Publications by authors named "Akira Ishiyama"

98 Publications

Cochlear Meniere's: A Distinct Clinical Entity With Isolated Cochlear Hydrops on High-Resolution MRI?

Front Surg 2021 16;8:680260. Epub 2021 Jun 16.

Department of Head and Neck Surgery, University of California, Los Angeles, Los Angeles, CA, United States.

Describe the clinical characteristics of patients with isolated cochlear endolymphatic hydrops (EH). Clinical case series. Tertiary Neurotology referral clinic. All subjects presenting to a University Neurotology clinic during a 1-year period from July 2015 until August 2016 who had isolated cochlear EH on MRI. Patients with a history of temporal bone surgery prior to the MRI were excluded. High-resolution delayed-intravenous contrast MRI. Audiometric and vestibular testing, clinical history analysis. 10 subjects demonstrated , unilateral cochlear hydrops on MRI. None of these patients met the criteria for Meniere's disease. Mean age of the group was 66.4 years and most were males (70%). Unilateral aural fullness (70%), tinnitus (80%), and hearing loss (90%) were frequently observed. Only one patient presented with unsteadiness (10%) and one patient had a single isolated spell of positional vertigo 1 month prior to the MRI (10%) but no further vertigo spells in the 4 years following the MRI. The mean PTA was 37.8 dB which was significantly decreased from the non-affected ear with PTA of 17.9 ( < 0.001). One patient developed vertiginous spells and unsteadiness 4 years after initial presentation and a repeat MRI revealed progression to utricular, saccular and cochlear hydrops. Vestibular testing was obtained in five patients with one patient presenting with 50% caloric paresis and all others normal. The most common treatment tried was acetazolamide in seven patients with 86% reporting subjective clinical improvement. Two out of the 10 patients had a history of migraine (20%). Patients with MRI exhibiting isolated cochlear EH present with predominantly auditory symptoms: mild to moderate low-frequency hearing loss, aural fullness, tinnitus without significant vertigo. Isolated cochlear hydrops is more common in males, average age in mid-60's and there is a low comorbidity of migraine headaches. This contrasts significantly with patients with isolated saccular hydrops on MRI from our prior studies. We believe that isolated cochlear EH with hearing loss but no vertigo is distinct from Meniere's disease or its variant delayed endolymphatic hydrops. We propose that cochlear Meniere's disease represents a distinct clinical entity that could be a variant of Meniere's disease.
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http://dx.doi.org/10.3389/fsurg.2021.680260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242163PMC
June 2021

Corrigendum: Characterizing Adult Cochlear Supporting Cell Transcriptional Diversity Using Single-Cell RNA-Seq: Validation in the Adult Mouse and Translational Implications for the Adult Human Cochlea.

Front Mol Neurosci 2021 3;14:699859. Epub 2021 Jun 3.

Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States.

[This corrects the article DOI: 10.3389/fnmol.2020.00013.].
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http://dx.doi.org/10.3389/fnmol.2021.699859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209547PMC
June 2021

Identification of a genetic variant underlying familial cases of recurrent benign paroxysmal positional vertigo.

PLoS One 2021 6;16(5):e0251386. Epub 2021 May 6.

Vestibular Genetics Laboratory, Boys Town National Research Hospital, Omaha, Nebraska, United States of America.

Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo in humans, yet the molecular etiology is currently unknown. Evidence suggests that genetic factors may play an important role in some cases of idiopathic BPPV, particularly in familial cases, but the responsible genetic variants have not been identified. In this study, we performed whole exome sequencing [including untranslated regions (UTRs)] of 12 families and Sanger sequencing of additional 30 families with recurrent BPPV in Caucasians from the United States (US) Midwest region, to identify the genetic variants responsible for heightened susceptibility to BPPV. Fifty non-BPPV families were included as controls. In silico and experimental analyses of candidate variants show that an insertion variant rs113784532 (frameshift causing truncation) in the neural cadherin gene PCDHGA10 (protocadherin-gamma A10) is an exceedingly strong candidate (p = 1.80x10-4 vs. sample controls; p = 5.85x10-19 vs. ExAC data; p = 4.9x10-3 vs. NHLBI exome data). The mutant protein forms large aggregates in BPPV samples even at young ages, and affected subjects carrying this variant have an earlier onset of the condition than those without [average 44.0±14.0 (n = 16) versus 54.4±16.1 (n = 36) years old, p = 0.054]. In both human and mouse inner ear tissues, PCDHGA10 is expressed in ganglia, hair cells and vestibular transitional epithelia. Fluorescent RNA in situ hybridization using mouse inner ear tissues shows that expression increases with age. In summary, our data show that a variant in the PCDHGA10 gene may be involved in causing or aggravating some familial cases of recurrent idiopathic BPPV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251386PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101739PMC
May 2021

Predictors of Fibrotic and Bone Tissue Formation With 3-D Reconstructions of Post-implantation Human Temporal Bones.

Otol Neurotol 2021 08;42(7):e942-e948

Department of Head and Neck Surgery.

Hypothesis: Years of implantation, surgical insertion approach, and electrode length will impact the volume of new tissue formation secondary to cochlear implantation.

Background: New tissue formation, fibrosis, and osteoneogenesis after cochlear implantation have been implicated in increasing impedance and affecting performance of the cochlear implant.

Methods: 3-D reconstructions of 15 archival human temporal bones from patients with a history of cochlear implantation (CI) were generated from H&E histopathologic slides to study factors which affect volume of tissue formation.

Results: Years of implantation was a predictor of osteoneogenesis (r = 0.638, p-value = 0.011) and total new tissue formation (r = 0.588, p-value = 0.021), however not of fibrosis (r = 0.235, p-value = 0.399). Median total tissue formation differed between cochleostomy and round window insertions, 25.98 and 10.34%, respectively (Mann-Whitney U = 7, p = 0.018). No correlations were found between electrode length or angular insertion depth and total new tissue (p = 0.192, p = 0.35), osteoneogenesis (p = 0.193, p = 0.27), and fibrosis (p = 0.498, p = 0.83), respectively. However, the type II error for electrode length and angular insertion depth ranged from 0.73 to 0.90, largely due to small numbers of the shorter electrodes.

Conclusions: With numbers of cochlear implant recipients increasing worldwide, an understanding of how to minimize intracochlear changes from implantation is important. The present study demonstrates that increasing years of implantation and inserting electrodes via a cochleostomy compared with a round window approach are associated with significantly greater degree of new tissue volume formation. While previous studies have demonstrated increased intracochlear damage in the setting of translocation with longer electrodes, length, and angular insertion depth of CI electrodes were not associated with increased tissue formation.
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http://dx.doi.org/10.1097/MAO.0000000000003106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282738PMC
August 2021

Bilateral and bimodal cochlear implant listeners can segregate competing speech using talker sex cues, but not spatial cues.

JASA Express Lett 2021 Jan;1(1):014401

Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.

Cochlear implant (CI) users have greater difficulty perceiving talker sex and spatial cues than do normal-hearing (NH) listeners. The present study measured recognition of target sentences in the presence of two co-located or spatially separated speech maskers in NH, bilateral CI, and bimodal CI listeners; masker sex was the same as or different than the target. NH listeners demonstrated a large masking release with masker sex and/or spatial cues. For CI listeners, significant masking release was observed with masker sex cues, but not with spatial cues, at least for the spatially symmetrically placed maskers and listening task used in this study.
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http://dx.doi.org/10.1121/10.0003049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814501PMC
January 2021

Temporal Trends and Regionalization of Acute Mastoiditis Management in the United States.

Otol Neurotol 2021 06;42(5):733-739

Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California.

Objective: To describe demographics and to analyze temporal trends in the inpatient management of acute mastoiditis admissions.

Study Design: Cross-sectional analysis.

Setting: National Inpatient Sample, 2002-2014.

Patients: 26,072 nonelective inpatient admissions with primary diagnosis of acute mastoiditis.

Intervention: Myringotomy, mastoidectomy, or no procedure.

Main Outcome Measures: We described the patient- and hospital-level demographics of acute mastoiditis admissions and the frequency of complications. We evaluated the percentage of patients requiring surgical management. Binary logistic regression was performed to determine whether there was a significant increase in the percentage of patients treated at academic institutions.

Results: The majority of patients were ≤40 years old (64.9%) and Elixhauser comorbidity index ≥4 (57.4%); 23.3% (SE 0.8%) presented with complications associated with acute mastoiditis, the most common of which was a subperiosteal abscess (11.5%, SE 0.7%). Among all admissions, 30.9% (SE 1.1%) underwent myringotomy, 13.8% (SE 0.8%) required both myringotomy and mastoidectomy. On multivariate analysis, there was a statistically significant increase in the percentage of mastoiditis admissions to teaching hospitals for all admissions (OR 1.55 [CI 1.22-1.97], p < 0.001) and even more evident for cases with associated complications (OR 1.85 [CI 1.21-2.83], p = 0.004).

Conclusions And Relevance: A sizeable percentage of patients with acute mastoiditis present with complications which may require surgical intervention. From 2002 to 2014, inpatient care of acute mastoiditis became increasingly regionalized to teaching hospitals, suggestive of increased specialization within certain facilities. This trend may have significant impacts on the cost and subsequent quality of care provided to these patients.
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http://dx.doi.org/10.1097/MAO.0000000000003050DOI Listing
June 2021

Isolated Saccular Hydrops on High-resolution MRI Is Associated With Full Spectrum Menière's Disease.

Otol Neurotol 2021 07;42(6):876-882

Department of Otolaryngology-Head and Neck Surgery.

Objective: To describe the clinical presentation of patients with isolated saccular endolymphathic hydrops (EH) detected.

Study Design: Clinical case series.

Setting: University-based tertiary referral center.

Patients: All subjects presenting with vertigo or hearing loss who had isolated saccular EH detected.

Intervention: High-resolution delayed-contrast magnetic resonance imaging (MRI) conducted between November 2015 and November 2016.

Main Outcome Measures: Audiovestibular testing results and analysis of clinical histories.

Results: Isolated saccular EH was detected in 18 subjects. Sixteen met criteria for definite Menière's disease (MD, n = 12) or delayed endolymphatic hydrops (DEH, n = 4). One had a history of sudden sensorineural hearing loss (SSNHL) and 3 years after MRI developed recurrent vertigo characteristic of DEH. One patient had a history of atypical DEH (Tumarkin falls without vertigo following SSNHL). Four patients had Tumarkin falls. Most (83%) demonstrated mild-to-severe low-frequency fluctuating loss, and six (33.3%) had a history of ipsilateral sudden profound SNHL. Nine of the 17 (53%) patients tested had an ipsilateral caloric paresis ranging from 26 to 67%. Ipsilateral vestibular-evoked myogenic potentials showed reduced or absent responses in 5 of the 17 tested (29%).

Conclusions: The full spectrum of MD may be associated with saccular hydrops. We propose that MD and DEH often begin in the saccule, and MRI may provide clues to the pathophysiology of MD. Saccular hydrops was present in one patient with SSNHL who did not develop vertigo spells until 3 years after MRI, indicating that saccular hydrops may be the first manifestation of MD or DEH.
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http://dx.doi.org/10.1097/MAO.0000000000003051DOI Listing
July 2021

Immunohistochemical location of Na, K-ATPase α1 subunit in the human inner ear.

Hear Res 2021 Feb 13;400:108113. Epub 2020 Nov 13.

Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, USA. Electronic address:

Na, K-ATPase (Na,K-ATPase) is an ubiquitous enzyme in the inner ear and a key factor in the maintenance of the osmotic gradient of the endolymph. This study uses Na,K-ATPase α1 subunit immunoreactivity (IR) to identify cellular structures in the normal and disease human cochlea. Formalin-fixed celloidin-embedded (FFCE) human temporal bone sections were immunoreacted with mouse monoclonal antibodies against Na,K-ATPase α1 subunit. Na,K-ATPase α1 IR was examined in the cochlea of 30 patients: four with normal hearing, 5 with Meniere's disease, and 21 with other inner ear diseases: 11 male, 19 female; ages 42 to 96 years-old (yo), average age of 77 yo. Na,K-ATPase α1 IR area was quantified using the ImageJ software program. Na,K-ATPase α1 IR was located in the stria vascularis, and in type I, II and IV fibrocytes of the spiral ligament in the cochlea from patients with normal hearing. Na,K-ATPase α1 IR was seen in Deiters's cells and inner phalangeal cells of the organ of Corti. Na,K-ATPase α1 IR was present in satellite cells that surround the neurons of the spiral ganglia. In the inner ear of pathological specimens, Na,K-ATPase IR area was decreased (compared to the normal) in the stria vascularis, supporting cells in the organ of Corti and satellite cells of the spiral ganglia. These results show that Na,K-ATPase α1 IR is a good marker to identify cellular structures of the human inner ear and may be used to study cellular changes in the cochlea associated with aging and disease. The ubiquitous localization of Na,K-ATPase α1 in the human cochlea is consistent with the Na,K-ATPase role in ionic homeostasis and osmolarity, similar to that seen in animal models.
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http://dx.doi.org/10.1016/j.heares.2020.108113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796994PMC
February 2021

Mouse Models of Human Pathogenic Variants of Associated with Non-Syndromic Deafness DFNB86 and DFNA65 and Syndromes Involving Deafness.

Genes (Basel) 2020 09 24;11(10). Epub 2020 Sep 24.

Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, Porter Neuroscience Research Center, National Institutes of Health, Bethesda, MD 20892, USA.

Human pathogenic variants of are associated with clinically heterogeneous phenotypes, including recessive nonsyndromic deafness DFNB86, dominant nonsyndromic deafness DFNA65, seizure accompanied by deafness, a variety of isolated seizure phenotypes and DOORS syndrome, characterized by deafness, onychodystrophy, osteodystrophy, intellectual disability and seizures. Thirty-five pathogenic variants of human associated with deafness have been reported. However, functions of TBC1D24 in the inner ear and the pathophysiology of TBC1D24-related deafness are unknown. In this study, a novel splice-site variant of c.965 + 1G > A in compound heterozygosity with c.641G > A p.(Arg214His) was found to be segregating in a Pakistani family. Affected individuals exhibited, either a deafness-seizure syndrome or nonsyndromic deafness. In human temporal bones, TBC1D24 immunolocalized in hair cells and spiral ganglion neurons, whereas in mouse cochlea, expression was detected only in spiral ganglion neurons. We engineered mouse models of p.(Asp70Tyr) and p.(Ser178Leu) nonsyndromic deafness and syndromic forms of deafness p.(His336Glnfs*12) that have the same pathogenic variants that were reported for human . Unexpectedly, no auditory dysfunction was detected in mutant mice, although homozygosity for some of the variants caused seizures or lethality. We provide some insightful supporting data to explain the phenotypic differences resulting from equivalent pathogenic variants of mouse and human .
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http://dx.doi.org/10.3390/genes11101122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598720PMC
September 2020

Immune Response of Macrophage Population to Cochlear Implantation: Cochlea Immune Cells.

Otol Neurotol 2020 10;41(9):1288-1295

University of California Los Angeles, Los Angeles, California.

Hypothesis: The presence and distribution of ionized calcium binding adaptor 1 and CD68 macrophages in the human cochlea is altered in cochlear implantation (CI) compared with the normative or nonimplanted cochlea.

Background: It has been hypothesized that CI induces an immunological response in macrophages leading to implant failure or reduced hearing. Macrophages are resident immune cells in human cochlea and have been shown to phagocytize implant material. In animal models, macrophage populations increase with surgical stress and with the introduction of a foreign body. However, the function and response of inner ear macrophages to CI are only beginning to be understood. This study seeks to investigate the inflammatory response to CI by comparing cochlear macrophages in implanted and nonimplanted human temporal bones.

Methods: Nineteen temporal bones from nine implanted ears, seven contralateral controls, and three normal control ears were evaluated for the presence and distribution of CD68 and Iba1 expressing positive macrophages.

Results: Three types of macrophage populations were detected 1) CD68 positive macrophages, 2) Iba1 positive macrophages, and 3) CD68 and Iba1 colocalizing macrophages. Macrophage distribution was ubiquitous: the stria vascularis, Rosenthal canal, and the mid-modiolus intermingled in the spiral ganglia. Iba1 and CD68 macrophages were found in the CI and non-CI contralateral and normal human cochlea. Most ionized calcium binding adaptor 1 expressing macrophages were ramified/amoeboid cells, while CD68 expressing macrophages were round shaped with foamy appearance in some areas. In the CI cochlea, both types of macrophages were detected in the fibrous sheath surrounding the CI path and within fibrotic areas within the scala tympani and the scala vestibuli in the case of CI translocation. In four cases, the density of macrophages was unchanged in the CI compared with the contralateral nonimplanted side, and in three cases, there was an increased number of macrophages in the implanted CI side compared with the nonimplanted side.

Conclusion: Multiple populations of macrophages exist within the cochlea which are present at baseline and in response to trauma from CI. These results further support evidence for a macrophage response to cochlear implantation. Further studies are indicated to evaluate whether these macrophages have a beneficial, detrimental, or a mixed effect in CI patients.
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http://dx.doi.org/10.1097/MAO.0000000000002764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855504PMC
October 2020

Histology of the Cochlear Outer Sulcus Cells in Normal Human Ears, Presbycusis, and Menière's Disease.

Otol Neurotol 2020 04;41(4):e507-e515

Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, Illinois, USA.

Hypothesis: Outer sulcus cell features and distribution are hypothesized to differ throughout regions of the human cochlea and between diseased and normal specimens.

Background: Outer sulcus cells play a role in inner ear fluid homeostasis. However, their anatomy and distribution in the human are not well described.

Methods: Temporal bone specimens with normal hearing (n = 10), Menière's disease (n = 10), presbycusis with flat audiograms (n = 4), and presbycusis with sloping audiograms (n = 5) were examined by light microscopy. Outer sulcus cells were assessed quantitatively and qualitatively in each cochlear turn. One specimen was stained for tubulin immunofluorescence and imaged using confocal microscopy.

Results: Outer sulcus cells interface with endolymph throughout the cochlea, with greatest contact in the apical turn. Mean outer sulcus cell counts in the upper apical turn (8.82) were generally smaller (all p < 0.05) than those of the upper basal (17.71), lower middle (18.99) upper middle (18.23), and lower apical (16.42) turns. Mean outer sulcus cell counts were higher (p < 0.05) in normal controls (20.1) than in diseased specimens (15.29). There was a significant correlation between mean cell counts and tonotopically expected hearing thresholds in the upper basal (r = -0.662, p = 0.0001), lower middle (r = -0.565, p = 0.0017), and upper middle (r = -0.507, p = 0.0136) regions. Other differences in cell morphology, distribution, or relationship with Claudius cells were not appreciated between normal and diseased specimens. Menière's specimens had no apparent unique features in the cochlear apex. Immunofluorescence staining demonstrated outer sulcus cells extending into the spiral ligament in bundles forming tapering processes which differed between the cochlear turns in morphology.

Conclusion: Outer sulcus cells vary throughout the cochlear turns and correlate with hearing status, but not in a manner specific to the underlying diagnoses of Menière's disease or presbycusis.
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http://dx.doi.org/10.1097/MAO.0000000000002535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275934PMC
April 2020

Human Temporal Bone Study of Vestibular Histopathology in Cochlear Implant Patients With Cochlear Hydrops.

Otol Neurotol 2020 06;41(5):e607-e614

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California.

Hypothesis: Endolymphatic hydrops (EH) associated with cochlear implantation are associated with vestibular dysfunction.

Background: Vestibular dysfunction is a known risk after cochlear implantation (CI). CI has been shown to cause cochlear hydrops due to fibrosis surrounding the ductus reuniens. However, the association of cochlear hydrops with vestibular hydrops and the relationship to vestibular symptoms remain unknown.

Methods: Histopathological analysis and clinical evaluation of the vestibular end organs of 17 human temporal bones (HTB)s exhibiting cochlear hydrops from 15 CI recipients.

Results: Eight of 15 patients with cochlear hydrops due to CI had complaints of dizziness, vertigo, or imbalance following CI. In all 17 HTBs with cochlear hydrops, there was fibrosis, atrophy, or obstruction of the ductus reuniens, and all had straight electrode CI via cochleostomy. In one of the eight reporting postoperative dizziness, labyrinthitis ossificans was deemed causative. Six of the seven remaining patients had EH of both the saccule and utricle. Fifteen of 17 HTBs (88.2%) had saccular EH. In contrast, 8 of 17 HTBs (47.0%) in 7 patients had utricular EH, of which 6 patients had postoperative vertigo spells. It seems that hydrops of the utricle closely corresponds to postoperative vertigo spells and vestibular complaints.

Conclusion: Implantation of the CI, when complicated by ductus reuniens fibrosis, may cause both cochlear hydrops and vestibular endolymphatic hydrops. Hydrops of the vestibular periphery when involving the utricle seems to be more likely associated with disabling vertigo symptoms. This study supports the round window technique of insertion rather than cochleostomy.
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http://dx.doi.org/10.1097/MAO.0000000000002609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415216PMC
June 2020

Characterizing Adult Cochlear Supporting Cell Transcriptional Diversity Using Single-Cell RNA-Seq: Validation in the Adult Mouse and Translational Implications for the Adult Human Cochlea.

Front Mol Neurosci 2020 5;13:13. Epub 2020 Feb 5.

Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States.

Hearing loss is a problem that impacts a significant proportion of the adult population. Cochlear hair cell (HC) loss due to loud noise, chemotherapy and aging is the major underlying cause. A significant proportion of these individuals are dissatisfied with available treatment options which include hearing aids and cochlear implants. An alternative approach to restore hearing would be to regenerate HCs. Such therapy would require a recapitulation of the complex architecture of the organ of Corti, necessitating regeneration of both mature HCs and supporting cells (SCs). Transcriptional profiles of the mature cell types in the cochlea are necessary to can provide a metric for eventual regeneration therapies. To assist in this effort, we sought to provide the first single-cell characterization of the adult cochlear SC transcriptome. We performed single-cell RNA-Seq on FACS-purified adult cochlear SCs from the adult mouse, in which SCs express GFP. We demonstrate that adult cochlear SCs are transcriptionally distinct from their perinatal counterparts. We establish cell-type-specific adult cochlear SC transcriptome profiles, and we validate these expression profiles through a combination of both fluorescent immunohistochemistry and hybridization co-localization and quantitative polymerase chain reaction (qPCR) of adult cochlear SCs. Furthermore, we demonstrate the relevance of these profiles to the adult human cochlea through immunofluorescent human temporal bone histopathology. Finally, we demonstrate cell cycle regulator expression in adult SCs and perform pathway analyses to identify potential mechanisms for facilitating mitotic regeneration (cell proliferation, differentiation, and eventually regeneration) in the adult mammalian cochlea. Our findings demonstrate the importance of characterizing mature as opposed to perinatal SCs.
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http://dx.doi.org/10.3389/fnmol.2020.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012811PMC
February 2020

Potential insertion complications with cochlear implant electrodes.

Cochlear Implants Int 2020 07 20;21(4):206-219. Epub 2020 Feb 20.

Clinical Affairs, Cochlear Ltd, Macquarie University, Sydney, Australia.

The aim of this discussion paper and literature review was to estimate the incidence of a variety of complications associated with the surgical placement of cochlear implant (CI) electrode arrays and to discuss the implications and management of sub-optimal electrode placement. A review of the peer-reviewed literature suggests that the incidence of incomplete electrode insertion and kinking is more prevalent in straight arrays and not more than about 2% in CI recipients with normal cochlear anatomy/patency. Incidence of tip fold-over is greater with perimodiolar arrays but also occurs with straight arrays and is typically less than 5%. Conversely, electrode migration is more common with straight arrays, and high rates (up to 46%) have been reported in some studies. Scalar translocations have also been reported for both perimodiolar and straight arrays. Higher rates have been reported for stylet-based perimodiolar electrodes inserted via cochleostomy (up to 56%), but with much lower rates (<10%) with both sheath-based perimodiolar arrays and lateral wall arrays. Electrode positioning complications represent a significant proportion of perioperative CI complications and compromise the level of benefit from the device. Careful surgical planning and appropriate pre- and intraoperative imaging can reduce the likelihood and impact of electrode positioning complications. There is also evidence that newer array designs are less prone to certain complications, particularly scalar translocation. It is important that implanting surgeons are aware of the impact of sub-optimal electrode placement and the steps that can be taken to avoid, identify and manage such complications.
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http://dx.doi.org/10.1080/14670100.2020.1730066DOI Listing
July 2020

Morphometric linear and angular measurements of the human cochlea in implant patients using 3-dimensional reconstruction.

Hear Res 2020 02 20;386:107874. Epub 2019 Dec 20.

UCLA David Geffen School of Medicine Department of Head and Neck Surgery, Los Angeles, CA, 90095, USA. Electronic address:

The present study is the first to evaluate the spiral ganglion neurons (SGNs) and the linear and angular measurements of the cochlea in temporal bones of cochlear implant (CI) recipients. There are no studies evaluating the morphometric measures in subjects after long-term CI use, and this study fills in this gap in current knowledge, greatly important for the design of CI electrodes. Amira based 3-D reconstructions of the cochlea were generated from stained histopathological slides of 15 celloidin-embedded human temporal bones. The SGN angular distance from the round window exhibited a narrow range from 684°-704°, corresponding to linear distances of 17.87 and 34.48 mm along the inner and outer wall of the scala tympani. The first turn measured an average of 14.21 mm along the inner wall and 23.92 mm along the outer wall. The outer wall average for the second turn was 11.11 mm and for the partial third apical turn was only 4.49 mm. The range for cochlear duct angular distance was 876° to 1051°, with a mean of 2.63 turns, corresponding to an average linear distance of 39.53 mm, ranging from 35.44 mm to 43.57 mm 6 out of 15 temporal bones demonstrated better preservation of SGN in the middle and apical segments of Rosenthal's canal. The present study demonstrates that the anatomy of the cochlea of CI patients does not differ significantly from that of normative subjects and establishes measurements using the round window as the 0° reference point, an important surgical landmark. The relevance of the measurements to cochlear implant design are discussed.
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http://dx.doi.org/10.1016/j.heares.2019.107874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100312PMC
February 2020

Investigations of the Microvasculature of the Human Macula Utricle in Meniere's Disease.

Front Cell Neurosci 2019 4;13:445. Epub 2019 Oct 4.

Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.

The integrity and permeability of the blood labyrinthine barrier (BLB) in the inner ear is important to maintain adequate blood supply, and to control the passage of fluids, molecules and ions. Identifying the cellular and structural components of the BLB, the vascular endothelial cells (VECs), pericytes, and the perivascular basement membrane, is critical to understand the pathophysiology of the inner ear microvasculature and to design efficient delivery of therapeutics across the BLB. A recent study of the normal and pathological ultrastructural changes in the human macula utricle microvasculature demonstrated that the VECs are damaged in Meniere's disease (MD), and further studies identified oxidative stress markers (iNOS and nitrotyrosine) in the VECs. Using fluorescence microscopy, the microvasculature was studied in the macula utricle of patients diagnosed with MD that required transmastoid labyrinthectomy for intractable vertigo ( = 5), and patients who required a translabyrinthine approach for vestibular schwannoma (VS) resection ( = 3). Normal utricles (controls) were also included ( = 3). VECs were identified using rabbit polyclonal antibodies against the glucose transporter-1 (GLUT-1) and pericytes were identified using mouse monoclonal antibodies against alpha-smooth muscle actin (α-SMA). Immunofluorescence (IF) staining was made in half of the utricle and flat mounted. The other half was used to study the integrity of the BLB using transmission electron microscopy (TEM). GLUT-1-IF, allowed delineation of the macula utricle microvasculature (located in the stroma underneath the sensory epithelia) in both MD and VS specimens. Three sizes of vessels were present in the utricle vasculature: Small size (<15 μm), medium size (15-25 μm) and large size >25 μm. α-SMA-IF was present in pericytes that surround the VECS in medium and thick size vessels. Thin size vessels showed almost no α-SMA-IF. AngioTool software was used for quantitative analysis. A significant decreased number of junctions, total vessel length, and average vessel length was detected in the microvasculature in MD specimens compared with VS and control specimens. The deeper understanding of the anatomy of the BLB in the human vestibular periphery and its pathological changes in disease will enable the development of non-invasive delivery strategy for the treatment of hearing and balance disorders.
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http://dx.doi.org/10.3389/fncel.2019.00445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787152PMC
October 2019

Histopathologic Characteristics of Internal Auditory Canal Diverticula.

Otol Neurotol 2019 07;40(6):e653-e656

House Ear Institute.

Hypothesis: We hypothesize that internal auditory canal (IAC) diverticula occur independent of otosclerosis as demonstrated by temporal bone histopathology.

Background: Diverticula at the anterior-inferior aspect of the IAC have been described histologically in the setting of cavitary otosclerosis. Recent radiographic studies show the prevalence of IAC diverticula that is higher than what can be accounted for by cavitary otosclerosis alone.

Methods: We examined hematoxylin and eosin temporal bone histopathology slides with otosclerosis involving the IAC. We also examined bones from normal hearing subjects with normal histologic findings. Temporal bones were included if donors were more than 18 years of age at time of death and adequate horizontal cuts were available to evaluate the area of interest.

Results: IAC diverticula were found in 33 of 47 (70%) temporal bones with IAC otosclerosis and in 5 of 20 (25%) normal temporal bones. The difference in mean pure tone averages (PTA) in the normal temporal bones with (PTA 7.3 ± 7) and without (PTA 8 ± 2) diverticula was not statistically significant (p = 0.86).

Conclusion: IAC diverticula which have been previously demonstrated to occur in the setting of cavitary otosclerosis can also occur independent from otosclerosis. Subjects with diverticula but without other temporal bone pathology have normal hearing thresholds.
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http://dx.doi.org/10.1097/MAO.0000000000002256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565456PMC
July 2019

Otopetrin-2 Immunolocalization in the Human Macula Utricle.

Ann Otol Rhinol Laryngol 2019 06;128(6_suppl):96S-102S

1 Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Background: In the present study, we investigated the localization of otopetrin-2-a member of the otopetrin family that encodes proton-selective ion channels-in the human macula utricle using immunohistochemistry.

Methods: Macula utricle were acquired at surgery from patients who required transmastoid labyrinthectomy for intractable vertigo due to Meniere's disease (MD; n = 3) and/or vestibular drops attacks (VDA; n = 2) and from temporal bones (n = 2) acquired at autopsy from individuals with no balance disorders. Immunofluorescence staining with otopetrin-2 (rabbit affinity purified polyclonal antibody) and GFAP (mouse monoclonal antibody) to identify vestibular supporting cells was made in formalin fixed cryostat sections or whole microdissected utricle (for flat mount preparations). Secondary antibodies against rabbit and mouse were used for the identification of both proteins. Digital fluorescent images were obtained using a high-resolution laser confocal microscope.

Results: Using cryostat sections and flat mount preparations otopetrin-2 immunofluorescence was seen as punctated signal throughout the supporting cells cytoplasm. GFAP immunofluorescence was present in the supporting cell cytoplasm. The distribution of otopetrin-2 was similar in the macula utricle obtained from MD, VDA, or autopsy normative patients.

Conclusions: Otopetrin-2 was localized in supporting cells in a similar fashion that otopetrin-1 previously reported in the mouse macula utricle. The differential expression of otopetrin-2 in the supporting cells of the human macula utricle suggest an important role in the vestibular sensory periphery homeostasis and otolith maintenance.
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http://dx.doi.org/10.1177/0003489419834952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767922PMC
June 2019

Perilymphatic Fistula After Penetrating Ear Trauma.

Clin Pract Cases Emerg Med 2019 May 4;3(2):115-118. Epub 2019 Mar 4.

David Geffen School of Medicine at the University of California Los Angeles, Department of Head and Neck Surgery, Los Angeles, California.

Pneumolabyrinth, defined as air within the labyrinth on high-resolution computed tomography, suggests that a perilymphatic fistula (PLF) is present. PLF describes an abnormal communication between the middle and inner ear, and can result in deafness, vertigo, and imbalance. In the setting of a penetrating injury to the temporal bone or inner ear, pneumolabyrinth should trigger prompt otolaryngology consultation and urgent surgical exploration. We describe a case in which a 49-year-old male presented with a traumatic PLF secondary to penetrating ear injury. Imaging demonstrated extensive pneumolabyrinth. Despite delay in diagnosis, expeditious surgical intervention resulted in successful preservation of inner ear function.
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http://dx.doi.org/10.5811/cpcem.2019.1.37404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497203PMC
May 2019

Temporal Bone Histopathology of First-Generation Cochlear Implant Electrode Translocation.

Otol Neurotol 2019 07;40(6):e581-e591

Department of Head and Neck Surgery.

Objective: To evaluate the histopathology of human temporal bones (HTBs) with cochlear implants (CI).

Background: Understanding CI translocation injuries is critical for improving outcomes.

Material And Methods: Thirteen HTBs from 12 CI patients were studied. Six HTBs exhibited translocation with localized injury (Group 1) and seven HTBs exhibited translocation with significant lateral wall injury (Group 2). There were no significant differences between Group 1 and Group 2 for age at death, age at implantation, and years with CI.

Results: Four out of six of Group 1 had round window approach, while all seven of Group 2 had cochleostomy approach. Translocation injuries tended to occur near 180 degrees of angular insertion with a mean of 186.36 ± 51.62 degrees. Average CI insertion length for Group 2 was 21.86 ± 2.55 mm, significantly longer than Group 1 at 18.50 ± 3.33 mm (p = 0.031). Group 1 had an average of 17300 ± 9415 spiral ganglia neurons (SGNs) while Group 2 had significantly fewer SGNs 6714 ± 4269 (p = 0.015). Group 1 average auditory performance of 66.55 ± 27.20% was higher than that of Group 2 of 39.86 ± 15.36%. Group 2 had a high degree of osteoneogenesis and infiltration of cells generally localized to areas of translocation injury and cochleostomy.

Conclusion: Translocation injuries tend to occur at an insertion angle of 180 degrees, at 9 to 10 mm. Lateral wall injury and damage to the organ of Corti incites fibrosis, osteoneogenesis, and infiltration, lower SGN count and poorer auditory performance. Longer electrodes were more prone to translocation and higher chance of significant intracochlear injury.
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http://dx.doi.org/10.1097/MAO.0000000000002247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565463PMC
July 2019

A Histopathologic Comparison of Eustachian Tube Anatomy in Pediatric and Adult Temporal Bones.

Otol Neurotol 2019 03;40(3):e233-e239

House Ear Clinic, Los Angeles, California.

Hypothesis: In children, the distance between the carotid canal (CC) and Eustachian tube (ET) is not significantly narrower than the adult population.

Background: ET dysfunction treated with ET dilation is FDA approved for adults. Several studies describe the close relationship between the CC and the ET in adults, but the anatomy of the ET has not been well defined in children. This study seeks to investigate these relationships in the pediatric population.

Methods: Histologic sections from 23 temporal bones of pediatric patients ages 0 to 18 were reviewed by two independent observers. The distance between the CC and the cartilaginous Eustachian tube (CET), bony-cartilaginous junction (BCJ), and bony Eustachian tube (BET) were measured. Fifteen adult temporal bones were used as a control group.

Results: The distance to the CC was narrowest at the BET, and was actually higher in the pediatric population when compared to adults (0.5 mm and 0.2 mm, respectively, p = 0.06). The CC-CET distance was smaller in the pediatric group (2.3 mm vs 3.3 mm, p < 0.01). The bony-cartilaginous junction is often the region of most concern during dilation. There was no significant difference between the CC-BET distance in pediatric and adult groups (1.9 vs 2.3 mm, p = 0.20).

Conclusions: CET-CC is smaller in the pediatric population, as expected due to smaller anatomic structures. However, the variable incline of the ET results in a CC-BCJ distance that is similar to the adult population. Although imaging studies are necessary.
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http://dx.doi.org/10.1097/MAO.0000000000002112DOI Listing
March 2019

Effect of Tinnitus and Duration of Deafness on Sound Localization and Speech Recognition in Noise in Patients With Single-Sided Deafness.

Trends Hear 2018 Jan-Dec;22:2331216518813802

4 Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Patients with single-sided deafness (SSD) often experience poor sound localization, reduced speech understanding in noise, reduced quality of life, and tinnitus. The present study aims to evaluate effects of tinnitus and duration of deafness on sound localization and speech recognition in noise by SSD subjects. Sound localization and speech recognition in noise were measured in 26 SSD and 10 normal-hearing (NH) subjects. Speech was always presented directly in front of the listener. Noise was presented to the deaf ear, in front of the listener, or to the better hearing ear. Tinnitus severity was measured using visual analog scale and Tinnitus Handicap Inventory. Relative to NH subjects, SSD subjects had significant deficits in sound localization and speech recognition in all listening conditions ( p < .001). For SSD subjects, speech recognition in noise was correlated with mean hearing thresholds in the better hearing ear ( p < .001) but not in the deaf ear. SSD subjects with tinnitus performed poorer in sound localization and speech recognition in noise than those without tinnitus. Shorter duration of deafness was associated with greater tinnitus and sound localization difficulty. Tinnitus visual analog scale and Tinnitus Handicap Inventory were highly correlated; the degree of tinnitus was negatively correlated with sound localization and speech recognition in noise. Those experiencing noticeable tinnitus may benefit more from cochlear implantation than those without; subjective tinnitus reduction may be correlated with improved sound localization and speech recognition in noise. Subjects with longer duration of deafness demonstrated better sound localization, suggesting long-term compensation for loss of binaural cues.
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http://dx.doi.org/10.1177/2331216518813802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291880PMC
April 2019

Middle ear lipoma mimicking a congenital cholesteatoma: A case report and review of the literature.

Int J Pediatr Otorhinolaryngol 2018 Dec 22;115:110-113. Epub 2018 Sep 22.

Department of Head & Neck Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, USA. Electronic address:

Objective: To describe a case of middle ear lipoma, review the current literature, and discuss the surgical approach.

Methods: Published case reports in the English literature of lipomas restricted to the middle ear were reviewed. The presentation, location, and management of the middle ear lipomas were analyzed.

Results: Histological examination of the resected middle ear lesion was compatible with lipoma. Review of the literature suggests middle ear lipomas are rare and involve the epitympanum.

Conclusion: Lipomas should be included in the differential diagnosis for middle ear lesions. Adequate surgical exposure can be achieved through a transcanal approach, with particular attention to carefully elevate the tympanic membrane off the malleus, preserving the integrity of the ossicular chain.
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http://dx.doi.org/10.1016/j.ijporl.2018.09.021DOI Listing
December 2018

Supporting cell survival after cochlear implant surgery.

Laryngoscope 2019 01 16;129(1):E36-E40. Epub 2018 Oct 16.

Department of Otolaryngology-Head and Neck Surgery, Georgetown University Medical Center, Washington, DC.

Supporting cells (SCs) provide structure and maintain an environment that allows hair cells to receive and transmit signals in the auditory pathway. After insult to hair cells and ganglion cells, SCs respond by marking unsalvageable cells for death and maintain structural integrity. Although the histopathology after cochlear implantation has been described regarding hair cells and neural structures, surviving SCs in the implanted ear have not. We present a patient whose posthumous examination of an implanted cochlea demonstrated SC survival. This finding has implications for SC function in maintaining electrical hearing and candidacy for future hair cell regeneration therapies. Laryngoscope, 129:E36-E40, 2019.
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http://dx.doi.org/10.1002/lary.27539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320269PMC
January 2019

Oxidative Stress in the Blood Labyrinthine Barrier in the Macula Utricle of Meniere's Disease Patients.

Front Physiol 2018 3;9:1068. Epub 2018 Sep 3.

Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.

The blood labyrinthine barrier (BLB) is critical in the maintenance of inner ear ionic and fluid homeostasis. Recent studies using imaging and histopathology demonstrate loss of integrity of the BLB in the affected inner ear of Meniere's disease (MD) patients. We hypothesized that oxidative stress is involved in the pathogenesis of BLB degeneration, and to date there are no studies of oxidative stress proteins in the human BLB. We investigated the ultrastructural and immunohistochemical changes of the BLB in the vestibular endorgan, the macula utricle, from patients with MD ( = 10), acoustic neuroma (AN) ( = 6) and normative autopsy specimens ( = 3) with no inner ear disease. Each subject had a well-documented clinical history and audiovestibular testing. Utricular maculae were studied using light and transmission electron microscopy and double labeling immunofluorescence. Vascular endothelial cells (VECs) were identified using isolectin B4 (IB4) and glucose-transporter-1 (GLUT-1). Pericytes were identified using alpha smooth muscle actin (αSMA) and phalloidin. IB4 staining of VECS was consistently seen in both AN and normative. In contrast, IB4 was nearly undetectable in all MD specimens, consistent with the significant VEC damage confirmed on transmission electron microscopy. GLUT-1 was present in MD, AN, and normative. αSMA and phalloidin were expressed consistently in the BLB pericytes in normative, AN specimen, and Meniere's specimens. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and nitrotyrosine were used as markers of oxidative stress. The VECs of the BLB in Meniere's had significantly higher levels of expression of iNOS and nitrotyrosine compared with normative and AN specimen. eNOS-IF staining showed similar patterns in normative and Meniere's specimens. Microarray-based gene expression profiling confirmed upregulation of iNOS mRNA from the macula utricle of Meniere's patients compared with AN. Nitrotyrosine, a marker recognized as a hallmark of inflammation, especially when seen in association with an upregulation of iNOS, was detected in the epithelial and stromal cells in addition to VECs in MD. Immunohistochemical and ultrastructural degenerative changes of the VEC suggest that these cells are the primary targets of oxidative stress, and pericyte pathology including degeneration and migration, likely also plays a role in the loss of integrity of the BLB and triggering of inflammatory pathways in MD. These studies advance our scientific understanding of oxidative stress in the human inner ear BLB and otopathology.
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http://dx.doi.org/10.3389/fphys.2018.01068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129601PMC
September 2018

Immunohistochemical localization of megalin and cubilin in the human inner ear.

Brain Res 2018 12 12;1701:153-160. Epub 2018 Sep 12.

Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, United States. Electronic address:

Megalin and cubilin are endocytic receptors expressed in many absorptive polarized epithelia. These receptors have been implicated in the transport of gentamicin in the inner ear as possible contributors to ototoxic damage. Megalin and cubilin have been characterized in detail in the mouse and rat inner ear, but not in the human inner ear. In this study, megalin and cubilin were localized by immunohistochemistry using affinity-purified antibodies in formalin fixed frozen cryostat and celloidin embedded sections of the human inner ear. In the cochlea megalin and cubilin were localized in marginal cells of the stria vascularis, epithelial cells of the spiral prominence and the Reissner's membrane. In the macula utricle and cristae ampullaris, megalin and cubilin were localized in transitional and dark cells, but not in vestibular hair cells and supporting cells. In the endolymphatic duct megalin and cubilin were localized in the epithelial cells. The localization of megalin and cubilin in the human inner ear is consistent with previous reports in the inner ear of animal models and suggest that these receptors may play an important role in the inner ear endocytic transport, and maybe potential targets for prevention of ototoxic damage or the delivery of medications.
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http://dx.doi.org/10.1016/j.brainres.2018.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289768PMC
December 2018

Sudden hearing loss after cialis (tadalafil) use: A unique case of cochlear hydrops.

Laryngoscope 2018 11 12;128(11):2615-2618. Epub 2018 Sep 12.

Department of Head and Neck Surgery, Los Angeles, California, U.S.A.

We discuss a unique case of sudden sensorineural hearing loss after Cialis (tadalafil) use, a phosphodiesterase 5 (PDE5) inhibitor, and the implication of ipsilateral cochlear hydrops seen on magnetic resonance imaging (MRI). We report a case of a 53-year-old male with unilateral low-frequency sudden sensorineural hearing loss (SSNHL) after ingestion of tadalafil. The SSNHL occurred 1 day after ingestion and was associated with aural fullness and tinnitus. There were no symptoms of vertigo. He received oral prednisone immediately after the onset of hearing loss without improvement. Delayed intravenous contrast-enhanced three-dimensional Fluid-attenuated inversion recovery MRI revealed ipsilateral dilation of the cochlear duct without any hydronic change in the vestibular system. Acetazolamide therapy was initiated, and his symptoms improved. A posttreatment audiogram revealed an increase in threshold of 15 dB. To the best of our knowledge, this is the first case of cochlear hydrops visualized on imaging after a PDE5 inhibitor induced SSNHL. Tadalafil and other PDE5 inhibitors have a known association with SSNHL. Despite several proposed mechanisms, there is inconclusive evidence of a causal relationship. Our presented case suggests that cochlear hydrops may be one possible mechanism of PDE5 inhibitor-associated SSNHL. MRI should be considered in the evaluation of such patients who do not respond to oral steroids as initial treatment. Laryngoscope, 2615-2618, 2018.
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http://dx.doi.org/10.1002/lary.27428DOI Listing
November 2018

Immunohistochemical localization of Nrf2 in the human cochlea.

Brain Res 2018 12 5;1700:1-8. Epub 2018 Jul 5.

Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, USA. Electronic address:

Oxidative stress plays an important role in several inner ear diseases and normal aging. Nuclear (erythroid-derived 2)-like 2, also known as Nrf2, is a transcription factor encoded by the NFE2L2 gene that controls the expression of genes necessary to reduce oxidative stress. There are no studies to the date on the localization of Nrf2 in the human inner ear in normal or pathological conditions. Therefore, we investigated the immunohistochemical localization of Nrf2 in the human cochlea and vestibule using formalin-fixed celloidin-embedded human temporal bone sections. Nrf2 immunoreactivity (IR) was found in the inner and outer hair cells and supporting cells of the organ of Corti throughout the cochlea. Nfr2-IR was also found in hair cells and supporting cells of the maculae and cristae vestibular sensory epithelia. Nrf2-IR was decreased in the organ of Corti of older age individuals. The immunolocalization of Nrf2 in both auditory and vestibular sensory epithelia suggest that this transcription factor may play a relevant role in protecting sensory hair cells from oxidative stress.
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http://dx.doi.org/10.1016/j.brainres.2018.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231984PMC
December 2018

Connexin 26 Immunohistochemistry in Temporal Bones With Cochlear Otosclerosis.

Ann Otol Rhinol Laryngol 2018 Aug 17;127(8):536-542. Epub 2018 Jun 17.

2 UCLA, Los Angeles, California, USA.

Hypothesis: Connexin-26 (Cx26) expression is diminished in the spiral ligament of subjects with hearing loss and cochlear otosclerosis (CO).

Background: Human temporal bone (HTB) studies have demonstrated that CO is associated with hyalinization of the spiral ligament. We hypothesize that hyalinization is associated with a loss of fibrocytes with a consequent decline in Cx26 expression. Cx26 and Connexin-30 (Cx30) encode gap junction proteins expressed in supporting cells of the organ of Corti, the spiral limbus, stria vascularis, and in fibrocytes of the spiral ligament. These gap junctions are critical for potassium recycling and maintenance of the endocochlear potential. Diminished expression of these proteins would likely be associated with hearing dysfunction.

Methods: Histopathology and clinical characteristics of 45 HTB specimens with CO and spiral ligament hyalinization were reviewed. Those with sensorineural or mixed hearing loss but normal or near-normal hair cell counts were analyzed with light microscopy, and Cx26-immunoreactive (IR) signal was qualitatively assessed.

Results: H&E staining demonstrated hyalinization in the spiral ligament and loss of type II and type III fibrocytes. Cx26-IR was diminished throughout the cochlea affected with CO compared with normal controls.

Conclusions: Cx26-IR reduction in the spiral ligament of subjects with CO likely plays a role in hearing loss.
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http://dx.doi.org/10.1177/0003489418779410DOI Listing
August 2018

Cochlear implant histopathology.

World J Otorhinolaryngol Head Neck Surg 2017 Dec 6;3(4):211-213. Epub 2018 Mar 6.

Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, USA.

The microscopic examination of fifty-five serially sectioned implanted temporal bones has provided insight into what is being stimulated; and the changes that are the result of the insertion and presence of the implant. The ganglion cell bodies (neurons) are structures being stimulated (two laboratories have reported an inverse relationship of the number of neurons and performance). Insertion through the round window, verses a cochleostomy, produces the least fibrosis and new bone. Fibrosis and new bone do not affect the implant function unless they form in the scala vestibuli in the region of the ductus reuniens, and, block it; and produce cochlear hydrops resulting in a delayed low tone loss of hearing in hybrid implants. Animal models cannot be applied to humans because of the difference in size and myelination of the neurons.
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http://dx.doi.org/10.1016/j.wjorl.2017.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956136PMC
December 2017
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