Hideaki Moteki

Achievement of hearing preservation in the presence of an electrode covering the residual hearing region

Abstract Conclusions: With full insertion with a long electrode, hearing preservation can be achieved even in the presence of a long electrode covering the residual hearing region. Objectives: Advances in developing new atraumatic concepts of electrode design as well as surgical technique have enabled hearing preservation after cochlear implantation surgery, and EAS (electric acoustic stimulation) accompanied with hearing preservation is a new trend for patients with residual hearing at the lower frequencies. However, full insertion with a long/medium electrode and hearing preservation is still a challenging field that calls for discussion. Method: In this study, round window insertion, an atraumatic electrode, and dexamethasone administration were used and atraumaticity (hearing preservation and conservation of vestibular function) was evaluated with full insertion of the electrode. Results: Postoperative evaluation after full insertion of the electrodes showed that hearing at low frequencies was well preserved in all five cases. Combined postoperative imaging with the referential tonotopic map confirmed achievement of full insertion and indicated the corresponding frequencies and the depth of the electrode. Achievement of atraumaticity of round window insertion in the present cases was confirmed from the viewpoint of the minimal drilling time as well as the preserved vestibular function.

IgG4-related chronic rhinosinusitis: A new clinical entity of nasal disease

Abstract Conclusion: IgG4-related disease involves nasal manifestations with chronic rhinosinusitis (CRS). This type of sinusitis is a new clinical entity of nasal disease associated with a high level of serum IgG4 for which steroid therapy is effective. Objectives. To confirm whether IgG4-related disease has distinctive chronic rhinosinusitis. Methods: We compared serum IgG4 levels as well as nasal computed tomography (CT) and clinicopathological findings before and after glucocorticoid treatment in 31 patients diagnosed as having IgG4-related disease with nasal manifestations. To evaluate immunohistochemical findings of nasal mucosa, we compared them with IgG4-related CRS and common CRS. Results: All patients had levels of high serum IgG4. Ten of the 31 patients had nasal obstruction, nasal discharge, postnasal discharge, hyposmia, and dull headache. They also demonstrated sinus lesions on radiological findings. After glucocorticoid treatment, serum IgG and IgG4 levels were markedly decreased and along with improvement of the symptoms, nasal sinus CT findings also revealed improvement of the sinus opacification. In immunohistochemical examination, the magnitude of IgG4-positive plasma cell infiltration in common CRS was almost the same as in the IgG4-related CRS group. Therefore, in nasal mucosa immunocytochemical positive staining for IgG4 is not specific for definition of IgG4-related disease.

Hearing preservation and clinical outcome of 32 consecutive electric acoustic stimulation (EAS) surgeries

Abstract Conclusions: Our results indicated that electric acoustic stimulation (EAS) is beneficial for Japanese-speaking patients, including those with less residual hearing at lower frequencies. Comparable outcomes for the patients with less residual hearing indicated that current audiological criteria for EAS could be expanded. Successful hearing preservation results, together with the progressive nature of loss of residual hearing in these patients, mean that minimally invasive full insertion of medium/long electrodes in cochlear implantation (CI) surgery is a desirable solution. The minimally invasive concepts that have been obtained through EAS surgery are, in fact, crucial for all CI patients. Objectives: This study was conducted to evaluate hearing preservation results and speech discrimination outcomes of hearing preservation surgeries using medium/long electrodes. Methods: A total of 32 consecutive minimally invasive hearing preservation CIs (using a round window approach with deep insertion of a flexible electrode) were performed in 30 Japanese patients (two were bilateral cases), including patients with less residual hearing. Hearing preservation rates as well as speech discrimination/perception scores were investigated on a multicenter basis. Results: Postoperative evaluation after full insertion of the flexible electrodes (24 mm, 31.5 mm) showed that residual hearing was well preserved in all 32 ears. In all patients, speech discrimination and perception scores were improved postoperatively.

Experience with the Vibrant Soundbridge RW-Coupler for round window Vibroplasty with tympanosclerosis

Abstract Usage of the Vibrant Soundbridge (VSB) with round window (RW)-Coupler placement at the RW has been shown to successfully treat mixed hearing loss. Coupling between the VSBs floating mass transducer (FMT) and the RW membrane is difficult in the case of sclerosis in the RW and drilling down the bony lip until the RW membrane can be seen completely can possibly induce a perilymphatic fistula. A 68-year-old woman who had bilateral mixed hearing loss with sclerosis in the RW due to tympanosclerosis underwent a RW-Vibroplasty with a RW-Coupler. Speech discrimination scores in quiet and noise and functional gain with the VSB with RW-Coupler were better than those using a conventional hearing aid. The results of the present case have shown the feasibility of implanting a VSB with RW-Coupler in patients with mixed hearing loss due to tympanosclerosis.

Patients with CDH23 mutations and the 1555A>G mitochondrial mutation are good candidates for electric acoustic stimulation (EAS)

Abstract Conclusions: CDH23 mutations and the 1555A>G mitochondrial mutation were identified among our series of electric acoustic stimulation (EAS) patients, confirming that these genes were important in hearing loss with involvement of high frequency. Successful hearing preservation as well as good outcomes from EAS indicated that patients with this combination of mutations are good candidates for EAS. Objectives: Screening for gene mutations that possibly cause hearing loss involving high frequency was performed to identify the responsible genes in patients with EAS. In addition to a review of the genetic background of the patients with residual hearing loss, the benefit of EAS for patients with particular gene mutations was evaluated. Methods: Eighteen patients (15 late-onset, 3 early-onset) with residual hearing who had received EAS were included in this study. Genetic analysis was performed to identify GJB2, CDH23, SLC26A4, and the 1555 mitochondrial mutations. Results: Three early-onset patients had CDH23 mutations. One late-onset patient had the 1555 A>G mitochondrial mutation.

Clinical profile of hearing loss in children with congenital cytomegalovirus (CMV) infection: CMV DNA diagnosis using preserved umbilical cord.

Abstract Conclusions: Congenital cytomegalovirus (CMV) infection is a major cause of bilateral and unilateral sensorineural hearing loss (SNHL) in children, accounting for 9.0% of SNHL cases. The diagnostic rate using combined genetic deafness test and CMV DNA detection test was determined to be 46.4% in bilateral profound SNHL. Objectives. The present study investigated the prevalence of congenital CMV infection diagnosed retrospectively by detection of CMV DNA in dried umbilical cord specimens from children with unilateral or bilateral SNHL up to the age of 12 years. Methods: Preserved dried umbilical cords were collected from 134 children with bilateral (46 children) or unilateral (88 children) SNHL. DNA was extracted from the dried umbilical cords and CMV DNA was detected by quantitative PCR. Genetic deafness tests based on the invader assay were performed in children with bilateral SNHL. Results: CMV DNA from the dried umbilical cords was detected in 8.7% of the bilateral SNHL and 9.1% of unilateral SNHL. Deafness gene mutations were identified in 21.7% (10/46) of children with bilateral SNHL.

TECTA mutations in Japanese with mid-frequency hearing loss affected by zona pellucida domain protein secretion

TECTA gene encodes α-tectorin, the major component of noncollagenous glycoprotein of the tectorial membrane, and has a role in intracochlear sound transmission. The TECTA mutations are one of the most frequent causes of autosomal dominant (AD) hearing loss and genotype–phenotype correlations are associated with mutations of TECTA in exons according to α-tectorin domains. In this study, we investigated the prevalence of hearing loss caused by TECTA mutations in Japanese AD hearing loss families, and confirmed genotype–phenotype correlation, as well as the intracellular localization of missense mutations in the α-tectorin domain. TECTA mutations were detected in 2.9% (4/139) of our Japanese AD hearing loss families, with the prevalence in moderate hearing loss being 7.7% (4/52), and all patients showed typical genotype–phenotype correlations as previously described. The present in vitro study showed differences of localization patterns between wild type and mutants, and suggested that each missense mutation may lead to a lack of assembly of secretion, and may reduce the incorporation of α-tectorin into the tectorial membrane.

Language development in Japanese children who receive cochlear implant and/or hearing aid

OBJECTIVES This study aimed to investigate a wide variety of factors that influence auditory, speech, and language development following pediatric cochlear implantation (CI). STUDY DESIGN Prospective collection of language tested data in profound hearing-impaired children. HYPOTHESIS Pediatric CI can potentially be effective to development of practical communication skills and early implantation is more effective. METHODS We proposed a set of language tests (assessment package of the language development for Japanese hearing-impaired children; ALADJIN) consisting of communication skills testing (test for question-answer interaction development; TQAID), comprehensive (Peabody Picture Vocabulary Test-Revised; PVT-R and Standardized Comprehension Test for Abstract Words; SCTAW) and productive vocabulary (Word Fluency Test; WFT), and comprehensive and productive syntax (Syntactic processing Test for Aphasia; STA). Of 638 hearing-impaired children recruited for this study, 282 (44.2%) with >70 dB hearing impairment had undergone CI. After excluding children with low birth weight (<1800 g), those with >11 points on the Pervasive Developmental Disorder ASJ Rating Scale for the test of autistic tendency, and those <2 SD on Ravens Colored Progressive Matrices for the test of non-verbal intelligence, 190 children were subjected to this set of language tests. RESULTS Sixty children (31.6%) were unilateral CI-only users, 128 (67.4%) were CI-hearing aid (HA) users, and 2 (1.1%) were bilateral CI users. Hearing loss level of CI users was significantly (p<0.01) worse than that of HA-only users. However, the threshold level, maximum speech discrimination score, and speech intelligibility rating in CI users were significantly (p<0.01) better than those in HA-only users. The scores for PVT-R (p<0.01), SCTAW, and WFT in CI users were better than those in HA-only users. STA and TQAID scores in CI-HA users were significantly (p<0.05) better than those in unilateral CI-only users. The high correlation (r=0.52) has been found between the age of CI and maximum speech discrimination score. The scores of speech and language tests in the implanted children before 24 months of age have been better than those in the implanted children after 24 months of age. CONCLUSIONS We could indicate that CI was effective for language development in Japanese hearing-impaired children and early CI was more effective for productive vocabulary and syntax.

RNA Interference Prevents Autosomal-Dominant Hearing Loss

Hearing impairment is the most common sensory deficit. It is frequently caused by the expression of an allele carrying a single dominant missense mutation. Herein, we show that a single intracochlear injection of an artificial microRNA carried in a viral vector can slow progression of hearing loss for up to 35 weeks in the Beethoven mouse, a murine model of non-syndromic human deafness caused by a dominant gain-of-function mutation in Tmc1 (transmembrane channel-like 1). This outcome is noteworthy because it demonstrates the feasibility of RNA-interference-mediated suppression of an endogenous deafness-causing allele to slow progression of hearing loss. Given that most autosomal-dominant non-syndromic hearing loss in humans is caused by this mechanism of action, microRNA-based therapeutics might be broadly applicable as a therapy for this type of deafness.

De Novo Mutation in X-Linked Hearing Loss–Associated POU3F4 in a Sporadic Case of Congenital Hearing Loss

Objectives: In this report, we present a male patient with no family history of hearing loss, in whom we identified a novel de novo mutation in the POU3F4 gene. Methods: One hundred ninety-four (194) Japanese subjects from unrelated and nonconsanguineous families were enrolled in this study. We used targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes for identifying the genetic causes of hearing loss. Results: A novel de novo frameshift mutation of POU3F4 to c.727_728insA (p.N244KfsX26) was identified. The patient was a 7-year-old male with congenital progressive hearing loss and inner ear deformity. Although the patient had received a cochlear implant, auditory skills were still limited. The patient also exhibited developmental delays similar to those previously associated with POU3F4 mutation. Conclusion: This is the first report of a mutation in POU3F4 causing hearing loss in a Japanese patient without a family history of hearing loss. This study underscores the importance of comprehensive genetic testing of patients with hearing loss for providing accurate prognostic information and guiding the optimal management of patient rehabilitation.