Update on CD164 and LMX1A genes to strengthen their causative role in autosomal dominant hearing loss.

Novel hearing loss (HL) genes are constantly being discovered, and evidence from independent studies is essential to strengthen their position as causes of hereditary HL. To address this issue, we searched our genetic data of families with autosomal dominant HL (ADHL) who had been tested with high-throughput DNA sequencing methods. For CD164, only one pathogenic variant in one family has so far been reported. For LMX1A, just two previous studies have revealed its involvement in ADHL. In this study we found two families with the same pathogenic variant in CD164 and one family with a novel variant in LMX1A (c.686C>A; p.(Ala229Asp)) that impairs its transcriptional activity. Our data show recurrence of the same CD164 variant in two HL families of different geographic origin, which strongly suggests it is a mutational hotspot. We also provide further evidence for haploinsufficiency as the pathogenic mechanism underlying LMX1A-related ADHL.

IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (NPs) in Western populations is associated with TH2 cytokine polarization. IL-25, an IL-17 family cytokine, was recently reported to induce TH2-type immune responses and to contribute to several allergic diseases, such as atopic dermatitis and asthma. However, the role of IL-25 in Asian patients with nasal polyposis remains unclear. OBJECTIVE: We sought to determine the role of IL-25 in Asian patients with nasal polyposis and CRS. METHODS: We investigated IL-25 expression and its cellular origins in NPs of human subjects using immunohistochemistry (IHC), quantitative RT-PCR, and ELISA of NP tissues. Correlations between IL-25 expression and expression of other inflammatory markers in NP tissues were also explored. Anti-IL-25 neutralizing antibody was administered in an ovalbumin- and staphylococcal enterotoxin B-induced murine NP model to confirm the function of IL-25 during nasal polypogenesis. RESULTS: IL-25 expression was upregulated in NP mucosa from patients with CRS with NPs compared with uncinate process tissue from control subjects and those with CRS without NPs. Overexpression of epithelial IL-25 was confirmed by using IHC, and double IHC staining showed that tryptase-positive cells were one of the main sources of IL-25 among immune cells. Furthermore, IL-17 receptor B levels were also increased in immune cells of patients with NPs compared with those in control subjects. In NPs IL-25 mRNA expression positively correlated with the expression of several inflammatory markers, including T-box transcription factor, RAR-related orphan receptor C, GATA3, eosinophil cationic protein, TGF-ß1, and TGF-ß2. IL-25 was more abundant in the murine NP model compared with control mice, and similar correlations between IL-25 and inflammatory markers were observed in murine models. Anti-IL-25 treatment reduced the number of polyps, mucosal edema thickness, collagen deposition, and infiltration of inflammatory cells, such as eosinophils and neutrophils. This treatment also inhibited expression of local inflammatory cytokines, such as IL-4 and IFN-γ. Furthermore, expression of CCL11, CXCL2, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in the nasal mucosa was suppressed in the anti-IL-25-treated group. CONCLUSION: Our results suggest that IL-25 secreted from the sinonasal epithelia and infiltrating mast cells plays a crucial role in the pathogenesis of CRS with NPs in Asian patients. In addition, our results suggest the novel possibility of treating nasal polyposis with anti-IL-25 therapy.

Optimal combination of neural temporal envelope and fine structure cues to explain speech identification in background noise.

The dichotomy between acoustic temporal envelope (ENV) and fine structure (TFS) cues has stimulated numerous studies over the past decade to understand the relative role of acoustic ENV and TFS in human speech perception. Such acoustic temporal speech cues produce distinct neural discharge patterns at the level of the auditory nerve, yet little is known about the central neural mechanisms underlying the dichotomy in speech perception between neural ENV and TFS cues. We explored the question of how the peripheral auditory system encodes neural ENV and TFS cues in steady or fluctuating background noise, and how the central auditory system combines these forms of neural information for speech identification. We sought to address this question by (1) measuring sentence identification in background noise for human subjects as a function of the degree of available acoustic TFS information and (2) examining the optimal combination of neural ENV and TFS cues to explain human speech perception performance using computational models of the peripheral auditory system and central neural observers. Speech-identification performance by human subjects decreased as the acoustic TFS information was degraded in the speech signals. The model predictions best matched human performance when a greater emphasis was placed on neural ENV coding rather than neural TFS. However, neural TFS cues were necessary to account for the full effect of background-noise modulations on human speech-identification performance.

Fabrication and evaluation of an improved polymer-based cochlear electrode array for atraumatic insertion.

An atraumatic cochlear electrode array has become indispensable to high-performance cochlear implants such as electric acoustic stimulation (EAS), wherein the preservation of residual hearing is significant. For an atraumatic implantation, we propose and demonstrate a new improved design of a cochlear electrode array based on liquid crystal polymer (LCP), which can be fabricated by precise batch processes and a thermal lamination process, in contrast to conventional wire-based cochlear electrode arrays. Using a thin-film process of LCP-film-mounted silicon wafer and thermal press lamination, we devise a multi-layered structure with variable layers of LCP films to achieve a sufficient degree of basal rigidity and a flexible tip. A peripheral blind via and self-aligned silicone elastomer molding process can reduce the width of the array. Measuring the insertion and extraction forces in a human scala tympani model, we investigate five human temporal bone insertion trials and record electrically evoked auditory brainstem responses (EABR) acutely in a guinea pig model. The diameters of the finalized electrode arrays are 0.3 mm (tip) and 0.75 mm (base). The insertion force with a displacement of 8 mm from a round window and the maximum extraction force are 2.4 mN and 34.0 mN, respectively. The electrode arrays can be inserted from 360° to 630° without trauma at the basal turn. The EABR data confirm the efficacy of the array. A new design of LCP-based cochlear electrode array for atraumatic implantation is fabricated. Verification indicates that foretells the development of an atraumatic cochlear electrode array and clinical implant.

Neurocognitive outcome in survivors of childhood acute lymphoblastic leukemia: experience at a tertiary care hospital in Korea.

This study was conducted to investigate long-term neurocognitive outcomes and to determine associated risk factors in a cohort of Korean survivors of childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL were compared with 42 healthy controls on measures of a neurocognitive test battery. We analysed potential risk factors (cranial irradiation, sex, age at diagnosis, elapsed time from diagnosis, and ALL risk group) on neurocognitive outcomes. ALL patients had lower, but non-significant full-scale intelligence quotient (FSIQ, 107.2±12.2 vs. 111.7±10.2), verbal intelligence quotient (VIQ, 107.7±13.6 vs. 112.2±11.4), and performance intelligence quotient (PIQ, 106.3±14.2 vs. 110.1±10.7) scores than healthy controls. However, patients treated with cranial irradiation performed significantly lower on FSIQ (102.2±8.1), VIQ (103.3±11.7), and PIQ (101.4±13.2) compared to non-irradiated patients and healthy controls. ALL patients also had poor attention, concentration, and executive functions. Among ALL survivors, cranial irradiation was a risk factor for poor FSIQ, being male was a risk factor for poor PIQ, and younger age was a risk factor for poor attention. Therefore, the delayed cognitive effects of ALL treatment and its impact on quality of life require continuing monitoring and management.

Long-term outcome of cochlear implant in patients with chronic otitis media: one-stage surgery is equivalent to two-stage surgery.

This study compared long-term speech performance after cochlear implantation (CI) between surgical strategies in patients with chronic otitis media (COM). Thirty patients with available open-set sentence scores measured more than 2 yr postoperatively were included: 17 who received one-stage surgeries (One-stage group), and the other 13 underwent two-stage surgeries (Two-stage group). Preoperative inflammatory status, intraoperative procedures, postoperative outcomes were compared. Among 17 patients in One-stage group, 12 underwent CI accompanied with the eradication of inflammation; CI without eradicating inflammation was performed on 3 patients; 2 underwent CIs via the transcanal approach. Thirteen patients in Two-stage group received the complete eradication of inflammation as first-stage surgery, and CI was performed as second-stage surgery after a mean interval of 8.2 months. Additional control of inflammation was performed in 2 patients at second-stage surgery for cavity problem and cholesteatoma, respectively. There were 2 cases of electrode exposure as postoperative complication in the two-stage group; new electrode arrays were inserted and covered by local flaps. The open-set sentence scores of Two-stage group were not significantly higher than those of One-stage group at 1, 2, 3, and 5 yr postoperatively. Postoperative long-term speech performance is equivalent when either of two surgical strategies is used to treat appropriately selected candidates.

Sensorineural hearing loss: a complication of acute otitis media in adults.

We aim to evaluate the incidence and clinical manifestations of sensorineural hearing loss (SNHL) in adult patients with acute otitis media (AOM). Seventy-five patients (age > 18 years; 83 ears) diagnosed with AOM between January 2008 and March 2011 at our clinic were enroled and retrospectively reviewed. We detected audiometrically confirmed SNHL during the course of AOM in eight patients. The clinical course, treatment, and audiometric final outcome of each case were reviewed. SNHL was associated with AOM in 8 out of 83 ears (9.3%). The mean age of patients was 57.5 years, and the mean follow-up period was 21.1 months (range 0.6-46.3 months). The most common symptom was tinnitus. Mean bone conduction hearing threshold was 39.5 dB in pure tone audiometry. All patients showed high-frequency HL, and three showed pan-frequency HL. All patients were treated with oral antibiotics at the initial visit. Seven ears were treated with a combination of oral steroids. Myringotomy was also performed. Seven of eight patients showed improvement; however, 8 kHz thresholds were not improved. This suggested that the inflammation spread through the round window. The mean duration of recovery was 18.6 days. SNHL associated with AOM in adult patients occurs during the early phases of the disease course. High-frequency hearing was commonly affected and was well treated with oral antibiotics, myringotomy, and steroid therapy. Audiometry can be helpful for treating adult patients with AOM. Active treatment, including myringotomy, should be performed during the early phase, if SNHL is suspected.

Transcriptomic analysis reveals prolonged neurodegeneration in the hippocampus of adult C57BL/6N mouse deafened by noise.

Introduction: Several studies have reported a significant correlation between noise-induced hearing loss and cognitive decline. However, comprehensive analyses of this relationship are rare. This study aimed to assess the influence of hearing impairment on cognitive functions by analyzing organ samples in the afferent auditory pathway of deafened mice using mRNA sequencing. Methods: We prepared 10 female 12-week-old C57BL/6N mice as the experimental and control groups in equal numbers. Mice in the experimental group were deafened with 120 dB sound pressure level (SPL) wideband noise for 2 h. Cochlea, auditory cortex, and hippocampus were obtained from all mice. After constructing cDNA libraries for the extracted RNA from the samples, we performed next-generation sequencing. Subsequently, we analyzed the results using gene ontologies (GOs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases for differentially expressed genes (DEGs) of each organ. Results: Our results revealed 102, 89, and 176 DEGs for cochlea, auditory cortex, and hippocampus, respectively. We identified 294, 203, and 211 GOs; 10, 7, and 17 KEGG pathways in the cochlea, auditory cortex, and hippocampus, respectively. In the long term (12 weeks) from noise-induced hearing loss, GOs and KEGG pathways related to apoptosis or inflammation persisted more actively in the order of hippocampus, auditory cortex, and cochlea. Discussion: This implies that the neurodegenerative effects of noise exposure persist more longer time in the central regions.

Microplastic polyethylene induced inner ear dysfunction in murine model.

While the hazardous effects of microplastics (MPs) are increasingly reported, it remains uncertain if MPs induce inner ear dysfunction. Nonetheless, prevalence of inner ear dysfunction was observed across all age groups. In this study, we investigated whether MP polyethylene affect inner ear function in a murine model. To detect hearing loss and balance defect after polyethylene (PE) exposure, we evaluated hearing threshold levels, assessed cerebral glucose metabolism, conducted transcriptome analysis, and performed behavioral studies. C57BL/6 J mice (5-week-old) were grouped into control (n = 10) and PE-fed groups (n = 10). Mice were orally administered 100 ppm/100 µL (equivalent to 10 µg) of PE every day for 4 months. We identified the accumulation of PE in the cochlea and vestibular region. The fragmented PE in inner ear was 3.00 ± 0.38 µm in size; the administered PE concentration was 1.14 ± 1.06 mg/g. Fourier transform infrared spectrometry confirmed that the properties of the MP were identical with those of PE fed to the mice. Transcriptomic analysis showed up-regulation of PER1, NR4A3 and CEBPB at the PE exposed inner ear tissue and it was confirmed using qRT-PCR, western blotting, and immunofluorescence staining. We observed abnormalities in balance related behavior assessment in the PE group. Exposure to PE increased the hearing thresholds and decreased glucose metabolism in the bilateral lateral entorhinal cortex, right primary auditory cortex, and right secondary auditory cortex. We can conclude that PE exposure induced inner ear dysfunction such as hearing loss and balance disorder.

Sex differences in associated factors for age-related hearing loss.

The prevalence and age of onset of hearing loss differ according to sex. This study aimed to identify associated factors for age-related hearing loss (ARHL) and determine whether there are differences between males and females regarding associated factors for ARHL. This cross-sectional study used data from adults who underwent medical examinations including hearing tests from 2011 to 2021. A total of 2,349 individuals were included. The study conducted sex-specific analyses using both univariate and multiple regression. Univariate analysis employed logistic regression, while multiple regression involved variable selection through the augmented backward elimination method. Separate multiple logistic regression analyses were conducted for each sex. In the univariate analysis, among males, age, underweight, alcohol consumption, weight, and height exhibited statistical significance. Among females, age, hypertension, diabetes, dyslipidemia, obesity, sarcopenia, weight, height, age at menarche, and duration of hormone exposure were found to be significant factors. However, in the multiple logistic regression model for males, underweight, and smoking emerged as significant, while in females, age, weight, obesity, and age at menarche retained their significance. We found that there are different associated factors for ARHL in each sex. Assessment and counseling for smoking, obstetric history, underweight, and obesity may be beneficial in managing patients with ARHL.

Management of External Auditory Canal Anterior Wall Defect: A Case Series and Literature Review.

OBJECTIVES: Although rare in etiology, anterior bony wall defects of the external auditory canal (EAC) accompanied by temporomandibular joint herniation may cause various otologic symptoms. Surgical treatment can be considered based on symptom severity because many previous case reports have highlighted its efficacy. This study aimed to review the long-term results of surgical treatment of EAC anterior wall defect and to suggest a stepwise approach when creating a treatment plan. METHODS: We performed a retrospective review of 10 patients who underwent surgical management to address the EAC anterior wall defect and its associated symptoms. Medical records, temporal bone computed tomography scans, audiometry, and endoscopic examination findings were analyzed. RESULTS: The primary repair of the EAC defect was the first to be surgically addressed in most cases, excluding one case with a severe combined infection. Of the 10 cases, 3 patients exhibited either postoperative complications or symptom recurrence. Six patients had resolved symptoms consequent to primary surgical repair, and four patients underwent revision surgery undergoing a more invasive procedure, such as canalplasty or mastoidectomy. CONCLUSION: Primary repair of the anterior wall defect of the EAC seems to be overpromoted for lasting results but is not as promising as previously noted. We therefore propose to create a novel treatment flowchart regarding the surgical treatment of anterior wall defects of the EAC based on clinical experience. LEVEL OF EVIDENCE: IV.

Increased Resting-State Positron Emission Tomography Activity After Cochlear Implantation in Adult Deafened Cats.

OBJECTIVES: Cochlear implants are widely used for hearing rehabilitation in patients with profound sensorineural hearing loss. However, Cochlear implants have variable. RESULTS: and central neural plasticity is considered to be a reason for this variability. We hypothesized that resting-state cortical networks play a role in conditions of profound hearing loss and are affected by cochlear implants. To investigate the resting-state neuronal networks after cochlear implantation, we acquired 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) images in experimental animals. METHODS: Eight adult domestic cats were enrolled in this study. The hearing threshold of the animals was within the normal range, as measured by auditory evoked potential. They were divided into control (n=4) and hearing loss (n=4) groups. Hearing loss was induced by co-administration of ethacrynic acid and kanamycin. FDG-PET was performed in a normal hearing state and 4 and 11 months after the deafening procedure. Cochlear implantation was performed in the right ear, and electrical cochlear stimulation was performed for 7 months (from 4 to 11 months after the deafening procedure). PET images were compared between the two groups at the three time points. RESULTS: Four months after hearing loss, the auditory cortical area's activity decreased, and activity in the associated visual area increased. After 7 months of cochlear stimulation, the superior marginal gyrus and cingulate gyrus, which are components of the default mode network, showed hypermetabolism. The inferior colliculi showed hypometabolism. CONCLUSION: Resting-state cortical activity in the default mode network components was elevated after cochlear stimulation. This suggests that the animals' awareness level was elevated after hearing restoration by the cochlear implantation.

Sleep disturbance and dysregulation of circadian clock machinery in sudden sensorineural hearing loss.

BACKGROUND: The cochlea contains a robust biological clock associated with auditory function, exhibiting diurnal sensitivity to noise or ototoxicity. OBJECTIVES: We examined the relationship between disrupted circadian rhythm and altered expression of circadian clock genes in patients with sudden sensorineural hearing loss (SSNHL) and explored whether the circadian clock genes serve as prognostic biomarkers. MATERIAL AND METHODS: Twelve patients with SSNHL were enrolled study group. Twelve people with normal hearing were enrolled voluntarily for comparison. Audiological evaluation was performed to evaluate hearing thresholds. Korean version of the Pittsburgh Sleep Quality Index Questionnaire was performed to evaluate sleep quality and patterns. Circadian clock genes including for PERI, PER2, PER3, CRYI, CRY2, CLOCK, ARNTL, CSNKIE, and TIMELESS expression in blood were evaluated using real-time quantitative PCR method. RESULTS: Compared with healthy controls without hearing loss, most of the circadian clock genes were markedly downregulated, coupled with low sleep quality and disturbing patterns, in patients with SSNHL. Intriguingly, a weak correlation between hearing improvement following steroid treatment and altered levels of circadian clock genes was observed. CONCLUSIONS AND SIGNIFICANCE: This study provides an additional basis for the relevance of disrupted circadian rhythm to SSNHL and suggests a possible prognostic biomarker for SSNHL treatment.

Early combination treatment with intratympanic steroid injection in severe to profound sudden sensorineural hearing loss improves speech discrimination performance.

The objective of the study was to determine the therapeutic efficacy of early combined treatment with intratympanic steroid injection (ITSI) in patients with severe to profound sudden sensorineural hearing loss (SSNHL), who did not respond to initial systemic steroid treatment (SST). The study design included historical controlled trials (retrospective analysis for the SST group). Patients (n = 73; 38 women and 35 men) diagnosed with severe to profound SSNHL at the time of their first visit in tertiary referral centers were recruited. Among these 73 patients, 30 patients who showed no early response within a week after the start of initial SST were prospectively included as the ITSI group. ITSI was performed twice a week for two consecutive weeks. In contrast, 43 patients with the same condition who did not receive ITSI were retrospectively included as the SST group. For each group, pure-tone audiogram (PTA) and speech discrimination score (SDS) tests were performed before SST and more than 2 months after termination of treatment in each group. After termination of each treatment, the final average gain on PTA showed no significant difference between the two groups; however, the final average gain of SDS demonstrated a significantly better recovery in the ITSI group. ITSI as part of an early combined therapy represents an effective treatment in terms of the improvement of SDS in severe to profound SSNHL showing no early response to initial SST.

Usefulness of computed tomography Hounsfield unit density in preoperative detection of cholesteatoma in mastoid ad antrum.

PURPOSE: This study was performed to evaluate the usefulness of Hounsfield unit (HU) to better distinguish cholesteatoma from other inflammatory conditions in the mastoid ad antrum before primary mastoid surgery. MATERIALS AND METHODS: We enrolled 82 patients who underwent tympanomastoidectomy for treatment of chronic otitis. Forty-one patients were pathologically diagnosed with cholesteatoma, whereas the others were diagnosed with inflammatory granulation. These lesions were confirmed, and HU was measured in preoperative computed tomography. The difference in HU between cholesteatoma and non-cholesteatoma tissues was analyzed, and the improvement in the diagnosis of cholesteatoma after inclusion of HU data was calculated. RESULTS: The HU was calculated as 42.68 ± 24.42 in the cholesteatoma group and 86.07 ± 26.50 in the non-cholesteatoma group. The differences between the 2 groups were statistically different (Student t test, P < .01). By applying the HU, the sensitivity (51.2%-80.5%), specificity (80.5%-87.8%), positive predictive value (72.4%-86.8%), and negative predictive value (62.3%-81.8%) to diagnose cholesteatoma improved. CONCLUSIONS: The HU density was found to be statistically different between cholesteatoma and inflammatory granulation tissue in mastoid antrum. An improved diagnosis of cholesteatoma was achieved after adjusting for the HU.

Clinicoradiologic Characteristics of Temporal Bone Meningioma: Multicenter Retrospective Analysis.

OBJECTIVES/HYPOTHESIS: Meningioma is a neoplasm arising from cells related to the arachnoid villi. The aim of the present study was to explore the clinical and radiological characteristics of temporal bone meningioma (TBM) in a multicenter cohort. STUDY DESIGN: Retrospective cohort study. METHODS: Thirteen patients diagnosed with TBM at eight medical institutes between 1998 and 2018 were retrospectively enrolled. The clinical procedures, symptoms, signs, and images that led to the diagnosis of TBM were investigated for all patients. RESULTS: The most common symptom at the initial visit was hearing loss (n = 12/13, 92.3%). All patients exhibited unilateral TBMs with varied symptom durations (1-60 months). Four patients presented masses occupying the external auditory canal; the tympanic membrane (TM) could not be evaluated. The other nine patients did not show TM perforation despite the presence of inflammatory signs. The majority of patients exhibited unilateral conductive or mixed hearing loss. A retrospective review of temporal bone computed tomography (TBCT) images revealed findings suggestive of a tumor in all patients. However, three patients had been misdiagnosed with chronic otitis media and were subjected to tympanomastoidectomy (n = 3/7, 42.9%). TBCT findings that suggested TBM included diffuse trabecular hyperostosis in the middle and posterior cranial fossae and widening and destruction of the temporal bone in the jugular bulb area. CONCLUSIONS: TBM should be suspected if patients exhibit persistent inflammatory symptoms or signs involving intact TM or unilateral conductive or mixed hearing loss with trabecular hyperostosis or destruction of the temporal bone on computed tomography images. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:173-178, 2021.

Transcriptome Analysis of Deafness: Intracellular Signal Transduction Signaling Pathways Regulate Neuroplastic Changes in the Auditory Cortex.

HYPOTHESIS AND BACKGROUND: Hearing loss leads to synaptic changes in auditory neurons and their networks, and functions as a consequence of the interplay between genes and proteins. However, cellular and molecular mechanisms leading to deafness-induced plasticity in the auditory cortex (AC) remain unclear. Here, we examined the changes in gene expression and key signaling pathways that regulate differentially expressed genes (DEGs) in the AC following auditory deafferentation using RNA-sequencing (RNA-Seq) analysis. METHODS: Cochlear ablation-induced bilaterally deafened Sprague-Dawley rats were maintained for 12 weeks and their ACs were harvested. RNA-seq analysis was performed on each sample to identify which genes were expressed. This information was then used for comparative analysis of DEGs between samples. The statistical significance of DEGs was determined by fold change (|FC| > 1.5) and independent t test (p < 0.05). RESULTS: RNA-seq analysis identified 72 DEGs, of which 19 were upregulated and 53 were down-regulated after bilateral deafening in the ACs. Gene ontology (GO) analysis revealed the potential involvement of mitogen-activated protein kinase, tumor necrosis factor, and cyclic adenosine 3',5'-monophosphate (e.g., Bdnf, Gli1, and c-Fos) signaling pathways in regulating changes in the expression of the genes listed herein. The DEGs of interest-including c-Fos, Arc, Ntf3, and Gli1-from the RNA-seq analysis were consistent with result of quantitative reverse transcriptase polymerase chain reaction. CONCLUSION: RNA-seq analysis revealed that auditory deprivation in adult rats elicited changes in gene expression, transcription factor levels, and their complex interaction at specific gene promoters in the AC. Particularly, activation of intracellular signal transduction signaling pathways may be key to neuronal plasticity in deafness.

Clinical Characteristics of Patients with Cochlear Fistulas Caused by Chronic Otitis Media with Cholesteatoma.

OBJECTIVES: To analyze the clinical characteristics of cochlear fistulas (CFs) and propose a new fistula classification system with regard to the cochlea. MATERIALS AND METHODS: A retrospective chart review was conducted between January 2008 and December 2015 to identify patients who had undergone surgery for cholesteatoma with an associated CF. The following data were collected: preoperative symptoms, findings of temporal bone computed tomography (TBCT), fistula stage, cholesteatoma classification, surgical technique, and pre- and postoperative pure-tone audiometry. RESULTS: We analyzed a total of 159 patients, out of which 9 (5.7%) were diagnosed with a CF. The average duration of the chronic otitis media was 19.8 years. Cholesteatomas that induced CF rarely existed in the nonaggressive state; recurrent otorrhea was observed in all but one of our subjects. All the patients with CF had a distinct origin of cholesteatoma that developed from the retraction of posterior pars tensa; further, 88.9% cholesteatomas extended to and filled the sinus tympani. Preoperative audiometry revealed total hearing loss in 4 (44.4%) patients. Further, five patients with residual hearing before surgery had stage I fistulas, and the bone conduction thresholds remained stable after surgery. CONCLUSION: Cochlear fistulas were often detected in patients with (1) a history of chronic otitis media (exceeding 10 years), (2) frequently recurring otorrhea, and (3) pars tensa cholesteatomas that extended to the posterior mesotympanum and filled the sinus tympani. Such patients can suffer from potentially severe and irreparable sensorineural hearing loss.

Influence of Cochlear Dead Regions on Hearing Outcome in Sudden Sensorineural Hearing Loss.

OBJECTIVE: The aims of this multicenter study were to prospectively evaluate the prevalence of dead regions (DRs) in sudden sensorineural hearing loss (SSNHL) and compare the clinical characteristics and hearing outcomes of SSNHL according to the presence of DRs. STUDY DESIGN: Prospective study. SETTING: Multicenter study. PATIENTS AND METHODS: The threshold-equalizing noise (TEN) test was prospectively performed on a total of 130 patients diagnosed with SSNHL. All patients received systemic steroid therapy and/or intratympanic steroid injection within 1 month after onset. Pure-tone audiograms and the TEN test were conducted before and after steroid treatment. Age, sex, side of affected ear, recurrence, onset of symptoms, presence of dizziness, and comorbid diseases were also collected. The prevalence of DRs in SSNHL and clinical factors related to the DRs were assessed. Hearing outcomes for SSNHL according to DRs were evaluated in 68 patients who followed a pure-tone audiogram. RESULTS: The overall prevalence of one or more DRs in SSNHL evaluated using the TEN test was 20.8% (27/130 subjects) and the overall frequency-specific prevalence of DR was 6.7% (61/910 DRs). Although the DRs (+)and DR (-) groups had similar initial pure-tone thresholds, the DRs (+) group had significantly worse initial WRS compared to the DRs (-) group (p = 0.015). The presence of DRs was not associated with hearing recovery in a multivariate logistic regression model, but it was significantly associated with the degree of hearing gain in a multivariate linear regression model (p = 0.018). CONCLUSIONS: The presence of DRs can be considered one of the poor prognostic factors for SSNHL and the TEN test may contribute to assess the prognosis of SSNHL in clinical settings.

Conductive Hearing Loss Aggravates Memory Decline in Alzheimer Model Mice.

The study of cognitive impairment associated with hearing loss has recently garnered considerable interest. Epidemiological data have demonstrated that hearing loss is a risk factor for cognitive decline as a result of aging. However, no previous study has examined the effect of hearing loss in patients with cognitive problems such as Alzheimer's disease. Therefore, we investigated the effect of conductive hearing loss in an Alzheimer's mouse model. Positron emission tomography (PET) and magnetic resonance imaging (MRI) were used to evaluate changes in glucose metabolism and gray matter concentrations in the 5xFAD Alzheimer's Disease (AD) transgenic mouse model with and without conductive hearing loss (HL). Conductive hearing loss was induced using chronic perforation of the tympanic membrane. Behavioral data from the Y-maze and passive avoidance tests revealed greater memory deficits in the AD with HL (AD-HL) group than in the AD group. Following induction of hearing loss, lower cerebral glucose metabolism in the frontal association cortex was observed in the AD-HL group than in the AD group. Although lower glucose metabolism in the hippocampus and cerebellum was found in the AD-HL group than in the AD group at 3 months, the gray matter concentrations in these regions were not significantly different between the groups. Furthermore, the gray matter concentrations in the simple lobule, cingulate/retrosplenial cortex, substantia nigra, retrosigmoid nucleus, medial geniculate nucleus, and anterior pretectal nucleus at 7 months were significantly lower in the AD-HL group than in the AD group. Taken together, these results indicate that even partial hearing loss can aggravate memory impairment in Alzheimer's disease.