Incidence of Mumps Deafness in Japan, 2005-2017: Analysis of Japanese Insurance Claims Database.

BACKGROUND: Mumps deafness causes serious problems, and incidence data are needed to identify its disease burden. However, such data are limited, and the reported incidence is highly variable. Nationwide studies in Japan with a large age range are lacking. METHODS: This was a retrospective observational investigation of the 2005-2017 mumps burden using employment-based health insurance claims data. Data were analyzed for 5,190,326 people aged 0-64 years to estimate the incidence of mumps deafness. RESULTS: Of 68,112 patients with mumps (36,423 males; 31,689 females), 102 (48 males; 54 females) developed mumps deafness-an incidence of 15.0 per 10,000 patients (1 in 668 patients). Fifty-four (52.9%) patients had mumps deafness in childhood (0-15 years), and 48 (47.1%) had mumps deafness in adolescence and adulthood (16-64 years); most cases occurred in childhood, the peak period for mumps onset. The incidence of mumps deafness per 10,000 patients was 73.6 in adolescence and adulthood, 8.4 times higher than the incidence of 8.8 in childhood (P < 0.001). In childhood, the incidence of mumps deafness was 7.2 times higher among 6-15-year-olds (13.8; 95% CI, 10.2-18.2) than among 0-5-year-olds (1.9; 95% CI, 0.6-4.5), and this difference was statistically significant (P < 0.001). No sex difference was observed. CONCLUSIONS: The incidence of mumps deafness per 10,000 patients aged 0-64 years was 15.0 (1 in 668 patients). A secondary risk of deafness following mumps virus infection was identified not only for children, but also for adolescents and adults.

Determination risk factors for severe and profound hearing loss in child candidates for cochlear implantation in southeast of Iran during 2014-2020.

BACKGROUND: Hearing loss can have a major impact on children's language development, academic success and hearing comprehension. The aim of the present study was to determinate risk factors for severe and profound hearing loss in child candidates for cochlear implantation in southeast of Iran during 2014-2020. MATERIALS AND METHODS: This case-control study consisted of 400 children referring to a cochlear implant center (in southeastern Iran) from Bandar Abbas, Zahedan and Kerman during the years 2014-2020 as cases. The subjects were selected using the random sampling method; 200 children hospitalized in Shafa and Afzalipour hospitals were selected as controls. RESULTS: Based on the results of the multivariate logistic regression, weight less than 1500 g (OR = 4.40: p < 0.05), hospitalization in NICU (OR = 7.21: p < 0.05), family history of hearing loss (OR = 11.47: p < 0.05), Gestational age over 35 (OR = 9.63: p < 0.05), intracranial hemorrhage (OR = 5.18: p < 0.05), consanguineous marriage (OR = 12.48: p < 0.05) and high fever and seizures (OR = 3.02: p < 0.05) were recognized as risk factors for sensorineural deafness in children. CONCLUSION: Most of the risk factors for deafness are preventable, and hereditary factors play an important role in congenital deafness in children. Therefore, genetic counseling before consanguineous marriage, early diagnosis, timely intervention can prevent many cases of hearing loss in children.

A Tmc1 mutation reduces calcium permeability and expression of mechanoelectrical transduction channels in cochlear hair cells.

Mechanoelectrical transducer (MET) currents were recorded from cochlear hair cells in mice with mutations of transmembrane channel-like protein TMC1 to study the effects on MET channel properties. We characterized a Tmc1 mouse with a single-amino-acid mutation (D569N), homologous to a dominant human deafness mutation. Measurements were made in both Tmc2 wild-type and Tmc2 knockout mice. By 30 d, Tmc1 pD569N heterozygote mice were profoundly deaf, and there was substantial loss of outer hair cells (OHCs). MET current in OHCs of Tmc1 pD569N mutants developed over the first neonatal week to attain a maximum amplitude one-third the size of that in Tmc1 wild-type mice, similar at apex and base, and lacking the tonotopic size gradient seen in wild type. The MET-channel Ca2+ permeability was reduced 3-fold in Tmc1 pD569N homozygotes, intermediate deficits being seen in heterozygotes. Reduced Ca2+ permeability resembled that of the Tmc1 pM412K Beethoven mutant, a previously studied semidominant mouse mutation. The MET channel unitary conductance, assayed by single-channel recordings and by measurements of current noise, was unaffected in mutant apical OHCs. We show that, in contrast to the Tmc1 M412K mutant, there was reduced expression of the TMC1 D569N channel at the transduction site assessed by immunolabeling, despite the persistence of tip links. The reduction in MET channel Ca2+ permeability seen in both mutants may be the proximate cause of hair-cell apoptosis, but changes in bundle shape and protein expression in Tmc1 D569N suggest another role for TMC1 apart from forming the channel.

Cochlear implantation among patients with otosclerosis: a systematic review of clinical characteristics and outcomes.

PURPOSE: There have been considerable advancements in cochlear implants in different clinical scenarios; however, their use in patients with otosclerosis remains challenging. This review aimed to investigate the surgical and clinical outcomes of cochlear implantation in patients with otosclerosis. METHODS: An electronic literature search was performed using four main databases through February 2021 to identify original studies of cochlear implantation in patients with otosclerosis for inclusion in this systematic review. The study protocol was registered with the Prospectively Registered Systematic Reviews and Meta-analyses (reference number: CRD42021234753). RESULTS: A total of 23 studies including 3162 patients were enrolled. Of these patients, only 392 had otosclerosis and underwent cochlear implantation. The duration of deafness was reported in only eight studies, extending up to 50 years. Far-advanced otosclerosis was observed in 153 patients. A total of 56 patients used hearing aids. Stapedectomy and stapedotomy were performed in 118 and 63 patients, respectively. In three studies, the temporary success of stapedectomy and stapedotomy was 6 (43%) and 5 (71%) patients, respectively. Computed tomography was used as a preoperative assessment tool in most studies (n = 14, 60.9%). Incomplete implant insertion occurred in 17 patients, while facial nerve stimulation occurred in 36 patients after implantation. CONCLUSION: Cochlear implantation is a relatively safe modality that can provide promising audiological outcomes in patients with otosclerosis. However, several factors, including cochlear ossification, duration of deafness, and previous operations, can affect its outcomes. Further studies with a larger sample population are recommended.

[The cochlear implantation in patients with syndromic deafness. Clinical examples]. / Osobennosti provedeniya kokhlearnoi implantatsii u patsientov s sindromal'noi glukhotoi.

OBJECTIVE: To describe clinical observations of patients with syndromic deafness. RESULTS: Deaf patients with CHARGE, Crouzon, and Wildervanck syndromes were monitored at the Russian Research Clinical Center for Audiology and Hearing Rehabilitation (Moscow) in different years. All of them were diagnosed having bilateral congenital deafness. After collecting anamnesis, evaluating the results of computed tomography of the temporal bones, and audiological examination, it was decided to conduct the cochlear implantation. CONCLUSION: The only method that allows patients with bilateral congenital deafness to gain hearing is the cochlear implantation. The malformations of the tympanic cavity structures, an abnormal course of the facial nerve canal lead to technical difficulties during the surgical stage of cochlear implantation. The navigation equipment, monitoring of the facial nerve makes it easier to find anatomical structures, as well as to avoid injuries.

Auditory function and dysfunction: estrogen makes a difference.

Estrogen is the major female hormone involved in reproductive functions, but it also exerts a variety of additional roles in non-reproductive organs. In this review, we highlight the preclinical and clinical studies that have pointed out sex differences and estrogenic influence on audition. We also describe the experimental evidences supporting a protective role of estrogen towards acquired forms of hearing loss. Although a high level of endogenous estrogen is associated with a better hearing function, hormonal treatments at menopause have provided contradictory outcomes. The various factors that are likely to explain these discrepancies include the treatment regimen as well as the hormonal status and responsiveness of the patients. The complexity of estrogen signaling is being untangled and many downstream effectors of its genomic and non-genomic actions have been identified in other systems. Based on these advances and on the common physio-pathological events that underlie age-related, drug or noise-induced hearing loss, we discuss potential mechanisms for their protective actions in the cochlea.

Spiral ganglion cell degeneration-induced deafness as a consequence of reduced GATA factor activity.

Zinc-finger transcription factors GATA2 and GATA3 are both expressed in the developing inner ear, although their overlapping versus distinct activities in adult definitive inner ear are not well understood. We show here that GATA2 and GATA3 are co-expressed in cochlear spiral ganglion cells and redundantly function in the maintenance of spiral ganglion cells and auditory neural circuitry. Notably, Gata2 and Gata3 compound heterozygous mutant mice had a diminished number of spiral ganglion cells due to enhanced apoptosis, which resulted in progressive hearing loss. The decrease in spiral ganglion cellularity was associated with lowered expression of neurotrophin receptor TrkC that is an essential factor for spiral ganglion cell survival. We further show that Gata2 null mutants that additionally bear a Gata2 YAC (yeast artificial chromosome) that counteracts the lethal hematopoietic deficiency due to complete Gata2 loss nonetheless failed to complement the deficiency in neonatal spiral ganglion neurons. Furthermore, cochlea-specific Gata2 deletion mice also had fewer spiral ganglion cells and resultant hearing impairment. These results show that GATA2 and GATA3 redundantly function to maintain spiral ganglion cells and hearing. We propose possible mechanisms underlying hearing loss in human GATA2- or GATA3-related genetic disorders.

Cochlear implantation in adults with single-sided deafness: generic and disease-specific long-term quality of life.

PURPOSE: To determine the 2-year outcome of health-related quality of life (HRQoL) in adults who received a cochlear implant (CI) for single-sided deafness (SSD). METHODS: Twenty adults (mean age at implantation: 47 ± 11 years) with SSD (PTA worse ear: 113 dB HL, PTA better ear: 14 dB HL) were administered the Nijmegen Cochlear Implant Questionnaire (NCIQ), and the Health Utility Index 3 (HUI 3). Questionnaire administration occurred before cochlear implantation and 3, 6, 12, and 24 months after implant activation. RESULTS: Of the 20 patients, 2 discontinued CI use within the observation period due to poor benefit. The NCIQ total score of the sample increased significantly over time (p = 0.003). The largest increase occurred within the first 3 months of CI use. Also, the HUI 3 multi-attribute utility score increased significantly (p = 0.03). The post-treatment increase of this score (+ 0.11 points) indicated that the gain in HRQoL was clinically relevant. Patients with a duration of deafness > 10 years had in all measures an equal HRQoL improvement than had patients with a duration of deafness < 10 years. CONCLUSION: Cochlear implantation led to significant improvement of hearing-specific and generic HRQoL in our patients. The improvement was seen after 3 or 6 months but did not increase further at later intervals. Patients with long-lasting SSD may be at higher risk of discontinuing CI use. However, if they adapt to the CI, they can experience an equal increase of HRQoL as patients with a short duration of SSD.

Transient-evoked otoacoustic emission findings in children (1-12 years) with cerebral palsy in Kano, Nigeria.

BACKGROUND: Children with cerebral palsy (CP) suffer from multiple problems and potential disabilities. These range from musculoskeletal problems, mental retardation, epilepsy, ophthalmologic and hearing impairment among others. Consequences of hearing loss include problems with speech and language development. Early detection in this difficult-to-test population may prevent these consequences of hearing loss. An otoacoustic emission assessment is useful in this regard. This study assessed transient-evoked otoacoustic emissions (TEOAEs) in children with CP. MATERIALS AND METHODS: The study population were children with CP who presented at the paediatric neurology clinic during the study period. An equal number of control population matched for age and sex were also recruited using simple random sampling. An interviewer-administered questionnaire was used to obtain relevant clinical information. All participants selected underwent a detailed ear, nose and throat examination and TEOAE testing. RESULTS: There were 330 participants in this study, categorised into CP cases (165) and non-CP controls (165). The age range of the participants was 1-12 years, with a mean age of 4.44 ± 2.92 among CP patients and 4.47 ± 2.90 among the controls. The male-to-female ratio was 2:1. TEOAEs were 'failed' in 83.6% of the CP patients and in 28.5% of the controls. This study found a statistically significant difference in 'failed' TEOAE result between the CP patients and the controls (P = 0.0001). CONCLUSION: This study found a high prevalence of 'failed' TEOAEs in children with CP in Kano.

Extrusion pump ABCC1 was first linked with nonsyndromic hearing loss in humans by stepwise genetic analysis.

PURPOSE: To determine the genetic etiology of deafness in a family (HN-SD01) with autosomal dominant nonsyndromic hearing loss (NSHL). METHODS: Stepwise genetic analysis was performed on family HN-SD01, including hotspot variant screening, exome sequencing, virtual hearing loss gene panel, and genome-wide linkage analysis. Targeted region sequencing was used to screen ABCC1 in additional cases. Cochlear expression of Abcc1 was evaluated by messenger RNA (mRNA) and protein levels. Computational prediction, immunofluorescence, real-time quantitative polymerase chain reaction, and flow cytometry were conducted to uncover functional consequences of candidate variants. RESULTS: Stepwise genetic analysis identified a heterozygous missense variant, ABCC1:c.1769A>G (p.Asn590Ser), cosegregating with phenotype in HN-SD01. Screening of ABCC1 in an additional 217 cases identified candidate pathogenic variants c.692G>A (p.Gly231Asp) in a sporadic case and c.887A>T (p.Glu296Val) in a familial proband. Abcc1 expressed in stria vascularis and auditory nerve of mouse cochlea. Immunofluorescence showed p.Asn590Ser distributed in cytomembrane and cytoplasm, while wild type was shown only in cytomembrane. Besides, it generated unstable mRNA and decreased efflux capacity of ABCC1. CONCLUSION: Stepwise genetic analysis is efficient to analyze the genetic etiology of NSHL. Variants in ABCC1 are linked with NSHL and suggest an important role of extruding pumps in maintaining cochlea function.

Perinatal Outcome and Long-Term Neurodevelopment after Intracranial Haemorrhage due to Fetal and Neonatal Alloimmune Thrombocytopenia.

OBJECTIVES: To evaluate the perinatal and long-term neurodevelopmental outcome in a cohort of children with intracranial haemorrhage (ICH) due to fetal and neonatal alloimmune thrombocytopenia (FNAIT) and to clearly outline the burden of this disease. SUBJECTS AND METHODS: We performed an observational cohort study and included all consecutive cases of ICH caused by FNAIT from 1993 to 2015 at Leiden University Medical Centre. Neurological, motor, and cognitive development were assessed at a minimum age of 1 year. The primary outcome was adverse outcome, defined as perinatal death or severe neurodevelopmental impairment (NDI). Severe NDI was defined as any of the following: cerebral palsy (Gross Motor Function Classification System [GMFCS] level ≥II), bilateral deafness, blindness, or severe motor and/or cognitive developmental delay (<-2 SD). RESULTS: In total, 21 cases of ICH due to FNAIT were included in the study. The perinatal mortality rate was 10/21 (48%). Long-term outcome was assessed in 10 children (n = 1 lost to follow-up). Severe and moderate NDI were diagnosed in 6/10 (60%) and 1/10 (10%) of the surviving children. The overall adverse outcome, including perinatal mortality or severe NDI, was 16/20 (80%). CONCLUSIONS: The risk of perinatal death or severe NDI in children with ICH due to FNAIT is high. Only screening and effective preventive treatment can avoid this burden.

Barakat syndrome revisited.

Barakat syndrome also known as HDR syndrome (Online Mendelian Inheritance in Man [OMIM] 146255), was first described by Barakat et al. in . It is a rare genetic disorder characterized by the triad of hypoparathyroidism "H," sensorineural deafness "D," and renal disease "R." The defect is caused by deletions in chromosome 10p14 or mutations in the GATA3 gene. Although the syndrome has been phenotypically defined by this triad the literature identifies cases with different components with, or without GATA3 defects making the definition of the syndrome confusing. We analyzed 180 cases and attempted to define the phenotype of the syndrome and suggest guidelines for diagnosis. We suggest that the diagnosis could be confirmed in patients who have all three components, and in those who have two components with a positive family history. GATA3 testing is optional to establish the diagnosis in these patients. The syndrome should be considered in patients with isolated "D" where other causes of "D" have been excluded and those with isolated "R," especially if there is family history of any of these components. In these instances, confirmatory GATA3 testing is indicated to confirm the diagnosis. In patients with nonsurgical "H," where "D" and "R" have been conclusively ruled out GATA3 studies are not needed as none of these patients were shown to be GATA3 haploinsufficient. Only 64.4% of patients in our review had "HDR." Some findings might have not been recognized or may could have appeared later in life, but it is evident that this syndrome is genotypically heterogeneous.

Remodeling of Dendritic Spines in the Avian Vocal Motor Cortex Following Deafening Depends on the Basal Ganglia Circuit.

Deafening elicits a deterioration of learned vocalization, in both humans and songbirds. In songbirds, learned vocal plasticity has been shown to depend on the basal ganglia-cortical circuit, but the underlying cellular basis remains to be clarified. Using confocal imaging and electron microscopy, we examined the effect of deafening on dendritic spines in avian vocal motor cortex, the robust nucleus of the arcopallium (RA), and investigated the role of the basal ganglia circuit in motor cortex plasticity. We found rapid structural changes to RA dendritic spines in response to hearing loss, accompanied by learned song degradation. In particular, the morphological characters of RA spine synaptic contacts between 2 major pathways were altered differently. However, experimental disruption of the basal ganglia circuit, through lesions in song-specialized basal ganglia nucleus Area X, largely prevented both the observed changes to RA dendritic spines and the song deterioration after hearing loss. Our results provide cellular evidence to highlight a key role of the basal ganglia circuit in the motor cortical plasticity that underlies learned vocal plasticity.

[A medical biography of Ludwig van Beethoven]. / Ludwig van Beethoven, el genio de Bonn atormentado por sus enfermedades: su historia médica.

Much emphasis has been given to the deafness of Ludwig van Beethoven and its potential causes. However, when analyzing several symptoms reported by himself throughout his life in many letters and his final illness, a common etiology emerges. This article reports the medical history of this artist, based on authoritative scientific sources.

[Analysis of audiological characteristics and genetic background in patients with nonsyndromic deafness and mitochondrial DNA 1555A>G mutation].

OBJECTIVE: To analyze the audiological features and genetic background of patients carrying mitochondrial DNA(mtDNA) 1555A>G mutation and factors which may influence the extent of nonsyndromic hearing loss associated with the mutation. METHODS: A literature search was carried out on databases including PubMed, CNKI, Wanfang, and VIP. Combined with author's data, the clinical features of the patients, in particular audiological characteristics, were summarized. RESULTS: A total of 857 effective cases were collected and analyzed. A significantly correlation was identified between history of aminoglycosides exposure and extent of hearing loss, in addition with a negative correlation between the age of onset and extent of hearing-impairment. Drug exposure was corelated with the age of onset but independent to the loss of high-frequency hearing loss. Heteroplasmies had a reverse correlation with the degree of hearing loss. Among the haplotypes of mitochondrial DNA, haplotype D was the most common one, while haplotype B had the highest penetrance. CONCLUSION: Nonsyndromic hearing loss associated with mitochondrial DNA 1555A>G mutation is influenced by factors such as aminoglycosides exposure, age, proportion of mutation, and haplotype of the mitochondrial DNA. Analysis of clinical cases is critical for identifying individuals carrying deafness susceptibility mutations and is the first step for early diagnosis.

[Correlation between FOXO3 gene polymorphisms and susceptibility to occupational noise-induced deafness].

Objective: To investigate the association between the single nucleotide polymorphisms of rs12212067 in FOXO3 gene and the susceptibility to occupational noise-induced deafness in a Chinese Han population. Methods: A total of 1 066 cases of noise exposure workers from a large chemical fiber factory in Jiangsu Province were selected as the study subjects. All subjects' basic data and field exposure data were collected through questionnaires and occupational health surveys. The subjects were divided into case group (531 persons, double ear high frequency average hearing threshold>25 dB) and control group (535 persons, double ear high frequency average hearing threshold≤25 dB) according to their results of pure tone hearing test .2ml fasting venous blood was collected for DNA extraction and genotyping was performed by TaqMan-PCR technique. Results: Genotyping results suggested that the GT+GG genotype is a risk factor for occupational noise-induced deafness, with an adjusted OR 95% confidence interval of 2.044 (1.51-2.78) . After the noise exposure intensity was stratified, the adjusted OR values and the 95% confidence intervals of noise intensity ≤85, 85-92 and>92 dB respectively 2.43 (1.52-3.90) , 2.17 (1.03-4.59) and 1.74 (1.07-2.83) . Conclusion: GT-GG genotype in rs12212067 of FOXO3 gene may be a risk factor for occupational noise-induced deafness.