Recurrent laryngeal motor nerve conduction studies in a rat model: Establishing an objective measure for investigating laryngeal innervation.

INTRODUCTION/AIMS: Disease or injury can cause neuromuscular changes to the larynx that can affect voice, breathing, and swallowing. Motor nerve conduction studies have had limited use in the study of laryngeal neurophysiology, despite their importance in other anatomic sites. The aim of this study was to explore the feasibility of performing recurrent laryngeal motor nerve conduction studies (rlMNCS) in a rat model. METHODS: rlMNCS were performed in 15 rats under anesthesia. A bipolar stimulating electrode was placed on the recurrent laryngeal nerve (RLN) 5 mm below the cricoid cartilage. Via direct laryngoscopy, a recording electrode was placed transorally into the thyroarytenoid muscle. The RLN was maximally stimulated to determine the compound muscle action potential (CMAP). Three consecutive trials were averaged. RESULTS: The mean stimulating threshold to the RLN to achieve a CMAP from the thyroarytenoid was 1.7 ± 0.6 mA. RLN stimulation caused a visible adductor twitch of the vocal fold in all animals. The mean negative amplitude was 2.0 ± 0.8 mV, and the total area was 1.0 ± 0.4 mV ms. The CMAP latency and negative duration were 1.0 ± 0.1 ms and 0.9 ± 0.2 ms, respectively. DISCUSSION: rlMNCS are feasible and may be useful in understanding laryngeal neurophysiology with disease or injury. This work could provide a tractable animal model for studying and monitoring treatment of neuromuscular conditions affecting voice, breathing, and swallowing.

Pediatric Salivary Gland Pathology.

Benign and malignant salivary gland disorders are uncommon in the pediatric population; however, these can be frequently seen in pediatric otolaryngology or oral and maxillofacial surgery practices. The astute clinician should be aware of the clinical presentation, diagnosis, and management options for common inflammatory, infectious, benign, and malignant disorders of salivary glands.

Neurophysiology of the Superior Laryngeal Nerve in an In Vivo Rat Model.

OBJECTIVE: The superior laryngeal nerve (SLN) is fundamental in laryngeal sensation, cough reflex, and pitch control. SLN injury has substantial consequences including altered sensation, aspiration, and dysphonia. To date, in vivo measurement of the SLN remains elusive. The purpose of this study was to assess the feasibility of recording motor and sensory evoked potentials in a rat SLN model. METHODS: Twenty-two rat hemi-laryngeal preparations (n = 11) were obtained from 4-month-old Sprague-Dawley rats and included in this study. Compound motor action potentials (CMAPs) and motor unit number estimation (MUNE) were calculated by stimulating the SLN at the point of medial extension near the carotid artery and by placing a recording electrode on the cricothyroid muscle. Sensory response was determined through stimulation of the SLN and laryngoscopic visualization of a laryngeal adductor reflex (LAR). SLN and cricothyroid muscle cross-sections were stained and histologic morphometrics were quantified. RESULTS: Laryngeal evoked potentials were successfully obtained in all trials. Mean CMAP latency and negative durations were 0.99 ± 0.57 ms and 1.49 ± 0.57 ms, respectively. The median MUNE was 2.06 (IQR 1.88, 3.51). LAR was induced with a mean intensity of 0.69 ± 0.20 mV. Mean axon count, myelin thickness, and g-ratio were 681 ± 192.2, 1.72 ± 0.26, and 0.45 ± 0.04, respectively. CONCLUSIONS: This study demonstrates the feasibility of recording evoked response potentials following SLN stimulation. We hypothesize that this work will provide a tractable animal model to study changes in laryngeal sensation and cricothyroid motor function with aging, neurodegenerative disease, aspiration, or nerve injury. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1778-1784, 2024.

Quantitative Evaluation of Vocal Bowing Following Bilateral Thyroplasty in Age-Related Vocal Atrophy.

OBJECTIVE: Age-related vocal atrophy (ARVA) is associated with vocal fold bowing, persistent glottal gap during phonation, and dysphonia. Bilateral medialization thyroplasty is sometimes performed in patients with ARVA to improve vocal fold closure and voice. We set out to quantify stroboscopic changes in vocal fold bowing, glottal closure, and abduction angle following bilateral thyroplasty and determine how these changes affect voice quality among patients with ARVA. METHODS: Fifteen individuals with ARVA who underwent bilateral medialization thyroplasty were included in this study. Two independent investigators calculated bowing index (BI), normalized glottal gap area (NGGA), and maximum abduction angle from laryngostroboscopic exams using ImageJ™. Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) and patient-reported measures were collected before and after thyroplasty. RESULTS: Thyroplasty resulted in a 10-point improvement in overall CAPE-V (Mean dif -10; 95% CI -17, -3.3, p < 0.01) and VHI-10 (mean dif -3.8; 95% CI -9.8, 2.3, p = 0.19, n = 8). NGGA and BI significantly decreased following surgery (mean dif -78; 95% CI -155, -1.5, p = 0.05; and mean dif -2.1; 95% CI -2.4, -0.84, p < 0.01, respectively). BI correlated with CAPE-V scores (r = 0.66, 95% CI 0.22, 0.87, p < 0.01). When considering the normalized combined contributions of both NGGA and BI, there was a stronger correlation in CAPE-V scores (r = 0.87, 95% CI 0.50, 0.97, p < 0.01) compared with either measure alone. CONCLUSIONS: Thyroplasty resulted in a decrease in vocal fold bowing, glottal gap area, and CAPE-V scores in patients with ARVA. Correction of vocal bowing and glottal gap, following bilateral thyroplasty, improved voice measures following surgery. Quantitative evaluation of vocal fold morphology may be valuable when assessing the severity and treatment-response in patients with ARVA following bilateral thyroplasty. Laryngoscope, 134:835-841, 2024.

Quantifying Health Utility of Age-related Vocal Atrophy.

OBJECTIVE: Age-related vocal atrophy (ARVA) negatively impacts voice and quality of life (QOL). This study aims to determine utility-based QOL in ARVA patients, correlate findings with traditional patient-reported outcome measures (PROMs), and generate utility-based inferences. METHODS: Forty ARVA patients were prospectively recruited from a tertiary care center. Health utility was measured using standard gamble, time trade-off, and visual analog scale, assessing participants' current health states relative to defined comparison states (blindness/death). Traditional PROMs (Voice Handicap Index-10 [VHI-10] and Voice-Related Quality of Life Scale [V-RQOL]) were also collected. Descriptive and paired statistics were performed to determine health utility, and Pearson correlation assessed the association between PROMs and health utilities. RESULTS: Mean health utility in ARVA was 0.84 ± 0.22, 0.88 ± 0.17, and 0.62 ± 0.25 using standard gamble, time trade-off, and visual analog scale, respectively. There were positive correlations between V-RQOL and time trade-off (r = 0.66; p < 0.0001) as well as with standard gamble (r = 0.47; p = 0.002). Participants with ARVA reported no difference in health utility impact between their voice impairment and monocular blindness (Mean dif 10.9; 95% CI -1.6, 23.5; p = 0.101). Patients with ARVA were willing to part with an average 4.6 ± 6.1 years of life to restore normal voice. CONCLUSIONS: ARVA patients view their voice impairment as a significant health decrement, comparable to monocular blindness. These findings underscore the substantial impact of ARVA on QOL and highlight the need for continued research and new therapies. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Recordings of Superior Laryngeal Nerve Sensory Nerve Action Potentials in a Rat Model.

OBJECTIVE: Superior laryngeal nerve (SLN) function is critical to laryngeal sensation. Sensory dysfunction in the larynx, mediated through the internal branch of the superior laryngeal nerve (iSLN), is thought to occur with aging and neurodegenerative disease. However, objective analysis of iSLN neurophysiology is difficult due to its anatomic location and small diameter. This study measures sensory nerve action potentials (SNAP) from the iSLN in a rat model. METHODS: SNAP data were obtained from two adult rat strains (Sprague-Dawley, SD and Fischer 344 × Brown Norway F1 Hybrid rats, FBN). Evoked responses were obtained by stimulating the main trunk of the SLN and recording the response using a 160-µm cuff electrode placed around the iSLN. SNAP were averaged from 10 stimulations. Laryngeal adductor reflex (LAR) threshold measurements were obtained with stimulation of the iSLN and direct laryngoscopy. The sections of the iSLN were obtained for histologic analysis. RESULTS: SLN-evoked responses were successfully obtained in 18 hemi-laryngeal preparations (SD n = 13 and FBN n = 5) with corresponding LAR threshold measurements. Mean(±SD) SNAP latency, total duration, amplitude, negative durations, and intensity were 2.28 ms (±0.56), 2.13 ms (±0.70), 879 µV (±535), and 0.69 mA (±0.25), respectively. SLN stimulation threshold to elicit an LAR was of 0.84 mA (±0.31). CONCLUSION: It is feasible to record evoked SLN responses in two adult rat strains. This work may lead to a tractable animal model for objective measurements of SLN neurophysiology with various disease states. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Cognition and saccadic eye movement performance are impaired in chronic rhinosinusitis.

BACKGROUND: Patients with chronic rhinosinusitis (CRS) can experience cognitive dysfunction. The literature on this topic mostly reflects patient-reported measurements. Our goal was to assess cognitive function in patients with CRS using objective measures, including saccadic eye movements-a behavioral response reflecting cognitive and sensory information integration that is often compromised in conditions with impaired cognition. METHODS: Participants (N = 24 with CRS, N = 23 non-CRS healthy controls) enrolled from rhinology clinic underwent sinonasal evaluation, quality of life assessment (Sino-nasal Outcome Test 22 [SNOT-22]), and cognitive assessment with the Neuro-QOL Cognitive Function-Short Form, the Montreal Cognitive Assessment (MoCA), and recording of eye movements using video-oculography. RESULTS: Participants with CRS were more likely to report cognitive dysfunction (Neuro-QOL; 45.8% vs. 8.7%; p = 0.005) and demonstrate mild or greater cognitive impairment (MoCA; 41.7% vs. 8.7%; p = 0.005) than controls. Additionally, participants with CRS performed worse on the MoCA overall and within the executive functioning and memory domains (all p < 0.05) and on the anti-saccade (p = 0.014) and delay saccade (p = 0.044) eye movement tasks. Poorer performance on the MoCA (r = -0.422; p = 0.003) and the anti-saccade (r = -0.347; p = 0.017) and delay saccade (r = -0.419; p = 0.004) eye movement tasks correlated with worse CRS severity according to SNOT-22 scores. CONCLUSION: This study is the first to utilize objective eye movement assessments in addition to researcher-administered cognitive testing in patients with CRS. These patients demonstrated a high prevalence of cognitive dysfunction, most notably within executive functioning and memory domains, with the degree of dysfunction correlating with the severity of CRS.

Histopathologic evaluation of Asian-American patients with chronic rhinosinusitis with nasal polyps.

KEY POINTS: Asian-American (AA) patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have comparable rates of tissue eosinophilia compared to Caucasians when defined as >10 eosinophils/high-powered field (HPF). AA patients with CRSwNP have significantly higher incidence of mixed inflammation defined as >10 eosinophils/HPF and >10 neutrophils/HPF.

Postmarketing Reporting of Paxlovid-Related Dysgeusia: A Real-World Pharmacovigilance Study.

OBJECTIVE: A novel COVID-19 therapeutic, nirmatrelvir/ritonavir (Paxlovid), is commonly associated with reports of dysgeusia. The Food and Drug Administration Adverse Event Reporting System (FAERS) database was used to determine the real-world reporting of Paxlovid-associated dysgeusia (PAD), identify associated factors, and describe the relative reporting rates of dysgeusia for Paxlovid compared to other COVID-19 therapeutics (OCT), ritonavir alone, and other protease inhibitors (OPI). STUDY DESIGN: Observational retrospective. SETTING: Tertiary academic medical center. METHODS: We collected patient and adverse event characteristics reported in the FAERS database between January 1968 and September 2022. Disproportionality analyses were used to compare the reporting of PAD to dysgeusia reported for OCT, ritonavir, and OPI. RESULTS: 345,229 adverse events were included in the present study. Dysgeusia was a frequently reported Paxlovid-associated adverse event (17.5%) and was associated with nonserious COVID-19 infection (reporting odds ratio [ROR] 1.4; 95% confidence interval [CI] 1.2, 1.7) and female sex (ROR = 1.7; 95% CI 1.6, 1.9). Paxlovid was more likely to be associated with the reporting of dysgeusia compared to OCT (ROR 305.4; 95% CI 164.1, 568.5), ritonavir (ROR 28.0; 95% CI 24.1, 32.7), and OPI (ROR 49.0; 95% CI 42.8, 56.1). CONCLUSION: Dysgeusia is much more likely to be reported by patients receiving Paxlovid than those receiving OCT, ritonavir alone, or OPI. These findings suggest a potential mechanism of dysgeusia that causes distorted taste out of proportion to the background effects of COVID-19 infection and specific to nirmatrelvir. Future studies are needed to determine the underlying pathophysiology and long-term clinical implications for patients who report dysgeusia with Paxlovid.

Endotype evaluation of Hispanic/Latinx-American patients with chronic rhinosinusitis with nasal polyps.

KEY POINTS: Hispanic-American patients with chronic rhinosinusitis with nasal polyps have a comparable level of tissue eosinophilia compared to their Caucasian counterparts in the United States. Mixed inflammation involving both neutrophils and eosinophils is more common in this population compared to Caucasians. Findings from this study may indicate that Hispanic-American patients have a unique endotype or endotypes that deserves further investigation.