Upper Esophageal Sphincter Response to Laryngeal Adductor Reflex Elicitation in Humans

Objective: The laryngeal adductor reflex (LAR) is an important mechanism to secure the airways from potential foreign body aspiration. An involvement of the upper esophageal sphincter (UES) in terms of a laryngo-UES contractile reflex has been identified after laryngeal mucosa stimulation. However, the LAR–UES relationship has not yet been fully explained. This study aimed to determine the magnitude, latency, and occurrence rate of the UES pressure response when the LAR is triggered in order to elucidate the functional relationship between the larynx and the UES. Methods: This prospective study included seven healthy volunteers (5 female, 2 male, age 22–34 years). Laryngeal penetration was simulated by eliciting the LAR 20 times in each individual by applying water-based microdroplets onto the laryngeal mucosa. UES pressures were measured simultaneously using high-resolution manometry. Results: Two distinct pressure phases (P1, P2) associated with the LAR were identified. P1 corresponded with a short-term UES pressure decrease in two subjects and a pressure increase in five subjects occurring 200 to 500 ms after the stimulus. In P2, all subjects experienced an increase in UES pressure with a latency time of approximately 800 to 1700 ms and an average of 40 to 90 mmHg above the UES resting tone. Conclusion: Foreign bodies penetrating the laryngeal inlet lead to a reflex contraction of the UES. Phase P1 could be a result of vocal fold activity caused by the LAR, leading to pressure changes in the UES. The constriction during P2 could strengthen the barrier function of the UES in preparation to a subsequent cough that may be triggered to clear the airways. Level of Evidence: 4 Laryngoscope, 2020. © 2020 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA)

An actuated larynx phantom for pre-clinical evaluation of droplet-based reflex-stimulating laryngoscopes

The laryngeal adductor reflex (LAR) is an important protective function of the larynx to prevent aspiration and potentially fatal aspiration pneumonia by rapidly closing the glottis. Recently, a novel method for targeted stimulation and evaluation of the LAR has been proposed to enable non-invasive and reproducible LAR performance grading and to extend the understanding of this reflexive mechanism. The method relies on the laryngoscopically controlled application of accelerated water droplets in association with a high-speed camera system for LAR stimulation site and reflex onset latency identification. Prototype laryngoscopes destined for this method require validation prior to extensive clinical trials. Furthermore, demonstrations using a realistic phantom could increase patient compliance in future clinical settings. For these purposes, a model of the human larynx including vocal fold actuation for LAR simulation was developed in this work. The combination of image processing based on a custom algorithm and individual motorization of each vocal fold enables spatio-temporal droplet impact detection and controlled vocal fold adduction. To simulate different LAR pathologies, the current implementation allows to individually adjust the reflex onset latency of the ipsi- and contralateral vocal fold with respect to the automatically detected impact location of the droplet as well as the maximum adduction angle of each vocal fold. An experimental study of the temporal offset between desired and observed LAR onset latency due to image processing was performed for three average droplet masses based on highspeed recordings of the phantom. Median offsets of 100, 120 and 128 ms were found (n=16). This offset most likely has a multifactorial cause (image processing delay, inertia of the mechanical components, droplet motion). The observed offset increased with increasing droplet mass, as fluid oscillations after impact may have been detected as motion. In future work, alternative methods for droplet impact detection could be explored and the observed offset could be used for compensation of this undesirable delay

An Evaluation of Otopathology in the MOV-13 Transgenic Mutant Mouse a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72482/1/j.1749-6632.1991.tb19595.x.pd

Stereo Laryngoscopic Impact Site Prediction for Droplet-Based Stimulation of the Laryngeal Adductor Reflex

The laryngeal adductor reflex (LAR) is a vital reflex of the human larynx. LAR malfunctions may cause life-threatening aspiration events. An objective, noninvasive, and reproducible method for LAR assessment is still lacking. Stimulation of the larynx by droplet impact, termed Microdroplet Impulse Testing of the LAR (MIT-LAR), may remedy this situation. However, droplet instability and imprecise stimulus application thus far prevented MIT-LAR from gaining clinical relevance. We present a system comprising two alternative, custom-built stereo laryngoscopes, each offering a distinct set of properties, a droplet applicator module, and image/point cloud processing algorithms to enable a targeted, droplet-based LAR stimulation. Droplet impact site prediction (ISP) is achieved by droplet trajectory identification and spatial target reconstruction. The reconstruction and ISP accuracies were experimentally evaluated. Global spatial reconstruction errors at the glottal area of (0.3±0.3) mm and (0.4±0.3) mm and global ISP errors of (0.9±0.6) mm and (1.3±0.8) mm were found for a rod lens-based and an alternative, fiberoptic laryngoscope, respectively. In the case of the rod lens-based system, 96% of all observed ISP error values are inferior to 2 mm; a value of 80% was found with the fiberoptic assembly. This contribution represents an important step towards introducing a reproducible and objective LAR screening method into the clinical routine

A systematic review and metanalysis of questionnaires used for auditory processing screening and evaluation

The recognition of Auditory Processing Disorder (APD) as a distinct clinical condition that impacts hearing capacity and mental health has gained attention. Although pure tone audiometry is the gold standard for assessing hearing, it inadequately reflects everyday hearing abilities, especially in challenging acoustic environments. Deficits in speech perception in noise, a key aspect of APD, have been linked to an increased risk of dementia. The World Health Organization emphasizes the need for evaluating central auditory function in cases of mild hearing loss and normal audiometry results. Specific questionnaires play a crucial role in documenting and quantifying the difficulties faced by individuals with APD. Validated questionnaires such as the Children's Auditory Processing Performance Scale, the Fisher's Auditory Problems Checklist, and the Auditory Processing Domains Questionnaire are available for children, while questionnaires for adults include items related to auditory functions associated with APD. This systematic review and meta-analysis identified six questionnaires used for screening and evaluating APD with a total of 783 participants across 12 studies. The questionnaires exhibited differences in domains evaluated, scoring methods, and evaluation of listening in quiet and noise. Meta-analysis results demonstrated that individuals with APD consistently exhibited worse scores compared to healthy controls across all questionnaires. Additionally, comparisons with clinical control groups showed varying results. The study highlights (i) the importance of standardized questionnaires in identifying and assessing APD, aiding in its diagnosis and management, and (ii) the need to use sub-scores as well as overall scores of questionnaires to elaborate on specific hearing and listening situations. There is a need to develop more APD specific questionnaires for the adult population as well as for more focused research on APD diagnosed individuals to further establish the validity and reliability of these questionnaires

A European perspective on auditory processing disorder-current knowledge and future research focus

Current notions of \u201chearing impairment,\u201d as reflected in clinical audiological practice, do not acknowledge the needs of individuals who have normal hearing pure tone sensitivity but who experience auditory processing difficulties in everyday life that are indexed by reduced performance in other more sophisticated audiometric tests such as speech audiometry in noise or complex non-speech sound perception. This disorder, defined as \u201cAuditory Processing Disorder\u201d (APD) or \u201cCentral Auditory Processing Disorder\u201d is classified in the current tenth version of the International Classification of diseases as H93.25 and in the forthcoming beta eleventh version. APDs may have detrimental effects on the affected individual, with low esteem, anxiety, and depression, and symptoms may remain into adulthood. These disorders may interfere with learning per se and with communication, social, emotional, and academic-work aspects of life. The objective of the present paper is to define a baseline European APD consensus formulated by experienced clinicians and researchers in this specific field of human auditory science. A secondary aim is to identify issues that future research needs to address in order to further clarify the nature of APD and thus assist in optimumdiagnosis and evidence-based management. This European consensus presents the main symptoms, conditions, and specific medical history elements that should lead to auditory processing evaluation. Consensus on definition of the disorder, optimum diagnostic pathway, and appropriate management are highlighted alongside a perspective on future research focus

Monoclonal antibodies to inner ear antigens: I. Antigens expressed by supporting cells of the guinea pig cochlea

Murine monoclonal antibodies against guinea pig cochlear epithelium were generated with the goal of identifying cochlea-specific antigens and elucidating their function. To compensate for the limited amount of cochlear tissue, intrasplenic immunization was used. Hybridoma supernatants were screened by ELISA for antibody production and for binding to homogenates from cochlea, liver, lung, kidney and brain. Hybrids producing antibody to cochlea were subcloned and tested immunocytochemically against frozen sections and surface preparations of paraformaldehyde-fixed cochlear tissue. KHRI-1, a low titer IgM antibody stained only Hensen cells. KHRI-2, also an IgM antibody, stained tectorial membrane, cells of the spiral limbus, cells bordering the space of Nuel, Hensen cells and the root cells of the spiral prominence. KHRI-3, an IgG1 antibody, stained the phalangeal processes of outer pillar cells and the apical portion of phalangeal processes of Deiters' cells in a distinctive wine goblet pattern on surface preparations. KHRI-3 antibody also reacted with peripheral nerves and pia mater of brain in unfixed frozen sections but the antigenic site was not stable to fixation in contrast to the epitope detected in the cochlea. In Western blots of detergent extracts from cochlea KHRI-3 stained a broad tissue-specific band of Mr 70-75 kDa; a narrower band of Mr 68-70 kDa was identified by KHRI-3 in extracts of tongue and brain. KHRI-1 and KHRI-2 did not detect any proteins in Western blots. The monoclonal antibodies KHRI-1, -2, and -3 which define epitopes expressed by discrete populations of supporting cells in the inner ear should be useful in characterizing the nature and function of cellular structures in the cochlea.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29422/1/0000501.pd

OSBPL2 encodes a protein of inner and outer hair cell stereocilia and is mutated in autosomal dominant hearing loss (DFNA67)

Background: Early-onset hearing loss is mostly of genetic origin. The complexity of the hearing process is reflected by its extensive genetic heterogeneity, with probably many causative genes remaining to be identified. Here, we aimed at identifying the genetic basis for autosomal dominant non-syndromic hearing loss (ADNSHL) in a large German family. Methods: A panel of 66 known deafness genes was analyzed for mutations by next-generation sequencing (NGS) in the index patient. We then conducted genome-wide linkage analysis, and whole-exome sequencing was carried out with samples of two patients. Expression of Osbpl2 in the mouse cochlea was determined by immunohistochemistry. Because Osbpl2 has been proposed as a target of miR-96, we investigated homozygous Mir96 mutant mice for its upregulation. Results: Onset of hearing loss in the investigated ADNSHL family is in childhood, initially affecting the high frequencies and progressing to profound deafness in adulthood. However, there is considerable intrafamilial variability. We mapped a novel ADNSHL locus, DFNA67, to chromosome 20q13.2-q13.33, and subsequently identified a co-segregating heterozygous frameshift mutation, c.141-142delTG (p.Arg50Alafs∗103), in OSBPL2, encoding a protein known to interact with the DFNA1 protein, DIAPH1. In mice, Osbpl2 was prominently expressed in stereocilia of cochlear outer and inner hair cells. We found no significant Osbpl2 upregulation at the mRNA level in homozygous Mir96 mutant mice. Conclusion: The function of OSBPL2 in the hearing process remains to be determined. Our study and the recent description of another frameshift mutation in a Chinese ADNSHL family identify OSBPL2 as a novel gene for progressive deafness.</p

A systematic review and metanalysis of questionnaires used for auditory processing screening and evaluation

The recognition of Auditory Processing Disorder (APD) as a distinct clinical condition that impacts hearing capacity and mental health has gained attention. Although pure tone audiometry is the gold standard for assessing hearing, it inadequately reflects everyday hearing abilities, especially in challenging acoustic environments. Deficits in speech perception in noise, a key aspect of APD, have been linked to an increased risk of dementia. The World Health Organization emphasizes the need for evaluating central auditory function in cases of mild hearing loss and normal audiometry results. Specific questionnaires play a crucial role in documenting and quantifying the difficulties faced by individuals with APD. Validated questionnaires such as the Children’s Auditory Processing Performance Scale, the Fisher’s Auditory Problems Checklist, and the Auditory Processing Domains Questionnaire are available for children, while questionnaires for adults include items related to auditory functions associated with APD. This systematic review and meta-analysis identified six questionnaires used for screening and evaluating APD with a total of 783 participants across 12 studies. The questionnaires exhibited differences in domains evaluated, scoring methods, and evaluation of listening in quiet and noise. Meta-analysis results demonstrated that individuals with APD consistently exhibited worse scores compared to healthy controls across all questionnaires. Additionally, comparisons with clinical control groups showed varying results. The study highlights (i) the importance of standardized questionnaires in identifying and assessing APD, aiding in its diagnosis and management, and (ii) the need to use sub-scores as well as overall scores of questionnaires to elaborate on specific hearing and listening situations. There is a need to develop more APD specific questionnaires for the adult population as well as for more focused research on APD diagnosed individuals to further establish the validity and reliability of these questionnaires