The Regenerative Effects of c-Met Agonistic Antibodies in Vocal Fold Atrophy.

BACKGROUND: Atrophy of the vocal folds and the accompanying glottic insufficiency affect the quality of life. Although growth factors have been used to treat muscle atrophy, their effectiveness is limited by their short half-life. METHODS: In total, 15 rabbits and 24 rats were used for the study. The right recurrent laryngeal nerves of all animals were transected. One month following nerve transection, PBS (PBS group), rHGF (HGF group), or a c-Met agonistic antibody (c-Met group) was injected into the paralyzed vocal folds. The larynges of the rabbits were harvested from each group for histologic examination and subjected to PCR analysis. RESULTS: Cross-sectional areas (CSAs) of thyroarytenoid muscles were evaluated. The c-Met group had increased CSAs compared to the PBS and HGF groups, but there were no significant differences compared to normal controls. The expression levels of myogenesis-related genes were evaluated three weeks after the injection. The expression levels of myosin heavy chain IIa were significantly increased in the PBS group, while the expression levels of MyoD were increased in the c-Met group. CONCLUSIONS: The c-Met agonistic antibody showed promise for promoting muscle regeneration in a vocal fold palsy model.

Laryngoscopic findings of age-related vocal fold atrophy are reliable but not specific.

OBJECTIVES: We aimed to evaluate the reliability of laryngoscopic features of vocal fold atrophy as assessed by novice otolaryngology trainees and expert laryngologists. DESIGN: Two expert fellowship-trained laryngologists and three non-expert otolaryngology resident trainees were recruited to view 50 anonymised laryngo-stroboscopic examinations of patients presenting with dysphonia and non-voice, laryngeal complaints. Reviewers were asked to stratify the patient's age, provide an opinion about the presence of age-related vocal fold atrophy and specify which laryngoscopy features were present to make the diagnosis. SETTING: Tertiary care laryngology practice. PARTICIPANTS: Two fellowship-trained laryngologists and three trainee otolaryngologists. MAIN OUTCOME MEASURES: Accuracy of age categorisation was determined and Kappa analysis was performed to assess inter-rater agreement. RESULTS: The mean age of patients was 54.9 years old with near equal male to female distribution. The overall accuracy of age category determination by raters was only 30.8%. Kappa analysis demonstrated fair agreement regarding the presence of vocal fold atrophy in non-expert reviewers, and moderate agreement amongst expert reviewers. Features of glottic gap, muscular atrophy of vocal folds and prominent vocal processes were all identified with high agreement (>80.0%). CONCLUSION: Our study illustrates that while raters can agree on the presence of age-related vocal fold atrophy, the findings may be non-specific and do not necessarily correlate with age.

Postoperative recurrent laryngeal nerve palsy is associated with pneumonia in minimally invasive esophagectomy for esophageal cancer.

BACKGROUND: During the past decade, minimally invasive esophagectomy (MIE) for esophageal cancer has been adopted worldwide with expectations of lower invasiveness. However, the rate of postoperative pneumonia, which is an independent risk factor for oncological prognosis in esophageal cancer, remains high. The aim of this retrospective follow-up study is to clarify whether there is a strong correlation between recurrent laryngeal nerve (RLN) palsy and postoperative pneumonia in MIE. METHODS: This retrospective follow-up study included 209 patients with esophageal cancer who underwent thoracoscopic esophagectomy in the prone position (TEP) at Kobe University between 2011 and 2018. Inclusion criteria included age 18-85 years; cT1-3, cN0-3 disease; upper mediastinal lymphadenectomy; and ability to undergo simultaneous esophagectomy and reconstruction of the gastric conduit or pedicled jejunum. Univariate and multivariate logistic regression were conducted to identify independent risk factors for pneumonia. RESULTS: Among 209 TEPs, pneumonia of Clavien-Dindo classification grade > II occurred in 44 patients (21%). In the pneumonia positive and negative groups, there were significant differences in age (67.9 ± 7.5 vs. 64.9 ± 8.6 years), 3-field lymph node dissection [27 (61%) vs. 67 (41%)], transfusion [20 (45%) vs. 41 (25%)], left RLN palsy [19 (43%) vs. 18 (11%)], and any RLN palsy [20 (45%) vs. 18 (11%)]. In multivariate analysis, any RLN palsy was associated with a higher incidence of pneumonia [odds ratio (OR), 6.210; 95% confidence interval (CI), 2.728-14.480; P < 0.0001]. In addition, age was associated with a higher incidence of pneumonia (OR, 1.049; 95% CI, 1.001-1.103; P = 0.046). Changes in the rate of any RLN palsy over time were quite similar to changes in the incidence of pneumonia. CONCLUSION: There is a strong correlation between RLN palsy and pneumonia in MIE for esophageal cancer. Prevention of RLN palsy may reduce the incidence of pneumonia, leading to better oncological prognosis.

Polyneuropathy in Young Siberian Huskies Caused by Degenerative and Inflammatory Diseases.

Polyneuropathy is defined as the simultaneous dysfunction of several peripheral nerves. In dogs, a number of breeds are predisposed to a variety of immune-mediated and/or degenerative inherited forms of polyneuropathy, with laryngeal paralysis and/or megaesophagus as important clinical features of many of these conditions. This case series describes degenerative and inflammatory polyneuropathies in 7 young Siberian huskies that were categorized based on clinicopathological characteristics as follows: (1) slowly progressive laryngeal paralysis and megaesophagus caused by primary axonal degeneration with large fiber loss (n = 2); (2) slowly progressive polyneuropathy without megaesophagus or laryngeal paralysis caused by primary axonal degeneration with large fiber loss (n = 2); (3) acute inflammatory demyelinating neuropathy causing sensory, motor and autonomic nerve deficits (n = 2); and (4) ganglioradiculitis (sensory neuronopathy; n = 1). Based on the predominantly young age at onset, slow progression, relatedness of affected dogs, and clinical and pathological similarities with inherited neuropathies reported in other dog breeds, a hereditary basis for the degenerative polyneuropathies in Siberian huskies is suspected. However, 5 different mutations in 3 genes known to cause polyneuropathy in other dog breeds (NDRG1, ARHGEF10, or RAB3GAP1) were not detected in the affected Siberian huskies suggesting that more genetic variants remain to be identified. This study highlights the varied underlying lesions of polyneuropathies in young Siberian huskies.

Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum.

The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by perturbations in signal transduction at the neuromuscular junction. Defects in muscle, skeletal, receptor tyrosine kinase (MuSK) cause two distinct phenotypes: fetal akinesia with multiple congenital anomalies (Fetal akinesia deformation sequence [MIM:208150]) and early onset congenital myasthenia (myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency [MIM:616325]). Myasthenia due to MuSK deficiency has variable clinical features, ranging from a milder presentation of isolated late-onset proximal muscle weakness; to a severe presentation of prenatal-onset diffuse weakness, ophthalmoplegia, respiratory failure, and vocal cord paralysis (VCP). Here, we propose to expand the phenotypic spectrum for MuSK deficiency to include isolated VCP with the absence of other classical myasthenic symptoms. We evaluated two brothers who presented in the neonatal period with respiratory failure secondary to isolated VCP. Research-based exome sequencing revealed biallelic likely pathogenic variants in MUSK (MIM:601296). Both children had normal gross motor and fine motor development. One brother had speech delay, likely due to a combination of tracheostomy status and ankyloglossia. This case report suggests that CMS should be on the differential diagnosis for familial recurrence of VCP.

Assessing pathological changes within the nucleus ambiguus of horses with recurrent laryngeal neuropathy: An extreme, length-dependent axonopathy.

INTRODUCTION: Equine recurrent laryngeal neuropathy (RLN) is a naturally occurring model of length-dependent axonopathy characterized by asymmetrical degeneration of recurrent laryngeal nerve axons (RLn). Distal RLn degeneration is marked, but it is unclear whether degeneration extends to include cell bodies (consistent with a neuronopathy). METHODS: With examiners blinded to RLN severity, brainstem location, and side, we examined correlations between RLN severity (assessed using left distal RLn myelinated axon count) and histopathological features (including chromatolysis and glial responses) in the nucleus ambiguus cell bodies, and myelinated axon count of the right distal RLn of 16 horses. RESULTS: RLN severity was not associated with RLn cell body number (P > .05), or degeneration. A positive correlation between the left and right distal RLn myelinated axon counts was identified (R2 = 0.57, P < .05). DISCUSSION: We confirm that RLN, a length-dependent distal axonopathy, occurs in the absence of detectable neuronopathy.

[The possibilities for the restoration of the laryngeal function: the current state-of-the-art]. / Vozmozhnosti vosstanovleniia funktsii gortani: sovremennyi podkhod.

The restoration of the functional competence of the larynx following bilateral laryngeal nerve damage and vocal fold paralysis is a serious challenge for the surgeon that has thus far no satisfactory solution. Physiological re-innervation that occurs naturally with time is non-selective and, in the majority of the cases, leads to synkinesis. Laryngeal pacing achieved with the application of the implantable microchips appears to be a promising approach. The animal experiments have demonstrated the possibility of successful restoration of all the functions of the larynx by means of laryngeal pacing but simultaneously revealed a number of technical issues that have to be addressed if the further progress in this field is to be achieved including the choice of the proper materials for implantation, solution of problems pertaining to the neuromuscular mapping during pacer implantation, etc.). The results of the first prospective clinical trial involving the human patients gave evidence suggesting that the laryngeal electrostimulation technology is both safe and efficient. Nevertheless, further investigations and modification of the method are needed before it can be recommended for the wider application in the routine clinical practice.

Functional Electrical Stimulation of the Feline Larynx With a Flexible Ribbon Electrode Array.

OBJECTIVES: Success of laryngeal reanimation through neurorrhaphy has been limited by synkinesis and preoperative muscle atrophy. The objective of this study was to investigate the use of epimysial electrode arrays as a means of delivering electrical stimulation to the posterior cricoarytenoid muscles in order to control laryngeal abduction. METHODS: Ribbon electrode arrays with 4 or 8 electrode contacts were used. Four cats underwent implantation of electrode arrays along the surface of the posterior cricoarytenoid muscles. The glottis was visualized with a 0° telescope while electrodes were stimulated at different amplitudes and pulse-width durations. Recordings of stimulated vocal folds were analyzed, and the degree of vocal fold abduction was measured in order to create recruitment curves for the left and right posterior cricoarytenoid. Recruitment curves from electrode channels within the array were compared. RESULTS: Electrodes oriented along the medial aspect of the posterior cricoarytenoid stimulated graded physiologic degrees of abduction depending on the amplitude of stimulation. Electrodes oriented laterally along the posterior cricoarytenoid stimulated greater degrees of simultaneous adduction with abduction. CONCLUSION: Acute studies of ribbon surface electrode arrays placed onto the posterior cricoarytenoid reproduce graded degrees of abduction necessary for the precise function of respiration and speech.

Effects of Functional Electrical Stimulation on Denervated Laryngeal Muscle in a Large Animal Model.

Bilateral vocal fold paralysis (BVCP) is a life-threatening condition that follows injury to the Recurrent Laryngeal nerve (RLn) and denervation of the intrinsic laryngeal musculature. Functional electrical stimulation (FES) enables restoration and control of a wide variety of motor functions impaired by lower motor neuron lesions. Here we evaluate the effects of FES on the sole arytenoid abductor, the posterior cricoarytenoid (PCA) muscle in a large animal model of RLn injury. Ten horses were instrumented with two quadripolar intramuscular electrodes in the left PCA muscle. Following a 12-week denervation period, the PCA was stimulated using a once-daily training session for 8 weeks in seven animals. Three animals were used as unstimulated controls. Denervation produced a significant increase in rheobase (P < 0.001). Electrical stimulation produced a 30% increase in fiber diameter in comparison with the unstimulated control group (33.9 ± 2.6 µm FES+, 23.6 ± 4.2 µm FES-, P = 0.04). A trend toward a decrease in the proportion of type 1 (slow) fibers and an increase in type 2a (fast) fibers was also observed. Despite these changes, improvement in PCA function at rest was not observed. These data suggest that electrical stimulation using a relatively conservative set of stimulation parameters can reverse the muscle fiber atrophy produced by complete denervation while avoiding a shift to a slow (type 1) fiber type.

Arytenoid repositioning device.

OBJECTIVES: We report development of a device and technique to manage laryngeal paralysis through minimal-access arytenoid adduction (for unilateral paralysis) and arytenoid abduction (for bilateral paralysis). METHODS: A human cadaver study coupled with directed engineering was used to develop instrumentation designed to secure the muscular process of the arytenoid into favorable adducted or abducted positions. Digital video, photography, and 3-dimensional computed tomographic (CT) imaging of cadaveric larynges were done to evaluate the surgical technique. RESULTS: Testing of prototypes identified the ideal implant to be a 0.36-mm wire with a distal spring-wound coil placed through a trocar via a small drill hole in the anterior thyroid cartilage. An endoscopic view of transilluminated light through the pyriform sinus mucosa identified the tip location of the trocar adjacent to the muscular process of the arytenoid cartilage. Placement of the device through the trocar permitted rotation to engage the muscular process and/or adjacent soft tissue with the distal coil. Implant fixation to the thyroid cartilage positioned the vocal cord into either adduction or abduction. Three-dimensional CT imaging coupled with review of the video documentation established the feasibility of this technique. CONCLUSIONS: We confirm the feasibility of minimal-access arytenoid adduction and abduction through development of a new technique and device.

Animal study: Basic mechanism of vocal cord paralysis caused by button battery ingestion in children.

PURPOSE: Vocal cord paralysis has been reported as a common complication of button battery (BB) ingestion, and there is a need to confirm the mechanism of vocal cord paralysis for the development of a standardized treatment. METHODS: A new CR2032 BB and artificial saliva were placed in a fresh pig esophagus with the recurrent laryngeal nerve (RLN); the negative electrode faced the nerve in the experimental group, while the positive electrode faced the nerve in the control group. The pH values of the intra- and extraesophageal walls were measured simultaneously. Pathological examination was performed after the esophagus and nerves were damaged. RESULTS: After BB ingestion, the pH near the intraesophageal negative electrode increased rapidly, reaching 11.5 at 30 min and over 14 at 6 h, while the extraesophageal pH did not change at 1 h and began to accelerate after 2 h, reaching 10 at 6 h. After 6 h of exposure, the pathological section showed that the structure of the mucosa, submucosa, and muscle layer were destroyed; chromatin in the nucleus faded, and part of the nerve bundle in the adventitia had liquefaction necrosis. CONCLUSION: The basic mechanism of vocal cord paralysis caused by BB ingestion is that the OH- generated by the electrolytic reaction of the negative electrode penetrates the esophageal wall and corrodes the RLN, which may be the cause of vocal cord paralysis caused by BB ingestion without esophageal perforation.

Should an involved but functioning recurrent laryngeal nerve be shaved or resected in a locally advanced papillary thyroid carcinoma?

BACKGROUND: The issue of whether an involved but functioning recurrent laryngeal nerve (RLN) should be shaved or resected in locally advanced papillary thyroid carcinoma (PTC) remains controversial. Our study aimed to compare the early and late outcomes between those who underwent shaving and those who underwent resection and also to identify independent prognostic factors in this subset of patients. METHODS: Of the 77 patients with 1 RLN involved by PTC, 39 (50.6%) underwent RLN preservation (group I) while 38 (49.4%) underwent RLN resection (group II). Early and late vocal cord function (as assessed by flexible laryngoscopy) and disease status were compared between the 2 groups. A multivariate Cox proportional hazards model was carried out to identify independent factors. RESULTS: Baseline characteristics were comparable between the 2 groups. Although temporary vocal cord palsy rate was similar between the 2 groups (p=0.532), 5 patients in group II (13.2%) suffered temporary bilateral vocal cord palsies with 1 requiring a tracheostomy lasting for 1 month. After a median follow-up of 113.8 months, 1 patient from each group developed new onset vocal cord palsy. Presence of distant metastases (hazard ratio [HR]=5.892, 95% CI=1.971-17.604, p=0.001) and incomplete surgical resection in non-RLN concomitant sites (HR=2.491, 95% CI=1.181-5.476, p=0.024) were the 2 independent predictors for a poor cancer-specific survival. CONCLUSIONS: Our data suggested that shaving could preserve the normal functionality in most of the involved RLNs (>90%) in the short to medium term. In the presence of distant metastases or incomplete resection in other non-RLN concomitant sites, the argument for shaving over resection appears even stronger.

Usefulness of computed tomography in the etiologic evaluation of adult unilateral vocal fold paralysis.

BACKGROUND: Unilateral vocal fold paralysis (UVFP) may present as an uncommon complication of extralaryngeal neoplasms, requiring diagnostic scrutiny to seek occult tumors or diseases. The aim of this study was to examine the utility of computed tomography (CT) in evaluating adult UVFP of unknown etiology. METHODS: From January 2010 to December 2011, UVFP was diagnosed in 822 patients at our tertiary-care center. In 634 patients, a readily identifiable cause of the UVFP was evident and therefore there was no need for any imaging; in the remaining 188 patients, the etiology could not be determined. Among this latter group, 153 patients underwent chest radiography (CXR) and contrast-enhanced CT imaging from the skull base to the midchest. RESULTS: In 36 of the 153 (23.5 %) patients, CT revealed the cause of the UVFP: lung cancer in 12 patients, thyroid carcinoma in 7 patients, skull-base tumor in 4 patients, aortic aneurysm in 4 patients, esophageal cancer in 3 patients, thymus tumor in 2 patients, pericardial effusion in 1 patient, and other neck lesions in 3 patients. CXR and neck ultrasonography also identified the etiology in 14 and 12 patients, respectively. During follow-up after the initial CT, none of the patients with idiopathic UVFP was determined to have an underlying disease that would have explained the paralysis. CONCLUSION: CT is a useful single-imaging method for evaluating the etiology of adult UVFP. This approach may reveal occult tumors or previously undiagnosed diseases as the cause of the paralysis, thus improving patient care.

Fascia implantation with fibroblast growth factor on vocal fold paralysis.

PURPOSE: The purpose of this prospective study was to determine the effect of autologous transplantation of fascia into the vocal fold (ATFV) with controlled release of basic fibroblast growth factor (bFGF) on unilateral vocal fold paralysis (UVFP) in a rat model. MATERIALS AND METHODS: Unilateral recurrent laryngeal nerve (RLN) section was performed on 15 rats. Ten rats received an autologous fascia implant and gelatin hydrogel with or without bFGF (1 µg) to their larynxes (fascia only, "fascia group"; bFGF + fascia, "fascia + bFGF group"), while the rest underwent RLN transection ("RLN section group"). Four months later, evaluation of the laryngeal glottal gap and histological analysis were performed. RESULTS: The glottal gap was significantly reduced in the fascia + bFGF group, and fat volume increased significantly relative to the RLN section. The volume of the remaining fascia in the bFGF + fascia group was significantly greater than that of the fascia group. CONCLUSIONS: ATFV with controlled release of bFGF may compensate for diminished laryngeal volume in UVFP by reducing resorption of the implanted fascia and increasing fat volume. Our findings suggest that this modality may represent an attractive option for treating UVFP.

[Clinical application of modified fistulectomy in the treatment of congenital pyriform sinus fistula based on segmental anatomy of fistula].

Objective:To discuss the clinical application and significance of the modified piriform fossa fistulectomy based on segmental anatomy of fistula. Methods:The clinical data of 84 patients with CPSF treated by modified pyriform sinus fistulectomy were analyzed retrospectively. The modified piriform fossa fistula resection adopts the fistula anterograde anatomy method to fine dissect the fistula. The operation procedure can be summarized into four parts: retrograde anatomy of recurrent laryngeal nerve, anatomy of external branch of superior laryngeal nerve, anterograde anatomy of fistula and partial thyroidectomy. Results:All 84 patients successfully completed the operation and discharged from the hospital. The operation time was（64.6±20.0） min, the intraoperative bleeding was（19.6±13.0） mL, and the average hospital stay was（6.8±1.1） d. Postoperative infection occurred in 1 case（1.19%）, temporary vocal cord paralysis in 1 case（1.19%）, no bleeding, pharyngeal fistula, dysphagia, permanent vocal cord paralysis and choking cough. The incidence of complications was 2.3%（2/84）. No complications such as permanent vocal cord paralysis and hypothyroidism occurred. Follow up for 57-106（Median 74） months showed no recurrence. Conclusion:A modified procedure based on segmental dissection of the fistula not only simplifies the traditional procedure, but also procedures the specific steps to provide a targeted and precise resection, which provides a proven surgical solution for complete eradication of the lesion and significantly reduces complications and recurrence.

To Explore the Changes and Differences of Microstructure of Vocal Fold in Vocal Fold Paralysis and Cricoarytenoid Joint Dislocation by Diffusion Tensor Imaging.

OBJECTIVE: The diffusion characteristics of water molecules were measured in the vocal folds of canines exhibiting unilateral vocal fold paralysis and unilateral cricoarytenoid joint dislocation. These characteristics were used in conjunction with a histological examination of the microstructural changes of vocal fold muscle fibers to explore the feasibility of diffusion tensor imaging (DTI) in distinguishing unilateral vocal fold paralysis and unilateral cricoarytenoid joint dislocation as well as evaluating microstructural changes. METHODS: Ten beagles were randomly divided into three groups: four in the unilateral vocal fold paralysis group, four in the unilateral cricoarytenoid joint dislocation group, and two in the normal group. Unilateral recurrent laryngeal nerve resection was performed in the vocal fold paralysis group. Unilateral cricoarytenoid joint dislocation surgery was performed in the dislocation group. No intervention was performed in the normal group. Four months postintervention, the larynges were excised and put into a magnetic resonance imaging (MRI) system (9.4T BioSpec MRI, Bruker, German) for scanning, followed by an analysis of diffusion parameters among the different groups for statistical significance. After MRI scanning, the vocal folds were cut into sections, stained with hematoxylin and eosin, and scanned digitally. The mean cross-sectional area of muscle fibers, and the mean diameter of muscle fibers in the vocal folds were calculated by target detection and extraction technology. Mean values of each measurement were used to compare the differences among the three groups. Pearson correlation analysis was performed on the DTI parameters and the results from histological section extraction. RESULTS: The paralysis group had significantly higher Fractional Anisotropy (FA) compared to the dislocation group and normal group (P = 0.004). The paralysis group also had a significantly lower Tensor Trace value compared to the dislocation group and normal group (P = 0.000). The average cross-sectional area of vocal fold muscle fibers in the paralysis group was significantly smaller than the dislocation group and normal group (P = 0.000). Pearson correlation analysis yielded values of, r = -0.785, P = 0.01 between the average cross-sectional area of vocal muscle fibers and FA, and values of r = 0.881, P = 0.00 between Tensor Trace and the average cross-sectional area of vocal muscle. CONCLUSION: FA and Tensor Trace can be used as effective parameters to reflect the changes of microstructure in vocal fold paralysis and cricoarytenoid joint dislocation. DTI is an objective and quantitative method to effectively evaluate unilateral vocal fold paralysis and unilateral cricoarytenoid joint dislocation, also capable of noninvasively evaluating vocal fold muscle fiber microstructure.

TRPV4 mutations in children with congenital distal spinal muscular atrophy.

Inherited disorders characterized by motor neuron loss and muscle weakness are genetically heterogeneous. The recent identification of mutations in the gene encoding transient receptor potential vanilloid 4 (TRPV4) in distal spinal muscular atrophy (dSMA) prompted us to screen for TRPV4 mutations in a small group of children with compatible phenotype. In a girl with dSMA and vocal cord paralysis, we detected a new variant (p.P97R) localized in the cytosolic N-terminus of the TRPV4 protein, upstream of the ankyrin-repeat domain, where the great majority of disease-associated mutations reside. In another child with congenital dSMA, in this case associated with bone abnormalities, we detected a previously reported mutation (p.R232C). Functional analysis of the novel p.P97R mutation in a heterologous system demonstrated a loss-of-function mechanism. Protein localization studies in muscle, skin, and cultured skin fibroblasts from both patients showed normal protein expression. No TRPV4 mutations were detected in four children with dSMA without bone or vocal cord involvement. Adding to the clinical and molecular heterogeneity of TRPV4-associated diseases, our results suggest that molecular testing of the TRPV4 gene is warranted in cases of congenital dSMA with bone abnormalities and vocal cord paralysis.

Radiology of vocal cord palsy.

Imaging is frequently carried out for the investigation of vocal cord palsy, and cord palsy needs to be considered as a sign of a more sinister underlying disease. The reporting radiologist needs to be aware of the relevant anatomy of the vagus and recurrent laryngeal nerves so that the responsible disease process can be identified. It is also important to recognize situations where a lesion at the level of the brainstem or skull base may be responsible, as a different imaging strategy often needs to be adopted in these cases. This review will also consider the laryngeal signs of cord palsy, as although cord palsy is often diagnosed clinically, up to 30% of cases may be asymptomatic and clinically unsuspected.