Superior Laryngeal Nerve Research Articles

Anatomical Variations of the External Branch of the Superior Laryngeal Nerve and its Correlations with the Superior Thyroid Artery and the Upper Pole of the Thyroid Gland: A Review of the Literature

Injury to the external branch of the superior laryngeal nerve (EBSLN) following thyroid or parathyroid surgery often results in devastating voice changes especially noticed by patients who use their voice professionally. The external branch arises from the vagus nerve which provides the motor supply to the cricothyroid muscle, an exclusive tensor of the vocal cords. The course of the EBSLN is subject to great anatomic variability. Damage to the nerve occurs during improper ligation of superior thyroid vessels close to the upper pole of thyroid gland in up to 58% of patients undergoing thyroid surgery. Thus, a thorough knowledge of the anatomy of the EBSLN and its variations, is essential requirement to minimize iatrogenic complications during surgery of the neck. Additionally, nerve monitoring methods have been developed to facilitate the localisation of the nerve, decreasing the possibility of nerve injury during thyroid surgery. The aim of this study is to analyze and review the anatomical variations of the EBSLN and its correlations with the superior thyroid artery and the upper pole of the thyroid gland. The literature search was performed during the period from February 1992 through November 2021. The position of the EBSLN was classified according to the Cernea and Kierner classification. Based on this classification, type 2a variant of EBSLN was the commonest followed by type 1. In addition, neuromonitoring allowed a higher identification rate than the visual identification.

Evaluation of intraoperative neuromonitoring (IONM) data with the Mainz IONM Quality Assurance and Analysis tool

Abstract Background Intraoperative neuromonitoring is widely used in thyroid and parathyroid surgery to prevent unilateral and especially bilateral recurrent nerve paresis. Reference values for amplitude and latency for the recurrent laryngeal nerve and vagus nerve have been published. However, data quality measures that exclude errors of the underlying intraoperative neuromonitoring (IONM) data (immanent software errors, false data labelling) before statistical analysis have not yet been implemented. Methods The authors developed an easy-to-use application (the Mainz IONM Quality Assurance and Analysis tool) using the programming language R. This tool allows visualization, automated and manual correction, and statistical analysis of complete raw data sets (electromyogram signals of all stimulations) from intermittent and continuous neuromonitoring in thyroid and parathyroid surgery. The Mainz IONM Quality Assurance and Analysis tool was used to evaluate IONM data generated and exported from ‘C2’ and ‘C2 Xplore’ neuromonitoring devices (inomed Medizintechnik GmbH) after surgery. For the first time, reference values for latency and amplitude were calculated based on ‘cleaned’ IONM data. Results Intraoperative neuromonitoring data files of 1935 patients consecutively operated on from June 2014 to May 2020 were included. Of 1921 readable files, 34 were excluded for missing data labelling. Automated plausibility checks revealed: less than 3 per cent device errors for electromyogram signal detection; 1138 files (approximately 60 per cent) contained potential labelling errors or inconsistencies necessitating manual review; and 915 files (48.5 per cent) were indeed erroneous. Mean(s.d.) reference onset latencies for the left vagus nerve, right vagus nerve, recurrent laryngeal nerve, and external branch of the superior laryngeal nerve were 6.8(1.1), 4.2(0.8), 2.5(1.1), and 2.1(0.5) ms, respectively. Conclusion Due to high error frequencies, IONM data should undergo in-depth review and multi-step cleaning processes before analysis to standardize scientific reporting. Device software calculates latencies differently; therefore reference values are device-specific (latency) and/or set-up-specific (amplitude). Novel C2-specific reference values for latency and amplitude deviate considerably from published values.

Study on Microsurgical Anatomy of External Branch of Superior Laryngeal Nerve Related to Carotid Endarterectomy.

To explore the methods of protecting the external branch of the superior laryngeal nerve during carotid endarterectomy through microsurgical anatomic study of the external branch of the superior laryngeal nerve in cadaveric specimens. A total of 30 cadaveric specimens (60 sides) were dissected to measure the thickness of the external branch of the superior laryngeal nerve. A triangular area was exposed, bounded by the lower border of the digastric muscle superiorly, the medial edge of the sternocleidomastoid muscle laterally, and the upper border of the superior thyroid artery inferiorly. The probability of the occurrence of the external branch of the superior laryngeal nerve in this area was observed and recorded. The distance among the midpoint of the external branch of the superior laryngeal nerve in this area with the tip of the mastoid process and the angle of the mandible as well as the bifurcation of the common carotid artery was measured and recorded. Among 30 specimens of cadaveric heads (60 sides) examined 53 external branches of the superior laryngeal nerve were observed while 7 were absent. Of the 53 branches observed, 5 were located outside the anatomic triangle region mentioned above, while the remaining 48 branches were located within the anatomic triangle region with a probability of ~80%. The thickness of the midpoint of the external branches of the superior laryngeal nerve within the anatomic triangle region was 0.93mm (0.72-1.15mm [±0.83 SD]), located 0.34cm [-1.62-2.43cm (±0.96 SD)] posterior to the angle of the mandible, 1.28cm (-1.33 to 3.42cm (±0.93 SD)] inferiorly; 2.84cm (0.51-5.14cm±1.09 SD) anterior to the tip of the mastoid process, 4.51cm (2.82-6.39cm±0.76 SD) inferiorly; 1.64cm [0.57-3.78cm (±0.89 SD)] superior to the bifurcation of the carotid artery. During carotid endarterectomy procedure, using the cervical anatomic triangle region, as well as the angle of the mandible, the tip of the mastoid process, and the bifurcation of the carotid artery as anatomic landmarks, is of significant clinical importance for protecting the external branches of the superior laryngeal nerve.

Comparison of intraoperative neural monitoring between endoscopic transoral and bilateral axillo-breast approach thyroidectomy.

The use of intraoperative neuromonitoring (IONM) during endoscopic thyroidectomy has not been fully explored, with limited studies focusing solely on the recurrent laryngeal nerve (RLN) and neglecting the external branch of the superior laryngeal nerve (EBSLN). This study aimed to compare the effectiveness of IONM in two endoscopic thyroidectomy techniques, namely the transoral and bilateral axillo-breast approach (BABA). We retrospectively reviewed patients who underwent endoscopic thyroidectomy with IONM and compared the outcomes between those who underwent different surgical techniques (transoral or BABA). We recorded the detection method and identification rate of the EBSLN and RLN, along with the amplitude and latency of the evoked potential. We monitored 98 nerves at risk (NAR) from 74 patients (60 and 38 in the transoral and BABA groups, respectively). Almost all EBSLNs were identified using electromyography (EMG) signals and/or cricothyroid muscle twitches, except for one patient in the transoral group who developed EBSLN palsy. Patients in the transoral group were more likely to have the sternothyroid muscle divided (75.0% vs. 15.8%, p < 0.001) and had a lower rate of visual recognition of the EBSLN fibers (10.0% vs. 31.6%, p = 0.007) than did those in the BABA group. All RLNs were identified in both groups; however, patients in the BABA group had a relatively higher rate of post-dissection amplitude reduction > 50% (15.8% vs. 5.0%, p = 0.072), and one patient had transient RLN palsy. Both the EBSLN and RLN could be adequately identified and monitored during endoscopic transoral and BABA thyroidectomies using IONM.

Revisiting Loré's retrograde thyroidectomy from the perspective of preserving the external branch of the superior laryngeal nerve.

Injury to the external branches of the superior laryngeal nerve (EBSLN) is the main reported cause of inexplicable post-thyroidectomy dysphonia (PTD) without recurrent laryngeal nerve (RLN) injury. Loré proposed a retrograde thyroidectomy (RT) technique in which the superior pole is dissected as a final step after the Berry ligament division, making this approach advantageous for protecting the EBSLN. However, evidence of this protective effect remains insufficient. We aimed to evaluate EBSLN function following RT and conventional thyroidectomy (CT) using postoperative electromyography (EMG). This is a retrospective cohort study conducted at a single tertiary center. Consecutive patients who had undergone CT or RT were included. Bilateral EMG of the cricothyroid muscle was performed 2-3 months postoperatively in all patients. Patient characteristics, postoperative findings of bleeding events, drain amount, hypocalcemia, calcium replacement, RLN function, and EBSLN function were thoroughly reviewed and compared between the two surgical approaches. Abnormalities in the EMG findings were reported based on the wave configuration, and the results were graded into four categories. Seven hundred and thirty-one consecutive patients who underwent CT (n=341), or RT (n=390) were included, and a total of 1,179 RLNs and EBSLNs were at risk in CT (n=601) and RT (n=578). The CT and RT groups had similar clinical characteristics and surgical data. Two groups presented similar postoperative results for bleeding incidence, drain amount, and hypocalcemia. All RLNs were identified in both groups and their permanent function was preserved. EBSLN was significantly less frequently identified in the surgical field during RT than it was during CT (0.3% vs. 4.2%, respectively; P<0.001). Abnormal rates of postoperative EMG on the EBSLN were significantly lower in the RT group than in the CT group (1.7% vs. 7.8%, respectively; P<0.001), while the CT group presented with a higher grade of abnormal EMG (P<0.001). The RT technique may be beneficial for preserving EBSLN function. Meticulous capsular dissection and appropriate traction of the upper pole facilitated by RT are crucial for decreasing the risk of EBSLN injury, which can be achieved without directly identifying the nerve.

Lateral Approach to Thyroid Surgery: An Alternative Open Thyroidectomy Technique

Background: Thyroidectomy is one of the common surgical procedures for thyroid related various pathology. Midline approach is the classical and common in which thyroid gland is approached after splitting the strap muscles in midline. The objective of this research is to elaborate the surgical technique of lateral thyroid approach for hemi-thyroidectomy, also to measure the efficacy in preserving the important anatomical structures and to assess the complications. Materials: A cross-sectional study was conducted in the department of ENT-Head and Neck Surgery of Bharatpur Hospital, Chitwan, Nepal during January 2019 to March 2021. Benign thyroid diseases that required hemi-thyroidectomy were included in this study. Surgical technique was discussed with special focus for access of superior pedicle and preservation of important anatomical structures. Results: Among 36 cases most of those 16(44.4%) were operated after 1 year of disease occurrence. Not a single case was undergone strap muscle cutting or sacrifice of superior belly of omohyoid muscle. Recurrent laryngeal nerve was found in 94.4% (33 cases). External branch of superior laryngeal nerve (EBSLN) was in 91.7 %( 33) cases. Superior parathyroid glands were found in majority of the cases but not found in 8.3 %( 3). Inferior parathyroid glands were found in all cases. Post-operative drainage was 38 ml(mean). Conclusion: Vital structures were preserved in more than 90% cases and major complication occurred in none of the cases. We conclude that this approach is good, safe and comfortable to the surgeon.

Upper cervical anterior fusion to C2 with temporary infrahyoid muscle detachment: a clinical case series and description of surgical technique

BackgroundAnterior cervical spine surgery to C2 (ACSS-C2) is a challenging procedure that often results in postoperative persistent dysphagia or dyspnea due to injury to the internal branch of the superior laryngeal nerve (iSLN) or the relatively narrow and soft oropharynx. This study aimed to describe the surgical outcomes of our modified approach with temporary infrahyoid muscle detachment during ACSS-C2.MethodsPatients who underwent ACSS-C2 at two institutions between June 2015 and January 2022 were prospectively enrolled. Intraoperatively, we performed temporary detachment of the infrahyoid muscle from the hyoid bone to improve laryngeal mobility and accessibility to C2. This procedure also allowed for the easy identification and preservation of the iSLN. We retrospectively investigated the surgery-related complications and outcomes of bony fusion.ResultsTwelve patients were enrolled in this study; five and seven patients underwent single- and multi-level fusion surgery, respectively. Intraoperative preservation of the iSLN and proper visualization of C2 were achieved in all cases. Subsequent decompression and instrumentation were successfully performed. Two older patients (78 and 81 years) who underwent multi-level fusion experienced transient postoperative dysphagia. None of the patients required unplanned reintubation or revision surgery because of instrumentation failure. Solid bony fusion was achieved in all cases.ConclusionsOur modified approach with temporary infrahyoid muscle detachment during ACSS-C2 reduces the incidence of postoperative persistent dysphagia and dyspnea. However, in older patients at high risk for postoperative dysphagia, multi-level fusion should be avoided, and alternative procedures should be considered.

Ultrasound-guided internal laryngeal nerve block for suppression of postoperative cough in a child undergoing endoscopic microlaryngeal surgery.

Ultrasound-guided internal laryngeal nerve block for suppression of postoperative cough in a child undergoing endoscopic microlaryngeal surgery.

Effectiveness of the recurrent laryngeal nerve monitoring during endoscopic thyroid surgery: systematic review and meta-analysis.

Thyroid disease is a common endocrine disorder, and thyroid surgeries and postoperative complications have increased recently. This study aimed to explore the effectiveness of intraoperative nerve monitoring (IONM) in endoscopic thyroid surgery using subgroup analysis and determine confounding factors. Two researchers individually searched for relevant studies published till November 2022 in the PubMed, Embase, Web of Science and Cochrane Library databases. Eventually, eight studies met the inclusion criteria. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. The odds ratio or risk difference were calculated using fixed-effects models. The weighted mean difference of continuous variables was calculated. Subgroup analysis was performed according to the disease type. Eight eligible papers included 915 patients and 1242 exposed nerves. The frequencies of transient, permanent and total recurrent laryngeal nerve (RLN) palsy were 2.64, 0.19 and 2.83%, respectively, in the IONM group and 6.15, 0.75 and 6.90%, respectively, in the conventional exposure group. In addition, analysis of the secondary outcome indicators for the average total length of surgery, localisation time of the RLN, recognition rate of the superior laryngeal nerve and length of incision revealed that IONM reduced the localisation time of the RLN and increased the identification rate of the superior laryngeal nerve. Subgroup analysis showed that IONM significantly reduced the incidence of RLN palsy in patients with malignancies. The use of IONM significantly reduced the incidence of transient RLN palsy during endoscopic thyroid surgery, but it did not significantly reduce the incidence of permanent RLN palsy. However, the reduction in the total RLN palsy was statistically significant. In addition, IONM can effectively reduce the location time of the RLN and increase the recognition rate of the superior laryngeal nerve. Therefore, the application of IONM for malignant tumours is recommended.

Impact of Sternothyroid Muscle Division on Patient-Reported Voice Outcomes After Thyroid Surgery: A Prospective Study.

Division of the sternothyroid muscle during thyroidectomy is a widely accepted surgical technique to provide improved exposure of the thyroid gland, thus facilitating the ligation of superior pole vessels and identification of the laryngeal nerves. However, few have examined the impact on voice outcomes. We evaluate the impact of sternothyroid muscle division on patient-perceived voice outcomes after thyroidectomy. Prospective cohort study. Tertiary academic institution. A prospective cohort study was conducted comparing pre- and postoperative voice outcome data after thyroidectomy, measured using Voice Handicap Index-10. The cohort of 109 patients underwent lobectomy or total thyroidectomy by a single surgeon at 1 institution. The sternothyroid muscle was fully divided in all surgeries. The integrity of the recurrent laryngeal and external branches of the superior laryngeal nerve was assessed using intraoperative nerve monitoring and postoperative laryngoscopy. Pre- and postoperative Voice Handicap Index-10 scores were compared. No statistically significant difference was found between total pre- and postoperative Voice Handicap Index-10 scores (μpreop = 1.92, μpostop = 1.83, p = .87). There were no questions yielding statistically significant responses between pre- and postoperative groups. This was consistent regardless of whether the sternothyroid muscle was cut unilaterally or bilaterally. Men showed a statistically significant improvement in score after surgery. These findings support no difference in postoperative voice outcomes after the intraoperative division of the sternothyroid muscle. This supports the usage of this technique as a safe means to facilitate exposure during thyroid surgery and will serve as important information to guide intraoperative surgical decision-making.

Thyroidectomy With or Without Nerve Identification: A Personal Experience and Technique.

Careful and precise dissection of the gland, away from the typical trajectory of the recurrent and external laryngeal nerves, poses a minimal or similar risk of nerve injuries compared to directly visualizing and identifying the nerves. In a randomized controlled study involving 150 patients with various thyroid disorders who underwent different surgical procedures (total, near total, and hemi thyroidectomy), the patients were randomly assigned into two groups using a coin toss. The first group (G1) consisted of 75 patients who underwent thyroidectomy with nerve visual identification, while the second group (G2) comprised 75 patients without the requirement of nerve visualization. The aim was to determine the method with a lower risk of complications. The incidence of external laryngeal nerve palsy (ELNP) was found to be higher in G1 patients compared to G2 patients (5.3% vs2%), while no cases of permanent recurrent laryngeal nerve (RLN) palsy were observed in either group. The frequency of total nerve injury was higher in G1, with 14 patients (10.2%), compared to G2, with eight patients (5.3%). However, there was no significant association between nerve identification and the rate of nerve injury (P value = 0.452). Among the different surgical procedures, total thyroidectomy for toxic goiter was the most common operation associated with transient external laryngeal nerve (TELN) injury and permanent external laryngeal nerve (PELN) injury. By employing meticulous dissection techniques in proximity to the thyroid capsule, experienced surgeons can effectively reduce the risk of nerve injury, even in the absence of direct nerve visualization.

To Identify the Dangerous Length of External Laryngeal Nerve In Relation to Thyroid Pole In Cadaveric Thyroid Glands

Introduction: The external laryngeal nerve passes through the “space of Reeve” cricothyroid space. It has also been described as lying in the Joll’s triangle. It is often inadvertently neglected during thyroid surgeries. It has been named after a singer who lost her voice after a thyroid surgery, as the “nerve of Galli Curci” Aim: To identify the dangerous length of the external laryngeal nerve in relation to the thyroid pole. Material and Methods: Fifty laryngeal nerves were dissected using conventional method of dissection, in twenty-five embalmed cadavers used for teaching purpose at Karpaga Vinayaga Institute of Medical Sciences and Research, Madurantakam. The observations were noted and photographs taken. The course and relations were carefully noted. Results: 38 specimens (76%) had the superior laryngeal nerve measuring 4cm. in 8 specimens (16%) it was 3.5 cm and in 04 specimens (8%) it measured 3.8 cm. It was observed that the external laryngeal nerve crossed the superior thyroid pole at less than 1cm only in three (6%) of the fifty nerves. Conclusions: The critical length of the nerve would be dangerous if the nerve crosses the superior thyroid pedicle close to thyroid pole at less than 1 cm. The consequences of neglecting the critical length would injure the nerve and cause dysphonia or raspy voice. KEY WORDS: Thyroid gland, Artery, Nerve, Laryngeal nerve, Pole of the thyroid.

갑상선 수술 중 신경모니터링의 훈련 프로그램 개발

Intraoperative neuromonitoring (IONM) for the recurrent laryngeal nerve and the external branch of the superior laryngeal nerve during thyroidectomy may be helpful to identify and preserve the nerves and let the surgeon predict the postoperative neural function. International Neural Monitoring Study Group (INMSG) recently presented the recommended training course for IONM during thyroidectomy. Based on such training course provided by an expert group, trainees may conduct standardized IONM and experience the technique's advantages. This review article presents the recommended guidelines to prepare for a training course in IONM during thyroidectomy.

Double-scope endoscopic submucosal dissection of superficial laryngeal cancer to preserve the superior laryngeal nerve.

Double-scope endoscopic submucosal dissection of superficial laryngeal cancer to preserve the superior laryngeal nerve.

Atropine facilitates water-evoked swallows via central muscarinic receptors in anesthetized rats.

Anticholinergic medication causes impaired swallowing with hyposalivation. However, the underlying mechanisms by which these drugs modulate the swallowing reflex remain unclear. This study investigated the effects of the muscarinic acetylcholine receptor (mAChR) nonspecific antagonist atropine on the initiation of swallowing. Experiments were performed on 124 urethane-anesthetized rats. A swallow was evoked by either topical laryngeal application of a small amount of distilled water (DW), saline, citric acid, or capsaicin; upper airway distention with a continuous airflow; electrical stimulation of the superior laryngeal nerve (SLN); or focal microinjection of N-methyl-d-aspartate (NMDA) into the lateral region of the nucleus of the solitary tract (L-nTS). Swallows were identified by electromyographic bursts of the digastric and thyrohyoid muscles. Either atropine, the peripheral mAChR antagonist methylatropine, or antagonists of mAChR subtypes M1-M5 were intravenously delivered. Atropine at a dose of 1 mg/kg increased the number of DW-evoked swallows compared with baseline and did not affect the number of swallows evoked by saline, citric acid, capsaicin, or upper airway distention. Methylatropine and M1-M5 antagonists did not significantly change the number of DW-evoked swallows. Bilateral SLN transection completely abolished DW-evoked swallows, and atropine decreased the swallowing threshold of SLN electrical stimulation. Finally, microinjection of NMDA receptor antagonist AP-5 into the L-nTS inhibited DW-evoked swallows, and atropine facilitated the initiation of swallowing evoked by NMDA microinjection into this region. These results suggest that atropine facilitates DW-evoked swallows via central mAChR actions.NEW & NOTEWORTHY Atropine facilitated the distilled water (DW)-evoked swallows in anesthetized rats. Atropine decreased the swallowing threshold evoked by electrical stimulation of the superior laryngeal nerve, which is a primary sensory nerve for the initiation of DW-evoked swallows. Atropine facilitated the swallows evoked by N-methyl-d-aspartate microinjection into the lateral region of the nucleus of the solitary tract, which is involved in the DW-evoked swallows. We speculate that atropine facilitates the DW-evoked swallows via central muscarinic receptor actions.

Effects of interferential current electrical stimulation (IFCS) on mastication and swallowing function in healthy young adults: A preliminary study.

This study aimed to investigate the effects of interferential current electrical stimulation (IFCS) on masticatory and swallowing function. Twenty healthy young adults were enrolled. The measurement items were spontaneous swallowing frequency (SSF), voluntary swallowing frequency (VSF), saliva secretion volume (SSV), glucose elution volume (GEV), and velocity of chew (VOC). All participants underwent both IFCS and sham stimulation (without stimulation, sham). Two sets of independent IFCS electrodes were placed on the bilateral neck. The precise location of the upper electrodes was just below the angle of the mandible, while the lower electrodes were placed at the anterior border of the sternocleidomastoid muscle. The intensity of IFCS was determined to be one level below the perceptual threshold that all participants felt discomfort. Statistical analysis was performed using a two-way repeated measures analysis of variance. For IFCS, the results of each measurement before and during stimulation were SSF: 1.16 and 1.46, VSF: 8.05 and 8.45, SSV: 5.33 and 5.56 g, GEV: 171.75 and 208.60 mg/dL, and VOC: 87.20 and 95.20, respectively. SSF, GEV, and VOC during stimulation were significantly increased by IFCS (SSF, p = .009; GEV, p = .048; and VOC, p = .007). Following sham stimulation, the results were SSF: 1.24 and 1.34, VSF: 7.75 and 7.90, SSV: 5.65 and 6.04 g, GEV: 176.45 and 187.35 mg/dL, and VOC: 91.35 and 88.25, respectively. While no significant differences were observed in the sham group, our findings suggest that IFCS of the superior laryngeal nerve may impact not only the swallowing function but also the masticatory function.

Developing Targeted Optogenetic Stimulation Approaches to Preserve Upper Airway Function in Amyotrophic Lateral Sclerosis (ALS) Using a Translational Mouse Model

Amyotrophic lateral sclerosis (ALS) results in debilitating upper airway (swallowing and breathing) impairment that profoundly degrades quality of life while increasing the risk of death by almost eight-fold. The underlying cause has been attributed to degeneration of the hypoglossal lower motor neurons (XII LMNs) that control tongue movement; therefore, treatment efforts are focused on slowing XII LMN degeneration. However, there is growing evidence that ALS is not a pure motor neuron disease – it also affects sensory neurons, including those in the nucleus tractus solitarius (NTS) involved in autonomic regulation of swallowing and breathing. We propose that upper airway impairment in ALS may be more effectively treated using sensorimotor approaches that collectively target XII LMNs and the NTS. Here, we are leveraging a translational mouse model of ALS (low copy number SOD1-G93A; LCN-SOD1) that we have shown develops progressive tongue atrophy, XII LMN degeneration, and “motor” dysphagia (slower tongue motility and swallow rates) resembling human ALS. These mice also show clinicopathological evidence of “sensory” dysphagia, specifically a higher swallow threshold (assessed via electrical stimulation of superior laryngeal nerve afferents) and degeneration of the NTS. Using this model, we have been developing tools and procedures to investigate the therapeutic effects of optogenetic stimulation (opto-stim) of XII LMNs and the NTS during voluntary swallow-related behaviors (drinking, eating, grooming) vs. spontaneous breathing in LCN-SOD1 mice. We have already achieved robust expression of the excitatory opsin channelrhodopsin (ChR2) in XII LMNs via adeno-associated virus delivery into the genioglossus muscle or XII nucleus. ChR2 transfection of XII LMNs was well-tolerated, without adverse effects on swallowing/breathing, general health, and survival. Functionally, XII LMN opto-stim evoked robust tongue protrusion (i.e., genioglossus contraction) in anesthetized mice and slowed lick rate during voluntary drinking in awake mice, which we hypothesize is due to resistive force against tongue movement, similar to resistance exercise. Currently, we are exploring the effects of opto-stim (10 ms pulses at 40 or 80 Hz in trains of 1 s ON/OFF for up to 1 h, 2X/wk) as a tongue resistance exercise in pre-clinical LCN-SOD1 mice. In parallel, we are also developing procedures for targeted opsin expression in the NTS via direct injection vs. pharyngeal mucosa application. We hypothesize that NTS opto-stim, in contrast to XII LMN, will assist swallowing by lowering the sensory threshold to unleash higher swallow rates. We propose these novel sensorimotor opto-stim approaches could ultimately translate into minimally invasive targeted treatments for upper airway impairment in ALS patients. This project is funded by NIH R21 NS123761 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Response patterns of NTS neurons during electrical stimulation of the superior laryngeal nerve: Influence of codeine

Electrical or mechanical activation of laryngeal afferents elicits the laryngeal adductor reflex (LAR), an airway defensive behavior that adducts the vocal folds to protect the airway from aspiration. This behavior is mediated, in part, by neurons in the NTS (nucleus of the solitary tract) and is sensitive to suppression by codeine. We hypothesized that NTS neuron responses to electrical stimulation of the superior laryngeal nerve (SLN) would be reduced by codeine, consistent with an action of the drug at this level of the brainstem to suppress the LAR. We recorded extracellular activity of multiple NTS neurons simultaneously in three anesthetized, spontaneously breathing cats using multiple microelectrode arrays. We also recorded bilateral EMG activity of upper airway and chest wall muscles. The neurons were tested with electrical stimulation of the SLN (2 Hz, 0.1 ms pulse duration, 1.5X threshold for inducing the LAR) during vehicle and a cumulative dose response to codeine (0.1-10.0 mg/kg iv). A total of 35 NTS neurons were recorded; some were identified as premotor to laryngeal or upper airway motoneuron pools by spike triggered averaging. Prior to codeine administration, approximately 30% of cells had short latency excitatory responses to electrical stimulation of the SLN; no inhibitory responses were observed. After codeine doses, changes in spontaneous activity were observed in most neurons (~80%). In response to codeine, both enhancement and suppression of short latency excitatory responses were observed in cells that were excited by SLN stimulation during vehicle. The data support complex actions of codeine on NTS neurons that do not easily account for opioid-suppression of the LAR. T32 HL134621, and NIH HL155721 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Superior Laryngeal Nerve Block in Transcutaneous Vocal Fold Injection: A Pilot Study

Topical lidocaine remains the mainstay for anesthesia in transcutaneous vocal fold injection (VFI). While using topical lidocaine, laryngologists sometimes encounter uncontrolled reflexes or poor compliance. Superior laryngeal nerve block (SLNB) provides deep and rapid anesthesia on the larynx above the vocal folds and abolishes the glottic closure reflex. Herein, we present a pilot study to evaluate the feasibility and safety of SLNB for transcutaneous VFI and explored its usefulness. Fifty-nine patients were prospectively anesthetized with SLNB during transcutaneous VFI for unilateral vocal fold paralysis. In the SLNB group, 0.5 to 1 mL of 2% lidocaine was infiltrated on bilateral SLNs through the thyrohyoid membrane. As the control group, we included previous 47 patients who underwent VFI with topical lidocaine. In the control group, 10% lidocaine spray was applied to the laryngopharyngeal mucosa. Demographic data, laryngeal exposure, patient compliance, procedural interruption, and complications were investigated. Patient compliance was evaluated based on the frequency of cough and swallowing during VFI procedures. SLNB enabled endoscopic contact on the epiglottis and pharyngeal wall without gag reflex and provided good exposure of the procedure field on the vocal folds. In the SLNB group, the laryngeal exposure is significantly better than in the control (P=0.005). The frequency of cough and swallowing was significantly lower in the SLNB group than in the control (P < 0.001). The number of procedural interruptions was lower in the SLNB group than in the control (P < 0.001). There was no acute or delayed complication related to SLNB such as bleeding, hematoma, delayed sensory/swallowing problems, or unscheduled hospital visits. SLNB might be safe and effective for anesthesia in transcutaneous VFI. SLNB could be a good anesthetic option for patients with poor compliance despite the sufficient application of topical lidocaine.

Characterization of a chronic cough in cerebellar ataxia, neuropathy, vestibular areflexia syndrome.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a common cause of late-onset ataxia that often presents with chronic cough. This study is the first to characterize the CANVAS cough both objectively and subjectively. A cross-sectional study of 13 patients was conducted. Medical records and available esophagram, modified barium swallow study, esophageal manometry, and video laryngostroboscopy data were reviewed. Leicester cough questionnaire (LCQ) and Eating Assessment Tool-10 were administered to evaluate quality of life (QoL) impairments and dysphagia symptoms, respectively. CANVAS history questionnaire was developed to characterize the clinical course. 92% of patients endorsed chronic cough that preceded gait instability by a median of 16 years. Cough was dry (67%), disturbed sleep (75%), triggered by various factors, including talking, eating, and dry/spicy foods, did not respond to standard reflux therapy, and inconsistently responded to neuromodulators and superior laryngeal nerve injections. Despite perceived cough severity worsening or remaining constant in most patients, no correlation was found between cough duration and total LCQ scores. Patients reported significantly more negative social QoL impacts compared to physical QoL impacts. Ataxia duration and years of cough before ataxia symptoms were directly and inversely correlated with total LCQ scores, respectively. Imaging data revealed esophageal dysmotility (71%), vestibular penetration (57%), vestibular aspiration (14%), supraglottic compression (63%), vocal fold lesions/atrophy (50%), and arytenoid erythema (38%). Chronic cough is a hallmark presenting symptom in CANVAS with predominantly psychosocial QoL effects and unrecognized laryngeal alterations. In cases of idiopathic, refractory chronic cough, genetic testing for CANVAS should be considered, especially in association with sensory, cerebellar, and/or vestibular involvement. VI.