Effect of Melatonin Administration on Nerve Regeneration after Recurrent Laryngeal Nerve Injury.

Recurrent Laryngeal Nerve (RLN) injury is a complication in neck surgery. The aim of this study is to evaluate the effect of primary suture repair with melatonin treatment on nerve regeneration after RLN damage. After the RLN damage, nerve repair was performed in the first and fourth groups. The third and fourth groups were given intraperitoneal melatonin therapy daily for six weeks. EMG was applied to all subjects and vocal cord movements were evaluated endoscopically. At the end of the sixth week, all subjects were sacrificed, and their larynx were examinedhistologically. Vocal cord paralysis (VCP) was observed in all subjects after RLN damage. In the sixth week, improvement was observed in the first and fourth group who underwent nerve repair, whereas none in the second and third group, who did not undergo nerve repair, improved. With EMG, the highest MUP was in the fourth group. Histologically, an increase in Schwann cells, a decrease in axon damage, and cytoplasmic vacuolization were in the fourth group. Myelin protein zero and Ki-67 staining were the most in the fourth group. In our study, laryngoscopic, electrophysiological and histopathological findings show that melatonin contributes to nerve healing but this could not translate into functional recovery.

Bilateral vocal cord palsy as complication of CNS tuberculosis.

BACKGROUND: Tuberculous meningitis, a rare but severe form of extrapulmonary tuberculosis, frequently affects cranial nerves. While nerves III, VI and VII are commonly involved, involvement of caudal cranial nerves is rarely described. Here, we report a rare case of bilateral vocal cord palsy secondary to caudal cranial nerve involvement in tuberculous meningoencephalitis, that occurred in Germany, a country with low tuberculosis incidence. CASE PRESENTATION: A 71-year-old woman was transferred for further treatment of hydrocephalus as a complication of presumed bacterial meningitis with unknown pathogen at that time. Because of decreased consciousness, intubation was performed and an empiric antibiotic therapy with ampicillin, ceftriaxone and acyclovir was initiated. Upon admission to our hospital, an external ventricular drainage was placed. Cerebrospinal fluid analysis revealed Mycobacterium tuberculosis as the causative pathogen, and antitubercular treatment was initiated. Extubation was possible one week after admission. Eleven days later, the patient developed inspiratory stridor that worsened within a few hours. Flexible endoscopic evaluation of swallowing (FEES) revealed new-onset bilateral vocal cord palsy as the cause of respiratory distress, which required re-intubation and tracheostomy. The bilateral vocal cord palsy persisted despite continued antitubercular therapy on the follow-up examination. CONCLUSION: Considering the aetiology of infectious meningitis, cranial nerve palsies may be suggestive for tuberculous meningitis as underlying disease given their rarity in other bacterial forms of meningitis. Nevertheless, intracranial involvement of inferior cranial nerves is rare even in this specific entity, as only extracranial lesions of inferior cranial nerves have been reported in tuberculosis. With this report of a rare case of bilateral vocal cord palsy due to intracranial involvement of the vagal nerves, we emphasize the importance of timely initiation of treatment for tuberculous meningitis. This may help to prevent serious complications and associated poor outcome since the response to anti-tuberculosis therapy may be limited.

Injection laryngoplasty with hyaluronic acid for glottal insufficiency in unilateral vocal fold paralysis: a systematic review of the literature.

BACKGROUND: Glottal insufficiency, mostly caused by unilateral vocal fold paralysis (UVFP) or vocal fold atrophy can be treated by injection laryngoplasty (IL). Materials such as hyaluronic acid (HA) gels are now widely available and used to improve voice quality. Various durability and effects of HA injection laryngoplasties have been reported. The aim of this study is to provide a systematic review of the literature for the use of HA in injection laryngoplasties. METHODS: A systematic literature search was conducted in PubMed and Cochrane Libraries. Three reviewers assessed original research studies concerning vocal fold augmentation with HA for eligibility. English written full-text human studies from 2000 to 2020 with EBM level 1b-2 were included. In vitro studies, animal studies, case reports, case-control studies, correspondence and review articles, and articles with other injection materials were excluded. Demographical data, indication, type of HA, evaluation methods, follow-up, durability of implanted material and complications were assessed. RESULTS: A total number of 311 articles were found in PubMed and Cochrane Library, 13 studies were eligible for final analysis with 1063 patients, mean age of patients was 58.7 years. Main indication for HA IL was unilateral vocal fold paralysis, evaluation methods were subjective-VHI (Voice Handicap Index) questionnaire and objective-acoustic and aerodynamic measurements, mean time of follow-up was 5.9 months. Large-particle HA gels were more favorable for longer durability than small-particle HA, reported time of resorption of HA gels ranges between 6 and 12 months, and complication rate was low. CONCLUSION: Hyaluronic acid injection laryngoplasty increases voice quality, improves results of voice therapy, and can be recommended as overlap treatment before permanent medialization surgery. Compared to other injected materials, HA seems to have more favorable effect on vibratory functions of the vocal folds and thus on the voice quality parameters.

Clinical study of injectable collagen scaffold with autologous fat cells for repair of severe vocal fold injury.

Cell retention and survival after transplantation remains a major problem for long-term efficiency in therapy of severe vocal fold injury with autologous cells. In this study, injectable collagen scaffold was used to deliver autologous fat cells (AFCs) for repairing of severe vocal fold injury. We found injectable collagen scaffold could enhance the retention and survival of green fluorescent protein (GFP) labeled fat cells in the transplantation sites in rats. Based on these data, a randomized controlled clinical trial was conducted to evaluate the safety and efficiency of transplantation of collagen scaffold with AFCs for severe vocal fold injury. Ten patients with vocal fold paralysis were randomly assigned to control (AFCs only) and intervention (AFCs + collagen) groups. AFCs with or without collagen scaffold were injected into vocal folds of patients under general anesthesia, respectively. The safety and efficacy were regularly assessed during 24 months post-surgery. No obvious complications occurred in all patients during the follow-up. The collagen scaffold maintained the stability of implants after injection and reconstructed the vocal fold structure. The improvement of voice quality of patients was observed through voice quality evaluation with the voice handicap index (VHI) questionnaire, as well as acoustic analysis of maximum phonation time, jitter, and shimmer. The VHI score of patients in AFCs + collagen group improved significantly than those in AFCs group at 6, 12 and 24 months post-surgery. It demonstrates the injectable collagen scaffold is safe and efficient for delivering AFCs for vocal fold injury.

Effect of Fascia Implantation and Controlled Release of Basic Fibroblast Growth Factor for Muscle Atrophy in Rat Laryngeal Paralysis.

OBJECTIVE: To improve lateral thyroarytenoid (TA) muscle atrophy after laryngeal paralysis, reconstruction of the vascular network of the atrophied muscle is necessary. We therefore evaluated whether the controlled release of basic fibroblast growth factor (bFGF) with autologous fascia implantation could affect vascular reconstruction in the lateral TA muscle. STUDY DESIGN: Animal experiment. SETTING: Laboratory. METHODS: Unilateral laryngeal paralysis was induced in 20 rats. The rats were implanted with autologous fascia and a gelatin hydrogel sheet with or without 1 µg of bFGF (fascia and bFGF + fascia groups; n = 5 each) and with only a gelatin hydrogel sheet with bFGF (bFGF group: n = 5). Another group remained untreated (n = 5) at 4 months after paralysis. At 3 months since transplantation, intra- and intergroup comparisons of the muscle volumes and total area of blood vessels in the lateral TA muscle were performed. RESULTS: When compared with the untreated group, the bFGF + fascia group showed a significant increase in muscle volume (P =.0008) and vascular area (P =.0002) in the lateral TA muscle, whereas the other 2 treated groups demonstrated an insufficient effect. CONCLUSION: bFGF + fascia implantation showed histologic improvement in severe laryngeal paralysis. We demonstrated that the decrease in lateral TA muscle mass after paralysis might be countered by the reconstruction of the vascular network. Our findings indicate that hypovascular and denervated areas of the laryngeal muscle can be regenerated by the implantation of growth factors and scaffolds with surgical stress. LEVEL OF EVIDENCE: 5.

Stridor Due to Cranial Nerve X Palsy Progressing to Polyneuropathy in a Teenager With COVID-19.

The neurologic manifestations of coronavirus disease 2019 (COVID-19) are wide-ranging, including various cranial neuropathies, beyond anosmia and dysgeusia, the exact neuropathological mechanism of which are yet unknown. Acute cranial nerve (CN) X neuritis with vocal cord paralysis has not been reported in COVID-19 and is a rare presentation of neuropathy in general. A girl aged 14 years was admitted with stridor. She was diagnosed with symptomatic COVID-19 8 days before. By presentation, fever had resolved, but she had developed stridor; sore throat with dysphagia; chest, shoulder, and back pain; and generalized weakness. Neurologic examination and laryngoscopy were consistent with isolated left CN X palsy. Steroids were started, but neurologic disease progressed with subjective pain, right lower face numbness, and eye fatigability. Respiratory distress increased, and she was intubated for airway protection. MRI revealed abnormal enhancement of CNs III, V, XII, and X. Cerebrospinal fluid studies were normal. Nasopharyngeal severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test result was positive. She was treated with intravenous immunoglobulin, a total of 2 g/kg, and steroids were continued. She made a full neurologic recovery and was discharged after 9 days of hospitalization. This is a case of a teenager who presented with an acute, life-threatening CN X palsy and development of a progressive polyneuropathy in the setting of COVID-19. Although there was concern for Guillain-Barre syndrome, a definitive diagnosis could not be made, and the unusual features of this case, including presentation with stridor and predominate CN involvement seem to indicate a separate symptomatic COVID-19-associated polyneuritis.

Objective evaluation of biomaterial effects after injection laryngoplasty - Introduction of artificial intelligence-based ultrasonic image analysis.

OBJECTIVE: Hyaluronic acid (HA) can be degraded over time. However, persistence of the effects after injection laryngoplasty (IL) for unilateral vocal fold paralysis (UVFP), longer than expected from HA longevity, has been observed. The purpose of the study was to develop a methodology with clinical utility for objective evaluation of the temporal change in HA volume after IL using artificial intelligence (AI)-based ultrasonic assessment. DESIGN, SETTING AND PARTICIPANTS: Imaging phantoms simulating injected HA were built in different volumes for designing the algorithm for machine learning. Subsequently, five adult patients who had undergone IL with HA for UVFP were recruited for clinical evaluation. MAIN OUTCOME MEASURES: Estimated volumes were evaluated for injected HA by the automatic algorithm as well as voice outcomes at 2 weeks, and 2 and 6 months after IL. RESULTS: On imaging phantoms, contours on each frame were described well by the algorithm and the volume could be estimated accordingly. The error rates were 0%-9.2%. Moreover, the resultant contours of the HA area were captured in detail for all participants. The estimated volume decreased to an average of 65.76% remaining at 2 months and to a minimal amount at 6 months while glottal closure remained improved. CONCLUSION: The volume change of the injected HA over time for an individual was estimated non-invasively by AI-based ultrasonic image analysis. The prolonged effect after treatment, longer than HA longevity, was demonstrated objectively for the first time. The information is beneficial to achieve optimal cost-effectiveness of IL and improve the life quality of the patients.

Additional Injection Laryngoplasty for Patients With Unilateral Vocal Fold Paralysis.

OBJECTIVES: In case of insufficient voice improvement after injection laryngoplasty (IL), additional IL will be one of the next option of treatments. However, little is known about the voice outcomes regarding an additional IL. STUDY DESIGN: Retrospective comparative study in single institution. METHODS: We enrolled the patients of unilateral vocal fold paralysis (UVFP), who received IL (N = 76) twice because of insufficient voice improvement. The etiologies of UVFP were related with thoracic and esophageal surgery (51.3%), neck surgery (30.3%), skull base surgery (7.9%), or unknown (10.5%). The subjective and objective voice parameters were collected before and after (mean: 5.3 months) each IL. RESULTS: Aspiration, maximum phonation time (MPT), jitter percentage, shimmer percentage, and noise to harmonic ratio (NHR) were significantly improved after both the first and second rounds of IL (P < .05). Voice handicap index (VHI)-30 was also significantly improved after both the first and second rounds of IL (P < .001). Regarding GRBAS score, overall grade of dysphonia (G), roughness (R), and breathiness (B) were significantly improved after the first IL, but only G and R after the second IL (P < .05). In comparison between postprocedural voice parameters of the first and second ILs, MPT was significantly improved from 5.5 ± 3.5 seconds to 7.3 ± 7.5 seconds (P = .001). Grade of dysphonia (1.9 ± 0.8) and breathiness (1.7 ± 0.9) of post-first IL were significantly (P < .001) improved to those of post-second IL (1.3 ± 0.7 and 1.2 ± 0.7, respectively). VHI-30 of post-first IL (72.0 ± 20) was significantly improved (P < .001) to those of the second IL (57.2 ± 23.7). CONCLUSIONS: In selected patients, additional IL could provide further improvement of voice in patient who had unsatisfactory voice results despite of initial IL. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

The impact of cricothyroid involvement on adductor recovery in unilateral vocal fold paralysis.

OBJECTIVES/HYPOTHESIS: Wide variation in postinjury functional recovery is a hallmark of unilateral vocal fold paralysis (UVFP), ranging from zero to full recovery. The present study examined the impact of cricothyroid (CT) muscle involvement on recovery using quantitative laryngeal electromyography (LEMG) of the thyroarytenoid-lateral cricoarytenoid (TA-LCA) muscle complex at multiple times postinjury. STUDY DESIGN: Prospective cohort study in a medical center. METHODS: Eighty-one patients with UVFP (37 males and 44 females) received an initial assessment of quantitative LEMG, stroboscope, acoustic voice analysis and 36-Item Short Form Survey quality-of-life questionnaire at 3 to 6 months after UVFP onset and a follow-up assessment at 12 months after UVFP onset. RESULTS: The initial and follow-up assessments were performed at 4.3 ± 1.9 and 12.5 ± 1.3 months after UVFP onset, respectively. The peak turn frequency of the TA-LCA muscle complex on the lesion side was improved at the follow-up (470 ± 294 Hz) compared with the initial assessment (300 ± 204 Hz) (P < .001). Patients were also divided into two groups with (n = 27) and without (n = 54) CT involvement, respectively. TA-LCA muscle complex turn frequency improved in patients without CT involvement (from 277 ± 198 to 511 ± 301 Hz; P < .001), but not in those with CT involvement (from 345 ± 211 to 386 ± 265 Hz; P = .46). Seventy-one of all patients received early intervention with intracordal hyaluronate injection, showing similar therapeutic effects in those with and without CT involvement. CONCLUSIONS: Acute UVFP with combined TA-LCA muscle complex and CT muscle involvement has a poor prognosis, with poorer recovery of TA-LCA muscle complex recruitment. Early interventions should be considered in patients with UVFP with CT involvement. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:139-145, 2020.

A Very Rare Complication of Hyaluronic Acid Injection for Medialization Laryngoplasty: A Case With Laryngeal Abscess.

Hyaluronic acid injection for medialization laryngoplasty is a safe procedure performed on patients with glottic incompetence. Laryngeal abscess formation as a complication of injection laryngoplasty is a very rare complication, and, as we know from the literature, there has been only one case of laryngeal abscess after injection laryngoplasty in a patient with a type-I laryngeal cleft. We document for the first time a laryngeal abscess resulting from hyaluronic acid injection laryngoplasty for unilateral vocal fold paralysis. Prompt evaluation of the patient was necessary. Our patient was treated with antibiotics and corticosteroids without a need for intubation. One year after injection, the patient's Voice Handicap Index-10 score was still good and within the range of normal values.

Stroboscopic assessment of unilateral vocal fold paralysis: a systematic review.

PURPOSE: To review the relevant basic stroboscopic evaluations in unilateral vocal fold paralysis (UVFP). Our aim was twofold: (1) to determine the frequency of use of stroboscopic parameters in outcome evaluation after surgical treatment of UVFP using a Pareto diagram; and (2) to select the most relevant parameters in terms of a significant difference between pre- and post-surgical intervention for UVFP. METHODS: A systematic review in PUBMED includes studies on stroboscopic evaluation in combination with UVFP and surgical treatment. The review was limited to English studies published between 1990 and March 2018. The most frequently used stroboscopic parameters were identified using a Pareto diagram. Then, 'the percentage of significance' for the most frequently stroboscopic parameters was identified by comparing the number of studies that showed a statistically significant change in pre- and post-treatment results with the total number of studies using the same parameters. RESULTS: Seven stroboscopic parameters were nominated using the Pareto diagram. In decreasing order of citation frequency, periodicity, edge bowing, mucosal wave, glottic gap, position of vocal fold, amplitude, and symmetry have respective percentages of significance of 87.5%, 83.3%, 77.7%, 64.5%, 60%, 57.1%, and 50%. Five pertinent scales were selected for the most frequent and significant stroboscopic parameters. CONCLUSIONS: The results indicate that periodicity, edge bowing, mucosal wave, glottic gap, and position of vocal fold represent the five most frequently used and relevant stroboscopic parameters in UVFP evaluation. The current review outlines a proposal scale of these stroboscopic parameters. PROSPERO REGISTRATION NUMBER: CRD42019126786.

Voice aerodynamics following office-based hyaluronate injection laryngoplasty.

OBJECTIVES: Neuromuscular control, glottal conformation and aerodynamics are the major factors affecting voice performance. We aimed to characterise the degree to which voice improvements following office-based intracordal hyaluronate injection laryngoplasty (HIL) depend on changes in voice aerodynamics in patients with unilateral vocal fold paralysis (UVFP), by assessing the correlations between these parameters. DESIGN: Prospective case series. SETTING: Otolaryngology Clinics in a Medical Center. PARTICIPANTS: Patients with UVFP within 6 months of their first outpatient visit who received single HIL. MAIN OUTCOME MEASURES: Videolaryngostroboscopy, aerodynamics and laboratory voice analysis were evaluated at baseline and 1 month after HIL. Quantitative laryngeal electromyography was evaluated at baseline to confirm UVFP. RESULTS: Seventy-five newly diagnosed patients with UVFP were analysed. The normalised glottal gap area (NGGA) decreased (P < 0.001) (Cohen's dz  = 0.94) and all aerodynamic parameters improved (all P < 0.05) (Cohen's dz  = 0.38-1.02) following HIL. Patients undergoing thoracic surgery had more profound aerodynamic impairments both before and after HIL. After adjusting for improvements in NGGA, the improvement in aerodynamics was correlated with voice improvement and most notably with maximum phonation time and jitter/shimmer. CONCLUSIONS: Hyaluronate injection laryngoplasty improved glottal conformation, aerodynamics and voice, highlighting the benefit of early HIL intervention for patients with UVFP. Patients with UVFP caused by thoracic surgery continued to have poorer aerodynamics post-HIL, indicating the importance of speech therapy in these patients.

In-Office Laryngology Injections.

The ability to perform in-office vocal fold injections has been greatly enhanced by advances in videolaryngoscopy technology. With improved optics and thin, channeled flexible laryngoscopes, in-office laryngeal injections have expanded from vocal fold augmentation for glottic insufficiency, vocal cold immobility, and botulinum toxin injections for spasmodic dysphonia, to vocal fold steroid injections for benign vocal fold lesions and scars and various injections for neurogenic cough. Efficacy, approaches, post-procedure management, and common complications of in-office laryngeal injections are outlined and supporting evidence discussed.

[Effect of cricothyroid and thyroarytenoid muscle botulinum toxin injection on patients with dyspnea caused by bilateral recurrent laryngeal nerve paresis].

Objective: To discuss the clinical effect of small dose of botulinum toxin injection in cricothyroid muscle and thyroarytenoid muscle on patients with incomplete bilateral recurrent laryngeal nerve paresis. Methods: Six patients were selected with Ⅰor Ⅱ or Ⅲ degree of dyspnea diagnosed as bilateral recurrent laryngeal nerve injury by laryngeal electromyography, and small dose of botulinum toxin injection was performed in cricothyroid muscle and thyroarytenoid muscle as a treatment. Degree of dyspnea was assessed one month before and after the treatment, and the stroboscopic laryngoscope results, acoustic parameters and CT image of the patients were collected in the 6 patients. The relevant parameters were also collected one month before and after treatment, including the degree of dyspnea, stroboscopic laryngoscope results, acoustic parameters and CT image of the patients. The angle between bilateral vocal cords in stroboscopy at full inspiratory was calculated, acoustic parameters (F0, jitter, shimmer) were analysed, and vocal length, width and the vocal region were measured. Then, the paired t test was performed for statistical analysis between before and after one month injection, the one way analysis of variance was performed among vocal parameters in CT image. Result: Botulinum toxin injection was successfully completed in the 6 patients, followed without any serious complications. The degree of dyspnea was alleviated to some extent after treatment in all 6 patients; the angle between bilateral vocal cords at the end of a deep inspiration was significantly increased (t=2.44, P<0.05) after the treatment. The changes of F0 and jitter between before and after treatment were not statistically significant (t=0.72, t=1.42, P>0.05). Shimmer was significantly decreased after treatment (t=2.61, P<0.05). Vocal fold length, width and vocal region increased with F0, there was a statistically significant difference between different F0 before injection, and there was no statistically significant difference between different F0 after injection. The follow-up time was respectively seven months, 1 year, 1 year, 18 months, 22 months and 2 years respectively. Conclusion: Small dose of botulinum toxin injection in bilateral cricothyroid muscles and thyroarytenoid muscles can relieve the dyspnea caused by bilateral vocal cords paresis to some extent, accompanied without serious complications, despite the sound quality was slightly worse.

Changes in Peak Airflow Measurement During Maximal Cough After Vocal Fold Augmentation in Patients With Glottic Insufficiency.

Importance: Compromised cough effectiveness is correlated with dysphagia and aspiration. Glottic insufficiency likely yields decreased cough strength and effectiveness. Although vocal fold augmentation favorably affects voice and likely improves cough strength, few data exist to support this hypothesis. Objective: To assess whether vocal fold augmentation improves peak airflow measurements during maximal-effort cough following augmentation. Design, Setting, and Participants: This case series study was conducted in a tertiary, academic laryngology clinic. Participants included 14 consecutive individuals with glottic insufficiency due to vocal fold paralysis, which was diagnosed via videostrobolaryngoscopy as a component of routine clinical examination. All participants who chose to proceed with augmentation were considered for the study whether office-based or operative augmentation was planned. Postaugmentation data were collected only at the first follow-up visit, which was targeted for 14 days after augmentation but varied on the basis of participant availability. Data were collected from June 5, 2014, to October 1, 2015. Data analysis took place between October 2, 2015, and March 3, 2017. Main Outcomes and Measures: Peak airflow during maximal volitional cough was quantified before and after vocal fold augmentation. Participants performed maximal coughs, and peak expiratory flow during the maximal cough was captured according to American Thoracic Society guidelines. Results: Among the 14 participants (7 men and 7 women), the mean (SD) age was 62 (18) years. Three types of injectable material were used for vocal fold augmentation: carboxymethylcellulose in 5 patients, hyaluronic acid in 5, and calcium hydroxylapatite in 4. Following augmentation, cough strength increased in 11 participants and decreased cough strength was observed in 3. Peak airflow measurements during maximal cough varied from a decrease of 40 L/min to an increase of 150 L/min following augmentation. When preaugmentation and postaugmentation peak airflow measurements were compared, the median improvement was 50 L/min (95% CI, 10-75 L/min; P = .01). Immediate peak airflow measurements during cough collected within 30 minutes of augmentation varied when compared with measurements collected at follow-up (103-380 vs 160-390 L/min). Conclusions and Relevance: Peak airflow during maximal cough may improve with vocal fold augmentation. Additional assessment and measurements are needed to further delineate which patients will benefit most regarding their cough from vocal fold augmentation.