The OTOA gene (Locus: DFNB22) is reported to be one of the causative genes for non-syndromic autosomal recessive hearing loss. The copy number variations (CNVs) identified in this gene are also known to cause hearing loss, but have not been identified in Japanese patients with hearing loss. Furthermore, the clinical features of OTOA-associated hearing loss have not yet been clarified. In this study, we performed CNV analyses of a large Japanese hearing loss cohort, and identified CNVs in 234 of 2262 (10.3%, 234/2262) patients with autosomal recessive hearing loss. Among the identified CNVs, OTOA gene-related CNVs were the second most frequent (0.6%, 14/2262). Among the 14 cases, 2 individuals carried OTOA homozygous deletions, 4 carried heterozygous deletions with single nucleotide variants (SNVs) in another allele. Additionally, 1 individual with homozygous SNVs in the OTOA gene was also identified. Finally, we identified 7 probands with OTOA-associated hearing loss, so that its prevalence in Japanese patients with autosomal recessive hearing loss was calculated to be 0.3% (7/2262). As novel clinical features identified in this study, the audiometric configurations of patients with OTOA-associated hearing loss were found to be mid-frequency. This is the first study focused on the detailed clinical features of hearing loss caused by this gene mutation and/or gene deletion.

The current study was undertaken to explore the impact of cisplatin ototoxicity at a young adult age on the development of age-related hearing loss, both in terms of age of onset and severity of the hearing loss. For the study, 21 Fischer 344/NHsd rats were tested. All rats were tested for auditory brainstem responses (ABRs) at age 7 months and then 15 of the rats were exposed to 7 mg/kg cisplatin by intra-peritoneal infusion. The other 6 rats received saline infusions to serve as controls. Seven of the cisplatin rats were euthanized after an ABR test 7 days after cisplatin exposure to assess acute damage. The other 14 rats were tested monthly until age 18 months. Cisplatin caused acute ABR threshold shift at 30 and 40 kHz, but that acute hearing loss led to less age-related hearing loss at those frequencies. Cisplatin exposure led to a primarily additive interaction with age-related hearing loss at 20 kHz, with some exacerbation of hearing loss at age 16-18 months, along with a larger lesion of missing outer hair cells in the corresponding region of the cochlea. ABR P1 amplitude input-output functions were not significantly affected by the cisplatin exposure when controlling for threshold shift. Results indicate that cisplatin ototoxicity and age-related hearing loss interact antagonistically in the cochlear region damaged by cisplatin, and primarily show an additive interaction in the frequencies lower than the focus of the cisplatin damage.

Background. Sudden sensorineural hearing loss (SSHL) caused by opiate abuse or overuse has been well documented in the medical literature. Most documented case reports have involved either heroin or hydrocodone/acetaminophen. Recently, case reposts of methadone induced SSHL have been published. Case Report. We present the case of a 31-year-old man who developed SSHL after a methadone overdose induced stupor. He was subsequently restarted on methadone at his regular dose. On follow-up audiometry exams, he displayed persistent moderately severe sensorineural hearing loss bilaterally. Discussion. This case is notable because unlike all but one previously reported case, the patient-who was restated on methadone-did not make a complete recovery. Conclusion. Methadone overuse in rare cases causes SSHL.

This report reviewed 39 school-age children diagnosed as having a functional hearing loss utilizing auditory brainstem response (ABR) audiometry during the past 5 years at the Department of Otolaryngology, Kyushu University Hospital in Japan. Twenty-seven cases were females and 12 were males. Seven cases had a hearing loss unilaterally and 32 bilaterally. Although pure-tone audiometry revealed a variety of audiogram shapes, two-thirds of the cases had a flat or saucer-shaped audiogram with a mild to moderately severe hearing loss. ABR audiometry for the frequencies of 1, 2 and 4 kHz indicated a normal hearing threshold in 65 ears of 35 patients, and mild threshold elevations of at least one frequency in the remaining 6 ears of 4 patients. Three illustrative cases were demonstrated, and a discussion was held regarding the features in audiometric tests, and environmental factors surrounding the children with this condition. We emphasized that the physiological hearing measurement such as ABR audiometry should be performed when any discrepancy was noted between the patient's history and results of pure-tone audiometry, because of not infrequent occurrence of functional hearing loss.

(1) Background: Several types of hearing aids are available for the rehabilitation of vestibular-schwannoma (VS)-related hearing loss. There is a lack of recently published papers regarding this theme. The aim of the present work is to organize current knowledge. (2) Methods: A review of the literature regarding the topics "vestibular schwannoma", "hearing loss", and "hearing aid" was performed. Nineteen studies were thus considered. (3) Results: Conventional hearing aids, contralateral routing of signal (CROS) aids, bone anchored hearing aids (BAHA), and others are available options for hearing rehabilitation in VS patients. The speech discrimination score (SDS) is considered the best measure to assess candidacy for rehabilitation with hearing aids. The best hearing rehabilitative conditions in VS patients when using conventional hearing aid devices are a mild-moderate hearing loss degree with good word recognition (more than 50% SDS). CROS-Aid and BAHA are reported to be beneficial. CROS-Aid expands on the area of receiving hearing. BAHA aids use direct bone-conduction stimulation. Unfortunately, there are no available studies focused specifically on VS patients that compare CROS and BAHA technologies. (4) Conclusions: Hearing aids, CROS, and BAHA are viable options for rehabilitating hearing impairment in VS, but require an accurate case-by-case audiological evaluation for rehabilitating hearing impairment in VS. Further studies are needed to prove if what is currently known about similar hearing illnesses can be confirmed, particularly in the case of VS.

Variants in the CDH23 gene are known to be responsible for both syndromic hearing loss (Usher syndrome type ID: USH1D) and non-syndromic hearing loss (DFNB12). Our series of studies demonstrated that CDH23 variants cause a broad range of phenotypes of non-syndromic hearing loss (DFNB12); from congenital profound hearing loss to late-onset high-frequency-involved progressive hearing loss. In this study, based on the genetic and clinical data from more than 10,000 patients, the mutational spectrum, clinical characteristics and genotype/phenotype correlations were evaluated. The present results reconfirmed that the variants in CDH23 are an important cause of non-syndromic sensorineural hearing loss. In addition, we showed that the mutational spectrum in the Japanese population, which is probably representative of the East Asian population in general, as well as frequent CDH23 variants that might be due to some founder effects. The present study demonstrated CDH23 variants cause a broad range of phenotypes, from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss. Genotype (variant combinations) and phenotype (association with retinal pigmentosa, onset age) are shown to be well correlated and are thought to be related to the residual function defined by the CDH23 variants.

Congenital hearing impairment affects nearly 1 in every 1000 live births and is the most frequent birth defect in developed societies. Hereditary types of hearing loss account for more than 50% of all congenital sensorineural hearing loss cases and are caused by genetic mutations. HL can be either nonsyndromic, which is restricted to the inner ear, or syndromic, a part of multiple anomalies affecting the body. Nonsyndromic HL can be categorised by mode of inheritance, such as autosomal dominant (called DFNA), autosomal recessive (DFNB), mitochondrial, and X-linked (DFN). To date, 125 deafness loci have been reported in the literature: 58 DFNA loci, 63 DFNB loci, and 4 X-linked loci. Mutations in genes that control the adhesion of hair cells, intracellular transport, neurotransmitter release, ionic hemeostasis, and cytoskeleton of hair cells can lead to malfunctions of the cochlea and inner ear. In recent years, with the increase in studies about genes involved in congenital hearing loss, genetic counselling and treatment options have emerged and increased in availability. This paper presents an overview of the currently known genes associated with nonsyndromic congenital hearing loss and mutations in the inner ear.

Dengue is an acute febrile infectious disease, with high fever followed by symptoms flu-like. Dengue hemorrhagic fever (DHF) is a vascular leak syndrome and could present spontaneous bleeding and worsening of symptoms after some days. Dengue could have some ENT manifestations, however hearing loss is not one of them. Sudden hearing loss is considered as sensorineural or perceptual hearing loss with a sudden onset in a person without other prior otological history. The relation between infectious diseases and sudden hearing are been investigated, some viruses were already linked, but the relation between dengue virus and sudden hearing still remains unknown. This article has the goal of presenting a case of DHF that evolved with SSHL in his hospitalization process.

Directing gaze towards auditory events is a natural behavior. In addition to the well-known accuracy of auditory elicited gaze responses for normal binaural listening, their latency is a measure of possible clinical interest and methodological importance. The aim was to develop a clinically feasible method to assess sound localization latency (SLL), and to study SLL as a function of simulated unilateral hearing loss (SUHL) and the relationship with accuracy. Eight healthy and normal-hearing adults (18-40 years) participated in this study. Horizontal gaze responses, recorded by non-invasive corneal reflection eye-tracking, were obtained during azimuthal shifts (24 trials) of a 3-min continuous auditory stimulus. In each trial, a sigmoid function was fitted to gaze samples. Latency was estimated by the abscissa corresponding to 50% of the arctangent amplitude. SLL was defined as the mean latency across trials. SLL was measured in normal-hearing and simulated SUHL conditions (SUHL30 and SUHL43: mean threshold of 30 dB HL and 43 dB HL across 0.5, 1, 2, and 4 kHz). In the normal-hearing condition, the mean ± SD SLL was 280 ± 40 ms (n = 8) with a test-retest SD = 20 ms. A linear mixed model showed a statistically significant effect of listening condition on SLL. The SUHL30 and SUHL43 conditions revealed a mean SLL of 370 ± 49 ms and 540 ± 120 ms, respectively. Repeated measures correlation analysis showed a clear relationship between SLL and the average sound localization accuracy (R2 = 0.94). The rapid and reliable method to obtain SLL may be an important clinical tool for evaluation of binaural processing. Future studies in clinical cohorts are needed to assess whether SLL may reveal information about binaural processing abilities beyond that afforded by sound localization accuracy.

Recent breakthroughs in our understanding of sensorineural hearing loss etiology have encouraged the identification of novel hearing therapeutics, paving the way for precision hearing medicine. Critical to this field is the curation of health resources on hearing data. A systematic review of the literature was conducted to map existing (inter)national and regional datasets that include hearing data to inform the development of future hearing repositories. Systematic literature review was performed adhering to Preferred Reporting Items for Systematic Review and MetaAnalysis recommendations. Databases, including those from gray literature, were searched to identify publications reporting on phenotypic and/ or genotypic hearing data in May 2019. The databases reviewed were Medline, PubMed, Embase databases, and Google Scholar. Publications on local datasets were excluded. All hearing datasets identified in the screening process were noted. For each dataset, geography, context, objective, period of time run, numbers and demographics of participants, genomic data, hearing measures and instruments used were extracted and cataloged. One hundred and eighty-eight datasets were identified, containing hearing data on populations ranging from 100 to 1.39 million individuals, and all extracted data have been cataloged. This searchable resource has been made accessible online. This unique catalog provides an overview of existing datasets that contain valuable information on hearing. This can be used to inform the development of national and international patient data repositories for hearing loss and guide strategic collaboration between key stakeholder groups, pivotal to the delivery and development of sensorineural hearing loss precision diagnostics and treatments.

Although the mitochondrial DNA (mtDNA) mutations m.1555A > G and m.3243A > G are the primary causes of maternally inherited sensorineural hearing loss (SNHL), several other mtDNA mutations are also reported to be associated with SNHL.

Hearing loss is the most common sensory impairment in humans and currently disables 466 million people across the world. Congenital deafness affects at least 1 in 500 newborns, and over 50% are hereditary in nature. To date, existing pharmacologic therapies for genetic and acquired etiologies of deafness are severely limited. With the advent of modern sequencing technologies, there is a vast compendium of growing genetic alterations that underlie human hearing loss, which can be targeted by therapeutics such as gene therapy. Recently, there has been tremendous progress in the development of gene therapy vectors to treat sensorineural hearing loss (SNHL) in animal models in vivo. Nevertheless, significant hurdles remain before such technologies can be translated toward clinical use. These include addressing the blood-labyrinth barrier, engineering more specific and effective delivery vehicles, improving surgical access, and validating novel targets. In this review, we both highlight recent progress and outline challenges associated with in vivo gene therapy for human SNHL.

The purpose of this study was two-fold: 1) to identify differences in the characteristics of adopters and non-adopters of hearing aids (HAs); and 2) to investigate factors influencing the purchase of HA.

Mitochondrial dysfunction is associated with aging and age-related hearing loss (AHL). However, the precise mechanisms underlying the pathophysiology of hearing loss remain unclear. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) enables efficient intramitochondrial translation by catalyzing the deposition of 2-methylthio modifications on mitochondrial tRNAs. Here we investigated the effect of defective mitochondrial protein translation on hearing and AHL in a Cdk5rap1 deficiency C57BL/6 mouse model. Compared to control C57BL/6 mice, Cdk5rap1-knockout female mice displayed hearing loss phenotypically similar to AHL from an early age. The premature hearing loss in Cdk5rap1-knockout mice was associated with the degeneration of the spiral ligament and reduction of endocochlear potentials following the loss of auditory sensory cells. Furthermore, cultured primary mouse embryonic fibroblasts displayed early onset of cellular senescence associated with high oxidative stress and cell death. These results indicate that the CDK5RAP1 deficiency-induced defective mitochondrial translation might cause early hearing loss through the induction of cellular senescence and cochlear dysfunction in the inner ear. Our results suggest that the accumulation of dysfunctional mitochondria might promote AHL progression. Furthermore, our findings suggest that mitochondrial dysfunction and dysregulated mitochondrial tRNA modifications mechanistically cause AHL. Understanding the mechanisms underlying AHL will guide future clinical investigations and interventions in the attempt to mitigate the consequences of AHL.

By means of a questionnaire it was investigated how in individuals who had previously had normal hearing deafness influences their pleasure and habits in listening to music, and which role a hearing aid can play in this respect. Out of 330 questionnaires returned, 206 could be statistically evaluated. 95% reported that formerly they had liked music, light music coming from the radio being the most frequently mentioned type of music and medium. 36% had formerly played an instrument or had enjoyed singing. 79% feel that their deafness has affected their pleasure in listening to music. Most common complaints refer to the fact that everything sounds distorted and wrong, melodies cannot be recognised any longer, the text of songs is not understood. 60% are fitted with one hearing aid, 40% have binaural hearing aids. 67% report that the hearing aid has rendered listening to music again more pleasurable, and 74% use their hearing aid more or less regularly when listening to music. The distorted sound and the fast alternating between "too soft" and "too loud", forcing the subject to continually adjusting his hearing aid, seem to be among the most annoying features.

Due to the aging society, the incidence of age-related hearing loss (ARHL) is strongly increasing. Hearing loss has a high impact on various aspects of life and may lead to social isolation, depression, loss of gain control, frailty and even mental decline. Comorbidity of cognitive and sensory impairment is not rare. This might have an impact on diagnostics and treatment in the geriatric setting.

In the last half century, the life expectancy of beta-thalassemia patients has strikingly increased mostly due to regular blood transfusions and chelation treatments. The improved survival, however, has allowed for the emergence of comorbidities, such as hearing loss, with a non-negligible impact on the patients' quality of life. This thorough review analyzes the acquired knowledge regarding hearing impairment in this hereditary hemoglobinopathy, aiming at defining its prevalence, features, course, and possible disease- or treatment-related pathogenic factors. Following PRISMA criteria, we retrieved 60 studies published between 1979 and 2021. Diagnostic tools and criteria, forms of hearing impairment, correlations with beta-thalassemia phenotypes, age and sex, chelation treatment and laboratory findings including iron overload, were carefully searched, analyzed and summarized. In spite of the relatively high number of studies in the last 40 years, our knowledge is rather limited, and large prospective studies with homogeneous diagnostic tools and criteria are required to define all the aforementioned issues. According to the literature, the overall prevalence rate of hearing impairment is 32.3%; age, sex, and laboratory findings do not seem to correlate with hearing deficits, while the weak relationship with clinical phenotype and chelation treatment seems to highlight the presence of further yet to be identified pathogenic factors.

Acute sudden sensorineural hearing loss has been extensively described in the literature and is a well recognized clinical entity. The exact etiology for this entity has been difficult to ascertain. Multiple etiologies have been promoted including infectious agents, vascular abnormalities, acoustic trauma, metabolic disorders, and autoimmune syndromes. In some cases, neoplasms such as acoustic neurinoma can be identified. On occasion, ototoxic medications are present in the history. Moulonguet and Gougelot have associated mitral valve prolapse, microemboli, transient hemiparesis and sudden hearing loss. This report describes a patient who had sudden sensorineural hearing loss in conjunction with unstable angina pectoris, in whom coronary bypass surgery appeared to have resulted in acute and significant hearing improvement and stabilization.

Age-related hearing loss typically affects the hearing of high frequencies in older adults. Such hearing loss influences the processing of spoken language, including higher-level processing such as that of complex sentences. Hearing aids may alleviate some of the speech processing disadvantages associated with hearing loss. However, little is known about the relation between hearing loss, hearing aid use, and their effects on higher-level language processes. This neuroimaging (fMRI) study examined these factors by measuring the comprehension and neural processing of simple and complex spoken sentences in hard-of-hearing older adults (n = 39). Neither hearing loss severity nor hearing aid experience influenced sentence comprehension at the behavioral level. In contrast, hearing loss severity was associated with increased activity in left superior frontal areas and the left anterior insula, but only when processing specific complex sentences (i.e. object-before-subject) compared to simple sentences. Longer hearing aid experience in a sub-set of participants (n = 19) was associated with recruitment of several areas outside of the core speech processing network in the right hemisphere, including the cerebellum, the precentral gyrus, and the cingulate cortex, but only when processing complex sentences. Overall, these results indicate that brain activation for language processing is affected by hearing loss as well as subsequent hearing aid use. Crucially, they show that these effects become apparent through investigation of complex but not simple sentences.

We planned this study to define the worldwide burden of health loss attributed to hearing impairment occurred during the past 10 years according to the 2019 Global Health Data Exchange (GHDx) database. The current worldwide burden of health loss due to all forms of hearing impairment is estimated at 43.4 million Years Lived with Disability (YLDs), representing 28% of cumulative YLDs due to all physical impairments in GHDx. The hearing loss-attributable YLDs have linearly increased (r = 0.997; P < 0.01) by 18.7% during the past 10 years. Reinforced policies are hence needed for preventing development of mild hearing impairment and/or progression toward more severe deficiencies.