Electric-acoustic stimulation with longer electrodes for potential deterioration in low-frequency hearing.

Background: Electric-acoustic stimulation (EAS) has emerged as a standard treatment for patients with high-frequency hearing loss. EAS is usually performed with shorter electrodes of 16-24 mm in length. As most EAS recipients gradually lose residual acoustic hearing in the implanted ear over time, EAS with longer electrodes without causing significant intra-cochlear damage might be ideal.Objective: The aim of this study was to investigate hearing preservation (HP) results after EAS surgery with longer electrodes.Methods: Ten patients (11 ears) with partial deafness that met the indications for EAS with a MED-EL FLEX28 electrode were included in this study. Auditory thresholds before and at 6 months after activation were examined.Results: In 100% of cases, HP was comfortably achieved, indicating that all patients could utilize acoustic amplification combined with electric stimulation.Conclusion: EAS with longer electrodes can offer broader cochlear coverage, resulting in natural frequency matching in comparison with shorter electrodes, even in EAS cases. The combination of advanced surgical techniques and flexible, long, straight electrodes permits deep insertion that reaches the apical region with little or no insertion trauma.

Genetic testing has the potential to impact hearing preservation following cochlear implantation.

Background: Recent advances in less-invasive surgery and electrode design allow for a high degree of hearing preservation (HP) after cochlear implantation (CI), although residual hearing still deteriorates in some patients. To date, the factors predictive of preserving residual hearing remain a controversial topic.Objective: The aim of this study was to investigate the predictive factors, including the etiology of hearing loss (HL) as a patient-related factor, influencing residual HP after CI.Methods: Forty-four patients (50 ears, 41 families) with residual acoustic hearing who underwent CI were included. Auditory thresholds before and at 6 months after initial activation were measured. Genetic testing was performed to identify the responsible genes for HL.Results: We identified the cause of HL in 21 families (51.2%). HP was marginally correlated with age at implantation, while it was independent of pre-operative low-frequency hearing thresholds, cochlear duct length, and electrode length. We found that patients who had pathogenic variants in the CDH23, MYO7A, or MYO15A gene showed statistically better HP scores compared with patients with HL due to other causes (p = .002).Conclusions: Identification of the etiology of HL using genetic testing is likely to facilitate the prediction of HP after implant surgery.

Comprehensive analysis of syndromic hearing loss patients in Japan.

More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

Targeted Allele Suppression Prevents Progressive Hearing Loss in the Mature Murine Model of Human TMC1 Deafness.

Hearing loss is the most common human sensory deficit. Its correction has been the goal of several gene-therapy based studies exploring a variety of interventions. Although these studies report varying degrees of success, all treatments have targeted developing inner ears in neonatal mice, a time point in the structural maturation of the cochlea prior to 26 weeks gestational age in humans. It is unclear whether cochlear gene therapy can salvage hearing in the mature organ of Corti. Herein, we report the first study to test gene therapy in an adult murine model of human deafness. Using a single intracochlear injection of an artificial microRNA carried in an AAV vector, we show that RNAi-mediated gene silencing can slow progression of hearing loss, improve inner hair cell survival, and prevent stereocilia bundle degeneration in the mature Beethoven mouse, a model of human TMC1 deafness. The ability to study gene therapy in mature murine ears constitutes a significant step toward its translation to human subjects.

Pneumolabyrinth, intracochlear and vestibular fluid loss after cochlear implantation.

The present case was a 38-year-old male who presented with progressive hearing loss, resulting in profound bilateral hearing loss. He had a past history of childhood medulloblastoma, which was treated with posterior fossa craniotomy and radiotherapy. A ventriculoperitoneal (VP) shunt was put in place to manage the hydrocephalus. Cochlear implantation (CI) was carried out on his right ear by a standard procedure. At CI activation, the electric impedance of the electrode was very high, and computed tomography revealed that there was no area of liquid density, suggesting depletion of the perilymph in the cochlea and vestibule. Eight months later, the impedance improved gradually, and the cochlea was filled with perilymph. Consequently, one of the causes of the pneumolabyrinth in the present case was that a scarred stenotic cochlear canaliculus secondary to surgery or radiation therapy might have prevented the CSF from filling the scala. In addition, it is also possible that the VP shunt might have altered the CSF pressure, leading to depletion of the perilymph.

Feasibility of hearing preservation for residual hearing with longer cochlear implant electrodes.

BACKGROUND: Hearing preservation is thought to be achievable following atraumatic surgery with thin cochlear implant electrodes; therefore, the surgical approach and implant electrode design are crucial considerations. OBJECTIVE: To assess the feasibility of hearing preservation with long electrodes for patients meeting the criteria for conventional cochlear implantation. METHODS: One hundred and two patients (132 ears) who underwent cochlear implant surgery were analyzed. Inclusion criteria included measurable residual hearing in the low frequency before implantation and not meeting the criteria for electric acoustic stimulation (EAS). RESULTS: Of the 18 patients with residual hearing in the low frequency enrolled, 17 subjects (94.4%) retained low frequency hearing. A younger age at surgery tended to contribute to better hearing preservation than that observed in older patients. There was no clear trend regarding the influence of insertion depth angle of the electrode on hearing preservation. CONCLUSION: It is possible to achieve hearing preservation in the lower frequency by the use of longer electrodes. This study underscores the importance of atraumatic surgery, even for patients with only limited residual hearing, and longer electrodes should be adopted for EAS.

Etiology of single-sided deafness and asymmetrical hearing loss.

CONCLUSIONS: The present study revealed that various etiologies are involved in single-sided deafness (SSD), and that the cause of SSD and asymmetrical hearing loss (AHL) differed greatly between congenital/early-onset cases and adult cases. Clarification of the etiology is the first step toward providing appropriate intervention. OBJECTIVES: The study aimed to clarify the etiology of SSD and AHL patients. METHODS: The etiology of a total of 527 SSD or AHL patients who visited Shinshu University Hospital between 2006 and 2016 were analyzed by imaging as well as serological tests for mumps virus, and CMV DNA testing. RESULTS: In our cohort of congenital/early-onset SSD (n = 210), the most prevalent cause in children was cochlear nerve deficiency (43.7%; 87 of 199 patients undergoing CT and/or MRI), followed by CMV infection, mumps infection, anomalies of the inner ear, ANSD, and other rare etiologies. In contrast, half of the adult SSD patients presented with idiopathic sensorineural hearing loss, followed by various types of otitis media, cerebellopontine angle tumor and other rare etiologies.

Long-term results of hearing preservation cochlear implant surgery in patients with residual low frequency hearing.

CONCLUSION: Differences were found between patients with stable hearing and those with progressive hearing loss in the lower frequencies with respect to the rate of progression in the contralateral ear. It is suggested that the electric acoustic stimulation (EAS) can provide improvement in hearing ability over the long-term if residual hearing might be lost to some extent. OBJECTIVE: To evaluate the long-term threshold changes in the low frequency hearing of the implanted ear as compared with the non-implanted ear, and the hearing abilities with EAS along with the extent of residual hearing. METHODS: Seventeen individuals were enrolled and received the EAS implant with a 24-mm FLEXeas electrode array. Hearing thresholds and speech perception were measured pre- and post-operatively for 1-5 years. Post-operative hearing preservation (HP) rates were calculated using the preservation numerical scale. RESULTS: The average linear regression coefficient for the decline in hearing preservation score was -6.9 for the implanted ear and the patients were subsequently categorized into two groups: those with better than average, stable hearing; and those with worse than average, progressive hearing loss. EAS showed better results than electric stimulation alone, in spite of an absence of speech perception with acoustic stimulation.

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.

Silicone impression material foreign body in the middle ear: Two case reports and literature review.

We report two cases of impression material foreign body in the middle ear. The first case had been affected with chronic otitis media. The silicone flowed into the middle ear through a tympanic membrane perforation during the process of making an ear mold. About 4 years and 8 months after, the patient had severe vertigo and deafness. We found bone erosion of the prominence of the lateral semicircular canal and diagnosed labyrinthitis caused by silicone impression material. In the second case silicone flowed into the canal wall down mastoid cavity. Both cases required surgery to remove the foreign body. The clinical courses in such cases are variable and timing of surgery is sometimes difficult. In addition to reporting these two cases, we present here a review of the literature regarding impression material foreign bodies.

Hearing loss caused by a P2RX2 mutation identified in a MELAS family with a coexisting mitochondrial 3243AG mutation.

OBJECTIVES: We present a family with a mitochondrial DNA 3243A>G mutation resulting in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), of which some members have hearing loss in which a novel mutation in the P2RX2 gene was identified. METHODS: One hundred ninety-four (194) Japanese subjects from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were performed to identify the genetic causes of hearing loss. RESULTS: A novel mutation in the P2RX2 gene that corresponded to c.601G>A (p.Asp201Tyr) was identified. Two patients carried the mutation and had severe sensorineural hearing loss, while other members with MELAS (who did not carry the P2RX2 mutation) had normal hearing. CONCLUSION: This is the first case report of a diagnosis of hearing loss caused by P2RX2 mutation in patients with MELAS. A potential explanation is that a decrease in adenosine triphosphate (ATP) production due to MELAS with a mitochondrial 3243A>G mutation might suppress activation of P2X2 receptors. We also suggest that hearing loss caused by the P2RX2 mutation might be influenced by the decrease in ATP production due to MELAS.

Novel PTPRQ mutations identified in three congenital hearing loss patients with various types of hearing loss.

OBJECTIVES: We present 3 patients with congenital sensorineural hearing loss (SNHL) caused by novel PTPRQ mutations, including clinical manifestations and phenotypic features. METHODS: Two hundred twenty (220) Japanese subjects with SNHL from unrelated and nonconsanguineous families were enrolled in the study. Targeted genomic enrichment with massively parallel DNA sequencing of all known nonsyndromic hearing loss genes was performed to identify the genetic cause of hearing loss. RESULTS: Four novel causative PTPRQ mutations were identified in 3 cases. Case 1 had progressive profound SNHL with a homozygous nonsense mutation. Case 2 had nonprogressive profound SNHL with a compound heterozygous mutation (nonsense and missense mutation). Case 3 had nonprogressive moderate SNHL with a compound heterozygous mutation (missense and splice site mutation). Caloric test and vestibular evoked myogenic potential (VEMP) test showed vestibular dysfunction in Case 1. CONCLUSION: Hearing loss levels and progression among the present cases were varied, and there seem to be no obvious correlations between genotypes and the phenotypic features of their hearing loss. The PTPRQ mutations appeared to be responsible for vestibular dysfunction.

Mutations in the MYO15A gene are a significant cause of nonsyndromic hearing loss: massively parallel DNA sequencing-based analysis.

OBJECTIVES: Screening for MYO15A mutations was carried out using a large cohort to clarify the frequency and clinical characteristics of patients with MYO15A (DFNB3) mutations in a hearing loss population. METHODS: Genetic analysis of 63 previously reported deafness genes based on massively parallel DNA sequencing (MPS) in 1120 Japanese hearing loss patients from 53 otorhinolaryngology departments was performed. Detailed clinical features of the patients with MYO15A mutations were then collected and analyzed. RESULTS: Eleven patients from 10 families were found to have compound heterozygosity for MYO15A. Audiograms showed profound or high frequency hearing loss, with some patients showing progressive hearing loss. Age at onset was found to vary from 0 to 14 years, which seemed to be associated with the mutation. Four children underwent bilateral cochlear implantation for congenital hearing loss, with all showing good results. CONCLUSION: Mutations in the MYO15A gene are a notable cause of nonsyndromic hearing loss. MPS technology successfully detected mutations in relatively rare deafness genes such as MYO15A.

The patients associated with TMPRSS3 mutations are good candidates for electric acoustic stimulation.

OBJECTIVES: To clarify the frequency of TMPRSS3 mutations in the hearing loss population, genetic analysis was performed, and detailed clinical characteristics were collected. Optical intervention for patients with TMPRSS3 mutations was also discussed. METHODS: Massively parallel DNA sequencing (MPS) was applied for the target exon-sequencing of 63 deafness genes in a population of 1120 Japanese hearing loss patients. RESULTS: Hearing loss in 5 patients was found to be caused by compound heterozygous TMPRSS3 mutations, and their detailed clinical features were collected and analyzed. Typically, all of the patients showed ski slope type audiograms and progressive hearing loss. Three of the 5 patients received electric acoustic stimulation (EAS), which showed good results. Further, the onset age was found to vary, and there were some correlations between genotype and phenotype (onset age). CONCLUSIONS: MPS is a powerful tool for the identification of rare causative deafness genes, such as TMPRSS3. The present clinical characteristics not only confirmed the findings from previous studies but also provided clinical evidence that EAS is beneficial for patients possessing TMPRSS3 mutations.

Significant pericardial involvement of immunoglobulin G4-related disease.

A 60-year-old woman was hospitalized with cardiac tamponade due to effusive pericarditis presenting with significant thickening of the pericardium. Serum immunoglobulin G4 (IgG4) level was elevated to 1,800 mg/dL, and an open biopsy specimen from the pericardium revealed massive infiltration of lymphocytes and IgG4-positive plasma cells. She had experienced adenopathies in the lacrimal and parotid glands 6 months earlier, and was diagnosed as having IgG4-related Mikulicz's disease by similar cell infiltration in the salivary gland biopsy. The significant involvement of the pericardium as a manifestation of IgG4-related disease is described, as well as the successful treatment with oral corticosteroids.

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

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.

Effects of EAS cochlear implantation surgery on vestibular function.

CONCLUSIONS: The patients who received electric acoustic stimulation (EAS) cochlear implantation had relatively good vestibular function compared with the patients who did not have residual hearing. The vestibular function was well preserved after atraumatic EAS surgery. The round window approach and soft electrode are preferred to decrease the risk of impairing vestibular function. OBJECTIVES: The aim of this study was to examine the characteristic features of vestibular functions before and after implantations in patients undergoing EAS. METHODS: Vestibular functions in patients who underwent EAS implantation were examined by caloric testing and vestibular evoked myogenic potential (VEMP) in 11 patients before and in 13 patients after implantation. RESULTS: Preoperative evaluation showed that of the 11 patients, most (73%) had good vestibular function. One of 11 patients (9%) had decreased response in postoperative VEMP but all of the patients had unchanged results in postoperative caloric testing.

A case of Mikulicz's disease complicated by malignant lymphoma: a postmortem histopathological finding.

A 66-year-old Japanese man with an 11-year history of Mikulicz's disease (MD) received continuous corticosteroid administration. At age 58, a left renal pelvic mass was identified and diagnosed as an IgG4-related inflammatory pseudotumor. The patient underwent an operation to remove the tumor. Subsequently, he contracted repeated pulmonary infections and eventually died of severe gastrointestinal bleeding. Autopsy revealed systemic lymph node swelling and infiltration in some organs, and diffuse large B-cell lymphoma (DLBCL) was diagnosed. These findings suggest that an IgG4-related disease can be causally related to the development of malignant lymphoma through the occurrence of mucosa-associated lymphoid tissue lymphoma.

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

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.