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Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype–phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype–phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a “typical” phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85–90% of the patients showed a hearing level of 20–39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed “true” auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype–phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype–phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

Background: Demographic data of patients with sensorineural hearing loss (SNHL) in super-aged societies are still limited.Aims/objectives: To report audiometric statistics of SNHL and hearing aid (...

Objectives The aim of this study was to retrospectively document prevalence rates of delayed-onset hearing loss (DOHL) under 7 years old after passing the newborn hearing screening (NHS) program using its database in Okayama Prefecture, as well as records from Okayama Kanariya Gakuen (OKG, Auditory Center for Hearing Impaired Children, Okayama Prefecture, Japan). We explored the percentage of children with DOHL among all children who underwent the NHS and surveyed risk factors abstracted from their clinical records. Methods We collected data of 1171 children, who first visited OKG from April 2006 to March 2018. DOHL children were defined as bilaterally hearing-impaired children who were diagnosed under 7 years old after passing the NHS at birth. Based on the medical records, we investigated age at diagnosis, hearing levels, and risk factors. As population-based data of 168,104 children, the percentage of DOHL subjects was retrospectively calculated among the total number of children who underwent the NHS in Okayama Prefecture from April 2005 to March 2017. Results During the period, we identified 96 children with bilateral DOHL, of which 34 children had failed the NHS unilaterally and 62 had passed the NHS bilaterally. Among all children who underwent the NHS in Okayama Prefecture, the prevalence rate of DOHL in unilaterally referred infants was 5.2%, and 0.037% in bilaterally passed children. The prevalence of bilateral DOHL was 0.057% overall. Unilaterally referred children with DOHL were diagnosed at an average of 13.9 months, while bilaterally passed children with DOHL were diagnosed at an average of 42.3 months. Approximately 59.4% of children with DOHL had risk factors, among which family history of hearing loss was the most frequent. Conclusion We propose the first English report of DOHL prevalence in the prefecture population in Japann, which is among the largest community-based population ever reported. The NHS is not a perfect strategy to detect all early-childhood hearing loss; therefore, careful assessment of hearing throughout childhood is recommended, especially in children with risk factors of hearing loss. Further interventional strategies must be established, such as regular hearing screening in high-risk children and assessments of hearing and speech/language development in public communities and nursery schools.

Pathologic mechanisms in cochleae immediately following the onset of noise-induced hearing loss (NIHL) remain unclear. In this study, mice were exposed to 120 dB of octave band noise for 2 h to induce NIHL. Three hours after noise exposure, expression levels of the whole mouse genome in cochleae were analyzed by RNA-seq and DNA microarray. Differentially expressed genes (DEGs) exhibiting >2-fold upregulation or downregulation in noise-exposed cochleae compared to controls without noise exposure were identified. RNA-seq and microarray analyses identified 273 DEGs regulated at 3 h post-noise (51 upregulated and 222 downregulated). Bioinformatic analysis revealed that these DEGs were associated with the functional gene pathway "neuroactive ligand-receptor interaction" and included 28 genes encoding receptors for neurotransmitters such as gamma-aminobutyric acid and glutamate. Other DEGs included 25 genes encoding transcription factors. Downregulation of 4 neurotransmitter receptors (Gabra3, Gabra5, Gabrb1, Grm1) and upregulations of 5 transcription factors (Atf3, Dbp, Helt, Maff, Nr1d1) were validated by RT-PCR. The differentially regulated transcription factor Atf3 immunolocalized to supporting cells and hair cells in the organ of Corti at 12-h post-noise. The present data serve as a basis for further studies aimed at developing medical treatments for acute sensorineural hearing loss.

To comprehensively analyze cochlear gene expressions related to innate immunity and glucocorticoid signaling at onset of acute noise-induced hearing loss (NIHL).Recent studies suggested innate immunity is involved in the cochlear pathology of NIHL. Glucocorticoids may modulate immune actions in cochleae.Mice were exposed to 120 dB-octave band noise for 2 hours. Twelve hours later, a targeted PCR array analyzed cochlear expressions of 84 key genes in inflammation and immune pathways and 84 genes in the glucocorticoid signaling pathway. Real-time RT-PCR was used to analyze expression of two immune-related genes, Ccl12 and Glycam1, in noise-exposed cochleae with or without dexamethasone.In inflammatory and immune gene pathways, 31.0% (26/84 genes) were significantly upregulated (2-fold change) or downregulated (0.5-fold change) (p 0.05) in noise-exposed cochleae compared with controls. Sixteen of these differentially expressed genes (DEGs) encoded chemokines. DEGs included Ccl12, Ccl2, Ccl4, Ccl7, Cxcl1, Cxcl10, and Ptgs2 (upregulated genes), and Ccr7, Cxcr2, Kng1, Ltb, and Tnfsf14 (downregulated genes). In the glucocorticoid signaling pathway, 92.9% (78/84 genes) were unchanged in noise-exposed cochleae without dexamethasone administration. Cochlear expressions of Ccl12 and Glycam1 were significantly upregulated by noise and downregulated by dexamethasone.The targeted PCR array demonstrated that several dozen genes involved in innate immunity are actively regulated in cochleae with NIHL. The glucocorticoid signaling pathway was not endogenously regulated at 12 hours post-noise trauma. Systemic dexamethasone downregulated Ccl12 and Glycam1, which are upregulated in noise-exposed cochleae. These data may provide a basis for genomic medicine treatment of acute sensorineural hearing loss.

To clarify how the pure-tone threshold (PTT) on the PTA predicts speech perception (SP) in elderly Japanese persons.Data on PTT and SP were cross-sectionally analyzed in Japanese persons (656 ears in 353 patients, aged ≥65 years). Correlations of SP and average PTT in all tested frequencies were evaluated by Pearson's correlation coefficient and simple linear regression. After adjusting for sex, laterality of ears, and age, the relationship of average and frequency-specific PTT with impaired SP ≤50% was estimated by logistic regression models.SP correlated well (r = -0.699) with the average PTT of all tested frequencies. On the other hand, the correlation between patient age and SP was weak, especially among ≤85-year-old persons (r = -0.092). Linear regression showed that the average PTT corresponding to SP of 50% was 76.4 dB nHL. Odds ratios for impaired SP were highest for PTT at 2000 Hz. Odds ratios were higher for middle (500, 1000, 2000 Hz) and high frequencies (4000, 8000 Hz) than low frequencies (125, 250 Hz).The PTT on the pure-tone audiogram (PTA) is a good predictor of SP by speech audiometry among older persons, which could provide clinically important information for hearing aid fitting and cochlear implantation.

To elucidate molecular mechanisms of noise-induced hearing loss (NIHL) and glucocorticoid therapy in the cochlea.Glucocorticoids are used to treat many forms of acute sensorineural hearing loss, but their molecular action in the cochlea remains poorly understood.Dexamethasone was administered intraperitoneally immediately following acoustic overstimulation at 120 dB SPL for 2 hours to mice. The whole cochlear transcriptome was analyzed 12 and 24 hours following noise trauma and dexamethasone administration by both next-generation sequencing (RNA-seq) and DNA microarray. Differentially expressed genes (DEGs) with more than 2-fold changes after noise trauma and dexamethasone administration were identified. The functions of these DEGs were analyzed by David Bioinformatics Resources and a literature search.Twelve hours after acoustic overstimulation, immune-related gene pathways such as "chemokine signaling activity," "cytokine-cytokine receptor interaction," and "cell adhesion molecules (CAMs) in the immune system" were significantly changed compared with the baseline level without noise. These DEGs were involved in immune and defense responses in the cochlea. Dexamethasone was administered to this NIHL model, and it modulated gene pathways of "cytokine-cytokine receptor interaction" and "cell adhesion molecules (CAMs) in the immune system" at 12 hours, compared with saline-injected control. Dexamethasone-dependent DEGs were also involved in immune and defense responses. A literature search showed that 10 other genes associated with hearing functions were regulated by dexamethasone both at 12 and 24 hours post-administration.Dexamethasone modulates the immune reaction in the traumatized cochlea following acoustic overstimulation. Dexamethasone may also regulate cochlear functions other than immunity.

Since April 2012, genetic testing for congenital hearing loss is covered by the public health insurance in Japan. Recent (since August 2015) developments in next-generation sequencing technology have enabled the detection of 154 mutations in 19 genes. Genetic testing provides valuable information on hearing phenotype, prognosis, and prediction of associated symptoms. We report a hearing-impaired patient in whom multiple genetic mutations were detected. This patient carries two missense mutations in GJB2 (p.G45E, p.Y136X), as well as a mitochondrial mutation (7445A>G). Since the number of genes detectable by genetic testing has increased, the diagnosis of hearing loss can be made with greater accuracy. However, it is often difficult to clinically understand and interpret the genotype information, especially when multiple gene variants are detected in one patient or family. Genetic counseling plays an important part in the intervention for or follow-up of such patients. Genotypic and phenotypic information of other family members is necessary, so that both the patient and the family can understand and accept the results of genetic testing.

Central auditory processing disorder (CAPD) is a condition in which dysfunction in the central auditory system causes difficulty in listening to conversations, particularly under noisy conditions, despite normal peripheral auditory function. Central auditory testing is generally performed in patients with normal hearing on the pure tone audiogram (PTA). This report shows that diagnosis of CAPD is possible even in the presence of an elevated threshold on the PTA, provided that the normal function of the peripheral auditory pathway was verified by distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR), and auditory steady state response (ASSR). Three pediatric cases (9- and 10-year-old girls and an 8-year-old boy) of CAPD with elevated thresholds on PTAs are presented. The chief complaint was difficulty in listening to conversations. PTA showed elevated thresholds, but the responses and thresholds for DPOAE, ABR, and ASSR were normal, showing that peripheral auditory function was normal. Significant findings of central auditory testing such as dichotic speech tests, time compression of speech signals, and binaural interaction tests confirmed the diagnosis of CAPD. These threshold shifts in PTA may provide a new concept of a clinical symptom due to central auditory dysfunction in CAPD.

The OTOF gene (Locus: DFNB9), encoding otoferlin, is reported to be one of the major causes of non-syndromic recessive sensorineural hearing loss, and is also reported to be the most common cause of non-syndromic recessive auditory neuropathy spectrum disorder (ANSD). In the present study, we performed OTOF mutation analysis using massively parallel DNA sequencing (MPS). The purpose of this study was to reveal the frequency and precise genetic and clinical background of OTOF-related hearing loss in a large hearing loss population. A total of 2,265 Japanese sensorineural hearing loss (SNHL) patients compatible with autosomal recessive inheritance (including sporadic cases) from 53 otorhinolaryngology departments nationwide participated in this study. The mutation analysis of 68 genes, including the OTOF gene, reported to cause non-syndromic hearing loss was performed using MPS. Thirty-nine out of the 2,265 patients (1.72%) carried homozygous or compound heterozygous mutations in the OTOF gene. It is assumed that the frequency of hearing loss associated with OTOF mutations is about 1.72% of autosomal recessive or sporadic SNHL cases. Hearing level information was available for 32 of 39 patients with biallelic OTOF mutations; 24 of them (75.0%) showed profound hearing loss, 7 (21.9%) showed severe hearing loss and 1 (3.1%) showed mild hearing loss. The hearing level of patients with biallelic OTOF mutations in this study was mostly severe to profound, which is consistent with the results of past reports. Eleven of the 39 patients with biallelic OTOF mutations had been diagnosed with ANSD. The genetic diagnosis of OTOF mutations has significant benefits in terms of clinical decision-making. Patients with OTOF mutations would be good candidates for cochlear implantation; therefore, the detection of OTOF mutations is quite beneficial for patients, especially for those with ANSD.

A heterozygous mutation in the Wolfram syndrome type 1 gene (WFS1) causes autosomal dominant nonsyndromic hereditary hearing loss, DFNA6/14/38, or Wolfram-like syndrome. To date, more than 40 different mutations have been reported to be responsible for DFNA6/14/38. In the present study, WFS1 variants were screened in a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA6/14/38 and Wolfram-like syndrome. Massively parallel DNA sequencing of 68 target genes was performed in 2,549 unrelated Japanese HL patients to identify genomic variations responsible for HL. The detailed clinical features in patients with WFS1 variants were collected from medical charts and analyzed. We successfully identified 13 WFS1 variants in 19 probands: eight of the 13 variants were previously reported mutations, including three mutations (p.A684V, p.K836N, and p.E864K) known to cause Wolfram-like syndrome, and five were novel mutations. Variants were detected in 15 probands (2.5%) in 602 families with presumably autosomal dominant or mitochondrial HL, and in four probands (0.7%) in 559 sporadic cases; however, no variants were detected in the other 1,388 probands with autosomal recessive or unknown family history. Among the 30 individuals possessing variants, marked variations were observed in the onset of HL as well as in the presence of progressive HL and tinnitus. Vestibular symptoms, which had been rarely reported, were present in 7 out of 30 (23%) of the affected individuals. The most prevalent audiometric configuration was low-frequency type; however, some individuals had high-frequency HL. Haplotype analysis in three mutations (p.A716T, p.K836T, and p.E864K) suggested that the mutations occurred at these mutation hot spots. The present study provided new insights into the audiovestibular phenotypes in patients with WFS1 mutations.

Permanent hearing impairment has a life-long impact on children and its early identification is important for language development. A newborn hearing screening (NHS) program has started in Okayama Prefecture, Japan, in 1999 to detect hearing impairment immediately after birth. We aim to examine the effect of this screening program on vocabulary development in pre-school children in a before and after comparative study design.A total of 107 5-year-old children who graduated from Okayama Kanariya Gakuen (an auditory center for hearing-impaired children) between 1998 and 2011 were enrolled in this study. The pre-NHS group (n=40) was defined as those who graduated between 1998 and 2003, while the post-NHS group (n=67) was defined as those who graduated between 2004 and 2011. The primary outcome was receptive vocabulary, which was assessed by the Picture Vocabulary Test [score18 (low) vs. score ≥18 (high)]. The secondary outcome was productive vocabulary, or the number of productive words, which was assessed by an original checklist [1773 words (low) vs. ≥1773 (high)]. We calculated odds ratios and 95% confidence intervals for vocabulary development and compared both groups.The adjusted Picture Vocabulary Test score and number of productive words were significantly higher (p0.01) in the post-NHS group than the pre-NHS group. Odds ratios were 2.63 (95% confidence interval: 1.17-5.89) for receptive vocabulary and 4.17 (95% confidence interval: 1.69-10.29) for productive vocabulary.The introduction of NHS in Okayama Prefecture significantly improved both receptive and productive vocabulary development in hearing-impaired children.

Objectives Reading and writing skills are important for hearing-impaired children since these skills help them to develop their language skills, but the prevalence of reading/writing difficulties and its effects on language development aspects among them are unclear. In this study, we identified language development features and demographic factors of Japanese hearing-impaired children diagnosed as having reading/writing difficulties. Methods We analyzed data from a total of 546 sever-to-profound pre-school and elementary school hearing-impaired children for this study. Children with reading/writing difficulties (Group A) were defined as children obtaining low scores (−1.5 SD compared to others in the same grade) in the Screening Test of Reading and Writing for Japanese Primary School Children (STRAW), and we compared other language development features (communication ability, vocabulary, syntax and academic achievement) and demographic factors to those of hearing-impaired children with normal reading and writing skills (Group B). We assessed language development domains as outcomes using the Assessment of Language Development for Japanese Children (ALADJIN) package, and analyzed the results stratified by age groups (5–6, 7–8, 9–10, and 11–12 years) using multiple regression analyses. Results The prevalence of reading/writing difficulties was 20.1% among the participants. Almost all point estimates in each language development domain showed better odds ratios (OR) except Criterion Referenced Test -II (CRT-II) mathematics in 11- to 12-year-olds in fully-adjusted models. Among 9- to 10-year-olds, the ORs (95% confidence interval) for fair academic achievement measured by CRT-II were 2.60 (1.09–6.20) for Japanese and 3.02 (1.29–7.11) for mathematics in Group B, even after adjusting for possible confounding factors. Conclusions Reading and writing are important for language development of hearing-impaired children, especially for academic achievement during the middle phase of elementary school. Screening for reading/writing difficulties is important for appropriate intervention and to prevent language and academic delays among hearing-impaired children.

The presence of hearing impairment deteriorates patients' quality of life by affecting their daily-life communication. Several self-report assessments are available to evaluate the subjective outcome of hearing aids, however, the procedures to evaluate the impairment of communication induced by hearing impairment has not been well established. A PC-recorded audio file prepared to evaluate the communication ability of hearing aid users, by extracting fifteen spoken language items from the Communication ADL Test: sp-CADL. A before and after study was performed among the hearing aid users who were attending Okayama University Hospital to evaluate the improvement in each of the 15 sp-CADL scores. Twenty-one adults were included in this study whose age ranged from 22 to 83 years old (mean: 56.7 years old). The total and individual scores of the sp-CADL improved significantly after the use of the hearing aids (p < 0.05). The total sp-CADL score of the patients with hearing aids showed a good correlation with the best scores of the speech discrimination test measured before wearing hearing aids.

The spread of neonatal hearing screening has made the identification of hearing loss in early childhood possible, and most of the children with hearing loss are diagnosed and provided with early intervention within several months after their birth. However, they have to wait to receive the Special Child Dependent's Allowance until their hearing levels are evaluated with audiometers. Under the Special Child Dependent's Allowance Act now in force, a delay of several years occurs for those children before they can receive the allowance after diagnosis. We retrospectively reviewed hearing test results of children who had not reacted at 90dBnHL bilaterally in ABR within 12 months after birth, and examined when those results were certain enough to determine their allowance eligibility. We found that the eligibility in children with hearing loss alone could be determined at 1 year of age; as for children who had other disorders, since it was mostly difficult to test them with an audiometer, the diagnosis of hearing loss must always be made carefully but it was also possible to determine the eligibility for the allowance at 1 year of age.

Audiological parameters alone do not determine the choice to use hearing aids (HA). Subjective hearing-related QoL is a major factor that determines whether or not an older person will continue to wear HA.This study aimed to identify which audiological parameters and quality-of-life (QoL) measures determine whether or not older persons will continue wearing HA.Charts of 157 patients aged ≥65 years who attended the HA service unit at the Otolaryngology Department were retrospectively reviewed. After HA fitting and a trial, the patients were divided into groups, depending upon whether or not they wanted to continue wearing the HA (users, 58.2%; non-users, 41.8%) and then audiological parameters were compared between them. At least 4 months after the HA fitting, the self-reported QoL questionnaire, Hearing Handicap Inventory for the Elderly (HHIE), was mailed to all 157 patients and HHIE scores were compared between HA users and non-users.Speech discrimination score and dynamic range did not significantly differ between HA users and non-users. A difference in the average hearing threshold was marginally significant. The response rate to the HHIE was 65.2%. Total HHIE and emotional scores were higher (more impaired) among HA users than non-users.

Objectives: The measurement of language development in hearing-impaired children is an important step in assessing the appropriateness of an intervention. We proposed a set of language tests (the Assessment Package for Language Development in Japanese Hearing-Impaired Children [ALADJIN]) to evaluate the development of practical communication skills. This package consisted of communication skills (TQAID), comprehensive (PVT-R and SCTAW) and productive vocabulary (WFT), comprehensive and productive syntax (STA), and the STRAW. Methods: A total of 638 children with greater than 70-dB hearing impairment were subjected to this set of language tests. Additional tests, including the PARS, the RCPM, and parental questionnaires, were administered to assess the backgrounds of the children. Results: A trimodal distribution was observed among hearing-impaired children by the histogram-based analysis of each test. Conclusions: The ALADJIN is a useful Japanese-language evaluation kit for hearing-impaired children.

Objectives: Early identification and intervention for prelingual bilateral severe to profound hearing loss is supposed to reduce the delay in language development. Many countries have implemented early detection and hearing intervention and conducted regional universal newborn hearing screening (UNHS). However, the benefits of UNHS in later childhood have not yet been confirmed, although language development at school age has a lifelong impact on children's future. Our Research on Sensory and Communicative Disorders project attempted to reveal the effects of UNHS and those of early intervention on the development of verbal communication in Japanese children. Methods: In this study, 319 children with prelingual bilateral severe to profound hearing loss, 4 to 10 years of age, were evaluated with the Test of Question-Answer Interaction Development used as an objective variable. Participation in UNHS and early intervention were used as explanatory variables. The adjusted odds ratio (AOR) was calculated after adjusting several confounding factors with use of logistic regression analysis. In addition, caregivers' answers were obtained by a questionnaire, and the process of diagnosis with and without UNHS was analyzed retrospectively. Results: Early intervention was significantly associated with better language development (AOR, 3.23; p < 0.01). Participation in UNHS may contribute to better language development to some extent (AOR, 1.32), but not one that was statistically significant (p = 0.37). However, UNHS was significantly associated with early intervention (AOR, 20.21; p < 0.001). The questionnaire results indicated a lag in treatment after UNHS in more than 40% of screened cases. Conclusions: Early intervention strongly influenced language development. It is necessary to ensure that early identification leads directly to early intervention.

Objectives: Language development is a key issue in hearing-impaired children. However, interpersonal differences complicate our understanding of the situation. The bimodal or trimodal distribution of language scores in our other reports in this publication imply the presence of fundamental differences among these groups. The characteristic aspects of each group were profiled according to language data. Methods: We divided 268 children with prelingual severe to profound hearing impairment into 3 groups according to their trimodal distribution observed on histogram-based analysis of their responses to the Test of Question-Answer Interaction Development. Test results in several language domains, including productive and comprehensive vocabulary, productive and comprehensive syntax, and academic achievement, were profiled and compared among these 3 groups. Results: Significant differences were observed in the results of the Word Fluency Test, the Picture Vocabulary Test–Revised, and the Syntax Test of Aphasia among the 3 groups. No significant difference was observed between groups who were lower-scoring and intermediate-scoring on the academic achievement tests referred to as Criterion Referenced Test–II and the Standardized Comprehension Test for Abstract Words. Only the higher-scoring group showed excellent results. The demographic factors were not significantly different among the 3 groups. Conclusions: Relatively poor academic achievement despite fair language production was the dominant feature of the intermediate-scoring group. This profile might correlate with academic failure in school.

Objectives: This study examined syntactic development of auditory comprehension of sentences in Japanese-speaking school-age children with and without hearing impairment. Methods: In total, 592 preschool and school-age children (421 normal-hearing and 171 hearing-impaired) were included in this cross-sectional observation study conducted using the Syntactic Processing Test for Aphasia for Japanese language users. Linear regression analysis was used to determine the estimated age at which each syntactic structure was acquired. Results: Acquisition of syntactic structures was observed in hearing-impaired and normal-hearing children. Basic word order sentences of agent-object-verb and the goal benefactive construction were acquired at preschool age (earlier group), whereas reverse word order sentences of object-agent-verb, source benefactive construction, passive voice, and relative clauses were acquired at school age (later group). The results showed that many hearing-impaired children may not acquire Japanese grammatical structures until the age of 12 years. Conclusions: Adequate screening for language development for school-age hearing-impaired children is required for an effective intervention.

先天性難聴の発生率は全出生中0.08から0.1%と報 告されており,先天性の神経疾患の中では最も頻度が 高いものの一つであることが知られている.従来,先 天性難聴は程度が高度であっても1,2歳で発見され ることが多く,軽度,中等度難聴や片側性の難聴であ れば就学前後に診断されることが稀ではなかった.し かし,言語発達には臨界期があり,難聴の発見が遅れ 適切な時期に適切な介入ができなかった場合,その遅 れは一生涯継続するものとなる可能性が高い.この ため,難聴の早期発見を目的として,新生児聴覚スク リーニング検査(以下聴覚スクリーニング)がモデル 事業として平成13年から本邦で導入された.聴覚スク リーニングの普及により,難聴児の早期発見が次第に 浸透しつつあり,厚生労働省の班研究では,既に難聴 幼児通園施設や聾学校に通う子どもたちの約半数が聴 覚スクリーニングで発見されていると報告されてい る.しかしながら,聴覚スクリーニングの体制や,そ の後の療育に関しては地域差がいまだみられ,確定診 断や療育への移行が早期に行われないケースも散見さ れるのが現状であり,難聴児に与えられている環境は 国内でも平等ではない. 我々は,この10年間で,こうした具体的な諸問題, すなわち難聴児にとって理想的な療育や必要なバック アップ体制について,様々な側面から追求すべく尽力 してきた.実際,行政や療育機関とのタイアップによ り,岡山県は難聴児の診断,療育体制が整備されてお り,他県の範となるシステムが作り上げられてきた. 今回,我々が行っている小児難聴に対する取り組みに ついて概説する.

The introduction of newborn-hearing screening has enabled early childhood hearing loss to be diagnosed and increased the number of children undergoing early care. Bilateral hearing loss is found in 0.08% of newborns and children whose hearing loss progresses or onset is delayed account for 4 to 30% of all pediatric hearing impairment. Children with perinatal risk factors tend to have deteriorated hearing or delayed-onset hearing loss in early childhood, necessitating audiometric follow-up. We also are aware of some children without risk factors who develop hearing impairment during infancy or early childhood. Hearing deterioration may be difficult to diagnose objectively, especially in young children, the presence of risk factors must be determines as soon as possible, especially given the lack of hearing management and close examination of children without apparent risk factors. We retrospectively studied children born from April 1998 to March 2007 and undergoing cochlear implantation as of April 2008. Among cases, we focused on 10 whose hearing impairment advanced during infancy -4 with risk factors known before hearing deterioration progressed, and 6 cases thought not to have any risk factors. We detected enlarged vestibular acquaduct in 3 of these 6 cases, and 3 more of whom had no risk factors -2 passing newborn-hearing screening and 1 in whom such screening detected hemilateral hearing loss. Our results underscore the need for early temporal computed tomography for detecting enlarged vestibular aquaduct. Even children with mild or hemilateral hearing loss should undergo audiometric and developmental testing at least every 6 months up to going to elementary school. Children suspected of impaired hearing should undergo thorough hearing tests regardless of newborn hearing-screening results to catch any problems early. Appropriate regular hearing and language development check-up tests must also be developed.

The prevalence of low-tone hearing loss (LTHL) is significantly high in spinocerebellar degeneration (SCD) with cerebellar predominance, including multiple-system atrophy C (MSA-C) and cortical cerebellar atrophy (CCA).This study aimed to test the hypothesis that SCD with cerebellar predominance, MSA-C and CCA may cause auditory symptoms.The shape and threshold of pure-tone audiograms were evaluated for MSA-C (n = 47; mean (± SD) age, 61.6 ± 8.9 years), CCA (n = 16; 62.8 ± 9.5 years), and age-matched controls (n = 169; 62.5 ± 10.7 years). To differentiate specific hearing loss for MSA-C and CCA from presbycusis, the shape of audiograms was examined based on previously established audiological criteria.When audiogram shape was defined according to audiological criteria, the odds ratio for LTHL in SCD compared to controls was 2.492 (95% confidence interval (CI) = 1.208-5.139; p 0.05, Pearson's Chi-square test) in MSA-C and 2.194 (95% CI = 0.709-6.795) in CCA. When the selection of audiogram shape according to these criteria was verified by three certified audiologists, odds ratios for LTHL in MSA-C and CCA were 3.243 (95% CI = 1.320-7.969) and 3.692 (95% CI = 1.052-12.957), respectively, significantly higher than in controls.

Early hearing detection and intervention (EHDI) is critical for achievement of age-appropriate speech perception and language development in hearing-impaired children. It has been 15 years since newborn hearing screening (NHS) was introduced in Japan, and its effectiveness for language development in hearing-impaired children has been extensively studied. Moreover, after over 20 years of cochlear implantation in Japan, many of the prelingual cochlear implant (CI) users have reached school age, and the effect of CI on language development have also been assessed. To identify prognostic factors for language development, audiological/language test scores and demographic factors were compared among prelingual severe-to-profound hearing-impaired children with CI divided into subgroups according to age at first hearing aid (HA) use and whether they received NHS.Prelingual severe-to-profound deafened children from the Research on Sensory and Communicative Disorders (RSCD) project who met the inclusion criteria were divided into groups according to the age (in months) of HA commencement (before 6 months: group A, after 7 months: group B), and the presence or absence of NHS (groups C and D). Language development and socio-economic data were obtained from audiological/language tests and a questionnaire completed by caregivers, respectively.In total, 210 children from the RSCD project participated in this study. Group A (n=49) showed significantly higher scores on comprehensive vocabulary and academic achievement (p0.05) than group B (n=161), with no difference in demographics except for significantly older age in group B. No differences in language scores were observed between group C (n=71) and group D (n=129), although participants of group D was significantly older and had used CIs longer (p0.05).Early use of HAs until the CI operation may result in better language perception and academic achievement among CI users with prelingual deafness. A long-term follow-up is required to assess the usefulness of NHS for language development.

Performance in consonant-vowel (CV) monosyllable speech perception after cochlear implantation (CI) in the elderly (≥ 65 years) is equivalent to that of young adults (18-64 years). Present data in the Japanese language supported the indication for CI in the elderly. Word recognition after CI was significantly lower in the elderly than young adults.This study compared outcomes of monosyllable perception and word recognition after CI between elderly patients and young adults with post-lingual deafness. Age-related differences in CV monosyllable speech perception in Japanese were examined.A retrospective chart review of 137 patients with post-lingual deafness who underwent CI at Okayama University Hospital during 1992-2014 [young adults aged 18-64 years (n = 96) and elderly aged ≥ 65 years (n = 41) at implantation] was conducted. CV monosyllable speech perception post-CI was compared among age groups (18-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89). CV monosyllable perception and word recognition scores post-CI were compared between the elderly and young adults.There was no significant difference in CV monosyllable speech perception among age groups. CV monosyllable speech perception in the elderly (61.4 ± 25.5%) did not differ from that of young adults (65.9 ± 24.8%). Word recognition scores were significantly lower in the elderly (64.3 ± 28.1%) than young adults (80.4 ± 25.9%) (p0.05).

Objective: This study examines ABHD12 mutation analysis in 2 PHARC patients, originally thought to be Usher syndrome. Methods: The ABHD12 gene of 2 patients, who suffered from deaf-blindness and dysfunctional central and peripheral nervous systems, were sequenced. Results: We identified that both cases carried the same novel splice site mutation in the ABHD12 gene. However, 1 had epilepsy and the other had peripheral neuropathy. Based on haplotype analysis, the mutation is likely not a hot spot, but rather could be attributable to a common ancestor. Conclusion: This study shows that PHARC has phenotypic variability, even within a family, which is consistent with previous reports. Differential diagnosis of “deaf-blindness” diseases is crucial. Confirming the presence of associated symptoms is necessary for differentiating some deaf-blindness syndromes. In addition, mutation analysis is a useful tool for confirming the diagnosis.

Perilymphatic fistula (PLF) is defined as an abnormal leakage between perilymph from the labyrinth to the middle ear. Symptoms include hearing loss, tinnitus, and vertigo. The standard mode of PLF detection is intraoperative visualization of perilymph leakage and fistula, which ostensibly confirms the existence of PLF. Other possible methods of diagnosis include confirmation of pneumolabyrinth via diagnostic imaging. Recently, a cochlin-tomoprotein (CTP) detection test has been developed that allows definitive diagnosis of PLF-related hearing loss. We report the case of a 45-year-old man who presented with right-sided tinnitus, hearing loss, and dizziness 30 years after stapes surgery. Middle ear lavage was performed after myringotomy. A preoperative diagnosis of PLF was reached using the CTP detection test. Intraoperative observations included a necrotic long process of the incus, displaced wire piston, and fibrous tissue in the oval window. Perilymph leakage was not evident. The oval window was closed with fascia, and vertigo disappeared within 2 weeks postoperatively. When PLF is suspected after stapes surgery, the CTP detection test can be a useful, highly sensitive, and less invasive method for preoperative diagnosis.

MicroRNAs (miRNAs) play functional roles in sound transduction in cochlea. This study focuses on the validity of cochlear culture as an in vitro experimental tool, in view of miRNA expression. E15 cochleae were dissected and maintained in vitro for 48 h before extraction of miRNAs. MiRNA expression was comprehensively screened in explanted cochleae using a miRNA array that covers 380 miRNAs. A strong correlation was observed between expression levels of miRNAs in in vitro and in in vivo cochleae. Levels of 43 miRNAs were altered in vitro and these changes were reproducible over three trials. These findings indicate that in vitro miRNA profiling is a viable method for analysis of gene expression and action of chemical compounds on cochleae.

Charcot-Marie-Tooth disease (CMT) is the most common form of hereditary sensorimotor neuropathy and sometimes involves disorders of the peripheral auditory system. We present a case of steroid-dependent auditory neuropathy associated with CMT, in which the patient experienced 3 episodes of acute exacerbation of hearing loss and successful rescue of hearing by prednisolone. An 8-year-old boy was referred to the otolaryngology department at the University Hospital. He had been diagnosed with CMT type 1 (demyelinating type) at the Child Neurology Department and was suffering from mild hearing loss due to auditory neuropathy. An audiological diagnosis of auditory neuropathy was confirmed by auditory brainstem response and distortion-product otoacoustic emissions. At 9 years and 0 months old, 9 years and 2 months old, and 10 years and 0 months old, he had experienced acute exacerbations of hearing loss, each of which was successfully rescued by intravenous or oral prednisolone within 2 weeks. Steroid-responsive cases of CMT have been reported, but this is the first case report of steroid-responsive sensorineural hearing loss in CMT. The present case may have implications for the mechanisms of action of glucocorticoids in the treatment of sensorineural hearing loss.

Objective: Decreasing language delay in hearing-impaired children is a key issue in the maintenance of their quality of life. Language training has been presented mainly by experience-based training; effective intervention programs are crucially important for their future. The aim of this study was to confirm the efficacy of 6-month domain-based language training of school-age, severe-to-profound hearing-impaired children. Methods: We conducted a controlled before–after study involving 728 severe-to-profound prelingual hearing-impaired children, including an intervention group (n = 60), control group (n = 30), and baseline study group (n = 638). Language scores of the participants and questionnaires to the caregivers/therapists were compared before and after the intervention. Average monthly increase in each language score of the control group and baseline study group were compared with those of the intervention group. Results: Language scores and the results of the questionnaire of the intervention group showed a significant improvement ( P < .05). The average monthly language growth of the intervention group was twice that of the control group and 3 to 4 times that of the baseline study group ( P < .05). The effect size was largest in communication (1.914), followed by syntax (0.931). Conclusion: Domain-based language training improved the language development and daily communication of hearing-impaired children without any adverse effects.

The dissemination of newborn hearing screening (NHS) has enabled those with mild to moderate hearing loss to be diagnosed in early infancy. The "handicapped independence support law", however, prevents those not determined to be physically handicapped; i.e., those with mild to moderate hearing loss-, from government assistance in purchasing hearing aids. This results either in (i) parents purchasing hearing aids at their own expense or (ii) nonpurchase of hearing aids. To redress this situation, subvention in purchasing hearing aids of mild to moderate hearing loss children has been begun by some local governments. We petitioned for such aid at the Okayama Prefecture Assembly. A society for supporting pediatric hearing difficulty in Okayama Prefecture also submitted a similar petition in September 2009, and subvention began in April 2010 for all such children in Okayama Prefecture. We report procedures and details leading to this subvention.

The occasional local recurrence of benign pleomorphic adenoma (PA) has generally been attributed to the vulnerability of the tumor capsule. Although some reports have also noted the presence of satellite tumors associated with PA recurrence, only few reports have focused on this issue. We paid special attention to the satellite lesions apart from the main tumors and discussed their frequency, origin, nature and the ways of treating them. A total of 108 specimens of primary parotid gland PA resected at the Okayama Saiseikai General Hospital from 1988 to 2008 were microscopically reviewed. Four (3.7%) patients displayed a main mass with satellite tumors in a single parotid gland. The immunohistochemical analysis of p53 and Ki-67 index showed no distinct difference between PAs with satellite tumors and those without. Satellite tumors surrounding the main mass of parotid PA is relatively rare. In most cases, such satellite tumors will arise from capsular perforation of the primary tumor cells. Preoperative evaluation to recognize the existence of satellite tumors would be important and capsular dissection should be discouraged. We could not find any evidence suggesting that primary PA with satellite tumors could be more biologically aggressive than those without.