A Comparison of Outcomes in Interventions for Unilateral Vocal Fold Paralysis: A Systematic Review

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1 The Laryngoscope VC 2015 The American Laryngological, Rhinological and Otological Society, Inc. Systematic Review A Comparison of Outcomes in Interventions for Unilateral Vocal Fold Paralysis: A Systematic Review Jennifer Siu, HBSc; Samantha Tam, MD; Kevin Fung, MD, FRCSC Objectives/Hypothesis: To critically review current literature comparing interventional approaches for unilateral vocal fold paralysis. Study Design: Systematic review of the literature. Methods: All English-language literature published in the PubMed database was eligible for inclusion. Inclusion criteria were: 1) the major topic must be a direct comparison of outcomes in interventions for unilateral vocal fold paralysis, 2) the subjects were 18 years or older, and 3) it was original research. Studies involving treatment of bilateral vocal fold paralysis and nonprocedural interventions were excluded. Included studies were categorized according to level of evidence. Outcomes analyzed were acoustic and aerodynamic, auditory perceptive evaluation, laryngoscopic findings, and complications. Results: Of the 504 studies retrieved from the search strategy, 17 studies met inclusion and exclusion criteria. Overall, four interventional approaches were used for treatment of unilateral vocal fold paralysis: medialization thyroplasty, injection laryngoplasty, arytenoid adduction, and laryngeal reinnervation. Aside from some select improvements in single outcome parameters, overall, the majority of studies show no difference in improvement of outcomes between techniques. Conclusions: Four surgical interventions for unilateral vocal fold paralysis are available for treatment of unilateral vocal cord paralysis. Multiple studies show favorable outcomes, but no significant differences between treatment arms based on perceptual, acoustic, quality of life, and laryngoscopic outcomes. Key Words: Unilateral vocal fold paralysis, medialization thyroplasty, injection laryngoplasty, laryngeal reinnervation, arytenoid adduction. Level of Evidence: NA Laryngoscope, 126: , 2016 INTRODUCTION Unilateral vocal fold paralysis (UVFP) is a common condition presenting to the otolaryngologist head and neck surgeon. The most common cause includes damage to the recurrent laryngeal nerve (RLN) either iatrogenically or from a neoplasm. Patients with UVFP typically present with voice changes, hoarseness, or aspiration. Examination on laryngoscopy shows impaired vocal fold motion, bowing of the fold, and incomplete glottic closure. Recovery from UVFP depends on the degree of RLN damage, which can range from temporary neuropraxia to complete neural disruption. Some patients may recover spontaneously over weeks to months with conservative management with voice therapy. However, further interventions may be necessary for patients who do not recover spontaneously, who have known iatrogenic nerve transection, or who experience debilitating voice dysfunction or aspiration. 1 A wide variety of interventional options are available in the otolaryngologist s armamentarium for treatment of nonresolving UVFP including medialization thyroplasty, injection laryngoplasty, arytenoid adduction, and laryngeal reinnervation. However, none of these procedures has been shown to be definitely superior over the others. The purpose of this study was to systematically review current literature comparing the interventional treatment approaches for unilateral vocal fold paralysis. From the School of Medicine (J.S.), Queen s University, Kingston, Ontario, Canada; Department of Otolaryngology Head and Neck Surgery (S.T., K.F.), Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Editor s Note: This Manuscript was accepted for publication September 22, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Kevin Fung, MD, 800 Commissioners Road East, Suite B3-427, London, Ontario, Canada N6G 5G1. kevin.fung@lhsc.on.ca DOI: /lary MATERIALS AND METHODS Due to the broad variety of outcome utilized in literature, study results were unable to be combined for metaanalysis. Therefore, a systematic review of the literature was performed. All literature published in the PubMed database up to November 2014 were eligible for inclusion. Search terms were vocal cord paralysis, vocal fold paralysis, voice disorders, dysphonia, aphonia, hoarseness, vocal cord dysfunction, vocal fold dysfunction, laryngeal nerve injuries, recurrent laryngeal nerve injuries, adult, human, nerve regeneration, prosthesis and implants, absorbable implants, electrodes,

2 implanted, electrodes, laryngoplasty, reinnervation, injection laryngoplasty, medialization thyroplasty, arytenoid adduction, cricothyroid subluxation, Isshiki type 1, vocal fold augmentation, and vocal cord augmentation. The following search terms were excluded: bilateral, pediatric, animals, and Teflon. Inclusion criteria were 1) major topic must be a direct comparison of outcomes between at least two different intervention techniques for unilateral vocal fold paralysis in human subjects; 2) subjects 18 years or older; and 3) original research including cohort studies, case control studies, case series with N > 10, and retrospective observational studies. Articles were excluded if they involved 1) outcomes from a single type of intervention rather than a comparison of two techniques, 2) treatment for bilateral vocal fold paralysis, 3) conservative or nonprocedural management of vocal fold paralysis, 4) outcomes in subjects less than 18 years of age, 5) outcomes in nonhuman subjects, and 5) non English-language articles. All abstracts retrieved were reviewed by two blinded investigators for inclusion in the study. If consensus was unable to be reached by the two investigators, a third investigator would determine inclusion or exclusion. Level of evidence of all included studies was determined by the Oxford Centre for Evidence-Based Medicine Level of Evidence. 2 RESULTS A total of 504 studies were retrieved utilizing the search strategy. Seventeen studies met all the inclusion criteria. All studies were published between 1998 and Six studies made comparisons between injection laryngoplasty and medialization thyroplasty (Table I). 3 8 Six studies investigated arytenoid adduction alone or with another procedure (Table II). 6,9 13 Six studies had laryngeal reinnervation as a main comparator of outcomes (Table III) One study was a randomized controlled trial. 16 Six studies were level 3 evidence, and 10 studies were level 4 evidence. Four major categories of outcomes were found. Acoustic and aerodynamic included acoustic analysis for jitter, shimmer, harmonic-to-noise ratio, maximum phonation time, glottic airflow, and subglottic pressure. Subjective evaluation included perceptual evaluation and ratings on disability or quality of life. Perceptual scales used included the Grade, Roughness, Breathiness, Asthenia, Strain scale and the Consensus Auditory-Perceptual Evaluation of Voice, and selfreported instruments included the Voice Handicap Index (VHI) and the Voice-Related Quality of Life scale. Laryngoscopic findings were utilized to characterize postoperative edema, degree of glottic closure, symmetry of glottic closure, periodicity of glottic closure, and mucosal wave. Last, other outcome included complication rates following each intervention. DISCUSSION Medialization Thyroplasty Medialization thyroplasty, first described by Isshiki, involves the creation of a window in the thyroid cartilage and insertion of a permanent alloplastic implant to medialize the vocal fold. 20 It has been considered the gold standard approach to treatment of UVFP, and its beneficial effects on long-term voice outcomes have been well established in the literature. 8 Commonly used alloplastic materials include Silastic polymeric silicone, polytetrafluoroethylene (Gore-Tex), titanium, and Montgomery implants. 21 Advantages of this technique include low cost, ability to adjust the implant intraoperatively, and reversibility of the procedure. 22 Rare complications include edema, wound complications, extrusion, and need for tracheotomy. 21 In this review, 14 out of 17 studies retrieved involve medialization thyroplasty as a direct comparator of outcomes to other techniques when used alone or in combination with other procedures. An analysis of these comparisons will be discussed below within the context of each approach. Injection Laryngoplasty Medialization of a unilateral paralyzed vocal fold can be achieved by injection of filler material into the paraglottic space. Br unings was the first to describe injection laryngoplasty in 1911 using paraffin. 23 Since then, the technique has been refined, and a variety of injected materials have been used including autologous fat, calcium hydroxylapatite microspheres, bovine collagen, and methylcellulose. 21 Seven of the 17 articles reviewed discussed injection laryngoplasty as a comparator to other techniques (Table I). Injection laryngoplasty and objective voice outcomes. Five articles focused on acoustics and aerodynamics as primary outcome. 3 6,9 All studies showed improvements in postoperative voice outcomes regardless of intervention type. Two studies found no difference in postoperative outcomes between injection laryngoplasty and medialization thyroplasty. 6,9 However, the effect of injection laryngoplasty was not permanent with 10 of 16 subjects, requiring multiple injections in one study. 6 Three studies found improved outcomes with injection laryngoplasty. Cantillo-Ba~nos et al. found that harmonic-to-noise ratio was significantly improved in the injection laryngoplasty group at 24 months compared to the medialization thyroplasty group. 3 Two studies by Umeno et al. showed significantly greater improvement in maximum phonation time, mean frequency range, and acoustic variables in the injection laryngoplasty group compared to medialization thyroplasty alone or in combination with arytenoid adduction. 4,5 These results were attributed to heterogeneity between the groups prior to surgical intervention, as there was a higher degree of premorbid respiratory disability (e.g., UVPF due to lung resection) and a greater vertical glottis height difference in the laryngeal framework group compared to the injection laryngoplasty group. Injection laryngoplasty and subjective voice outcomes. All three studies that focused on subjective voice outcomes as a primary outcome show postoperative improvement in subjective voice outcomes. 3,7,8 Cantillo- Ba~nos et al. found that aside from higher postoperative VHI scores in medialization thyroplasty compared to injection laryngoplasty, there were no differences in subjective voice outcomes including jitter, shimmer, and 1617

3 TABLE I. Outcome Measures Comparing Injection Laryngoplasty With Other Interventions. Article LoE Comparison Outcome Measure Follow-up Improvement?* Comparison of Interventions Conclusions/Additional Information Acoustic and aerodynamic outcomes Cantillo-Banos et al. 3 4 IL vs. MT Jitter, shimmer, HNR 6 and 24 months IL had no improvement in shimmer Umeno et al. 4 4 IL vs. MT MPT, MFR, acoustic variables 12 months 4 years In all outcome Andrews et al. 6 3 IL vs. MT MPT 8 17 months In all outcome Mortensen et al. 9 4 IL vs. MT vs. (AA 1 MT) Umeno et al. 5 3 IL vs. LF (AA/MT/MT 1 AA) Jitter, shimmer, HNR, MPT, MFR 3 months In all outcome MPT, MFR 12 months 3 years In all outcome Subjective voice outcomes Cantillo- Ba~nos et al. 3 4 IL vs. MT VHI 6 and 24 months In all outcome Morgan et al. 7 4 IL vs. MT CAPE-V, VHI 1 9 months In all outcome, but not significantly different Vinson et al. 8 3 IL vs. MT CAPE-V, VHI 1 24 months Stats not available Laryngoscopic outcomes Morgan et al. 7 4 IL vs. MT Symmetry, amplitude, periodicity,closure patterns, glottic closure Vinson et al. 8 3 IL vs. MT Glottic closure, symmetry,amplitude, periodicity 1 9 months In all outcome 1 24 months In all outcome IL had better HNR score compared to MT at 24 months (P <.05), but not 6 months IL had better change in MPT and MFR (P <.001) Both effective at voice improvements over 24- month period; improvement in HNR better sustained in IL compared to MT Difference may be due to preoperative differences in respiratory function (UVFP due to lung resection) No difference IL and MT both effective options for revision, but IL is temporary and may require repeat procedures (10/16 needed reinjection) No difference No difference in improvement of outcomes between groups IL had greater improvement in all outcomes compared to laryngeal framework (P <.05) MT had better VHI outcome at 6 and 24 months (P <.05) Difference seen with IL may be due to preoperative differences in glottal level height Both show postoperative improvement, but MT shows better improvement in VHI compared to IL over short and long term No difference Both have comparable outcomes No difference Both have comparable outcomes No difference Both have comparable outcomes No difference Both have comparable outcomes * improvement with P <.05 AA 5 arytenoid adduction; CAPE-V 5 Consensus Auditory Perceptual Evaluation-Voice; HNR 5 harmonics to noise ratio; IL 5 injection laryngoplasty; LoE 5 level of evidence; MFR 5 mean airflow rate; MPT 5 maximum phonation time; MT 5 medialization thyroplasty; VHI 5 Voice Handicap Index. 1618

4 TABLE II. Outcome Measures Comparing Arytenoid Adduction With Other Interventions. Article LoE Comparison Outcome Measure Follow-up Improvement Comparison of Interventions Conclusions Acoustic and aerodynamic outcomes Mortensen et al. 9 4 (AA 1 MT) vs. IL vs. MT Murata et al (eaa 1 IL) vs. (eaa 1 MT) Sonoda et al (AA/lateral traction) vs. (AA 1 MT) Subjective voice outcomes Jitter, shimmer, HNR, MPT, MFR Jitter, shimmer, HNR, MPT, MFR 3 months In all outcome 6 months 1 year In all outcome MPT NA In all outcome Andrews et al. 6 3 (AA 1 MT)vs. IL GRBAS 8 17 months In all outcome Laryngoscopic outcomes Significant improvement in degree of change of acoustic and aerodynamic parameters for AA 1 MT AA 1 MT may correct the physiology of the incompetent larynx better than MT or IL alone No difference No difference in improvement of outcomes between groups No difference No difference in improvement of outcomes between groups No difference No difference in improvement of outcomes between groups Li et al (AA 1 MT) vs. MT Glottic gap 9 weeks NA No difference Usefulness of AA for large glottis gaps and vertical height discrepancies may not be warranted Abraham et al (AA 1 MT) vs. MT Glottic gap NA NA (AA 1 MT) had better posterior glottic gap closure (P ) Complications Abraham et al (AA 1 MT) vs. MT Complication rates NA NA Increased mean time of surgery and hospital stay for AA 1 MT; increased wound complications, risk of tracheotomy, edema with AA 1 MT Murata et al eaa vs. (eaa 1 MT) vs. (eaa 1 IL) Complication rates 6 months 1 year NA Two minor complications in endoscopic AA patients Improved closure of the posterior glottis with addition of AA Increased complication rate with MT 1 AA Endoscopic AA a safe option for UVFP and can be used in combination with MT and IL AA 5 arytenoid adduction; eaa 5 endoscopic arytenoid adduction; GRBAS 5 Grade, Roughness, Breathiness, Asthenia, Strain; HNR 5 harmonic to noise ratio; IL 5 injection laryngoplasty; LoE 5 level of evidence; MFR 5 mean airflow rate; MPT 5 mean phonation time; MT 5 medialization thyroplasty; NA 5 not available; UVFP 5 unilateral vocal fold paralysis. 1619

5 TABLE III. Outcome Measures Comparing Laryngeal Reinnervation With Other Interventions. Article LoE Comparison Outcome Measure Follow-up Improvement Comparison of Interventions Conclusions Acoustic and aerodynamic outcomes Chhetri et al (LR 1 AA) vs. AA Laryngeal air flow, subglottic pressure Hassan et al (NMP 1 AA) vs. (AA 1 MT) Jitter, shimmer, HNR, MPT NA In all outcome 3, 12, 24 months In all outcome Paniello et al LR vs. (MT 6 AA) MPT, CPP 6, 12 months In all outcome Subjective voice outcomes Hassan et al (NMP 1 AA) vs. (AA 1 MT) GRBAS (G and B only) 3, 12, and 24 months In all outcome Havas and 4 LR vs. IL vs. MT Voice outcomes scale 2 months 8 years Stats not Priestley 17 available Tucker 18 4 (NMP 1 MT) vs. MT Perceptual voice ratings 6 months and 2 years Stats not available Paniello et al LR vs. (MT 6 AA) GRBAS, VRQOL 12 months In all outcome Laryngoscopic outcomes Chhetri et al (LR 1 AA) vs. AA Glottic closure, mucosal wave, glottic symmetry Narajos et al (LR/NMP 1 AA) vs. AA Degree peak edema postoperatively NA In all outcome day 3 improvement No difference LR 1 AA and AA both effective in improving voice outcomes, with no difference in outcome between groups. (AA 1 NMP) had greater improvement in MPT compared to (AA 1 MT) at 12 and 24 months (MT 6 AA) had better improvement in MPT compared to LR at 6 months, (P <.009); LR had better CPP score than (MT 1 AA) at 12 months (P <.05) (NMP 1 AA) had better G (P <.05) and B (P <.01) scores at 24 months AA 1 NMP may provide longerterm benefits in acoustic voice parameters Delayed onset of improved MPT in LR group; better maintenance of cepstral peak in LR group compared to (MT 6 AA) (AA 1 NMP) may provide longterm benefit over (AA 1 MT) in perceptual voice outcomes Stats not available Multiple effective options for treatment of UVFP; successful rehabilitations requires consideration of patient characteristics (NMP 1 MT) had improvement at 2 years, and MT had deterioration (NS) Long-term improvement in (NMP 1 MT) compared to MT No difference Both LR and (MT 6 AA) effective in improving both GRBAS and VRQOL; younger subjects in both groups had better results (P 5.048) No difference LR 1 AA and AA provide significant improvement in laryngoscopic findings but no differences in improvement between groups No difference No difference in postoperative edema between groups AA 5 arytenoid adduction; CPP 5 cepstral peak prominence; GRBAS 5 Grade, Roughness, Breathiness, Asthenia, Strain; HNR 5 harmonics to noise ratio; IL 5 injection laryngoplasty; LoE 5 level of evidence; LR 5 laryngeal reinnervation; MPT 5 maximum phonation time; MT 5 medialization thyroplasty; NA 5 not available; NMP 5 neuromuscular pedicle; NS 5 not significant; UVFP 5 unilateral vocal fold paralysis; VRQOL 5 voice-related quality of life. 1620

6 harmonic-to-noise parameters between these two interventions. 3 Similarly, two other studies reported no difference in subjective voice outcome parameters when injection laryngoplasty was compared to medialization thyroplasty. 7,8 Laryngoscopy. The two studies that used glottic closure, symmetry, and amplitude periodicity on laryngoscopic examination as primary outcome both showed no difference in outcomes between injection laryngoplasty and medialization thyroplasty. 7,8 Arytenoid Adduction First described by Isshiki et al. in 1978, arytenoid adduction involves medialization of the posterior vocal fold by placement of a suture in the muscular portion of the arytenoid, thereby simulating contraction of the lateral cricoarytenoid muscle. 24 Theoretically, this results in an improvement in posterior glottic gap closure. Although arytenoid adduction offers several advantages over other procedures, it is a technically challenging procedure that involves significant laryngeal manipulation of the cricoarytenoid joint. Compared to medialization thyroplasty, it is associated with an increase in overall complications including airway obstruction due to laryngeal edema, dysphagia, and increased operating time. 13 Addition of arytenoid adduction to medialization thyroplasty or injection laryngoplasty. Arytenoid adduction is often performed in combination with medialization thyroplasty or injection laryngoplasty. Andrews et al. found no difference between subjective voice outcomes between arytenoid adduction with medialization thyroplasty compared to injection laryngoplasty. Mortensen et al. found that there was an added benefit of arytenoid adduction to acoustic or aerodynamic outcome including jitter, shimmer, harmonic-to-noise ratio, mean phonation time, mean phonatory flow, or subglottic pressure, but this did not reach statistical significance. Multivariate analysis showed a statistically greater degree of change of acoustic and aerodynamic parameters in this group. 9 Two studies investigated laryngoscopic outcomes. Abraham et al. conducted the largest study with 194 patients: 98 underwent medialization thyroplasty alone compared with 96 who underwent medialization thyroplasty combined with arytenoid adduction. In this study, the addition of arytenoid adduction to medialization thyroplasty resulted in significantly improved closure of the posterior glottis on laryngoscopy, with no statistical difference in complication rates. 13 This improvement in glottic closure was not reproducible in a study by Li et al. However, this was a much smaller-scale study involving 10 patients who had medialization thyroplasty and arytenoid adduction compared to 35 patients who had medialization thyroplasty alone. 12 Differences in results between these two studies may also be due to variability between groups in terms of preoperative comorbidities, glottic closure patterns, and vertical height discrepancies. Arytenoid adduction and technique modifications. To address the increased complication rates associated with the increased technical difficulty of arytenoid adduction, two studies introduced modified arytenoid adduction methods in attempt to reduce complication rates. 10,11 Murata et al. found that endoscopicassisted arytenoid adduction surgery yielded similar postoperative acoustic and aerodynamic results, with no significant added complication rates when performed alone and in combination with medialization thyroplasty or injection laryngoplasty. 10 Sonoda et al. introduced a modified open arytenoid adduction technique to avoid dissection of the posterior edge of the thyroid cartilage and damage to the surrounding tissues. Lateral traction is applied to the cricoarytenoid muscle using nylon sutures pulled anterocaudally. 11 This modified open technique was found to have similar results as compared to arytenoid adduction and medialization thyroplasty in achieving successful voice outcomes as measured by maximum phonation time of more than 10 seconds. Arytenoid adduction summary. Arytenoid adduction can be performed either alone or in combination with other techniques. The hypothesis that this technique results in an improvement in posterior glottic gap was demonstrated in one study, but not in another. 12,13 Mortensen et al. also demonstrated no statistically significant added benefit of arytenoid adduction to medialization thyroplasty on acoustic and aerodynamic voice outcomes. 9 Modified arytenoid adduction techniques have been developed to improve complication rates associated with the traditional approach. Further research is necessary to improve comparisons between approaches. Laryngeal Reinnervation Laryngeal reinnervation was introduced as a technique to prevent long-term atrophy and decreased stiffness of a paralyzed vocal fold, which can occur with medialization thyroplasty. Vocal fold bulk, stiffness, and tension are maintained by providing nerve supply to the thyroarytenoid adductor muscles. It is the resultant medialization of the vocal fold, rather than complete restoration of dynamic vocal fold movement, that leads to voice improvements with this technique. Functional restoration of the vocal fold is limited by disorganized axon regrowth, resulting in synkinesis. There are a variety of approaches to reinnervation including primary anastomosis of the transected recurrent laryngeal, nerve-muscle pedicle transfer to the thyroarytenoid muscle, direct ansa cervicalis nerve implantation onto the thyroarytenoid muscle, and anastomosis between a donor nerve (usually the hypoglossal, phrenic, or ansa cervicalis) and the recurrent laryngeal nerve. 25 Laryngeal reinnervation alone. Paniello et al. conducted the most robust study directly comparing laryngeal reinnervation with medialization thyroplasty in a multicenter randomized control trial with 12 subjects in each arm. 16 Results from the study suggest a delayed onset of improved outcomes with reinnervation. Minimal differences in auditory and perceptual voice 1621

7 outcomes at 6 months were found; however, subjects undergoing laryngeal reinnervation had continued improvement and better maintenance of results at 12 months. Subgroup age analysis showed that subjects aged less than 52 years had better outcomes with laryngeal reinnervation compared to medialization thyroplasty at any age, and significantly better outcomes than subjects greater than 52 years old with laryngeal reinnervation, suggesting that younger patients may have more benefit from laryngeal reinnervation and older patients better outcomes with medialization thyroplasty. However, Havas and Priestley reported less successful voice outcomes with only four out of 12 subjects undergoing reinnervation achieving satisfactory voice results. 17 Laryngeal reinnervation in combination with other techniques. Three studies evaluated the added effect of laryngeal reinnervation with a laryngeal framework procedure. 14,15,18 These included the combination of neuromuscular pedicle with either medialization thyroplasty or arytenoid adduction, and ansa-rln in combination with arytenoid adduction. In one study, significant improvements in acoustic and aerodynamic parameters persisted up to 2 years postoperatively following a neuromuscular pedicle and medialization thyroplasty combination procedure. 15 Furthermore, this study found that perceptual voice outcomes improved in those undergoing the combined procedure, whereas voice deterioration was seen in those undergoing medialization thyroplasty alone. 18 Hassan et al. also found that the combination of neuromuscular pedicle with arytenoid adduction resulted in significantly greater improvements in maximum phonation time that persisted up to 2 years. 15 Together, these results suggest that the addition of a neuromuscular pedicle to medialization thyroplasty not only prevents the voice deterioration that occurs with medialization thyroplasty alone, but also results in improved long-term voice outcomes due to the increased bulk and vocal fold mass provided by the reinnervation. 18 Unfortunately, similar results were not found when ansa cervicalis anastomosis reinnervation was combined with arytenoid adduction. Chhetri et al. found no added benefit of ansa cervicalis anastomosis to arytenoid adduction in aerodynamic parameter outcomes, auditory and perceptual outcomes, or laryngoscopic outcomes. 14 However, in this study, a significant portion of patients were lost to follow-up, and patients had variable postoperative follow-up intervals, which may explain in variability in the results. Laryngeal reinnervation complications. Importantly, in comparison to framework surgery alone, laryngeal reinnervation procedures were shown to be safe when performed alone or in combination with arytenoid adduction. Blumin and Merati found no difference in minor or major complication rates between laryngeal reinnervation and other laryngeal framework procedures. 26 Narajos et al. added evidence to the safety profile of laryngeal reinnervation by demonstrating no difference in degree of edema in different subsites of the larynx following arytenoid adduction with or without laryngeal reinnervation Laryngeal reinnervation summary. Overall, when employed alone or in combination with laryngeal framework procedures, reinnervation is associated with improved subjective and objective voice outcomes preand postintervention without the expense of increased complications. Patients who have undergone laryngeal reinnervation have been shown to have a delayed benefit in voice outcome, with maximal benefit reached several months after surgery, whereas results from medialization thyroplasty are achieved almost immediately. Results from studies in this review suggest that the marginal benefits compared to other medialization techniques may not outweigh the technical challenges that microneural surgery presents. Overall Observations A wide variety of effective procedural interventions are available for patients with UVFP. Each of these techniques may be performed in isolation or in combination with other techniques. Each technique has relative strengths and weaknesses. Patient selection, etiology of the paralysis, and preoperative laryngoscopic findings are all necessary considerations when considering an optimal, individualized approach. Table IV summarizes the overall observations of each technique according the findings of this study. Limitations A wide breadth of literature has been published on the topic of UVFP. This study was conducted in an attempt to systematically review all head-to-head comparisons between interventions. This study, as a systemic review, is limited by the quality of the included studies. Because it is a collection of findings from various other studies, it provides an overview of the direction of the literature, but is unable to show new findings. This study is not a meta-analysis, and study results have not been statistically combined for more powerful results. As well, only English-language studies were able to be included in this review. Interpretation of the pooled dataset was particularly challenging due to a variety of factors. First, there is significant variation across the studies in methodology and study design. Lack of standardization in outcome and differences in reporting outcome data make generalizability between studies difficult. Furthermore, there was significant heterogeneity in preoperative patient population, length of postprocedural followup, and breadth of surgical combinations. All of these factors could contribute to why there were no differences seen in the outcome across interventions. Second, differences in surgical technique and preferred materials are vast between institutions and surgeons. Within each surgical technique, there is significant variability in the amount of material injected, durability of the injected material, and type of injection or implant. All of these factors make comparisons of the results between institutions additionally challenging. Finally, as with any comparison of surgical technique, surgeon

8 TABLE IV. Summary of Interventions by Strengths and Weaknesses. Technique Strengths Weakness Medialization thyroplasty Immediate result May lack long-term effect due to continued vocal fold atrophy when done alone Simple procedure Requires operating room time Injection laryngoplasty Can be completed in a clinic setting May not be ideal for patients who cannot tolerate an office-based procedure under local anesthesia or general anesthetic May be used as an effective temporizing measure for UVFP May require multiple injections Arytenoid adduction Laryngeal reinnervation UVFP 5 unilateral vocal fold paralysis. May be useful in correcting posterior glottic gaps and vertical height discrepancies Prevents vocal fold atrophy, resulting in long-term results Technically challenging More manipulation of the larynx resulting in more complications compared to medialization thyroplasty Requires operating room time Technically challenging No immediate result when done alone Requires operating room time experience and institutional volume plays a large role in patient outcomes. Reported outcomes in the literature often represent institutions with large volumes. This may limit the external validity of the findings. Therefore, individual experience and comfort with each technique should be taken into consideration when choosing the best intervention for each patient scenario. FUTURE DIRECTIONS Overall, standardized study protocols outlining outcome, method of reporting measurements, and follow-up intervals would facilitate future analysis of data, including meta-analyses. In this review, only one study attempted to investigate aspiration outcomes in a systematic way. As aspiration is a major complication of UVFP, further studies objectively investigating this outcome measure may direct decisions for intervention in this subset of patients. CONCLUSION Based on this review, there is no definitive evidence suggesting superiority of any one technique on acoustic and aerodynamic parameters, perceptual voice outcomes, and laryngoscopic findings. Current evidence suggests that although voice outcomes are similar between medialization thyroplasty and injection laryngoplasty initially following the procedures, long-term results may favor the former. Furthermore, injection laryngoplasty may be favored in patients who are unable to tolerate general anesthetic and those who wish to have a more immediate short-term benefit. Laryngeal reinnervation techniques may be best used in combination with other laryngeal framework techniques for longer-term benefit and may be best reserved for younger patients. All procedures were shown to be safe, and not associated with any significant perioperative morbidity. Overall, a variety of procedures are available within the otolaryngologist s armamentarium for treating patients with UVFP. Because of the variability in surgical combinations, surgeon expertise, and inconsistencies in techniques of assessment, it is difficult to generalize based on this literature review as to which operative procedure is superior. Multiple studies have shown no significant differences between treatment arms based on laryngoscopic, perceptual, acoustic, and quality of life. Ultimately, patient preference and expectations, preoperative laryngoscopy findings, procedural cost, onset, and duration of therapeutic effect, and surgeon preference are all essential components in determining the most optimal intervention for the patient with UVFP. BIBLIOGRAPHY 1. Havas T, Lowinger D, Priestley J. Unilateral vocal fold paralysis: causes, options and outcomes. Aust N Z J Surg 1999;69: Howick J, Chalmers I, Glasziou P, et al. The 2011 Oxford CEBM levels of evidence. Oxford Centre for Evidence-Based Medicine website. Available at: Accessed December 12, Cantillo- Ba~nos E, Jurado-Ramos A, Gutierrez-Jodas J, Ariza-Vargas L. Vocal fold insufficiency: medialization laryngoplasty vs calcium hydroxylapatite microspheres (Radiesse Voice). Acta Otolaryngol 2013;133: Umeno H, Chitose S, Sato K, Nakashima T. Comparative study of framework surgery and fat injection laryngoplasty. J Laryngol Otol Suppl 2009;123: Umeno H, Chitose S-I, Sato K, Ueda Y, Nakashima T. 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