (sustained /s/, /z/, /a/) were measured preoperatively and post-operatively at 13, 9, and 33 months (each time period corresponding to one of the three patients). ResultsMean preoperative and post-operative variables were as follows: shimmer, 9.65±1.02% vs. 4.46±0.71% (p=0.01); NHR, 0.296±0.063 vs. 0.127±0.011 (p=0.04); jitter, 3.57±0.89% vs. 1.46±0.54% (p=0.08); F0, 274.6±35.4Hz vs. 282.2±70.6Hz (p=0.44); maximum phonation time, 7.46±1.40s vs. 9.79±1.84s (p=0.22); /s:z/ ratio, 1.28±0.22 vs.1.07±0.09 (p=0.26). ConclusionsThere was statistically significant improvement in shimmer and NHR. Jitter improvement approached statistical significance. All other variables failed to show significant improvement among this small sample size. RLN reinnervation for pediatric patients is an option for the treatment of vocal cord paralysis. Further studies with larger cohorts are needed to show the full benefits.

Ansa to recurrent laryngeal neurorrhaphy in the setting of laryngeal nerve sacrifice: a cadaveric study to evaluate a reconstructive option

ObjectiveIn certain cases, the recurrent laryngeal nerve (RLN) has to be sacrificed. This often results in an inadequate length of residual RLN to be used in a reinnervation procedure. We investigated the length of the distal stump of the RLN from the inferior border of the inferior pharyngeal constrictor muscle (IPCM), where it is frequently compromised, to its entrance into the larynx. Our objective was to determine whether this residual nerve stock was sufficient for margin clearance and neurorrhaphy. Study designCadaveric study MethodsRecurrent laryngeal nerves were identified in fresh frozen cadavers. The IPCM was divided, revealing the distal stump of the RLN, which was measured. ResultsDissection was performed in 20 cadavers (40 nerves). The average length of the right RLN and the left RLN from the IPCM until it entered the larynx was 15mm and 14mm, respectively. All residual RLN remnants were of sufficient length for neurorrhaphy. ConclusionConcomitant RLN reinnervation procedures in the setting of nerve sacrifice are not well described. A barrier to reinnervation in this setting may be insufficient residual nerve length for a neurorrhaphy. Often, when the RLN is sacrificed intraoperatively either iatrogenically or due to tumor invasion, it is close to the cricoarytenoid joint, at the inferior border of the IPCM. This study demonstrates that by splitting the IPCM, sufficient length can be obtained for neurorrhaphy.

Long-term efficacy of primary intraoperative recurrent laryngeal nerve reinnervation in the management of thyroidectomy-related unilateral vocal fold paralysis

Conclusion: Primary intraoperative recurrent laryngeal nerve (RLN) reinnervation techniques demonstrated significant voice improvement at 24 months postoperatively and could be an effective alternative treatment for thyroidectomy-related permanent unilateral vocal fold paralysis (VFP). Objectives: To assess the long-term efficacy of intraoperative RLN reinnervation techniques in the management of thyroidectomy-related unilateral VFP. Methods: A prospective study was conducted from January 2008 to June 2012 at Soonchunhyang University Bucheon Hospital. Nineteen patients who underwent RLN reinnervation with either direct reinnervation (neurorrhaphy) or ansa cervicalis to RLN (ansa-RLN) anastomosis and completed subjective and objective voice measurement over a 1-year follow-up period were included in this study. Results: The causes of VFP were cancer involving the RLN (68.4%, 13/19) and iatrogenic nerve transection (31.5%, 6/19). Reinnervation techniques were direct neurorrhaphy (63.2%, 12/19) and ansa-RLN anastomosis (36.8%, 7/19). Subjective parameters such as the Voice Handicap Index (VHI), posterior glottic closure, and mucosal wave demonstrated significant improvement 6 months postoperatively, and the majority of parameters remained stable up to 24 months (p < 0.05). Objective parameters, such as maximum phonation time (MPT), jitter, shimmer, and the harmonics-to-noise ration (HNR), demonstrated significant improvement at 12 months and most remained stable at 24 months (p < 0.05).

Differential expression of glial-derived neurotrophic factor in rat laryngeal muscles during reinnervation.

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. Laboratory experiment. 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. 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. 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.

Effect of duration of denervation on outcomes of ansa‐recurrent laryngeal nerve reinnervation

To investigate the efficacy of laryngeal reinnervation with ansa cervicalis among unilateral vocal fold paralysis (UVFP) patients with different denervation durations. 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. 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. 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). 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.

Embryologic innervation of the rat laryngeal musculature—a model for investigation of recurrent laryngeal nerve reinnervation

Optimal management of vocal fold paralysis would entail recurrent laryngeal nerve (RLN) reinnervation resulting in normal vocal fold motion. Unfortunately, RLN reinnervation currently results in a nonfunctional vocal fold due to synkinetic reinnervation. Therapeutic interventions that guide regenerating axons back to the appropriate muscle would prevent synkinesis and restore vocal fold and glottal function. The initial step toward developing these therapies is the elucidation of the embryologic innervation of the larynx. This study aimed to identify the age of occurrence, timing, and pattern of embryologic innervation of the rat larynx, hypothesizing that differences in these parameters exist between distinct laryngeal muscles. Descriptive anatomic study. The larynx of rats aged embryologic day (E) 15, 16, 17, 19, and 21 were harvested and then sectioned. Two rats were used for each age. Sections were colabeled with neuronal class III β-tubulin polyclonal antibody to identify the presence of axons and alexa 488 conjugate α-bungarotoxin to identify the presence of motor endplates. The age at which axons and motor endplates were first present was noted. The position and pattern of the axons and motor endplates was recorded in relation to each other as well as the musculoskeletal anatomy of the larynx. The time at which axons appeared to innervate the medial thyroarytenoid (MTA) muscle, lateral thyroarytenoid (LTA) muscle, and the posterior cricoarytenoid (PCA) muscle was documented. Findings in the rat suggest the RLN reaches the larynx and begins branching by E15. Axons branch dorsally first and reach the PCA muscle before the other muscles. Branching toward the MTA muscle occurs only after axons have reached the LTA muscle. By E19, RLN axons have been guided to and selected their respective muscles with formation of neuromuscular junctions (NMJs) in the PCA, LTA and MTA muscles, though the formation of NMJs in the MTA muscle was comparatively delayed. This study describes the embryologic innervation of the rat larynx and suggests that there are distinct differences in the age of occurrence, timing, and pattern of innervation of the PCA, LTA, and MTA muscles of the rat. These findings lay the foundation for studies investigating the role of guidance cues in RLN axon guidance and the utility of these cues in the treatment of RLN injury via the stimulation of functional, nonsynkinetic reinnervation.

Optimal Management of Acute Recurrent Laryngeal Nerve Injury During Thyroidectomy

Recurrent laryngeal nerve (RLN) injury is commonly encountered by thyroid surgeons and may carry with it great morbidity. Whether the injury is accidental or due to deliberate resection for oncologic soundness, the surgeon must be prepared to offer the best available treatment to patients, either at the time of injury or early in the recovery process. We review advances in treatment that allow optimal management of an acute RLN injury: ansa cervicalis–RLN reinnervation, in-office unsedated vocal fold injection augmentation, and electromyographic prognostication. The benefits and advantages of each procedure as well as relevant anatomy and techniques are delineated.