Cochlear implantation and single-sided deafness.

PURPOSE OF REVIEW: Recently, more patients with single-sided deafness (SSD) have been undergoing cochlear implantation. We review recent studies and case reports to provide an overview of the efficacy of cochlear implants to rehabilitate patients with SSD with regards to sound localization, speech discrimination, and tinnitus suppression. RECENT FINDINGS: There are a growing number of studies evaluating the effect of cochlear implantation for rehabilitation of the deficits associated with SSD over the past several years as more centers offer this treatment modality to patients with SSD. Although individual studies have few patients and are underpowered, the vast majority report improvement in sound localization, speech understanding in quiet and noise, and tinnitus. In some cases, the outcomes with cochlear implant appear superior to those achieved with other devices, including contralateral routing of sound devices and osseointegrated implants. SUMMARY: Although cochlear implant is not a Food and Drug Administration-approved treatment for SSD, several recent studies show improvements in speech understanding, sound localization, and tinnitus. Because of the low number of cases, it is difficult to conclusively compare outcomes achieved with cochlear implants and those provided by other devices. However, on the basis of encouraging early results and the unique ability to restore binaural sound processing, a growing number of centers offer cochlear implants as treatment for SSD. Forthcoming studies will help define outcome expectations in different populations.

Resection of the innominate artery to prevent an impending tracheoinnominate fistula and to permit tracheotomy in a patient with subglottic stenosis and high-riding innominate.

OBJECTIVE: This study aimed to determine the long-term viability of innominate artery resection and tracheotomy for a patient at high risk of developing a tracheoinnominate fistula (TIF) in the setting of subglottic stenosis and a high-riding innominate artery. METHODS: Chart review with 2-year follow-up. RESULTS: A 45-year-old diabetic man with obstructive sleep apnea and multiple admissions for coma and delirium tremens associated with alcohol abuse developed subglottic stenosis. He was found to have a palpable supraclavicular pulse during preoperative examination for a tracheotomy. Computed tomography examination revealed a high-riding innominate artery at the level of stenosis along with granulation tissue and disruption of the cartilaginous trachea, suggesting a high risk of impending TIF. The patient underwent a sternotomy-approach resection of the innominate artery with closure of the distal stump with a sternohyoid muscle flap. Intraoperatively, a plane of adhesions between the posterior innominate artery and trachea was dissected. The anterior tracheal wall appeared calcified but without evidence of erosion of either the trachea or the artery. Six weeks later, a tracheotomy was performed. Follow-up at 27 months did not identify complications from the innominate artery resection. CONCLUSION: Resection of the innominate artery is an option for some patients either to address the warning signs of TIF or to permit a tracheotomy to be performed in the presence of a high innominate artery.

The mechanotransduction machinery of hair cells.

Mechanotransduction, the conversion of mechanical force into an electrochemical signal, allows living organisms to detect touch, hear, register movement and gravity, and sense changes in cell volume and shape. Hair cells in the vertebrate inner ear are mechanoreceptor cells specialized for the detection of sound and head movement. Each hair cell contains, at the apical surface, rows of stereocilia that are connected by extracellular filaments to form an exquisitely organized bundle. Mechanotransduction channels, localized near the tips of the stereocilia, are gated by the gating spring, an elastic element that is stretched upon stereocilia deflection and mediates rapid channel opening. Components of the mechanotransduction machinery in hair cells have been identified and several are encoded by genes linked to deafness in humans, which indicates that defects in the mechanotransduction machinery are the underlying cause of some forms of hearing impairment.

Tip links in hair cells: molecular composition and role in hearing loss.

PURPOSE OF REVIEW: Tip links are thought to be an essential element of the mechanoelectrical transduction (MET) apparatus in sensory hair cells of the inner ear. The molecules that form tip links have recently been identified, and the analysis of their properties has not only changed our view of MET but also suggests that tip-link defects can cause hearing loss. RECENT FINDINGS: Structural, histological and biochemical studies show that the extracellular domains of two deafness-associated cadherins, cadherin 23 (CDH23) and protocadherin 15 (PCDH15), interact in trans to form the upper and lower part of each tip link, respectively. High-speed Ca imaging suggests that MET channels are localized exclusively at the lower end of each tip link. Biochemical and genetic studies provide evidence that defects in tip links cause hearing impairment in humans. SUMMARY: The identification of the proteins that form tip links have shed new light on the molecular basis of MET and the mechanisms causing hereditary deafness, noise-induced hearing loss and presbycusis.

A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells.

Deafness is the most common form of sensory impairment in humans and is frequently caused by single gene mutations. Interestingly, different mutations in a gene can cause syndromic and nonsyndromic forms of deafness, as well as progressive and age-related hearing loss. We provide here an explanation for the phenotypic variability associated with mutations in the cadherin 23 gene (CDH23). CDH23 null alleles cause deaf-blindness (Usher syndrome type 1D; USH1D), whereas missense mutations cause nonsyndromic deafness (DFNB12). In a forward genetic screen, we have identified salsa mice, which suffer from hearing loss due to a Cdh23 missense mutation modeling DFNB12. In contrast to waltzer mice, which carry a CDH23 null allele mimicking USH1D, hair cell development is unaffected in salsa mice. Instead, tip links, which are thought to gate mechanotransduction channels in hair cells, are progressively lost. Our findings suggest that DFNB12 belongs to a new class of disorder that is caused by defects in tip links. We propose that mutations in other genes that cause USH1 and nonsyndromic deafness may also have distinct effects on hair cell development and function.

Dynamic compartmentalization of protein tyrosine phosphatase receptor Q at the proximal end of stereocilia: implication of myosin VI-based transport.

Hair cell stereocilia are apical membrane protrusions filled with uniformly polarized actin filament bundles. Protein tyrosine phosphatase receptor Q (PTPRQ), a membrane protein with extracellular fibronectin repeats has been shown to localize at the stereocilia base and the apical hair cell surface, and to be essential for stereocilia integrity. We analyzed the distribution of PTPRQ and a possible mechanism for its compartmentalization. Using immunofluorescence we demonstrate that PTPRQ is compartmentalized at the stereocilia base with a decaying gradient from base to apex. This distribution can be explained by a model of transport directed toward the stereocilia base, which counteracts diffusion of the molecules. By mathematical analysis, we show that this counter transport is consistent with the minus end-directed movement of myosin VI along the stereocilia actin filaments. Myosin VI is localized at the stereocilia base, and exogenously expressed myosin VI and PTPRQ colocalize in the perinuclear endosomes in COS-7 cells. In myosin VI-deficient mice, PTPRQ is distributed along the entire stereocilia. PTPRQ-deficient mice show a pattern of stereocilia disruption that is similar to that reported in myosin VI-deficient mice, where the predominant features are loss of tapered base, and fusion of adjacent stereocilia. Thin section and freeze-etching electron microscopy showed that localization of PTPRQ coincides with the presence of a dense cell surface coat. Our results suggest that PTPRQ and myosin VI form a complex that dynamically maintains the organization of the cell surface coat at the stereocilia base and helps maintain the structure of the overall stereocilia bundle.

Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells.

Hair cells of the inner ear are mechanosensors that transduce mechanical forces arising from sound waves and head movement into electrochemical signals to provide our sense of hearing and balance. Each hair cell contains at the apical surface a bundle of stereocilia. Mechanoelectrical transduction takes place close to the tips of stereocilia in proximity to extracellular tip-link filaments that connect the stereocilia and are thought to gate the mechanoelectrical transduction channel. Recent reports on the composition, properties and function of tip links are conflicting. Here we demonstrate that two cadherins that are linked to inherited forms of deafness in humans interact to form tip links. Immunohistochemical studies using rodent hair cells show that cadherin 23 (CDH23) and protocadherin 15 (PCDH15) localize to the upper and lower part of tip links, respectively. The amino termini of the two cadherins co-localize on tip-link filaments. Biochemical experiments show that CDH23 homodimers interact in trans with PCDH15 homodimers to form a filament with structural similarity to tip links. Ions that affect tip-link integrity and a mutation in PCDH15 that causes a recessive form of deafness disrupt interactions between CDH23 and PCDH15. Our studies define the molecular composition of tip links and provide a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15.

Unbiased stereological estimation of the spiral ligament and stria vascularis volumes in aging and Ménière's disease using archival human temporal bones.

The present study applies the unbiased stereological technique-Cavalieri principle to measure the volumes of the stria vascularis (SV) and the spiral ligament (SL) using postmortem archival human temporal bones from normal young and older subjects and subjects with Ménière's disease. Normative data was obtained from subjects without ages ranging from 15 to 84 years old who had no history of audiovestibular disease (N=25). For comparison purposes, the normative specimens were divided into three groups: group 1 (n=8) had ages ranging from 15 to 38 years old, average age=23.9; group 2 (n=8) had ages ranging from 51 to 59 years old, average age=55.1; group 3 (n=9) had ages ranging from 64 to 84 years old, average age=74.3. The average SV volume of group 3 (0.479 mm3) was significantly lower than that of group 1 (0.705 mm3) (p<0.0005) and was significantly lower than that of group 2 (0.603 mm3) (p=0.01). The average SL volume of group 3 (8.42 mm3) was significantly lower than that of group 1 (9.54 mm3) (p<0.05), but was not significantly lower than that of group 2 (8.58 mm3). Five subjects with Ménière's disease, confirmed by histopathological examination (ages ranging from 63 to 91 years old, average age=73.4), were studied. The average SV volume in Ménière's subjects (0.378 mm3) was significantly lower than age-matched controls (p<0.05). The average SL volume in Ménière's subjects (7.01 mm3) was also significantly lower than age-matched controls (p<0.05). The SV and SL volumes were unaffected by gender. The present study demonstrates for the first time the use of the unbiased stereological technique-Cavalieri principle-as a reliable and efficient method to obtain volumetric estimates of the SV and the SL by using archival human temporal bone specimens.

Regional estimates of hair cells and supporting cells in the human crista ampullaris.

Regional estimates of type I and type II vestibular hair cells (HC) and supporting cell (SC) numbers were obtained from the horizontal crista ampullaris by using design-based stereology in human. Cristae were microdissected from temporal bones obtained post-mortem (N=16, age range 26-98 years). Three groups were made according to age: group 1, n=5, ages between 26 and 67 years, average age 51 years; group 2, n=4, average age 84 years; and group 3, n=7, average age 94 years. For group 1, the average total HC number was 8,005+/-214, corresponding to 4,119+/-107 type I HC, 3,886+/-117 type II HC, and 10,274+/-224 SC. The type I:type II HC ratio was 1.06+/-0.01, and HC density was 0.80 cells/100 microm2. For group 2, the average total HC number was 7,074+/-489, corresponding to 3,733+/-212 type I HC, 3,341+/-314 type II HC, and 9,321+/-858 SC. The type I:II HC ratio was 1.12+/-0.06, and HC density was 0.75 cells/100 microm2. For group 3, the average HC number was 6,009+/-327, corresponding to 3,380+/-223 type I HC, 2,628+/-235 type II HC, and 10,185+/-182 SC. The type I:II HC ratio was 1.34+/-0.10, and HC density was 0.63 cells/100 microm2. A significant decline in type I, type II, and total HC number and density was found in groups 2 and 3, with individuals exceeding the average human life span.